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Preparing International Travelers 

Preparing International Travelers
Chapter:
Preparing International Travelers
Author(s):

Gary W. Brunette

and Jeffrey B. Nemhauser

DOI:
10.1093/med/9780190928933.003.0002
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date: 07 April 2020

The Pretravel Consultation

The pretravel consultation offers a dedicated time to prepare travelers for the health concerns that might arise during their trips. The objectives of the pretravel consultation are to:

  1. 1. Perform an individual risk assessment.

  2. 2. Communicate to the traveler anticipated health risks.

  3. 3. Provide risk management measures, including immunizations, malaria prophylaxis, and other medications as indicated.

The Travel Medicine Specialist

Travel medicine specialists have in-depth knowledge of immunizations, risks associated with specific destinations, and the implications of traveling with underlying conditions. Therefore, a comprehensive consultation with a travel medicine expert is indicated for all travelers, and is particularly important for those with a complicated health history, special risks (such as traveling at high altitudes or working in refugee camps), or exotic or complicated itineraries. Clinicians who wish to be travel medicine providers are encouraged to join the International Society of Travel Medicine (ISTM) and consider specialty training and certification.

Components of a Pretravel Consultation

Effective pretravel consultations require attention to the health background of the traveler and incorporate the itinerary, trip duration, travel purpose, and activities, all of which determine health risks (Table 2-1). The pretravel consultation is the major opportunity to educate the traveler about health risks at the destination and how to mitigate them. The typical pretravel consultation does not include a physical examination; a separate appointment with the same or a different provider may be necessary to assess a person’s fitness to travel. Because travel medicine clinics are not available in some communities, primary care physicians should seek guidance (by phone or other communication, if available) from travel medicine specialists to address areas of uncertainty.

Table 2-1. Information necessary for a risk assessment during pretravel consultations

Health Background

Past medical history

Age

Sex

Underlying conditions

Allergies (especially any pertaining to vaccines, eggs, or latex)

Medications

Special conditions

Pregnancy (including trimester)

Breastfeeding

Disability or handicap

Immunocompromising conditions or medications

Older age

Psychiatric condition

Seizure disorder

Recent surgery

Recent cardiopulmonary event

Recent cerebrovascular event

History of Guillain-Barré syndrome

Severe allergies

Immunization history

Routine vaccines

Travel vaccines

Prior travel experience

Experience with malaria chemoprophylaxis

Experience with altitude

Illnesses related to prior travel

Trip Details

Itinerary

Countries and specific regions, including order of countries if >1 country

Rural or urban

Timing

Trip duration

Season of travel

Time to departure

Reason for travel

Tourism

Business

Visiting friends and relatives

Volunteer, missionary, or aid work

Research or education

Adventure

Pilgrimage

Adoption

Seeking health care (medical tourism)

Travel style

Independent travel or package tour

Propensity for “adventurous” eating

Traveler risk tolerance

General hygiene standards at destination

Modes of transportation

Accommodations (such as tourist or luxury hotel, guest house, hostel or budget hotel, dormitory, local home or host family, or tent)

Special activities

Disaster relief

Medical care (providing or receiving)

High altitude

Diving

Cruise ship

Rafting or other water exposure

Cycling

Extreme sports

Spelunking

Anticipated interactions with animals

Anticipated sexual encounters

Travel health advice should be personalized, highlighting the likely exposures and also reminding the traveler of ubiquitous risks, such as injury, foodborne and waterborne infections, vectorborne disease, respiratory tract infections, and bloodborne and sexually transmitted infections. Balancing the cautions with an appreciation of the positive aspects of the journey leads to a more meaningful pretravel consultation. Attention to the cost of recommended interventions may be critical. Some travelers may not be able to afford all of the recommended immunizations and medications, a situation that requires prioritizing interventions. (See Prioritizing Care for the Resource-Limited Traveler later in this chapter.)

Assess Individual Risk

Many elements merit consideration in assessing a traveler’s health risks (Table 2-1). Certain travelers may confront special risks. Recent hospitalization for serious problems may lead the travel health provider to recommend delaying travel. Air travel is contraindicated for certain conditions, such as <3 weeks after an uncomplicated myocardial infarction and <10 days after thoracic or abdominal surgery. The travel health provider and traveler should consult with the relevant health care providers most familiar with the underlying illnesses. Other travelers with specific risks include travelers who are visiting friends and relatives, long-term travelers, travelers with small children, travelers with chronic illnesses, immunocompromised travelers, and pregnant travelers. More comprehensive discussion on advising travelers who have additional health considerations is available in Chapter 5. Providers should determine whether recent outbreaks or other safety notices have been posted for the traveler’s destination; information is available on the CDC and US Department of State websites, and in various other resources.

In addition to recognizing the traveler’s characteristics, health background, and destination-specific risks, the exposures related to special activities also merit discussion. For example, river rafting could expose a traveler to schistosomiasis or leptospirosis, and spelunking in Central America could put the traveler at risk of histoplasmosis. Flying from lowlands to high-altitude areas and trekking or climbing in mountainous regions introduces the risk of altitude illness. Therefore, the provider should inquire about plans for specific leisure, business, and health care–seeking activities.

Communicate Risk

Once destination-specific risks for a particular itinerary have been assessed by the provider, they should be clearly communicated to the traveler. The process of risk communication is a 2-way exchange of information between the clinician and traveler, in which they discuss potential health hazards at the destination and the effectiveness of preventive measures, with the goal of improving understanding of risk and promoting more informed decision making. Risk communication is among the most challenging aspects of a pretravel consultation, because travelers’ perception of and tolerance for risk can vary widely. For a more detailed discussion, see Perspectives: Travelers’ Perception of Risk in this chapter.

Manage Risk

Immunizations are a crucial component of pretravel consultations, and the risk assessment forms the basis of recommendations for travel vaccines. For example, providers should consider whether there is sufficient time before travel to complete a vaccine series; the purpose of travel and specific destination within a country will inform the need for particular vaccinations. At the same time, the pretravel consultation presents an opportunity to update routine vaccines (Table 2-2). Particular attention should be paid to vaccines for which immunity may have waned over time or following a recent immunocompromising condition (such as after a hematopoietic stem cell transplant). Asking the question, “Do you have any plans to travel again in the next 1–2 years?” may help the traveler justify an immunization for travel over a number of years rather than only the upcoming trip, such as rabies preexposure or Japanese encephalitis. Travelers should receive a record of immunizations administered and instructions to follow up as needed to complete a vaccine series.

Table 2-2. Vaccines to update or consider during pretravel consultations

Vaccine

Travel-Related Occurrences and Recommendations

Routine Vaccines (Vaccination considerations should be based on ACIP guidelines.)

Haemophilus influenzae type b

No report of travel-related infection, although organism is ubiquitous.

Hepatitis B

Recommended for travelers visiting countries where HBsAg prevalence is ≥2%. Vaccination may be considered for all international travelers, regardless of destination, depending upon the traveler’s behavioral risk and potential for exposure as determined by the provider and traveler.

Human papillomavirus (HPV)

No report of travel-acquired infection; however, sexual activity during travel may lead to HPV and other sexually transmitted infections.

Influenza

Year-round transmission may occur in tropical areas. Outbreaks have occurred on cruise ships, and 2009 influenza A (H1N1) illustrated the rapidity of spread via travel. Novel influenza viruses such as avian influenza H5N1 and H7N9 can be transmitted to travelers visiting areas with circulation of these viruses.

Measles, mumps, rubella

Infections are common in countries and communities that do not immunize children routinely, including Europe. Outbreaks have occurred in the United States as a result of infection in returning travelers.

Meningococcal

Outbreaks occur regularly in sub-Saharan Africa in the “meningitis belt” during the dry season, generally December through June, although transmission may occur at other times for those with close contact with local populations. Outbreaks have occurred with Hajj pilgrimage, and the Kingdom of Saudi Arabia requires the quadrivalent vaccine for pilgrims.

Pneumococcal

Organism is ubiquitous, and causal relationship to travel is difficult to establish.

Polio

Unimmunized or underimmunized travelers can become infected with either wild poliovirus or vaccine-derived poliovirus. Because the international spread of wild poliovirus in 2014 was declared a Public Health Emergency of International Concern under the International Health Regulations, temporary recommendations for polio vaccination are in place for countries with wild poliovirus circulation for their residents, long-term visitors, and international travelers.

Rotavirus

Common in developing countries, although not a common cause of travelers’ diarrhea in adults. The vaccine is only recommended in young children.

Tetanus, diphtheria, pertussis

Rare cases of diphtheria have been attributed to travel. Pertussis has occurred in travelers, recently in adults whose immunity has waned.

Varicella

Infections are common in countries that do not immunize children routinely, as in most developing countries. Naturally occurring disease tends to affect adults.

Zoster

Travel (a form of stress) may trigger varicella zoster reactivation, but causal relationship is difficult to establish.

Travel Vaccines

Cholera

Cases in travelers have occurred in association with travel to Haiti.

Hepatitis A

Prevalence of hepatitis A virus infection may vary among regions within a country. Serologic testing may be considered in travelers from highly endemic countries since they may be immune. Some travel health providers advise people traveling outside the United States to consider hepatitis A vaccination regardless of their country of destination.

Japanese encephalitis

Rare cases have occurred, estimated at <1 case/1 million travelers to endemic countries. However, the severe neurologic sequelae and high fatality rate warrant detailed review of trip plans to assess the level of risk.

Rabies

Rabies preexposure immunization simplifies postexposure immunoprophylaxis, as adequately screened immunoglobulin may be difficult to obtain in many destinations.

Tickborne encephalitis (vaccine not available in the United States)

Cases have been identified in travelers with an estimated risk of 1/10,000 person-months in travelers. Endemic areas are expanding in Europe.

Typhoid

UK surveillance found the highest risk to be travel to India (6 cases/100,000 visits), Pakistan (9 cases/100,000 visits), and Bangladesh (21 cases/100,000 visits), although risk is substantial in many destinations.

Yellow fever

Risk occurs mainly in defined areas of sub-Saharan Africa and the Amazonian regions of South America. Some countries require proof of vaccination for entry. For travelers visiting multiple countries, order of travel may make a difference in the requirements.

Abbreviation: HBsAg, hepatitis B surface antigen.

Another major focus of pretravel consultations for many destinations is the prevention of malaria. Malaria continues to cause substantial morbidity and mortality in travelers. Since 1973, the annual number of US malaria cases reported to CDC has shown an increasing trend; therefore, pretravel consultation must carefully assess travelers’ risk for malaria and recommend preventive measures. For travelers going to malaria-endemic countries, it is imperative to discuss malaria transmission, ways to reduce risk, recommendations for prophylaxis, and symptoms of malaria.

Travelers with underlying health conditions require attention to their health issues as they relate to the destination and activities. For example, a traveler with a history of cardiac disease should carry medical reports, including a recent electrocardiogram. Asthma may flare in a traveler visiting a polluted city or from physical exertion during a hike; travelers should be encouraged to discuss with their primary care provider how to plan for treatment and bring necessary medication in case of asthma exacerbation. Travelers should be counseled on how to obtain travel medical insurance and how they can find reputable medical facilities at their destination, such as using the ISTM website (www.istm.org), the American Society of Tropical Medicine and Hygiene website (www.astmh.org), or the State Department Travel website (https://travel.state.gov/content/travel/en/international-travel/before-you-go/your-health-abroad.html). Any allergies or serious medical conditions should be identified on a bracelet or a card to expedite medical care in emergency situations.

The pretravel consultation also provides another setting to remind travelers of basic health practices during travel, including frequent handwashing, wearing seatbelts, using car seats for infants and children, and safe sexual practices. Topics to be explored are numerous and could be organized into a checklist, placing priority on the most serious and frequently encountered issues (Table 2-3, Box 2-1). General issues such as preventing injury and sunburn also deserve mention. Written information is essential to supplement oral advice and enable travelers to review the instructions from their clinic visits; educational material is available on the CDC Travelers Health webpage (www.cdc.gov/travel). Advice on self-treatable conditions may minimize the need for travelers to seek medical care while abroad and possibly lead to faster return to good health.

Table 2-3. Major topics for discussion during pretravel consultations

Immunizations

Review routine immunizations and those travel immunizations indicated for the specific itinerary and based on the traveler’s medical history.

Discuss utility of titers when records are unavailable or unreliable, particularly for measles, mumps, rubella, hepatitis A, and varicella.

Screen for chronic hepatitis B for people born in countries with HBsAg prevalence ≥2% (see Map 4-4).

Discuss indications for, effectiveness of, and adverse reactions to immunizations.

Malaria chemoprophylaxis

Determine if there is a risk of malaria.

Discuss personal protective measures.

Discuss risks and benefits of chemoprophylaxis and recommended choices of chemoprophylaxis for the itinerary.

Other vectorborne diseases

Define risk of disease in specific itinerary and insect precautions needed.

Respiratory illnesses

Discuss areas of particular concern (such as avian influenza in Asia or MERS in the Arabian Peninsula).

Consider influenza self-treatment for high-risk travelers.

Travelers’ diarrhea

Recommend strategies to decrease risk of diarrhea.

Discuss antibiotics for self-treatment, adjunct medications such as loperamide, and staying hydrated.

Altitude illness

Determine if the itinerary puts the traveler at risk of altitude illness.

Discuss preventive measures such as gradual ascent, adequate hydration, and medications to prevent and treat.

Other environmental hazards

Caution travelers to avoid contact with animals to reduce the potential for bites and scratches that can transmit rabies.

Advise travelers to avoid walking barefoot to avoid certain parasitic infections.

Advise travelers to avoid wading or swimming in freshwater where there is risk for schistosomiasis or leptospirosis.

Remind travelers to apply sunscreen to skin exposed to the sun.

Personal safety

Discuss precautions travelers can take to minimize risks, such as traffic accidents, alcohol excess, personal assault, robbery, or drowning.

Provide information on travel health and medical evacuation insurance.

Advise travelers to look for security bulletins related to their destination and consider areas to avoid.

Bloodborne pathogens

Inform travelers who will provide health care overseas what to do in case of needlestick or bloodborne pathogen exposure.

Discuss use of postexposure prophylaxis for HIV.

See Box 2-1 for summary on sexual health recommendations for travelers.

Disease-specific counseling

Remind travelers to keep medications and supplies in carry-on luggage.

Advise travelers to prepare for exacerbations or complications from underlying disease.

Abbreviations: HBsAg, hepatitis B surface antigen; MERS, Middle East respiratory syndrome.

Self-Treatable Conditions

Despite providers’ best efforts, some travelers will become ill. Obtaining reliable and timely medical care during travel can be problematic in many destinations. As a result, prescribing certain medications in advance can empower the traveler to self-diagnose and treat common health problems. With some activities in remote settings, such as trekking, the only alternative to self-treatment would be no treatment. Pretravel counseling may result in a more accurate self-diagnosis and treatment than relying on local medical care in some areas. In addition, the increasing awareness of substandard and counterfeit drugs in pharmacies in the developing world makes it more important for travelers to bring quality manufactured drugs with them from a reliable supplier in their own country (see Chapter 6, Perspectives: Avoiding Poorly Regulated Medicines and Medical Products during Travel).

Travel health providers need to recognize the conditions for which the traveler may be at risk, and educate the traveler about the diagnosis and treatment of those conditions. The keys to successful self-treatment strategies are providing a simple disease or condition definition, providing a treatment, and educating the traveler about the expected outcome of treatment. Using travelers’ diarrhea as an example, a practitioner could provide the following advice:

  • “Travelers’ diarrhea” is the sudden onset of abnormally loose, frequent stools.

  • Most cases will resolve within 2–5 days, and symptoms can be managed with loperamide or bismuth subsalicylate.

  • For diarrhea severe enough to interrupt travel plans, an antibiotic can be prescribed that travelers can carry with them (see Travelers’ Diarrhea section in this chapter).

  • The traveler should feel better within 6–24 hours.

  • If symptoms persist for 24–36 hours despite self-treatment, it may be necessary to seek medical attention.

To minimize the potential negative effects of a self-treatment strategy, the recommendations should follow a few key points:

  • Drugs recommended must be safe, well tolerated, and effective for use as self-treatment.

  • A drug’s toxicity or potential for harm, if used incorrectly or in an overdose situation, should be minimal.

  • Simple and clear directions are critical. Consider providing handouts describing how to use the drugs. Keeping the directions simple will increase the effectiveness of the strategy.

The following are some of the most common situations in which people would find self-treatment useful. The extent of self-treatment recommendations offered to the traveler should reflect the remoteness and difficulty of travel and the availability of reliable medical care at the destination. The recommended self-treatment options for each disease are provided in the designated section of the Yellow Book or discussed below.

  • Travelers’ diarrhea (Chapter 2, Travelers’ Diarrhea)

  • Altitude illness (Chapter 3, High-Altitude Travel & Altitude Illness)

  • Jet lag (Chapter 8, Jet Lag)

  • Motion sickness (Chapter 8, Motion Sickness)

  • Respiratory infections (Chapter 11, Respiratory Infections)

  • Skin conditions such as allergic reactions or superficial fungal infections (Chapter 11, Skin & Soft Tissue Infections)

  • Urinary tract infections: common among many women; carrying an antibiotic for empiric treatment may be valuable

  • Vaginal yeast infections: self-treatment course of patient’s preferred antifungal medication can be prescribed for women who are prone to infections, sexually active, or who may be receiving antibiotics for other reasons (including doxycycline for malaria chemoprophylaxis)

  • Occupational exposure to HIV (Chapter 9, Health Care Workers, Including Public Health Researchers and Laboratorians)

  • Malaria self-treatment (see Chapter 4, Malaria)

In sum, travelers should be encouraged to carry a travel health kit with prescription and nonprescription medications. Providers should review medication lists for possible drug interactions. More detailed information for providers and travelers is given in Chapter 6, Travel Health Kits; supplementary travel health kit information for travelers with specific needs is given in Chapter 5.

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…perspectives Travelers’ Perception of Risk

Travel medicine is based on the concept of risk reduction. In the context of travel medicine, “risk” refers to the possibility of harm occurring during the course of a trip. Some risks may be avoidable, while others may not. For example, vaccine-preventable diseases may be mostly avoidable, depending on the protective efficacy of the vaccine. Perception of risk is a subjective evaluation of whether a risk is considered large or small; is 1 in 10,000 a large risk or a small risk? Tolerance refers to acknowledging a risk and accepting it; a risk of 1 in 100,000 may be tolerable for one traveler but not for another.

For many years, travel medicine practitioners have felt that statistics for a given risk could help them objectively advise travelers about that risk. However, the rates of diseases in a particular country or location, such as typhoid fever, malaria, or Japanese encephalitis (JE), may not help clinicians or travelers determine the threshold for making a decision based on those statistics alone. With risks of diseases ranging from 1 in 500 (an estimate of the risk of typhoid in unvaccinated travelers in Nepal), to 1 in 1,000,000 (an assessment of the risk of JE in travelers to Asia), travelers still need to determine what these statistics mean. Additional information to help make an informed decision may include length of travel, type of travel, and proposed accommodations.

Even when risk is low, travelers’ decisions will still reflect their perception and tolerance of risk. When told that the risk of JE is 1 in 1,000,000, one traveler might reply, “Then I guess I don’t have to worry about it,” while another traveler might say, “That one traveler will be me!” Each traveler will have ideas about the risks, benefits, and costs of vaccines and drug prophylaxis, and these should be discussed in detail with their clinician.

Perception and tolerance of risk are connected to the concept of commitment, particularly in regards to remote, adventurous travel. Commitment refers to the fact that certain parts of a journey may not easily be reversed once entered upon. For example, a traveler trekking into a remote area may need to accept that rescue, if available at all, may be delayed for days. A traveler who has a myocardial infarction in a country with no advanced cardiac services may have a difficult time obtaining definitive medical care. If the traveler has already contemplated these concerns and accepted them, it will be easier to deal with them if they occur.

The goal of travel medicine should be to assess the risks for the traveler, and educate the traveler to skillfully manage and minimize risk rather than try to eliminate it. Travel medicine practitioners should discuss available risk statistics and assess their clients’ perception and tolerance of risk. Once this is done, the provider can then help travelers find their individual comfort level when making decisions about destinations, activities, and prophylactic measures.

Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official recommendations contained in the book. The views and opinions expressed in this section are those of the author and do not necessarily represent the official position of CDC.

Last-Minute Travelers

Although all travelers are encouraged to access pretravel services at least 1 month before departure, clinicians can provide pretravel care to those leaving on short notice, even within days or sometimes hours of departure. The category of “last-minute travelers” can include people who are leaving on short notice (such as humanitarian aid workers) or people who have planned a trip for some time but delayed receiving pretravel care.

Providing complete pretravel services to last-minute travelers can be challenging and there is typically time for only a single encounter.

Vaccinations

Consider the traveler’s itinerary, trip activities, and risk of infection at the destination. Note that immunity varies by vaccine, so emphasize preventive behaviors for travelers who might not be adequately protected if they are vaccinated immediately before travel.

Routine Vaccinations

Most travelers who attended school in the United States have received standard routine vaccinations. If the traveler is not up-to-date, even when departure is imminent, provide the first or additional doses of routine vaccines, including a seasonal influenza vaccination, if needed.

Recommended Vaccinations: Single-Dose Protection

Even when a traveler has limited time before departure, research supports the use of certain single-dose vaccines, if indicated, to initiate protection. These include hepatitis A (monovalent), typhoid (injectable), polio (inactivated), cholera, and quadrivalent (ACWY) meningococcal meningitis vaccines (see the respective disease sections in Chapter 4 for indications and dosing).

Recommended Vaccinations: Multiple Doses Needed

Last-minute travelers often cannot complete the full course of vaccines that require multiple doses to induce full protection. If a traveler needs protection against hepatitis B, Japanese encephalitis, or rabies, the clinician can consider approved accelerated schedules or information on resources for vaccination at the destination. It is unclear what level of protection any given traveler will have if he or she does not complete a full series of multi-dose vaccination.

Hepatitis B

As time allows, the traveler should receive the accelerated monovalent hepatitis B (Engerix-B) schedule (0, 1, and 2 months, plus a 12-month booster) or the super-accelerated combination hepatitis A/B (Twinrix) schedule (0, 7, 21–30 days, plus a 12-month booster). If an accelerated schedule cannot be completed before travel, start the vaccination series and schedule a follow-up visit to complete it or, for extended-stay travelers or expatriates, help them identify resources at the destination to complete the series.

Japanese Encephalitis

Japanese encephalitis vaccine is administered as 2 doses on days 0 and 7–28 (see Chapter 4, Japanese Encephalitis). A study of adults given 2 doses of Ixiaro 7 days apart found that 99% were protected. However, people who receive only a single dose may have a suboptimal response and may not be protected. Travelers who cannot complete the primary vaccine series ≥1 week before travel should be counseled to adhere rigidly to mosquito precautions if they will be at risk for Japanese encephalitis. Alternatively, the clinician can help them identify resources for vaccination with Ixiaro or several alternative vaccines that may be available at their destination, particularly if they will be long-stay travelers (Imojev Sanofi, SA14-14-2 Chengdu). However, travelers should be aware that vaccines received in some countries may be of substandard quality (see Chapter 6, Perspectives: Avoiding Poorly Regulated Medicines and Medical Products during Travel).

Rabies

Because of the multiple immunizations required to complete a primary rabies vaccine series (0, 7, and 21 or 28 days), last-minute travelers may not be able to complete the series before departure. A person who starts but does not complete a primary series and is exposed should receive the same postexposure prophylaxis as a completely unimmunized person. Counsel travelers on animal avoidance and the need to seek care urgently after an exposure. Travelers should consider purchasing travel health insurance to pay for care and medical evacuation insurance in case evacuation is needed to receive timely postexposure prophylaxis.

Required Vaccinations

Yellow fever vaccination certificates are valid 10 days after vaccine administration (the length of time considered necessary for immunity to develop). If a traveler plans to visit a country with a yellow fever vaccine requirement within this 10-day window, it may be necessary to rearrange the order of travel or reschedule the trip. Otherwise, the traveler risks being denied entry at the country’s border and would be at risk for yellow fever. Travelers for whom the yellow fever vaccination is contraindicated can be issued a medical waiver letter if a country entry requirement (and not risk of yellow fever infection) is the only reason to vaccinate.

Quadrivalent (ACWY) meningococcal vaccine is required of all travelers to Saudi Arabia for religious pilgrimage, including Hajj. Hajj visas cannot be issued without proof that applicants received meningococcal vaccine ≥10 days and ≤3 years (≤5 years for conjugate vaccine) before arriving in Saudi Arabia.

Certain countries require departing travelers to show proof of polio vaccination if they have been in the country >4 weeks. This requirement should not present a problem to travelers receiving the vaccine at the last minute. Countries with this requirement can change. Consult the CDC website (wwwnc.cdc.gov/travel/news-announcements/polio-guidance-new-requirements) for a current list. For more information, see Chapter 4, Poliomyelitis.

Malaria

The choice of malaria prophylaxis for last-minute travelers must factor in time until departure. For travelers leaving in <2 weeks, doxycycline, atovaquone-proguanil, or, when appropriate, primaquine should be used.

Health Counseling

Pretravel counseling is critical for last-minute travelers. During your risk assessment, determine prior knowledge and experience with travel health risks. Focus on major risks of the trip, and deliver simple messages about prevention and self-care. Provide travelers with education and prescriptions for travelers’ diarrhea and, if indicated, altitude illness. Encourage last-minute travelers to purchase all medications in the United States before departure to avoid buying medications that may be of poor quality or counterfeit. As time allows, provide counseling on topics such as preventing injuries, adhering to food and water precautions, and insect bite prevention (see The Pretravel Consultation in this chapter).

Special Challenges and Additional Considerations

The Traveler Leaving in a Few Hours

If time does not permit an appointment, the clinician can still provide general prevention messages and recommendations for care by telephone or secure digital messaging. Refer the traveler to useful websites such as CDC (www.cdc.gov/travel), the Department of State (www.travel.state.gov), the Heading Home Healthy Program (www.headinghomehealthy.org), and the International Society of Travel Medicine clinic directory (www.istm.org). Emphasize and reassure the traveler that many travel health risks can be prevented by adhering to healthy behaviors.

The Traveler with Preexisting Medical Conditions

These patients may be at increased risk for travel-related illness if they have inadequate time for preparation. They should consider purchasing travel health insurance, trip insurance, and medical evacuation insurance, and should carry an extra supply of all medications and a portable medical record. Emphasize the importance of a pretravel appointment or conversation with their treating clinician. Some conditions, such as pregnancy and immunosuppression, often require additional discussion and advance planning and may warrant delaying departure.

The Last-Minute, Extended-Stay Traveler

Advise these travelers to arrange an early visit with a qualified clinician at their destination for additional evaluation and education. A last-minute consultation does not provide an expatriate with adequate time for a full medical and psychological evaluation.

Recurring Last-Minute Travelers

Any clinic that frequently sees last-minute travelers may want to address this as an administrative issue. Consider building flexibility into the clinic schedule and proactively identifying people likely to travel at the last minute (such as college students and corporate employees). For these travelers, preemptive vaccinations for certain itineraries might also be considered.

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Complementary & Integrative Health Approaches

Travelers often ask their health care providers about the use of complementary or integrative health approaches for travel-related illnesses and conditions. This should come as no surprise, given that many people—approximately 1 in 3 American adults—report using these types of products and practices. Some complementary approaches for travel-related health problems are promoted widely, especially on the Internet. However, little of the promotional material is supported by research evidence, and some of it is misleading or false. This section focuses on claims that have been made about alleged benefits of complementary approaches for travel-related health problems and what the science says about some of the herbal products, dietary supplements (see Box 2-2), and other complementary approaches suggested for travel-related ailments and hazards.

Complementary Approaches to Travel Wellness: Claims vs. Science

Malaria Prophylaxis and Treatment

Claims

Many consumer websites promote “natural” ways to prevent or treat malaria, which often involve dietary changes or herbal products, such as quinine from the cinchona tree (Cinchona spp.) or extracts and material from the artemisia plant (Artemisia annua L. or sweet wormword).

What the Science Says

Urge patients to follow official recommendations and not rely on unproven “natural” approaches in an attempt to prevent or treat such a serious disease. Recommended drugs to prevent and treat malaria are described in Chapter 4, Malaria.

Zika Prophylaxis and Treatment

Claims

Consumer websites and online videos have claimed, without credible evidence, that various herbs or other natural products will protect against or treat the Zika virus.

What the Science Says

There is no evidence that any of these products can prevent or treat Zika virus infection. For more information see Chapter 4, Zika.

Travelers’ Diarrhea Prevention and Treatment

Claims

It has been claimed that a variety of products, including probiotics, goldenseal, activated charcoal, and grapefruit seed extract, can prevent or treat travelers’ diarrhea (TD).

What the Science Says

Probiotics

Using probiotics for the prevention of TD is controversial. Although some studies have had promising results, meta-analyses have reached conflicting conclusions. It is difficult to interpret the evidence because studies have used a variety of microbial strains, some studies were not well controlled, and the optimal dose and duration of use have not been defined. For more information, see Traveler’s Diarrhea in this chapter.

Goldenseal

No high-quality research on goldenseal for TD has been published. Studies show that goldenseal inhibits cytochrome P450 enzymes, raising concerns that it may increase the toxicity or alter the effects of drugs.

Activated Charcoal

No solid evidence supports claims that activated charcoal helps with TD, bloating, stomach cramps, or gas. The side effects of activated charcoal have not been well documented but were mild when it was tested on healthy people. Warning: Children should not be given activated charcoal for diarrhea and dehydration. It may absorb nutrients, enzymes, and antibiotics in the intestine and mask the severity of fluid loss.

Grapefruit Seed Extract

Claims that grapefruit seed extract can prevent bacterial foodborne illnesses are unfounded and not supported by research. People who need to avoid grapefruit because it interacts with medicine that they are taking should also avoid grapefruit seed extract.

Altitude Illness Prevention and Treatment

Claims

A variety of natural products, including coca, garlic, Ginkgo biloba, and vitamin E, have been promoted for the prevention or treatment of altitude illness.

What the Science Says

Coca

Coca tea has been used for altitude illness, but there is no strong evidence on whether it works or has adverse effects. It will result in a positive drug test for cocaine metabolites. For more information, see Chapter 10, Peru: Cusco, Machu Picchu & Other Regions.

Garlic

There is no evidence supporting claims that garlic helps reduce altitude illness. Garlic supplements appear safe for most adults. Possible side effects include breath and body odor, heartburn, and upset stomach. Some people have allergic reactions to garlic. Short-term use of most commercially available garlic supplements poses only a limited risk of drug interactions.

Ginkgo Biloba

Studies of ginkgo for preventing altitude illness have had inconsistent but mostly negative results. Whether the differences in results relate to the different preparations used in the studies has not been determined. Products made from standardized ginkgo leaf extracts appear to be safe when used as directed. However, ginkgo may increase the risk of bleeding in some people and interact with anticoagulants. In addition, studies by the National Toxicology Program showed that rodents developed liver and thyroid tumors after being given a ginkgo extract for up to 2 years.

Vitamin E

One study investigated vitamin E, in combination with other antioxidants, for altitude illness; the results were negative.

For more information on altitude illness, see Chapter 3, High-Altitude Travel & Altitude Illness.

Motion Sickness

Claims

Complementary approaches advocated for preventing or treating motion sickness include acupressure, magnets, ginger, pyridoxine (vitamin B6), and homeopathic remedies.

What the Science Says

Acupressure and Magnets

Research does not support the use of acupressure or magnets for motion sickness.

Ginger

Although some studies have shown that ginger may ease pregnancy-related nausea and vomiting and may help control nausea related to cancer chemotherapy when used in addition to conventional medication, there is no strong evidence that ginger helps with motion sickness. In some people, ginger can have mild side effects such as abdominal discomfort. Research has not definitively shown whether ginger interacts with medications, but concerns have been raised that it might interact with anticoagulants. The effect of using ginger supplements with common over-the-counter drugs for motion sickness (such as dimenhydrinate [Dramamine]) is unknown.

Pyridoxine (Vitamin B6)

Although an American Congress of Obstetrics and Gynecology 2015 Practice Bulletin Summary recommends pyridoxine (vitamin B6) alone or in combination with doxylamine (an antihistamine) as a safe and effective treatment for nausea and vomiting associated with pregnancy, there is no evidence supporting claims that pyridoxine prevents or alleviates motion sickness. Taking excessive doses of pyridoxine supplements for long periods of time can affect nerve function.

Homeopathic Products

There is no evidence supporting claims that homeopathic products prevent or alleviate motion sickness.

Jet Lag/Sleep Problems

Claims

Complementary approaches that have been suggested for jet lag or other sleep problems include the dietary supplement melatonin; relaxation techniques and other mind and body practices; aromatherapy; and herbs such as chamomile, kava, and valerian.

What the Science Says

Melatonin

Some evidence suggests that melatonin supplements may help with sleep problems caused by jet lag. Recent systematic reviews indicate that it may be of some benefit for people traveling in either an eastward or westward direction. Before suggesting melatonin to your patients, consider the following:

  • People with epilepsy or who take an oral anticoagulant should never use melatonin without medical supervision.

  • Melatonin supplements appear to be safe for most people when used short-term; less is known about their long-term safety. Side effects from melatonin are uncommon but can include drowsiness, headache, dizziness, or nausea.

  • Melatonin should not be taken early in the day, as it may cause sleepiness and delay adaptation to local time.

  • Melatonin is sold as a dietary supplement. Dietary supplements are regulated less strictly than drugs. The amounts of ingredients in dietary supplements may vary, and product contamination is a potential concern. A 2017 analysis of melatonin supplements sold in Canada found that their actual melatonin content ranged from –83% to +478% of the labeled content and that there was substantial lot-to-lot variation. Also, 26% of products contained serotonin as a contaminant.

Relaxation Techniques and Other Mind and Body Practices

Relaxation techniques, such as progressive relaxation, and other mind and body practices, such as mindfulness-based stress reduction, may help with insomnia, but it has not been established whether they are effective for jet lag.

Aromatherapy and Herbs

There is very little evidence that aromatherapy or the herbs chamomile or valerian help with insomnia. Significant side effects are uncommon, but chamomile can cause allergic reactions. Another herb, kava, is also promoted for sleep but good research on its effectiveness is lacking. More importantly, kava supplements have been linked to a risk of severe liver damage.

Colds and Flu

Claims

Although colds and flu are not uniquely travel-related hazards, many people are concerned about trying to avoid these illnesses during a trip. They may turn to complementary health approaches that have been advocated for preventing or treating colds or flu, including zinc products, neti pots and other forms of saline nasal irrigation, vitamin C, probiotics, echinacea, and others.

What the Science Says

Zinc

Zinc taken orally (often in the form of lozenges) may reduce the duration of a cold. Zinc, particularly in large doses, can have side effects including nausea and diarrhea. The intranasal use of zinc can cause anosmia (loss of sense of smell), which may be long-lasting or permanent.

Saline irrigation

Nasal saline irrigation, such as with neti pots, may be useful and safe for chronic sinusitis. However, even in places where tap water is safe to drink, people should use only sterile, distilled, boiled-then-cooled, or specially filtered water for nasal irrigation to avoid the risk of introducing waterborne pathogens. Nasal saline irrigation may help relieve the symptoms of acute upper respiratory tract infections, but the evidence is not definitive.

Vitamin C

Taking vitamin C supplements regularly reduces the risk of catching a cold among people who perform intense physical exercise but not in the general population. Taking vitamin C on a regular basis may lead to shorter colds, but taking it only after a cold starts does not. Vitamin C supplements appear safe, even at high doses.

Probiotics

Probiotics might reduce susceptibility to colds or other upper respiratory tract infections and the duration of the illnesses, but the quality of the evidence is low or very low.

Echinacea

Numerous studies have tested the herb echinacea to see whether it can prevent colds or relieve cold symptoms. A 2014 systematic review concluded that echinacea has not been convincingly shown to be effective; however, a weak effect has not been ruled out.

Other

There is no strong evidence that garlic, Chinese herbs, oil of oregano, or eucalyptus essential oil prevent or treat colds, or that the homeopathic product Oscillococcinum prevents or treats influenza or influenzalike illness.

Insect Protection: Botanical Repellents

Claims

Many products are promoted as “natural” insect repellents, and their use may appeal to people who prefer not to use synthetic products. Products promoted as natural mosquito repellents include citronella products, oil of lemon eucalyptus (OLE), and neem oil (a component of agricultural insecticide products that is promoted on some websites for home use). Essential oils and other natural products are promoted to repel bed bugs.

What the Science Says

Mosquitoes

Laboratory-based studies found that botanicals, including citronella products, worked for shorter periods than products containing DEET. For people wishing to use botanicals, CDC recommends Environmental Protection Agency (EPA)–registered products containing OLE. There are no high-quality studies on the effectiveness or safety of neem oil for preventing mosquito bites (see Chapter 3, Mosquitoes, Ticks & Other Arthropods).

Bed bugs

There is no evidence that the natural products marketed to repel bed bugs are effective. Instead, travelers should be encouraged to follow steps to detect and avoid bed bugs, such as inspecting their mattresses and keeping their luggage off the floor or bed. Information is available on CDC’s website at www.cdc.gov/parasites/bedbugs and Box 3-2, Bed bugs and international travel.

Sun Protection

Claims

Many “natural” sunscreen products are promoted online, as are recipes for making your own and advice on consuming dietary supplements or drinking teas to protect against sun damage.

What the Science Says

Studies have not proven that any herbal product or dietary supplement, including aloe vera, beta carotene, selenium, or epigallocatechin gallate (EGCG), an extract from green tea, reduces the risk of skin cancer or sun damage. For more information, see Chapter 3, Sun Exposure.

Homeopathic Vaccines

Claims

Proponents of homeopathy claim that products called “nosodes” or homeopathic vaccines are effective substitutes for conventional immunizations.

What the Science Says

There is no credible scientific evidence or plausible scientific rationale to support these claims. For more information, see Vaccination & Immunoprophylaxis: General Recommendations in this chapter.

Untested Therapies in Other Countries

CDC does not recommend traveling to other countries for untested medical interventions or to buy medications that are not approved in the United States. For more information see Medical Tourism in Chapter 9.

Talking to Travelers About Complementary Health Approaches

Given the vast number of complementary or integrative interventions and the wealth of potentially misleading information about them that can be found on the internet, discussing the use of these approaches with patients may seem daunting. However, it is important to be proactive, as surveys show that many patients are reluctant to raise the topic with their health care providers. Federal agencies, such as the National Center for Complementary and Integrative Health (NCCIH), offer evidence-based resources (nccih.nih.gov/health/providers) to help you and your patients have a meaningful discussion about complementary approaches.

Acknowledgments

The authors thank Mr. Philip Kibak of ICF for his editorial assistance.

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Prioritizing Care for the Resource-Limited Traveler

Travelers seen in pretravel clinic consultations often have financial constraints and must pay out of pocket for pretravel care, as many health insurance plans provide no or limited coverage for travel immunizations and prophylactic medications. The variety of insurance plans, number of travelers without adequate insurance coverage, and number of student and budget travelers challenges even the most savvy travel medicine clinicians. As an example, the estimated cost of a US pretravel consultation for a backpacker planning a 4-week trip to West Africa may be as high as $1,400 for the initial consultation and vaccinations, excluding malaria prophylaxis.

Travelers with limited budgets may be at higher risk for travel-associated infections, as they often visit remote areas, stay in more modest accommodations, and eat in restaurants with lower hygiene standards. The total cost of a becoming ill with a vaccine- or prophylaxis-preventable disease (e.g., hospitalization, treatment, lost wages) may, in many cases, outweigh the initial cost of vaccination and prophylaxis, making a pretravel consultation particularly important. The cost and benefit of obtaining travel health insurance and evacuation insurance before travel must also be considered (see Chapter 6, Travel Insurance, Travel Health Insurance & Medical Evacuation Insurance). The goal of this section is to guide travel health recommendations for travelers with financial constraints.

Vaccines

Required Vaccines

Only 2 vaccines are required categorically for some travelers: meningococcal vaccine for pilgrims traveling to Mecca during the Hajj and yellow fever vaccine for travelers to certain countries in Africa and South America (see Yellow Fever Vaccine & Malaria Prophylaxis Information, by Country in this chapter). Prioritize these vaccines, since the traveler may be denied entry to the country without proof of vaccination. Note that those staying in a yellow fever–endemic country only briefly (such as during an airport layover) may still need evidence of vaccination to enter other countries on their itinerary.

In a few specific circumstances, travelers to polio-affected countries may be asked to show proof of polio vaccination before departure if their duration of stay is >4 weeks (see Chapter 4, Poliomyelitis). Travelers and clinicians are advised to check the latest recommendations for their destinations.

Routine Vaccines

All travelers should be up-to-date with routine vaccines before international travel, regardless of destination. The benefits of these vaccines extend beyond the travel period, and in many cases lifelong immunity is achieved. Since these vaccines are mass-produced as part of the scheduled national childhood and adult vaccination programs, associated costs are generally low, and many insurance companies reimburse the patient for the cost of administration. Travelers can also obtain these vaccines in a health department or primary care setting, where costs may be lower than those at a travel clinic. Prioritize the routine vaccines that protect against diseases for which the traveler is most likely to be at general risk, for example influenza, measles, and hepatitis A.

Some travelers may be immune to the disease for which immunization is being considered. Pretravel antibody testing may be covered by insurance when vaccines are not. The decision to test rather than vaccinate will also depend on time to departure.

Recommended Vaccines

Consider time until departure, risk of disease at the destination, effectiveness and safety of vaccine, and likelihood of repeat travel. For example, although currently not a routine vaccine for US adults, hepatitis A vaccine can provide lifelong immunity and should be considered for travel to all destinations. On the other hand, hepatitis B (also not a routine vaccine for US adults) is not as significantly associated with travel, and vaccination may be a lower priority. Typhoid vaccine for both adults and children has limited effectiveness, and protection lasts only 2–5 years depending on formulation, thus making it more valuable just for higher-risk destinations or those where typhoid is more likely to be acquired (such as the Indian subcontinent).

Review the itinerary in detail to determine need for Japanese encephalitis vaccine. Some travelers may be able to obtain single-dose vaccine at a much lower cost outside the United States, bearing in mind issues surrounding quality of vaccines in many countries (see Chapter 6, Perspectives: Avoiding Poorly Regulated Medicines and Medical Products during Travel). Those who decline vaccine should have a clear understanding of when and how to use insect repellents and other measures to prevent mosquito bites.

When considering rabies vaccine for resource-limited travelers, consider the risk of animal exposure, access to local health care, and availability of rabies immune globulin and rabies vaccine at the traveler’s destination. Travelers who decline preexposure immunization should have a plan of action if an exposure occurs. In many areas, rabies vaccine or immune globulin are difficult or impossible to obtain, and travelers may need to be evacuated to receive postexposure prophylaxis.

Malaria Prophylaxis

Every pretravel consultation should include detailed advice about preventing mosquito bites (see Chapter 3, Mosquitoes, Ticks & Other Arthropods). The risk of acquiring malaria varies widely depending on destination, accommodations, and activities during travel. Costs associated with the different regimens vary widely. Providers should stay up-to-date on the usual cost of antimalarial medications in their region and at the pharmacies used by their travelers so that the most cost effective drug can be recommended to the traveler for their itinerary. Travelers who raise the question of purchasing antimalarial drugs at their destination should be advised about the risk of inappropriate, substandard, and counterfeit medications and discouraged from this practice (see Chapter 6, Perspectives: Avoiding Poorly Regulated Medicines and Medical Products during Travel).

Travelers’ Diarrhea

Travelers’ diarrhea (TD) is among the most common travel-related illnesses. Antibiotics to treat moderate to severe diarrhea should be considered; prophylaxis may be indicated only in select cases of patients at high risk for TD-related complications (see Travelers’ Diarrhea later in this chapter). As with antimalarial drugs purchased at the destination, advise travelers about the risk of purchasing counterfeit antibiotics overseas.

Preventive Behaviors

Budget travelers and those who cannot afford travel vaccines will continue to challenge travel medicine practitioners. When immunization or prophylactic medications cannot be given because of financial constraints, educate travelers about alternative ways to reduce risk. For example, advise travelers to avoid animal bites, use insect precautions, follow safe sex practices, wash their hands or use alcohol-based hand sanitizer frequently, and observe food and water precautions to the best of their ability.

Travelers can be reassured that the actions they take to avoid these preventable hazards may, in the long run, protect against travel-associated risks that are more prevalent than certain vaccine-preventable diseases.

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Telemedicine

What is Telemedicine?

Telemedicine is commonly referred to as providing diagnostics and therapeutic services via information and communication technologies. Telemedicine interventions can be as simple as 2 doctors discussing a case over the phone to decide on an intervention or as complex as real-time monitoring of astronauts at the International Space Station.

Benefits of telemedicine include reducing cost and time associated with unnecessary transportation of patients, quicker access to care with minimized waiting time, access to subspecialty care, and maintaining patients in familiar environments. Telemedicine has benefits in both rural and urban areas, but it is not always a viable option. In remote rural areas, there may not be the bandwidth and connectivity capable of supporting the communication technologies. In the urban setting, users may contend with internal firewalls and security settings.

Telemedicine can serve as an alternative to a pretravel clinical visit. It can be used directly with patients when traveling to answer questions or provide guidance to distant clinicians in case of emergencies, which can help maintain continuity of care. In addition, it may be used to assist clinicians with posttravel evaluations when there are unusual clinical findings and subspecialty assistance is needed.

Conducting a Remote Pretravel Consultation

Telemedicine enables a convenient method to deliver pretravel consultations with the same elements as in an in-person visit. Providers should continue to follow the professional standards as with in-person consultations, including the same code of ethics, security and privacy practices, and adherence to clinical guidelines. What can and can’t be done in a remote consultation varies by state, so providers will need to check with their state medical boards about any restrictions. A valuable resource on telemedicine, including requirements by state, is available at https://prognocis.com/wp-content/uploads/2017/01/Telemedicine-Whitepaper.pdf.

Practices should provide patients with a resource that outlines the expectations and outcomes of telemedicine before they schedule the consultation, including the limitations of a remote consultation. Intake information, including medical history, prior medical records, or diagnostic information, may be requested of the patient and made available to the provider in advance. Patients are encouraged to set up in advance and test their connections to the telemedicine software or equipment.

At the time of the consultation, it is important to establish informed consent with the patient and ensure that the patient is in an appropriate care setting (for example, depending on the state, the patient may need to physically be in a location where the provider is licensed to practice medicine at the time of the consultation). Depending on the circumstances, a telepresenter (such as another health care provider or even a translator) may need to be present with the patient to assist with the intake and exam.

Prescription Medications and Vaccines

Medications and vaccinations can be prescribed during a telemedicine encounter. Remote vaccine prescriptions are allowed in several states. Pharmacies receive the prescription electronically or over the phone, and the pharmacist may be able to administer any injectable vaccines (see www.pharmacist.com/article/pharmacist-administered-immunizations-what-does-your-state-allow). Yellow fever vaccine can only be administered at specially registered clinics, so a traveler may need a separate clinic visit to receive this vaccine. For medications and vaccines that may not be routinely stocked in a traveler’s local pharmacy, such as malaria prophylaxis, the traveler should allow time for the pharmacy to order them.

When a Traveler is Overseas

A travel medicine provider may be called on to provide a consultation for a traveler overseas for any number of reasons. The provider’s willingness and ability to provide a remote overseas consultation will vary with type of question or the nature of the problem, willingness to work pro bono (or ability to charge for services), and perhaps the time of day, but it is important to remember that the same security and privacy practices apply as in a domestic consultation. In the case of lost medication, CDC does not endorse procuring medication or filling prescriptions overseas because of the risk of counterfeit drugs. However, in an emergency, such as with lost or stolen antimalarial drugs, a provider may be able to help a traveler locate a reputable source for replacing them.

Technology Requirements

When communicating with patients abroad, legal obligations under the Health Insurance Portability and Accountability Act (“HIPAA”) remain relevant. Providers must also ensure that the chosen technology to conduct telemedicine encounters, whether store-and-forward or live-video, is HIPAA compliant. Although encryption is not specifically addressed under HIPAA, it would be best to ensure technology is encrypted because of requirements to safeguard patient health information.

Providers must also consider bandwidth and connectivity. In the United States today, connectivity in some rural communities is often inadequate, and accessing websites is often difficult because of internal firewalls. Mobile hotspots may be used in some situations in lieu of dial-up or Ethernet connections.

Certain telemedicine vendors have optimized software to work in a low-bandwidth setting, while others have focused on targeted, established markets. Discuss needs with telemedicine vendors to understand the minimum bandwidth at which their software will meet expectations.

Legal Issues

The Health Insurance Portability and Accountability Act (HIPAA) must be taken into account in discussions about patient data in health care today, and conversations around telemedicine will certainly include HIPAA compliance. When beginning to provide remote pretravel consultations, providers should use video software that already is HIPAA compliant. Providers should investigate specific legal requirements of the country where the traveler is located, as well as maintain compliance with federal and state privacy and security laws. In the United States, each state medical board has its own telemedicine regulations. Some states do not permit providers to practice telemedicine across state lines; some do not permit the prescribing of certain medications. It is critical that the travel clinic carefully read these medical board regulations before embarking on telemedicine consults.

In addition, particularly if providers are not part of a larger system or they are sole practitioners, they should explore whether or not there is a need for a business associate agreement or business associate contract.

When working with international partners, such as companies based outside the country in which the provider practices, additional legal issues may arise and should be considered.

Reimbursement

Much like reimbursement for face-to-face encounters, providers need to ensure that the clinic meets certain legal requirements and payer guidelines. In the United States, the pretravel consultation is generally not reimbursed by health insurance companies, so a telemedicine practice may be primarily fee-for-service. If corporate personnel are traveling and their companies are paying for the service, it is wise to make sure the company is willing to permit their employees to engage in telemedicine and that they will reimburse for this service.

For during- and posttravel consults, issues such as eligibility for payment and licensure may surface. The provider’s medical board and the traveler’s payer may have to be queried as to whether teleconsultation is permissible, and which current procedural terminology (CPT) codes are usable.

Telemedicine Resources

Additional information relating to telemedicine standards, guidelines, and practice may be available through the following resources:

…perspectives Legal Issues in Travel Medicine

Travel medicine providers—as in other medical specialties—are at risk of legal action. Claims for medical negligence may involve any of the following: 1) failure of duty of care; 2) failure to uphold the standard of practice; 3) care resulting in physical, financial or psychological loss; and 4) failure to reach the standard of care directly caused this loss.

Although travel medicine practitioners come from many backgrounds, in the travel medicine arena they are preventive medicine specialists. As such, in giving advice, they provide education and not generally “hands on” patient care. Although misunderstandings and legal action may occur despite best efforts, certain guidance is helpful.

Communication.

The likelihood of a lawsuit is lessened by good communication between the provider and the traveler patient. All elements of a pretravel consultation must be covered either verbally during the visit or given as written material for the patient to take home. Since time is a limitation, clinics need to provide handouts on how to avoid common health problems not discussed during the consultation. It is also is helpful to provide written information about medications and vaccinations (see below) that are being given or prescribed.

Documentation.

Clinics should have a method for documenting all aspects of the consultation as well as an area within the record for the provider to comment on the patient’s questions or responses to recommendations. Many electronic medical records enable the provider to add items unique to travel health and to add comments regarding the consultation.

Identification of problems.

Providers are encouraged to consult with their risk management personnel or legal advisors in the event of a contentious office visit or exchange after the visit. Good documentation of all communications in a nonjudgmental fashion between traveler patient and provider is critical.

Examples of Legal Issues in Travel Medicine

Prescription Medications

Fluoroquinolones

Fluoroquinolone use is sometimes associated with tendinitis, tendon rupture, peripheral neuropathy, and central nervous system adverse events. Lawsuits regarding these problems continue, and it is unknown whether a single dose of a fluoroquinolone used for the self-treatment of travelers’ diarrhea can lead to such events. Thus, despite the fact that prescriptions come from pharmacies with directions and adverse event information, providers should also discuss potential adverse events with their patients.

Mefloquine

Mefloquine may cause serious neuropsychiatric adverse events, including visual hallucinations, psychosis, insomnia, seizures, nightmares, neuropathies (motor and sensory), and dizziness. These adverse events can persist after discontinuation of the drug. Providers should not prescribe mefloquine to patients with a seizure disorder or a psychiatric disorder (depression, generalized anxiety disorder, psychosis, or schizophrenia). CDC also recommends against its use in patients with cardiac conduction abnormalities. Travelers receiving a prescription for mefloquine should receive a copy of the US Food and Drug Administration (FDA) medication guide (www.accessdata.fda.gov/drugsatfda_docs/label/2008/019591s023lbl.pdf). Because of its low cost and convenient weekly dosing, however, mefloquine remains an attractive option for some travelers. Therefore, providers recommending mefloquine for malaria prophylaxis should document clearly and carefully why they selected this drug over other antimalarial drugs; a notation that the provider reviewed the medical history for potential contraindications should also be included as part of the patient record.

Primaquine and tafenoquine

These drugs may cause potentially fatal hemolysis in G6PD-deficient patients. Thus, clinicians should screen anyone receiving a prescription for either of these medications for G6PD deficiency.

Drug interactions

Drug interactions may occur among medications prescribed for a traveler. Medication reconciliation is an essential part of the travel history. Electronic medical records and other pharmacy aids are useful to alert clinicians of drug interactions in real time, when decisions are being made about travel medication prescriptions. Use fluoroquinolones and macrolides with caution in traveler patients taking other QT interval–prolonging agents. Concurrent use of antibiotics with cholera or oral typhoid vaccines may produce a reduced vaccine immune response. Antibody-containing products may affect live attenuated vaccines.

Off-label use

Sometimes providers find it useful to recommend to travelers medications not approved by FDA for that specific purpose. Examples include use of primaquine alone for malaria prophylaxis and rifaximin to prevent travelers’ diarrhea. However, advisors will sometimes recommend medication uses other than those considered standard of care, and these should be discussed with the traveler prior to prescribing and be documented along with the traveler’s acceptance.

Vaccine Side Effects and Contraindications

To deliver effective and safe vaccinations, travel health providers should review carefully the patient’s past medical history, allergies, and vaccination history. Failure to administer a vaccine correctly can cause an adverse event or result in a traveler acquiring a preventable disease abroad. Travel health providers should discuss and then document any relevant conversations regarding the risk of acquiring a disease, should the patient refuse a vaccine. Travelers known to be immunocompromised, whose immune status may preclude a robust, protective antibody response to vaccination, should be made aware of such.

Serious vaccine-associated adverse events may be due to a variety of causes. Allergic reactions to vaccine components are common. Immunocompromised travelers may particularly suffer adverse events after receiving live vaccines. Eliciting a history of pregnancy, breastfeeding status, immunosuppressive medications, immunocompromised status, and allergies becomes crucial to minimizing vaccine-associated adverse events. Vaccine information statements should be available in the clinic and reviewed with the traveler patient (www.cdc.gov/vaccines/hcp/vis/index.html).

It is essential to document a patient’s history and the data used in decision making, especially when a vaccine is not given or when a provider administers a vaccine despite precautions about its use. It is critical that patients understand (and clinicians document the discussion) about any risks associated with non–FDA-approved dosing schedules, such as those used for the accelerated delivery of some vaccines.

Deep Vein Thrombosis (DVT)

Long-distance travel increases the risk of DVT and pulmonary embolism by approximately 3-fold. The association is stronger with flights of longer duration. Travel medicine providers should counsel patients about DVT and recommend measures to decrease its risk (occasional walking, aisle seat selection, and exercises), and document this discussion in the medical record (see Chapter 8, Deep Vein Thrombosis & Pulmonary Embolism).

Summary and Recommendations

Maintaining a standard of care in one’s practice is important not only for the patient’s protection but for the provider as well. This section gives examples of issues that may bring legal action in the travel medicine arena. Clinic providers should have adequate training in travel medicine and engage in continuing education. It is wise for at least 1 provider at each location to have earned the Certificate in Travel Health (CTH), awarded by the International Society of Travel Medicine (ISTM) upon successful completion of the CTH examination. It is also advisable for providers to remain current in the field by accessing continuing education programs offered by CDC and ISTM.

Bibliography

1. Burton B. Australian army faces legal action over mefloquine. BMJ. 2004;329(7474):1062.Find this resource:

2. Hinrichs-Krapels S, Bussmann S, Dobyns C, Kácha O, Ratzmann N, Holm Thorvaldsen J, et al. Key considerations for an economic and legal framework facilitating medical travel. Front Public Health. 2016;4:47.Find this resource:

3. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, et al. Prevention of VTE in nonsurgical patients. Chest. 2012 Feb;141(2):e195S–226S.Find this resource:

4. Kennedy KM, Flaherty GT. Medico-legal risk, clinical negligence and the practice of travel medicine. J Travel Med. 2016;23(5):doi: 10.1093/jtm/taw048.Find this resource:

5. Lapostolle F, Surget V, Borron SW, Desmaizières M, Sordelet D, Lapandry C, et al. Severe pulmonary embolism associated with air travel. N Engl J Med. 2001;345(11):779–83.Find this resource:

Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official recommendations contained in the book. The views and opinions expressed in this section are those of the authors and do not necessarily represent the official position of CDC.

Vaccination & Immunoprophylaxis: General Recommendations

Evaluation of people before travel should include a review and provision of routine vaccines recommended based on age and other individual characteristics. Additionally, some routine vaccines are recommended at earlier ages for international travelers. For example, MMR (measles-mumps-rubella) vaccine and hepatitis A vaccine are recommended for infants aged 6–11 months who travel abroad. Recommendations for specific vaccines related to travel will depend on itinerary, duration of travel, and host factors. Vaccinations against diphtheria, tetanus, pertussis, measles, mumps, rubella, varicella, poliomyelitis, hepatitis A, hepatitis B, Haemophilus influenzae type b (Hib), rotavirus, human papillomavirus (HPV), and pneumococcal and meningococcal invasive disease are routinely administered in the United States, usually in childhood or adolescence. Influenza vaccine is routinely recommended for all people aged ≥6 months, each year. Herpes zoster (shingles) vaccine is recommended for adults aged ≥50 years.

If a person does not have a history of adequate protection against these diseases, immunizations appropriate to age and previous immunization status should be obtained, whether or not international travel is planned. A visit to a clinician for travel-related immunizations should be seen as an opportunity to bring an incompletely vaccinated person up-to-date on his or her routine vaccinations. For additional details on specific vaccines’ and toxoids’ recommendations, backgrounds, adverse reactions, precautions, and contraindications, refer to the respective ACIP recommendations (www.cdc.gov/vaccines/acip/index.html). For information on vaccinating travelers with altered immune function, see Chapter 5, Immunocompromised Travelers.

Spacing of Immunobiologics

Simultaneous Administration

With some exceptions (such as PCV13 and PPSV23, PCV13 and MenACWY-D [Menactra], and Menactra and DTaP), all commonly used vaccines can safely and effectively be given simultaneously (on the same day) at separate sites without impairing antibody responses or increasing rates of adverse reactions. This knowledge is particularly helpful for international travelers, for whom exposure to several infectious diseases might be imminent. Simultaneous administration of all indicated vaccines is encouraged for people who are the recommended age to receive these vaccines and for whom no contraindications exist. With the same exceptions as listed above for simultaneous vaccination, if not administered on the same day, an inactivated vaccine may be given at any time before or after a different inactivated vaccine or a live-virus vaccine. PCV13 and PPSV23 should be administered 8 weeks apart. PCV13 and Menactra should be administered 4 weeks apart in some high-risk groups. Menactra and DTaP should be administered 6 months apart in some high-risk groups.

The immune response to an injected or intranasal live-virus vaccine (such as MMR, varicella, or live attenuated influenza vaccines) might be impaired if administered within 28 days of another live-virus vaccine. Typically, the immune response is impaired only for the live-virus vaccine administered second. Whenever possible, injected or intranasal live-virus vaccines administered on different days should be given ≥28 days apart. If 2 injected or intranasal live-virus vaccines are not administered on the same day but <28 days apart, the second vaccine should be repeated in ≥28 days.

No evidence exists that inactivated vaccines interfere with the immune response to yellow fever vaccine. Therefore, inactivated vaccines can be administered either simultaneously or at any time before or after yellow fever vaccination. ACIP recommends that yellow fever vaccine be given at the same time as other live-virus vaccines.

Limited data suggest that coadministration of yellow fever vaccine with measles-rubella or MMR vaccines might decrease the immune response. One study involving the simultaneous administration of yellow fever and MMR vaccines and a second involving simultaneous administration of yellow fever and measles-rubella vaccines in children demonstrated a decreased immune response against all antigens except measles when the vaccines were given on the same day versus 30 days apart. Additional studies are needed to confirm these findings, but they suggest that, if possible, yellow fever and MMR should be given 30 days apart.

Additional data suggest that oral Ty21a typhoid vaccine, a live bacterial vaccine, can be administered simultaneously or at any interval before or after yellow fever vaccine. There are no data on the immune response to live attenuated oral cholera vaccine (Vaxchora) or nasally administered live attenuated influenza vaccine administered simultaneously with yellow fever vaccine. However, data from live attenuated influenza and MMR vaccines found no evidence of interference. If yellow fever vaccine and another injectable live-virus vaccine are not administered either simultaneously or ≥30 days apart, providers may consider measuring the patient’s neutralizing antibody response to vaccination before travel. Contact the state health department or the CDC Arboviral Disease Branch (970-221-6400) to discuss serologic testing.

No data are available on concomitant administration of the currently available formulation of oral cholera vaccine with other vaccines, including the enteric-coated oral typhoid vaccine. Based on expert opinion of how oral cholera vaccine buffer might interfere with the enteric-coated oral typhoid vaccine formulation, taking the first oral typhoid vaccine dose ≥8 hours after ingestion of oral cholera vaccine might decrease potential interference of the vaccine buffer with oral typhoid vaccine.

Measles and other live-virus vaccines may interfere with the response to tuberculin skin testing and the interferon-γ‎ release assay. Tuberculin testing, if otherwise indicated, can be done either on the same day that live-virus vaccines are administered or 4–6 weeks later. Tuberculin skin testing is not a prerequisite for administration of any vaccine. Neither oral typhoid vaccine nor oral cholera vaccine have been associated with suppressing the response to tuberculosis testing.

Missed Doses and Boosters

In some cases, a scheduled dose of vaccine may not be given on time. If this occurs, the dose should be given at the next visit. However, travelers may forget to return to complete a series or for a booster at the specified time. Available data indicate that intervals between doses longer than those routinely recommended do not affect seroconversion rate or titer when the schedule is completed. Consequently, it is not necessary to restart the series or add doses of any vaccine because of an extended interval between doses. There are some exceptions to this rule. Some experts recommend repeating the series of oral typhoid vaccine if the 4-dose series is extended to more than 3 weeks. If an extended interval passes between doses of the preexposure rabies vaccine series, immune status should be assessed by serologic testing 7–14 days after the final dose in the series.

Antibody-Containing Blood Products

Antibody-containing blood products from the United States, such as immune globulin (IG) products, do not interfere with the immune response to yellow fever vaccine and are not believed to interfere with the response to live typhoid, live attenuated influenza, rotavirus, or zoster vaccines. When MMR and varicella vaccines are given shortly before, simultaneously with, or after an antibody-containing blood product, response to the vaccine can be diminished. The duration of inhibition of MMR and varicella vaccines is related to the dose of IG in the product. MMR and varicella vaccines either should be administered ≥2 weeks before receipt of a blood product or should be delayed 3–11 months after receipt of the blood product, depending on the dose and type of blood product (Table 2-4).

Table 2-4. Recommended intervals between administration of antibody-containing products and measles-containing vaccine or varicella-containing vaccine1

Indication

Dose and Route

Recommended Interval Before Measles or Varicella Vaccination

Blood transfusion

Red blood cells (RBCs), washed

10 mL/kg (negligible IgG/kg) IV

None

RBCs, adenine-saline added

10 mL/kg (10 mg IgG/kg) IV

3 months

Packed RBCs (hematocrit 65%)2

10 mL/kg (60 mg IgG/kg) IV

6 months

Whole blood (hematocrit 35%–50%)2

10 mL/kg (80–100 mg IgG/kg) IV

6 months

Plasma/platelet products

10 mL/kg (160 mg IgG/kg) IV

7 months

Botulism immune globulin, intravenous (human)

1.0 mL/kg (50 mg IgG/kg) IV

6 months

Cytomegalovirus prophylaxis (CMV IGIV)

150 mg/kg IV (maximum)

6 months

Hepatitis A (IG), duration of international travel

<2-month stay

0.1 mL/kg (3.3 mg IgG/kg) IM

3 months

≥2-month stay

0.2 mL/kg (10 mg IgG/kg) IM

3 months

Hepatitis B prophylaxis (HBIG)

0.06 mL/kg (10 mg IgG/kg) IM

3 months

Intravenous immune globulin (IVIG)

Replacement therapy3

300–400 mg/kg IV3

8 months

Immune thrombocytopenic purpura (ITP)

400 mg/kg IV or 1 g/kg IV

8 months or 10 months4

Postexposure measles prophylaxis (for immunocompromised people)

400 mg/kg IV

400 mg/kg IV

8 months

8 months

Postexposure varicella prophylaxis5

400 mg/kg IV

8 months

Kawasaki disease

2 mg/kg IV

11 months

Measles prophylaxis (IG)

Immunocompetent contact

0.5 mL/kg (80 mg IgG/kg) IM

6 months

Monoclonal antibody to respiratory syncytial virus (RSV) F protein (Synagis [MedImmune])6

15 mg/kg IM

None

Rabies prophylaxis (HRIG)

20 IU/kg (22 mg IgG/kg) IM

4 months

Tetanus (TIG)

250 units (10 mg IgG/kg) IM

3 months

Varicella zoster immune globulin4,5

125 units/10 kg (60–200 mg IgG/kg) IM (maximum 625 units)

5 months

Abbreviations: IG, immune globulin; IM, intramuscular; IV, intravenous.

1 Adapted from Table 3.5, Kroger AT, Duchin J, Vázquez M. General best practice guidelines for immunization. Best practices guidance of the Advisory Committee on Immunization Practices (ACIP). Atlanta, GA: CDC [cited 2018 Jan 18]. Available from: www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf. This table is not intended for determining the correct indications and dosage for the use of IG preparations. Unvaccinated people may not be fully protected against measles during the entire recommended interval, and additional doses of IG or measles vaccine may be indicated after measles exposure. Concentrations of measles antibody in an IG preparation can vary by manufacturer’s lot. For example, more than a 4-fold variation in the amount of measles antibody titers has been demonstrated in different IG preparations. Rates of antibody clearance after receipt of an IG preparation can also vary. Recommended intervals are extrapolated from an estimated half-life of 30 days for passively acquired antibody and an observed interference with the immune response to measles vaccine for 5 months after a dose of 80 mg IgG/kg (Source: Mason W, Takahashi M, Schneider T. Persisting passively acquired measles antibody following gamma globulin therapy for Kawasaki disease and response to live virus vaccination [abstract 311]. Presented at the 32nd meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy, Los Angeles, California, October 1992). Does not include zoster vaccine. Zoster vaccine may be given with antibody-containing products.

2 Assumes a serum IgG concentration of 16 mg/mL.

3 Measles vaccination is recommended for children with mild or moderate immunosuppression from HIV infections and varicella vaccination may be considered for children with mild or moderate immunosuppression from HIV infections, but both are contraindicated for people with severe immunosuppression from HIV, with any other immunosuppressive disorder, or on immunosuppressive medications.

4 Recommendation adapted from Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190–207.

5 If varicella zoster immune globulin is not available, IVIG can be used. The recommendation for use of IVIG is based on best judgment of experts and is supported by reports comparing varicella IgG titers measured in both IVIG and varicella zoster immune globulin preparations and patients given IVIG and varicella zoster immune globulin. Although licensed IVIG preparations contain antivaricella antibodies, the titer of any specific lot of IVIG is uncertain, because IVIG is not tested routinely for antivaricella antibodies. No clinical data demonstrating effectiveness of IVIG for postexposure prophylaxis of varicella are available. The recommended IVIG dose for postexposure prophylaxis of varicella is 1 dose of 400 mg/kg, intravenously (see http://redbook.solutions.aap.org/chapter.aspx?sectionid=88187270&bookid=1484).

6 Contains only antibody to respiratory syncytial virus.

IG administration may become necessary for another indication after MMR or varicella vaccines have been given. In such a situation, the IG may interfere with the immune response to the MMR or varicella vaccines. Vaccine virus replication and stimulation of immunity usually occur 2–3 weeks after vaccination. If the interval between administration of 1 of these vaccines and the subsequent administration of an IG preparation is ≥14 days, the vaccine need not be readministered. If the interval is <14 days, the vaccine should be readministered after the interval shown in Table 2-4, unless serologic testing indicates that antibodies have been produced. Such testing should be performed after the interval shown in Table 2-4, to avoid detecting antibodies from the IG preparation.

When IG is given with the first dose of hepatitis A vaccine, the proportion of recipients who develop a protective level of antibody is not affected, but antibody concentrations are lower. Because the final concentrations of antibody are many times higher than those considered protective, this reduced immunogenicity is not expected to be clinically relevant. However, the effect of reduced antibody concentrations on long-term protection is unknown.

IG preparations interact minimally with other inactivated vaccines and toxoids. Other inactivated vaccines may be given simultaneously or at any time interval before or after an antibody-containing blood product is used. However, such vaccines should be administered at different sites from the IG.

Vaccinating People With Acute Illnesses

Every opportunity should be taken to provide needed vaccinations. The decision to delay vaccination because of a current or recent acute illness depends on the severity of the symptoms and their cause. Although a moderate or severe acute illness is sufficient reason to postpone vaccination, minor illnesses (such as diarrhea, mild upper respiratory infection with or without low-grade fever, or other low-grade febrile illness) are not contraindications to vaccination.

Antimicrobial therapy is not a contraindication to vaccination, with several exceptions:

  • Antibiotics may interfere with the response to oral typhoid vaccine and oral cholera vaccine.

  • Antiviral agents active against herpes viruses (such as acyclovir) may interfere with the response to varicella-containing vaccines.

  • Antiviral agents active against influenza virus (such as zanamivir and oseltamivir) may interfere with the response to live attenuated influenza vaccine.

Vaccination Scheduling for Selected Travel Vaccines

Table 2-5 lists the minimum age and minimum interval between doses for vaccines routinely recommended in the United States.

Table 2-5. Recommended and minimum ages and intervals vaccine doses1,2

Vaccine and Dose Number

Recommended Age for this Dose

Minimum Age for this Dose

Minimum Interval to Next Dose3

Japanese encephalitis, Vero cell (Ixiaro)-14

2 months - 17 years18–65 years

≥2 months≥18 years

28 days7 days

Ixiaro-2

2 months -17 years: 28 days after dose 118–65 years: 7 days after dose 1

28 days after dose 17 days after dose 1

NA

Live cholera vaccine (Vaxchora)

Rabies-1 (preexposure)

18–64 years

See footnote 5

18 years

NA

Rabies-2

7 days after dose 1

7 days after dose 1

14 days

Rabies-3

21 days after dose 1

21 days after dose 1

NA

Typhoid, inactivated (ViCPS)

≥2 years

≥2 years

NA

Typhoid, live attenuated (Ty21a)

≥6 years

≥6 years

See footnote 6

Yellow fever

≥9 months7

≥9 months7

10 years

1 Adapted from Table 1, CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(RR-2):1–61.

2 Combination vaccines are available. Use of licensed combination vaccines is generally preferred over separate injections of their equivalent component vaccines (CDC. Combination vaccines for childhood immunization. MMWR Recomm Rep. 1999 May 14;48[RR-5]:1–14.). When administering combination vaccines, the minimum age for administration is the oldest age for any of the individual components (exception: the minimum age for the first dose of MenHibrix is 6 weeks); the minimum interval between doses is equal to the largest interval of any of the individual components.

3 See www.cdc.gov/vaccines/schedules for recommended revaccination (booster) schedules.

4 Ixiaro is approved by the Food and Drug Administration for people aged ≥2 months.

5 There is no minimum age for preexposure immunization for rabies (CDC. Human rabies prevention—United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008 May 23;57[RR-3]:1–28).

6 Oral typhoid vaccine is recommended to be administered 1 hour before a meal with a cold or lukewarm drink (temperature not to exceed body temperature—98.6°F [37°C]) on alternate days, for a total of 4 doses.

7 Yellow fever vaccine may be administered to children aged <9 months in certain situations (CDC. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR Recomm Rep. 2010 Jul 30;59[RR-7]:1–27.).

Allergy to Vaccine Components

Vaccine components can cause allergic reactions in some recipients. These reactions can be local or systemic and can include anaphylaxis or anaphylacticlike responses. The vaccine components responsible can include the vaccine antigen, animal proteins, antibiotics, preservatives (such as thimerosal), or stabilizers (such as gelatin). The most common animal protein allergen is egg protein in vaccines prepared by using embryonated chicken eggs (influenza and yellow fever vaccines). People with a history of egg allergy who have experienced only hives after exposure to egg should receive influenza vaccine. Any licensed inactivated influenza vaccine that is otherwise appropriate for the recipient’s age and health status may be used.

People who report having had reactions to egg involving symptoms other than hives, such as angioedema, respiratory distress, lightheadedness, or recurrent emesis, or who required epinephrine or another emergency medical intervention, may similarly receive any licensed inactivated influenza vaccine that is otherwise appropriate for the recipient’s age and health status. If a person has a severe egg sensitivity or has a positive skin test to yellow fever vaccine but the vaccination is recommended because of their travel destination–specific risk, desensitization can be performed under direct supervision of a physician experienced in the management of anaphylaxis. In such circumstances, both yellow fever and influenza vaccines should be administered in an inpatient or outpatient medical setting. Vaccine administration should be supervised by a health care provider who is able to recognize and manage severe allergic reactions. A previous severe allergic reaction to any vaccine, regardless of the component suspected of being responsible for the reaction, is a contraindication to future receipt of the vaccine.

Some vaccines contain a preservative or trace amounts of antibiotics to which people might be allergic. Providers administering the vaccines should carefully review the prescribing information before deciding if the rare person with such an allergy should receive the vaccine. No recommended vaccine contains penicillin or penicillin derivatives. Some vaccines (MMR vaccine, inactivated polio vaccine [IPV], hepatitis A vaccine, some hepatitis B vaccines, some influenza vaccines, rabies vaccine, varicella vaccine, and smallpox vaccine) contain trace amounts of neomycin or other antibiotics; the amount is less than would normally be used for the skin test to determine hypersensitivity. However, people who have experienced anaphylactic reactions to this antibiotic generally should not receive these vaccines. Most often, neomycin allergy is a contact dermatitis— a manifestation of a delayed-type (cell-mediated) immune response rather than anaphylaxis. A history of delayed-type reactions to neomycin is not a contraindication to receiving these vaccines.

Thimerosal, an organic mercurial compound in use since the 1930s, has been added to certain immunobiologic products as a preservative. Thimerosal is present at preservative concentrations in multidose vials of some brands of vaccine. Receiving thimerosal-containing vaccines has been postulated to lead to induction of allergy. However, there is limited scientific evidence for this assertion. Allergy to thimerosal usually consists of local delayed-type hypersensitivity reactions. Thimerosal elicits positive delayed-type hypersensitivity patch tests in 1%–18% of people tested, but these tests have limited or no clinical relevance. Most people do not experience reactions to thimerosal administered as a component of vaccines, even when patch or intradermal tests for thimerosal indicate hypersensitivity. A localized or delayed-type hypersensitivity reaction to thimerosal is not a contraindication to receipt of a vaccine that contains thimerosal.

Since mid-2001, vaccines routinely recommended for infants have been manufactured without thimerosal as a preservative. Vaccines that still contain thimerosal as a preservative include some influenza vaccines, DT, and 1 Td vaccine. Additional information about thimerosal and the thimerosal content of vaccines is available on the FDA website (www.fda.gov/cber/vaccine/thimerosal.htm).

Reporting Adverse Events After Immunization

Modern vaccines are extremely safe and effective. Benefits and risks are associated with the use of all immunobiologics—no vaccine is completely effective or completely safe for all recipients. Adverse events after immunization have been reported with all vaccines, ranging from frequent, minor, local reactions to extremely rare, severe, systemic illness, such as that associated with yellow fever vaccine. Adverse events following specific vaccines and toxoids are discussed in detail in each ACIP statement. In the United States, clinicians are required by law to report selected adverse events occurring after vaccination with any vaccine in the recommended childhood series. In addition, CDC strongly recommends that all vaccine adverse events be reported to the Vaccine Adverse Event Reporting System (VAERS), even if a causal relation to vaccination is not certain. VAERS reporting forms and information are available electronically at www.vaers.hhs.gov, or they may be requested by telephone: 800-822-7967 (toll-free). Clinicians are encouraged to report electronically at https://vaers.hhs.gov/esub/step1.

Injection Route and Injection Site

Injectable vaccines are administered by intramuscular, intradermal, and subcutaneous routes. The method of administration of injectable vaccines depends in part on the presence of an adjuvant in some vaccines. The term adjuvant refers to a vaccine component distinct from the antigen, which enhances the immune response to the antigen. Vaccines containing an adjuvant (DTaP, DT, HPV, RZV, Td, Tdap, pneumococcal conjugate, Hib, hepatitis A, hepatitis B) should be injected into a muscle mass, because administration subcutaneously or intradermally can cause local irritation, induration, skin discoloration, inflammation, and granuloma formation. Detailed discussion and recommendations about vaccination of people with bleeding disorders or receiving anticoagulant therapy are available in the ACIP general best practices guidelines for immunization.

Routes of administration are recommended by the manufacturer for each immunobiologic. Deviation from the recommended route of administration may reduce vaccine efficacy or increase local adverse reactions. Detailed recommendations on the route and site for all vaccines have been published in ACIP recommendations; a compiled list of these publications is available on the CDC website at www.cdc.gov/vaccines/hcp/acip-recs (also see Appendix B).

Bibliography

1. CDC. Human rabies prevention—United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008 May 23;57(RR-3):1–28.Find this resource:

2. CDC. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in adults aged 65 years and older—Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep. 2012 Jun 29;61(25):468–70.Find this resource:

3. Cohn AC, MacNeil JR, Clark TA, Ortega-Sanchez IR, Briere EZ, Meissner HC, et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013 Mar 22;62(2):1–28.Find this resource:

4. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices— United States, 2017–2018 influenza season. MMWR Recomm Rep. 2017;66(RR-2):1–22.Find this resource:

5. Kobayashi M, Bennett NM, Gierke R, Almendares O, Moore MR, Whitney CG, et al. Intervals between PCV13 and PPSV23 vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2015 Sep 4;64(64):944–7.Find this resource:

6. Kroger AT, Duchin J, Vázquez M. General best practice guidelines for immunization. Best practices guidance of the Advisory Committee on Immunization Practices (ACIP). Atlanta, GA: CDC [cited 2018 Jan 18]. Available from: www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf.

7. McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS, CDC. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013 Jun 14;62(RR-04):1–34.Find this resource:

8. Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190–207.Find this resource:

9. Shimabukuro TT, Nguyen M, Martin D, DeStefano F. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine. 2015 Aug 26;33(36):4398–405.Find this resource:

10. Staples JE, Gershman M, Fischer M, CDC. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 Jul 30;59(RR-7):1–27.Find this resource:

Interactions Between Travel Vaccines & Drugs

Potential interactions between vaccines and medications, including those already taken by the traveler, must be considered during pretravel consultations. The importance of this topic is highlighted by a study identifying potential drug–drug interactions with travel-related medications in 45% of travelers using chronic medications, and 3.5% of interactions are potentially serious. Interactions of commonly used travel-related vaccines and medications are discussed here.

Interactions Between Vaccines

Concomitant administration of multiple vaccines, including live attenuated vaccines, generally is safe and effective. However, the spacing between the administration of some vaccines that are not given at the same time needs consideration.

A single study suggested that in adults, concomitant administration of the 13-valent pneumococcal conjugate vaccine (PCV13) with the trivalent inactivated influenza vaccine results in lower immunogenicity to the PCV13 components. The clinical significance of this observation is uncertain, as responses still met FDA criteria of noninferiority. Infants given PCV13 and inactivated influenza vaccine concomitantly had a slightly increased risk of fever and febrile seizure, but this risk must be weighed against the need for both vaccines before travel and the time available to separate them.

Administering a live-virus vaccine within 4 weeks after administration of another live-virus vaccine can decrease immunogenicity to the second administered vaccine; therefore, live-virus vaccines should be administered the same day or ≥4 weeks apart. If the 4-week span is not achievable, the second vaccine may be administered sooner to afford some protection, but should be readministered ≥4 weeks later if the traveler is at continued risk. A study examining concurrent administration of the yellow fever vaccine with the measles-mumps-rubella (MMR) vaccine in 12-month-old children showed slightly reduced immunogenicity to yellow fever and mumps components, compared with responses following separate vaccination with MMR and yellow fever vaccines 30 days apart. (See “Simultaneous Administration” in Chapter 4, Yellow Fever.) Similarly, risk for varicella vaccine failure among people who received varicella vaccine within 28 days of MMR vaccination was 3-fold higher than among people who received varicella vaccine >28 days after MMR vaccination.

Concerns about spacing between doses of live vaccines not given at the same visit applies only to live injectable or intranasal vaccines, so live oral cholera vaccine (CVD 103-HgR, Vaxchora, PaxVax) may be administered simultaneously or at any interval before or after administration of most other vaccines. One exception to this rule is the Ty21a oral typhoid vaccine. Oral cholera vaccine should be administered before Ty21a vaccine, and 8 hours should separate the cholera vaccine and the first dose of Ty21a.

Interactions Between Travel Vaccines and Drugs

Live Attenuated Oral Typhoid and Cholera Vaccines

Live attenuated vaccines generally should be avoided in immunocompromised travelers, including those taking immunomodulators, calcineurin inhibitors, cytotoxic agents, antimetabolites, and high-dose steroids (see Table 5-2).

Antimicrobial agents may be active against the vaccine strains in the oral typhoid and cholera vaccines and may prevent adequate immune response to these vaccines. Vaccination with oral typhoid vaccine should be delayed for >72 hours and with oral cholera vaccine for >14 days after administration of antimicrobial agents. Parenteral typhoid vaccine is an alternative to oral vaccine, but there is no parenteral cholera vaccine currently available, and no killed oral cholera vaccines are licensed in the United States.

Chloroquine and atovaquone-proguanil at doses used for malaria chemoprophylaxis may be given concurrently with oral typhoid vaccine. Data from an older formulation of the CVD 103-HgR oral cholera vaccine suggest that the immune response to the vaccine may be diminished when it is given concomitantly with chloroquine. Live attenuated oral cholera vaccine should be given at least 10 days before beginning antimalarial prophylaxis with chloroquine. A study in children using oral cholera vaccine suggested no decrease in immunogenicity when given with atovaquone-proguanil.

Rabies Vaccine

Concomitant use of chloroquine may reduce the antibody response to intradermal rabies vaccine administered for preexposure vaccination. The intramuscular route should be used for people taking chloroquine concurrently. (Currently, intradermal administration of rabies vaccine is not approved in the United States.)

Interactions Between Antimalarials and Selected Other Drugs

This section describes some of the more commonly encountered drug interactions. Any time a new medication is prescribed, clinicians should check for any interactions and inform the traveler of the potential risk.

Mefloquine

Mefloquine may interact with several categories of drugs, including other antimalarial drugs, drugs that alter cardiac conduction, and anticonvulsants. Mefloquine is associated with increased toxicities of the antimalarial drug lumefantrine (available in the United States in fixed combination to treat people with uncomplicated Plasmodium falciparum malaria), potentially causing fatal prolongation of the QTc interval. Lumefantrine should therefore be avoided or used with caution in patients taking mefloquine prophylaxis. Although no conclusive data are available with regard to coadministration of mefloquine and other drugs that may affect cardiac conduction, mefloquine should be used with caution or avoided in patients taking antiarrhythmic or β‎-blocking agents, calcium-channel blockers, antihistamines, H1-blocking agents, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), or phenothiazines. Mefloquine may also lower plasma levels of a number of anticonvulsants, such as valproic acid, carbamazepine, phenobarbital, and phenytoin; concurrent use of mefloquine with these agents should be avoided. In general, mefloquine should be avoided in travelers with a history of seizures, mood disorders, or psychiatric disease. Mefloquine can also lead to increased levels of calcineurin inhibitors and mTOR inhibitors (tacrolimus, cyclosporine A, and sirolimus). Potent CYP3A4 inhibitors such as macrolides (azithromycin, clarithromycin, erythromycin), azole antifungals (ketoconazole, voriconazole, posaconazole and itraconazole), SSRIs (fluoxetine, sertraline, fluvoxamine), antiretroviral protease inhibitors (ritonavir, lopinavir, darunavir, atazanavir, saquinavir), and cobicistat (available in a combination with elvitegravir) may increase levels of mefloquine, increasing the risk for QT prolongation. CYP3A4 inducers such as efavirenz, nevirapine, etravirine, rifampin, rifabutin, St John’s wort, and glucocorticoids may reduce plasma concentrations of mefloquine, and concurrent use should be avoided. Concurrent use of mefloquine with the direct-acting protease inhibitors boceprevir and telaprevir used to treat hepatitis C should also be avoided. The newer direct-acting protease inhibitors (grazoprevir, paritaprevir, simeprevir) are believed to be associated with fewer drug–drug interactions, but as safety data are lacking, alternatives to mefloquine should be considered pending additional data.

Chloroquine

Chloroquine may increase risk of prolonged QTc interval when given with other QT-prolonging agents (such as sotalol, amiodarone, and lumefantrine), and the combination should be avoided. The antiretroviral rilpivirine has also been shown to prolong QTc, and coadministration should be avoided. Chloroquine inhibits CYP2D6; when given concomitantly with substrates of this enzyme (such as metoprolol, propranolol, fluoxetine, paroxetine, flecainide), increased monitoring for side effects may be warranted. Chloroquine absorption may be reduced by antacids or kaolin; ≥4 hours should elapse between doses of these medications. Concomitant use of cimetidine and chloroquine should be avoided, as cimetidine can inhibit the metabolism of chloroquine and may increase drug levels. CYP3A4 inhibitors such as ritonavir, ketoconazole, and erythromycin may also increase chloroquine levels, and concomitant use should be avoided. Chloroquine inhibits bioavailability of ampicillin, and 2 hours should elapse between doses. Chloroquine is also reported to decrease the bioavailability of ciprofloxacin and methotrexate. Chloroquine may increase digoxin levels; increased digoxin monitoring is warranted. Use of chloroquine could possibly also lead to increased levels of calcineurin inhibitors and should be used with caution.

Atovaquone-Proguanil

Tetracycline, rifampin, and rifabutin may reduce plasma concentrations of atovaquone and should not be used concurrently with atovaquone-proguanil. Metoclopramide may reduce bioavailability of atovaquone; unless no other antiemetics are available, this antiemetic should not be used to treat the vomiting that may accompany use of atovaquone at treatment doses. Atovaquone-proguanil should not be used with other medications that contain proguanil. Patients on warfarin may need to reduce their anticoagulant dose or monitor their prothrombin time more closely while taking atovaquone-proguanil, although coadministration of these drugs is not contraindicated. The use of novel oral anticoagulants (dabigatran, rivaroxaban and apixaban) is not expected to cause significant interactions, and their use has been suggested as an alternative in patients in need of anticoagulation. Atovaquone-proguanil may interact with the antiretroviral protease inhibitors ritonavir, darunavir, atazanavir, indinavir, and lopinavir, in addition to the nonnucleoside reverse transcriptase inhibitors nevirapine, etravirine, and efavirenz, resulting in decreased levels of atovaquone-proguanil. Despite the potential for interactions, atovaquone-proguanil is well tolerated in most patients receiving these antivirals and is the preferred antimalarial for short-term travel. Cimetidine and fluvoxamine interfere with the metabolism of proguanil and should therefore be avoided.

Doxycycline

Phenytoin, carbamazepine, and barbiturates may decrease the half-life of doxycycline. Patients on anticoagulants may need to reduce their anticoagulant dose while taking doxycycline because of its ability to depress plasma prothrombin activity. Absorption of tetracyclines may be impaired by bismuth subsalicylate, preparations containing iron, and antacids containing calcium, magnesium, or aluminum; these preparations should not be taken within 3 hours of taking doxycycline. Doxycycline may interfere with the bactericidal activity of penicillin, so in general, these drugs should not be taken together. Doxycycline has no known interaction with antiretroviral agents, but concurrent use may lead to increased levels of calcineurin inhibitors and mTOR inhibitors (sirolimus).

Interactions With Drugs Used to Treat Travelers’ Diarrhea

Azithromycin

Close monitoring for side effects of azithromycin is recommended when azithromycin is used with nelfinavir. Increased anticoagulant effects have been noted when azithromycin is used with warfarin; monitoring prothrombin time is recommended for people taking these drugs concomitantly. Additive QTc prolongation may occur when azithromycin is used with the antimalarial artemether, and concomitant therapy should be avoided. Drug interactions have been reported with macrolides and antiretroviral protease inhibitors, as well as efavirenz and nevirapine, and can increase risk of QTc prolongation, though a short treatment course is not contraindicated for those without an underlying cardiac abnormality. Concurrent use with macrolides may lead to increased levels of calcineurin inhibitors.

Fluoroquinolones

Increase in the international normalized ratio (INR) has been reported when levofloxacin and warfarin are used concurrently. Concurrent administration of ciprofloxacin and antacids that contain magnesium or aluminum hydroxide may reduce bioavailability of ciprofloxacin. Ciprofloxacin decreases clearance of theophylline and caffeine; theophylline levels should be monitored when ciprofloxacin is used concurrently. Ciprofloxacin and other fluoroquinolones should not be used with tizanidine. Sildenafil should not be used in patients on ciprofloxacin, as concomitant use is associated with increased rates of adverse effects. Fluoroquinolones have no known interaction with antiretroviral agents, but concurrent use may increase levels of calcineurin inhibitors and fluoroquinolone levels, and use should reflect renal function.

Rifaximin

Rifaximin is not absorbed in appreciable amounts by intact bowel, and no clinically significant drug interactions have been reported to date with rifaximin except for minor changes in INR when used concurrently with warfarin.

Rifamycin SV

No clinical drug interactions have been studied. Because of minimal systemic rifamycin concentrations observed after the recommended dose, clinically relevant drug interactions are not expected.

Interactions With Drugs Used for Travel to High Altitudes

Acetazolamide

Acetazolamide produces alkaline urine that can increase the rate of excretion of barbiturates and salicylates and may potentiate salicylate toxicity, particularly if taking a high dose of aspirin. Decreased excretion of dextroamphetamine, anticholinergics, mecamylamine, ephedrine, mexiletine, or quinidine may also occur. Hypokalemia caused by corticosteroids may be potentiated by concurrent use of acetazolamide. Acetazolamide should not be given to patients taking the anticonvulsant topiramate, as concurrent use is associated with increased toxicity. Increased monitoring of cyclosporine, tacrolimus, and sirolimus is warranted if these drugs are given with acetazolamide. Concurrent administration of metformin and acetazolamide should be done with caution, as there may be an additive risk for lactic acidosis. Acetaminophen and diclofenac sodium form complex bonds with acetazolamide in the stomach’s acidic environment, impairing absorption. These agents should not be taken within 30 minutes of acetazolamide.

Dexamethasone

Dexamethasone interacts with multiple classes of drugs. Using this drug to treat altitude illness may, however, be lifesaving. Interactions may occur with dexamethasone and the following drugs and drug classes: macrolide antibiotics, anticholinesterases, anticoagulants, hypoglycemic agents, isoniazid, digitalis preparations, oral contraceptives, and phenytoin.

Drug Interactions in Patients on HIV Medications

Patients with HIV can be a challenge in the pretravel consultation (See Chapter 5, Immunocompromised Travelers). A study in Europe showed that as many as 29% of HIV-positive travelers do not disclose their disease and medication status when seeking pretravel advice. Antiretroviral medications have multiple drug interactions, especially through activation or inhibition of CYP3A4 and CYP2D6. There are several reports of antimalarial treatment failure and prophylaxis failure in patients on protease inhibitors and both nucleoside and nonnucleoside reverse transcriptase inhibitors, whereas entry and integrase inhibitors are not a common cause of drug–drug interactions with commonly administered travel-related medications. A number of the potential interactions are listed above, and 2 excellent resources for HIV medication interactions can be found at www.hiv-druginteractions.org and at www.aidsinfo.nih.gov. Preexposure prophylaxis with emtricitabine/tenofovir is not a contraindication for any of the commonly used travel-related medications.

Interactions With Herbal or Nutritional Supplements

As many as 30% of travelers take herbal or nutritional supplements, and many consider them to be of no clinical relevance and will not disclose their use unless specifically asked during the pretravel consultation. Special attention should be given to supplements that activate or inhibit CYP2D6 or CYP3A4 like ginseng, hypericum, St. John’s wort, and grapefruit extract. Coadministration with medications that are substrates of CYP2D6 or 3A4 should be avoided (chloroquine, mefloquine, macrolides).

Bibliography

1. Frenck RW Jr, Gurtman A, Rubino J, Smith W, van Cleeff M, Jayawardene D, et al. Randomized, controlled trial of a 13-valent pneumococcal conjugate vaccine administered concomitantly with an influenza vaccine in healthy adults. Clin Vaccine Immunol. 2012 Aug;19(8):1296–303.Find this resource:

2. Jabeen E, Qureshi R, Shah A. Interaction of antihypertensive acetazolamide with nonsteroidal anti-inflammatory drugs. J Photochem Photobiol B. 2013 Aug 5;125:155–63.Find this resource:

3. Kollaritsch H, Que JU, Kunz C, Wiedermann G, Herzog C, Cryz SJ Jr. Safety and immunogenicity of live oral cholera and typhoid vaccines administered alone or in combination with antimalarial drugs, oral polio vaccine, or yellow fever vaccine. J Infect Dis. 1997 Apr;175(4):871–5.Find this resource:

4. Nascimento Silva JR, Camacho LA, Siqueira MM, Freire Mde S, Castro YP, Maia Mde L, et al. Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella. Vaccine. 2011 Aug 26;29(37):6327–34.Find this resource:

5. Nielsen US, Jensen-Fangel S, Pedersen G, Lohse N, Pedersen C, Kronborg G, et al. Travelling with HIV: a cross sectional analysis of Danish HIV-infected patients. Travel Med Infect Dis. 2014 Jan–Feb;12(1):72–8.Find this resource:

6. Ridtitid W, Wongnawa M, Mahatthanatrakul W, Raungsri N, Sunbhanich M. Ketoconazole increases plasma concentrations of antimalarial mefloquine in healthy human volunteers. J Clin Pharm Ther. 2005 Jun;30(3):285–90.Find this resource:

7. Sbaih N, Buss B, Goyal D, Rao SR, Benefield R, Walker AT, et al. Potentially serious drug interactions resulting from the pre-travel health encounter. Open Forum Infect Dis. 2018 Oct 22;5(11):ofy266.Find this resource:

8. Stienlauf S, Meltzer E, Kurnik D, Leshem E, Kopel E, Streltsin B, et al. Potential drug interactions in travelers with chronic illnesses: a large retrospective cohort study. Travel Med Infect Dis. 2014 Sep–Oct;12(5):499–504.Find this resource:

Yellow Fever Vaccine & Malaria Prophylaxis Information, by Country

The following pages present country-specific information on yellow fever (YF) vaccine requirements and recommendations (Table 2-6) and malaria transmission information and prophylaxis recommendations. Country-specific maps of malaria transmission areas, country-specific maps depicting yellow fever vaccine recommendations, and a reference map of China are included to aid in interpreting the information. The information was accurate at the time of publication; however, this information is subject to change at any time as a result of changes in disease transmission or, in the case of YF, changing country entry requirements. Updated information reflecting changes since publication can be found in the online version of this book (www.cdc.gov/yellowbook) and on the CDC Travelers’ Health website (www.cdc.gov/travel). General recommendations for other vaccines to consider during the pretravel consultation can be found on the CDC Travelers’ Health website (www.cdc.gov/travel).

Table 2-6. Categories of recommendations for yellow fever (YF) vaccination

YF Vaccination Category

Rationale for Recommendation

Recommended

Vaccination recommended for all travelers ≥9 months of age to areas with endemic or transitional YF risk, as determined by persistent or periodic YF virus transmission.

Generally not recommended

Vaccination generally not recommended in areas where the potential for YF virus exposure is low, as determined by absence of reports of human YF and past evidence suggestive of only low levels of YF virus transmission. However, vaccination might be considered for a small subset of travelers who are at increased risk for exposure to YF virus because of prolonged travel, heavy exposure to mosquitoes, or inability to avoid mosquito bites.

Not recommended

Vaccination not recommended in areas where there is no risk of YF virus transmission, as determined by absence of past or present evidence of YF virus circulation in the area or environmental conditions not conducive to YF virus transmission.

Yellow Fever

Since publication of the 2018 edition of the CDC Yellow Book, large YF outbreaks occurred in eastern Brazil in 2017 and 2018, involving states where YF was not previously considered endemic. Notably, human YF cases occurred within the greater metropolitan area of São Paulo City and not far from the metropolitan limits of Rio de Janeiro City. In response, the Brazil Ministry of Health conducted mass vaccination campaigns in the newly affected areas. Based on a review of the situation by the World Health Organization (WHO) Scientific and Technical Advisory Group on Geographical Yellow Fever Risk Mapping, in which CDC participates, preliminary expanded YF vaccination recommendations were made for international travelers to the eastern and southeastern states of Brazil. Given that the Brazil Ministry of Health has initiated its plan to vaccinate the entire population of Brazil against YF by mid-2019, these preliminary vaccination recommendations for international travel will likely be made permanent by the advisory group.

Revaccination against yellow fever was previously required by certain countries at 10-year intervals to comply with International Health Regulations (IHR). In 2014, the World Health Assembly (of WHO) adopted the recommendation to amend the IHR by removing the 10-year booster dose requirement, and stipulated a 2-year transition period for this change. Consequently, as of July 11, 2016, a completed International Certificate of Vaccination or Prophylaxis (ICVP) is valid for the lifetime of the vaccinee. Moreover, countries cannot require proof of revaccination (booster) against yellow fever as a condition of entry, even if the last vaccination was >10 years prior.

In the United States, the Advisory Committee on Immunization Practices (ACIP) published a new recommendation in 2015 that 1 dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. The recommendation also identifies specific groups of travelers who should receive additional doses and others for whom additional doses may be considered. For details, see Chapter 4, Yellow Fever. For the most up-to-date information about yellow fever vaccine boosters, consult the CDC Travelers’ Health website or the specific publication posted on the ACIP website (www.cdc.gov/mmwr/pdf/wk/mm6423.pdf).

Ultimately, the clinician’s decision whether or not to vaccinate any traveler must take into account the traveler’s risk of being infected with YF virus, country entry requirements, and individual risk factors for serious adverse events after YF vaccination (such as age and immune status). For a thorough discussion of YF and guidance for vaccination, see Chapter 4, Yellow Fever.

NOTE: Despite the recent changes to the IHR regarding YF vaccine boosters, it is uncertain whether all countries with YF vaccination entry requirements will fully adopt this change. Even if countries modify their official policies to extend the validity period of the ICVP from 10 years to the lifetime of the vaccinee, there is no guarantee that all national border officials will be aware of such policy change or be able to enforce it. CDC obtains information yearly from WHO about official country entry requirements. WHO likely will not be asking countries about YF vaccine booster entry requirements in the yearly questionnaires, because it will be assumed that countries are complying with the amended IHR. This could leave a gap in the foreseeable future in accurate published information about entry requirements for YF vaccine boosters for certain countries. Past experience has demonstrated that information given by consulates and embassies about vaccination requirements is often not accurate. Therefore, providers and travelers should not rely solely on such information when determining current YF vaccination entry requirements for specific destinations. With the caveats described above, readers should refer to the online version of this book (www.cdc.gov/yellowbook) and the CDC Travelers’ Health website (www.cdc.gov/travel) for any reported updates to country entry requirements since publication of this edition.

Malaria

The following recommendations to protect travelers from malaria were developed by using the best available data from multiple sources. Countries are not required to submit malaria surveillance data to CDC. On an ongoing basis, CDC actively solicits data from multiple sources, including WHO (main and regional offices); national malaria control programs; international organizations, such as the International Society of Travel Medicine; CDC overseas staff; US military; academic, research, and aid organizations; and published records from the medical literature. The reliability and accuracy of those data are also assessed. If the information is available, trends in malaria incidence and other data are considered in the context of malaria control activities within a given country or other mitigating factors such as natural disasters, wars, and other events that may affect the ability to control malaria or accurately count and report it. Factors such as the volume of travel to that country and the number of acquired cases reported in the US surveillance system are also examined. Based on all those considerations, recommendations are developed to try to accurately describe areas of the country where transmission occurs, substantial occurrences of antimalarial drug resistance, the proportions of species present, and the recommended prophylaxis options.

These recommendations should be used in conjunction with an individual risk assessment, taking into account not only the destination country but also the detailed itinerary including specific cities, types of accommodation, season, and style of travel, as well as special health conditions such as pregnancy.

Several medications are available for malaria prophylaxis. When deciding which drug to use, clinicians should consider the specific itinerary, length of trip, drug costs, previous adverse reactions to antimalarials, drug allergies, and medical history.

For a thorough discussion of malaria and guidance for prophylaxis, see Chapter 4, Malaria.

Country-Specific Information

Afghanistan

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age.1

  • Recommendations: None

Malaria

  • Areas with malaria: April–December in all areas <2,500 m (8,202 ft).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 95%, P. falciparum 5%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Albania

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Algeria

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

American Samoa (US)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Andorra

Yellow Fever

  • Requirements: None

  • Recommendations: None

  • MALARIA

  • No malaria transmission.

Angola

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. ovale 5%, P. vivax 5%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Anguilla (UK)

Yellow Fever

  • Requirements: None

  • Recommendations: None

  • MALARIA

  • No malaria transmission.

Antarctica

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Antigua and Barbuda

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Argentina

Yellow Fever

  • Requirements: None

  • Recommendations:

  • Recommended for travelers ≥9 months of age going to Corrientes and Misiones Provinces.

  • Generally not recommended for travelers going to Formosa Province and designated areas of Chaco, Jujuy, and Salta Provinces (Map 2-1).

  • Not recommended for all travelers whose itineraries are limited to areas and provinces not listed above.

Map 2-1. Yellow fever vaccine recommendations in Argentina1

Map 2-1. Yellow fever vaccine recommendations in Argentina1

1,2,3See footnotes on page 101

Malaria

  • No malaria transmission.

Armenia

Yellow Fever

Malaria

  • No malaria transmission.

Aruba

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Australia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission. This requirement excludes Galápagos Islands in Ecuador and the island of Tobago; it is limited to Misiones Province in Argentina.

  • Recommendations: None

Malaria

  • No malaria transmission.

Austria

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Azerbaijan

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Azores (Portugal)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Bahamas, The

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Bahrain

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Bangladesh

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • Areas with malaria: All areas, except in the city of Dhaka.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. vivax 10%, and P. malariae rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Barbados

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1 This requirement excludes Guyana and the island of Trinidad.

  • Recommendations: None

Malaria

  • No malaria transmission.

Belarus

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Belgium

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Belize

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Rare locally transmitted cases. None in Belize City and islands frequented by tourists, such as Ambergris Caye.

  • Drug resistance3: None.

  • Malaria species: P. vivax 100%.

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Benin

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Bermuda (UK)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Bhutan

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Rare cases in rural areas <1,700 m (5,577 ft) in districts along the southern border shared with India. Rare seasonal cases May–September in Ha, Lhuentse, Monggar, Punakha, Trashigang, Trongsa, Tsirang, Yangtse, and Wangdue. None in districts of Bumthang, Gaza, Paro, and Thimphu.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 70%, P. vivax 30%.

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Bolivia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations:

  • Recommended for all travelers ≥9 months of age traveling to the following areas <2,300 m (7,546 ft) in elevation and east of the Andes Mountains: the entire departments of Beni, Pando, Santa Cruz, and designated areas (Map 2-2) of Chuquisaca, Cochabamba, La Paz, and Tarija departments.

  • Not recommended for travelers whose itineraries are limited to areas >2,300 m (7,546 ft) in elevation and all areas not listed above, including the cities of La Paz and Sucre.

Map 2-2. Yellow fever vaccine recommendations in Bolivia1

Map 2-2. Yellow fever vaccine recommendations in Bolivia1

1,2See footnotes on page 101

Malaria

  • Areas with malaria: All areas <2,500 m (8,202 ft). None in the city of La Paz (Map 2-3).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 93%, P. falciparum 7%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, primaquine4, or tafenoquine.4

Bonaire

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Bosnia and Herzegovina

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Botswana

Yellow Fever

  • Requirements: Required if traveling from or having passed through a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present in the following subdistricts: Botete, Chobe (including Chobe National Park), Ngami, Okavango, and Tuteme. Also present in the following districts: Bobirwa, Northeast (including Francistown), Ghanzi, Mahalapaye, and Serowe Palapye. Rare cases in the districts of Kgalagadi North, Keneng West, and Southern. None in the city of Gaborone (Map 2-4).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. vivax 5%, P. ovale 5%.

  • Recommended chemoprophylaxis: Subdistricts of Botete, Chobe (including Chobe National Park), Ngami, Okavango, and Tuteme and districts or Bobirwa, Northeast (including Francistown), Ghanzi, Mahalapaye, and Serowe Palapye: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4 Areas with rare cases: None (practice mosquito avoidance).

Brazil

Yellow Fever

  • Requirements: None

  • Recommendations:

  • Recommended for all travelers ≥9 months of age going to the following areas: the entire states of Acre, Amapá, Amazonas, Distrito Federal (including the capital city of Brasília), Espirito Santo,* Goiás, Maranhão, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Pará, Paraná,* Rio de Janeiro (including the city of Rio de Janeiro and all coastal islands),* Rio Grande do Sul,* Rondonia, Roraima, Santa Catarina,* São Paulo (including the city of São Paulo and all coastal islands),* and Tocantins and designated areas (Map 2-5) of the following states: Bahia* and Piauí. Vaccination is also recommended for travelers visiting Iguaçu Falls.

  • Not recommended for travelers whose itineraries are limited to areas not listed above, including the cities of Fortaleza and Recife (Map 2-5).

  • *Note: In 2017, CDC expanded YF vaccination recommendations for travelers to Brazil in response to a large YF outbreak in multiple eastern states. A list of areas in Bahia state for which vaccination is now recommended can be found at www.who.int/ith/ith-country-list.pdf. The expanded YF vaccination recommendations for these states are preliminary. For updates, refer to the CDC Travelers’ Health website at www.cdc.gov/travel.

Map 2-5. Yellow fever vaccine recommendations in Brazil1

Map 2-5. Yellow fever vaccine recommendations in Brazil1

1,2,3See footnotes on page 101

Malaria

  • Areas with malaria: All areas of the states of Acre, Amapá, Amazonas, Rondonia, and Roraima. Also present in the states of Maranhão, Mato Grosso, and Para, but rare cases in their capital cities. Rare cases in the rural areas of the states of Espirito Santo, Goiás, Mato Grosso do Sul, Piauí, and Tocantins. Rare cases in the rural forested areas of the states of Rio de Janeiro and São Paolo. No malaria in the cities of Brasilia, Rio de Janeiro, São Paolo, and none at Iguaçu Falls (Map 2-6).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 85%, P. falciparum 15%.

  • Recommended chemoprophylaxis: States of Acre, Amapá, Amazonas, Rondonia, and Roraima. States of Maranhão, Mato Grosso, and Para (but not their capital cities): Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4 Areas with rare cases: None (practice mosquito avoidance).

British Indian Ocean Territory; Includes Diego Garcia (UK)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Brunei

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Bulgaria

Yellow Fever

Malaria

  • No malaria transmission.

Burkina Faso

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit in an airport located in a country with risk of YF virus transmission.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >80%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Burma (Myanmar)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present at altitudes <1,000 m (3,281 ft), including Bagan. Rare transmission above 1,000 m (3,281 ft) (Map 2-7).

  • Drug resistance3: Chloroquine and mefloquine.

  • Malaria species: P. falciparum 60%, P. vivax 35%, P. malariae, P. ovale, and P. knowlesi rare.

  • Recommended chemoprophylaxis: In the provinces of Bago, Kachin, Kayah, Kayin, Shan, and Tanintharyi <1,000 m (3,281 ft): Atovaquone-proguanil, doxycycline, or tafenoquine.4

  • All other areas <1,000 m (3,281 ft): Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

  • Above 1,000 m (3,281 ft): None (practice mosquito avoidance).

Burundi

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 86%, P. malariae, P. ovale, and P. vivax 14% combined.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Cambodia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present throughout the country, including Siem Reap city. None in the city of Phnom Penh and at the temple complex at Angkor Wat.

  • Drug resistance3: Chloroquine and mefloquine.

  • Malaria species: P. falciparum 60%, P. vivax 40%.

  • Recommended chemoprophylaxis: In the provinces of Banteay Meanchey, Battambang, Kampot, Koh Kong, Odder Meanchey, Pailin, Preah Vihear, Pursat, and Siem Reap bordering Thailand: Atovaquone-proguanil, doxycycline, or tafenoquine.4 All other areas with malaria: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Cameroon

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Canada

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Canary Islands (Spain)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Cape Verde

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Rare cases in São Tiago Island.

  • Drug resistance3: Chloroquine.

  • Malaria species: Primarily P. falciparum.

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Cayman Islands (UK)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Central African Republic

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 85%, P. malariae, P. ovale, and P. vivax 15% combined.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Chad

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations:

  • Recommended for all travelers ≥9 months of age traveling to areas south of the Sahara Desert (Map 4-13).

  • Not recommended for travelers whose itineraries are limited to areas in the Sahara Desert (Map 4-13).

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 85%, P. malariae, P. ovale, and P. vivax 15% combined.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Chile

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

China (Map 2-8)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1 This requirement does not apply to travelers whose itineraries are limited to Hong Kong Special Administrative Region (SAR) and Macao SAR.

  • Recommendations: None

Malaria

  • Areas with malaria: Rare cases in the counties along the China-Burma (Myanmar) border in Yunnan Province and Motuo County in Tibet. No malaria in areas where most major river cruises pass.

  • Drug resistance3: Chloroquine and mefloquine.

  • Malaria species: Primarily P. vivax; P. falciparum in Yunnan Province.

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Christmas Island (Australia)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1 This requirement excludes Galápagos Islands in Ecuador and the island of Tobago; it is limited to Misiones Province in Argentina.

  • Recommendations: None

Malaria

  • No malaria transmission.

Cocos (Keeling) Islands (Australia)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1 This requirement excludes Galápagos Islands in Ecuador and the island of Tobago; it is limited to Misiones Province in Argentina.

  • Recommendations: None

Malaria

  • No malaria transmission.

Colombia

Yellow Fever

  • Requirements: Required if arriving from Angola, Brazil, Democratic Republic of the Congo, or Uganda and ≥1 year of age and for travelers who have transited >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations:

  • Recommended for all travelers ≥9 months of age except as mentioned below.

  • Generally not recommended for travelers to the cities of Barranquilla, Cali, Cartagena, and Medellín (Map 2-9).

  • Not recommended for travelers whose itineraries are limited to all areas >2,300 m (7,546 ft) in elevation, the department of San Andrès y Providencia, and the capital city of Bogotá.

Map 2-9. Yellow fever vaccine recommendations in Colombia1

Map 2-9. Yellow fever vaccine recommendations in Colombia1

1,2See footnotes on page 101

Malaria

  • Areas with malaria: All areas <1,700 m (5,577 ft). None in Bogotá, Cartagena, and Medellín. (Map 2-10).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 50%, P. vivax 50%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Comoros

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: Primarily P. falciparum.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Congo, Republic of the (Congo-Brazzaville)

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Cook Islands (New Zealand)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Costa Rica

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age.1 This requirement excludes Argentina and Panama.

  • Recommendations: None

Malaria

  • Areas with malaria: Rare local cases in Matina Canton in Limón Province, Sarapiquí Canton in Heredia Province, and Pital District in San Carlos Canton in Alajuela Province.

  • Drug resistance3: None.

  • Malaria species: P. vivax.

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Croatia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Cuba

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

CuraçAo

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Cyprus

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Czech Republic

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

CôTe D'Ivoire (Ivory Coast)

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, and tafenoquine.4

Democratic Republic of the Congo (Congo-Kinshasa)

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >90%, P. ovale 5%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Denmark

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Djibouti

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. vivax 5%–10%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Dominica

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Dominican Republic

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: Primarily in the provinces by the border with Haiti, and the provinces (including resort areas) of Santo Domingo and La Altagracia. Rare locally transmitted cases in the city of Santo Domingo (Distrito Nacional) and other provinces.

  • Drug resistance3: None.

  • Malaria species: P. falciparum 100%

  • Recommended chemoprophylaxis: Provinces bordering Haiti, and provinces of Santo Domingo (except Santo Domingo city [Distrito Nacional]) and La Altagracia: Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, or tafenoquine.4 Santo Domingo (Distrito Nacional) city and other provinces: None (practice mosquito avoidance).

Easter Island (Chile)

Yellow Fever

  • Requirements: This country has not stated its YF vaccination certificate requirements.

  • Recommendations: None

Malaria

  • No malaria transmission.

Ecuador, Including the GaláPagos Islands

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations:

  • Recommended for all travelers ≥9 months of age traveling to areas <2,300 m (7,546 ft) in elevation in the following provinces east of the Andes Mountains: Morona Santiago, Napo, Orellana, Pastaza, Sucumbios, and Zamora-Chinchipe (Map 2-11).

  • Generally not recommended for travelers whose itineraries are limited to areas <2,300 m (7,546 ft) in elevation in the following provinces west of the Andes mountains: Esmeraldas,* Guayas, Los Rios, Santa Elena, Santo Domingo de los Tsachilas, and designated areas of Azuay, Bolivar, Canar, Carchi, Chimborazo, Cotopaxi, El Oro, Imbabura, Loja, Pichincha, and Tungurahua (Map 2-11).

  • Not recommended for travelers whose itineraries are limited to all areas >2,300 m (7,546 ft) in elevation, the cities of Guayaquil and Quito, or the Galápagos Islands (Map 2-11).

  • *The CDC vaccination recommendation for Esmeraldas Province differs from that published on the WHO International Travel and Health website.

Map 2-11. Yellow fever vaccine recommendations in Ecuador1

Map 2-11. Yellow fever vaccine recommendations in Ecuador1

1,2See footnotes on page 101

Malaria

  • Areas with malaria: Areas at altitudes <1,500 m (4,921 ft) in the provinces of Carchi, Esmeraldas, Morona Santiago, Orellana, and Pastaza. Rare cases in other provinces in areas <1,500 m (4,921 ft). Not present in the cities of Guayaquil and Quito or the Galápagos Islands (Map 2-12).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 72%, P. falciparum 28%.

  • Recommended chemoprophylaxis: Areas with malaria in Carchi, Esmeraldas, Morona Santiago, Orellana, and Pastaza Provinces: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4 Other areas with rare cases of malaria: None (practice mosquito avoidance).

Egypt

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission. This includes Eritrea, Rwanda, Somalia, Tanzania, and Zambia.1 In the absence of a vaccination certificate, the person will be detained in quarantine for up to 6 days after departure from an area at risk of YF virus transmission.

  • Recommendations: None

Malaria

  • No malaria transmission.

El Salvador

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YFV transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Rare cases along Guatemalan border.

  • Drug resistance3: None.

  • Malaria species: P. vivax 99%, P. falciparum <1%.

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Equatorial Guinea

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥6 months of age.1

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 85%; P. malariae, P. ovale, and P. vivax 15% combined.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Eritrea

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations:

  • Generally not recommended for travelers going to the following states: Anseba, Debub, Gash Barka, Mae Kel, and Semenawi Keih Bahri.

  • Not recommended for all areas not listed above, including the Dahlak Archipelago (Map 4-13).

Malaria

  • Areas with malaria: All areas <2,200 m (7,218 ft). None in Asmara.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 85%, P. vivax 10%–15%, P. ovale rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Estonia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Eswatini (Swaziland)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present in eastern areas bordering Mozambique and South Africa, including all of Lubombo district and the eastern half of Hhohho, Manzini, and Shiselweni districts.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. vivax 5%, P. ovale 5%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Ethiopia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations:

  • Recommended for all travelers ≥9 months of age, except as mentioned below.

  • Generally not recommended for travelers whose itinerary is limited to the Afar and Somali Provinces (Map 2-13).

Map 2-13. Yellow fever vaccine recommendations in Ethiopia1

Map 2-13. Yellow fever vaccine recommendations in Ethiopia1

1,2See footnotes on page 101

Malaria

  • Areas with malaria: All areas below 2,500 m (8,202 ft), except none in the city of Addis Ababa (Map 2-14).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 60%–70%, P. vivax 30%–40%, P. malariae and P. ovale rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Falkland Islands (Islas Malvinas)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Faroe Islands (Denmark)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Fiji

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Finland

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

France

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

French Guiana

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥1 year of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All areas, including Matoury, Macouria, and Kourou, except none in coastal areas west of Kourou and Cayenne City.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax >70%, P. falciparum 20%–30%, P. malariae rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

French Polynesia, Including the Island Groups of Society Islands (Tahiti, Moorea, and Bora-Bora); Marquesas Islands (Hiva OA and UA Huka); and Austral Islands (Tubuai and Rurutu)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Gabon

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥1 year of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. malariae, P. ovale, and P. vivax 10% combined.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Gambia, The

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age.1

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum ≥85%, P. ovale 5%–10%, P. malariae and P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Georgia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Germany

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Ghana

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Gibraltar (UK)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Greece

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: Rare local transmission May–November associated with imported malaria cases, in agricultural areas. None in tourist areas.

  • Drug resistance3: Not applicable.

  • Malaria species: P. vivax 100%.

  • Recommended chemoprophylaxis: None.

Greenland (Denmark)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Grenada

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Guadeloupe

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Guam (US)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Guatemala

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Rural areas only at altitudes <1,500 m (4,921 ft). None in Antigua, Guatemala City, or Lake Atitlán.

  • Drug resistance3: None.

  • Malaria species: P. vivax 97%, P. falciparum 3%.

  • Recommended chemoprophylaxis: Escuintla Province: Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, or tafenoquine.4 All other areas with malaria: Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, primaquine,4 or tafenoquine.4

Guinea

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Guinea-Bissau

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥1 year of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Guyana

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All areas. Rare cases in the cities of Amsterdam and Georgetown.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 50%, P. vivax 50%.

  • Recommended chemoprophylaxis: Areas with malaria except cities of Amsterdam and Georgetown: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4 Cities of Georgetown and Amsterdam: None (practice mosquito avoidance).

Haiti

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • Areas with malaria: All (including Port Labadee).

  • Drug resistance3: None.

  • Malaria species: P. falciparum 99%, P. malariae rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, or tafenoquine.4

Honduras

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present throughout the country and in Roatán and other Bay Islands. None in San Pedro Sula and Tegucigalpa.

  • Drug resistance3: None.

  • Malaria species: P. vivax 93%, P. falciparum 7%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, primaquine,4 or tafenoquine.4

Hong Kong Sar (China)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Hungary

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Iceland

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

India

Yellow Fever

  • Requirements: Any traveler (except infants <9 months old) arriving by air or sea without a yellow fever vaccination certificate is detained in isolation for up to 6 days if that person

    • arrives within 6 days of departure from an area with risk of YF virus transmission,

    • has been in such an area in transit (except those passengers and members of flight crews who, while in transit through an airport in an area with risk of YF virus transmission, remained in the airport during their entire stay and the health officer agrees to such an exemption),

    • arrives on a ship that started from or touched at any port in an area with risk of YF virus transmission up to 30 days before its arrival in India, unless such a ship has been disinsected in accordance with the procedure recommended by WHO, or

    • arrives on an aircraft that has been in an area with risk of YF virus transmission and has not been disinsected in accordance with the Indian Aircraft Public Health Rules, 1954, or as recommended by WHO.

      1. 1) The following are regarded as countries and areas with risk of YF virus transmission:

      2. 2) Africa: Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Congo, Côte d’Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Ethiopia, Gabon, The Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Liberia, Mali, Mauritania, Niger, Nigeria, Rwanda, Senegal, Sierra Leone, South Sudan, Sudan, Togo, and Uganda.

      3. 3) Americas: Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Panama, Paraguay, Peru, Suriname, Trinidad and Tobago (Trinidad only), and Venezuela.

      4. 4) Note: When a case of yellow fever is reported from any country, that country is regarded by the government of India as a country with risk of YF virus transmission and is added to the above list.

  • Recommendations: None

Malaria

  • Areas with malaria: All areas throughout the country, including cities of Bombay (Mumbai) and Delhi, except none in areas >2,000 m (6,562 ft) in Himachal Pradesh, Jammu and Kashmir, and Sikkim (Map 2-15).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 50%, P. falciparum >40%, P. malariae and P. ovale rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Indonesia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age.1

  • Recommendations: None

Malaria

  • Areas with malaria: All areas of eastern Indonesia (provinces of Maluku, Maluku Utara, Nusa Tenggara Timur, Papua, and Papua Barat), including the town of Labuan Bajo and Komodo Islands in the Nusa Tenggara region. Rural areas of Kalimantan (Borneo), Nusa Tenggara Barat (includes the island of Lombok), Sulawesi, and Sumatra. Low transmission in rural areas of Java, including Pangandaran, Sukalumi, and Ujung Kulong. None in cities of Jakarta and Ubud, resort areas of Bali and Java, and Gili Islands and the Thousand Islands (Pulau Seribu).

  • Drug resistance3: Chloroquine (P. falciparum and P. vivax).

  • Malaria species: P. falciparum 57%, P. vivax. 43%, P. malariae, P. knowlesi, P. ovale rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Iran

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: March–November in rural areas of Fars Province, Sistan-Baluchestan Province, and southern, tropical parts of Hormozgan and Kerman Provinces.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 93%, P. falciparum 7%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Iraq

Yellow Fever

  • Requirements: Required if traveling from to a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Ireland

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Israel

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Italy Including Holy See (Vatican City)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Jamaica

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Japan

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Jordan

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Kazakhstan

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Kenya

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations:

  • Recommended for all travelers ≥9 months of age, except as mentioned below.

  • Generally not recommended for travelers whose itinerary is limited to the following areas: the entire North Eastern Province; the states of Kilifi, Kwale, Lamu, Malindi, and Tanariver in the Coast Province; and the cities of Mombasa and Nairobi (Map 2-16).

Map 2-16. Yellow fever vaccine recommendations in Kenya1

Map 2-16. Yellow fever vaccine recommendations in Kenya1

1,2See footnotes on page 101

Malaria

  • Areas with malaria: Present in all areas (including game parks) at altitudes <2,500 m (8,202 ft), including the city of Nairobi (Map 2-17).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. vivax 5%–10%, P. ovale rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine4

Kiribati (Formerly Gilbert Islands), Includes Tarawa, Tabuaeran (Fanning Island), and Banaba (Ocean Island)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Kosovo

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Kuwait

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Kyrgyzstan

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Laos

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: All, except none in the city of Vientiane.

  • Drug resistance3: Chloroquine and mefloquine.

  • Malaria species: P. falciparum 65%, P. vivax 34%, P. malariae and P. ovale 1% combined.

  • Recommended chemoprophylaxis: Along the Laos-Burma (Myanmar) border in the provinces of Bokeo and Louang Namtha and along the Laos-Thailand border in the province of Champasak and Saravan, along the Laos-Cambodia border, and along the Laos-Vietnam border: Atovaquone-proguanil, doxycycline, or tafenoquine.4 All other areas with malaria: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Latvia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Lebanon

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Lesotho

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥6 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Liberia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YFV transmission and ≥9 months of age.1

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Libya

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Liechtenstein

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Lithuania

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Luxembourg

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Macau Sar (China)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Macedonia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Madagascar

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: All areas, except rare cases in the city of Antananarivo.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 85%, P. vivax 5%–10%, P. ovale 5%.

  • Recommended chemoprophylaxis: All areas except the city of Antananarivo: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4 Antananarivo: None (practice mosquito avoidance).

Madeira Islands (Portugal)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Malawi

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%; P. malariae, P. ovale, and P. vivax 10% combined.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Malaysia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present in rural areas. None in Georgetown, Kuala Lumpur, and Penang State (includes Penang Island).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum, P. vivax, P. Knowlesi, P. malariae, and P. ovale.

  • Recommended chemoprophylaxis: Rural areas: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Maldives

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Mali

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥1 year of age.

  • Recommendations:

  • Recommended for all travelers ≥9 months of age going to areas south of the Sahara Desert (Map 4-13).

  • Not recommended for travelers whose itineraries are limited to areas in the Sahara Desert (Map 4-13).

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Malta

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1 If indicated on epidemiologic grounds, infants <9 months of age are subject to isolation or surveillance if coming from an area with risk of YF virus transmission.

  • Recommendations: None

Malaria

  • No malaria transmission.

Marshall Islands

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Martinique (France)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Mauritania

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations:

  • Recommended for all travelers ≥9 months of age traveling to areas south of the Sahara Desert (Map 4-13).

  • Not recommended for travelers whose itineraries are limited to areas in the Sahara Desert (Map 4-13).

Malaria

  • Areas with malaria: All areas except Dakhlet-Nouadhibou and Tiris-Zemour in the north.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Mauritius

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Mayotte (France)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Rare cases.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 93%, P. vivax 5%, P. malariae and P. ovale 2%.

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Mexico

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: Present in Chiapas and southern part of Chihuahua. Rare cases in Campeche, Durango, Jalisco, Nayarit, Quintana Roo, San Luis Potosi, Sinaloa, Sonora, and Tabasco. No malaria along the US-Mexico border (Map 2-18).

  • Drug resistance3: None.

  • Malaria species: P. vivax 100%.

  • Recommended chemoprophylaxis: States of Chiapas and southern part of Chihuahua: Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, primaquine,4 or tafenoquine.4 States of Campeche, Durango, Jalisco, Nayarit, Quintana Roo, San Luis Potosi, Sinaloa, Sonora, and Tabasco: None (practice mosquito avoidance).

Micronesia, Federated States of; Includes Yap Islands, Pohnpei, Chuuk, and Kosrae

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Moldova

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

Monaco

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Mongolia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Montenegro

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Montserrat (UK)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Morocco

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Mozambique

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >90%, P. malariae, P. ovale, and P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Namibia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present in the regions of Kavango (East and West), Kunene, Ohangwena, Omusati, Oshana, Oshikoto, Otjozondjupa, and Zambezi. Rare cases in other parts of the country. No malaria in city of Windhoek (Map 2-19).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >90%; P. malariae, P. ovale, and P. vivax rare.

  • Recommended chemoprophylaxis: Kavango (East and West), Kunene, Ohangwena, Omusati, Oshana, Oshikoto, Otjozunupa, and Zambezi: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4 Other parts of the country with rare cases: None (practice mosquito avoidance).

Nauru

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Nepal

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present throughout the country at altitudes <2,000 m (6,562 ft). None in Kathmandu and on typical Himalayan treks.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 85%, P. falciparum 15%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Netherlands

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

New Caledonia (France)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1Note: In the event of an epidemic threat to the territory, a specific vaccination certificate may be required.

  • Recommendations: None

Malaria

  • No malaria transmission.

New Zealand

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Nicaragua

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.

  • Recommendations: None

Malaria

  • Areas with malaria: Present in Región Autónoma Atlántico Norte (RAAN) and Región Autónoma Atlántico Sur (RAAS). Rare cases in Boaco, Chinandega, Esteli, Jinotega, Leon, Matagalpa, and Nueva Segovia. No malaria in the city of Managua (Map 2-20).

  • Drug resistance3: None.

  • Malaria species: P. vivax 90%, P. falciparum 10%.

  • Recommended chemoprophylaxis: Región Autónoma Atlántico Norte (RAAN) and Región Autónoma Atlántico Sur (RAAS): Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, or tafenoquine.4 Other areas with malaria: None (practice mosquito avoidance).

Niger

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥1 year of age. The government of Niger recommends vaccine for travelers departing Niger.

  • Recommendations:

  • Recommended for all travelers ≥9 months of age traveling to areas south of the Sahara Desert (Map 4-13).

  • Not recommended for travelers whose itineraries are limited to areas in the Sahara Desert (Map 4-13).

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Nigeria

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Niue (New Zealand)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Norfolk Island (Australia)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission. This requirement excludes Galápagos Islands in Ecuador and the island of Tobago; it is limited to Misiones Province in Argentina.1

  • Recommendations: None

Malaria

  • No malaria transmission.

North Korea

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present in southern provinces.

  • Drug resistance3: None.

  • Malaria species: Presumed to be 100% P. vivax.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, primaquine,4 or tafenoquine.4

Northern Mariana Islands (US), Includes Saipan, Tinian, and Rota Island

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Norway

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Oman

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Sporadic transmission in Dakhliyah, North Batinah, and North and South Sharqiyah.

  • Drug resistance3: Chloroquine

  • Malaria species: P. falciparum and P. vivax

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Pakistan

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: All areas (including all cities) <2,500 m (<8,202 ft).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 70%, P. falciparum 30%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Palau

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Panama

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations:

  • Recommended for all travelers ≥9 months of age traveling to all mainland areas east of the area surrounding the canal (the entire provinces of Darién, Emberá, and Kuna Yala [also spelled Guna Yala] and areas of the provinces of Colón and Panama that are east of the canal) (Map 2-21).

  • Not recommended for travelers whose itineraries are limited to areas west of the canal, the city of Panama, the canal area itself, and the Balboa Islands (Pearl Islands) and San Blas Islands (Map 2-21).

Map 2-21. Yellow fever vaccine recommendations in Panama1

Map 2-21. Yellow fever vaccine recommendations in Panama1

1See footnotes on page 101

Malaria

  • Areas with malaria: Present in the provinces of Darién, Kuna Yala (also spelled Guna Yala), Ngäbe-Buglé, and eastern Panama province. None in Panama Oeste, the Canal Zone, and Panama City (Map 2-22).

  • Drug resistance3: Chloroquine (east of the Panama Canal).

  • Malaria species: P. vivax 99%, P. falciparum 1%.

  • Recommended chemoprophylaxis: Provinces of Darién, Guna Yala, and eastern Panama province: Atovaquone-proguanil, doxycycline, mefloquine, primaquine,4 or tafenoquine.4 Ngäbe-Buglé: Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, primaquine,4 or tafenoquine.4

Papua New Guinea

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: Present throughout the country at altitudes <2,000 m (6,561 ft).

  • Drug resistance3: Chloroquine (both P. falciparum and P. vivax).

  • Malaria species: P. falciparum 65%–80%, P. vivax 10%–30%, P. malariae and P. ovale rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Paraguay

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations:

  • Recommended for all travelers ≥9 months of age, except as mentioned below.

  • Generally not recommended for travelers whose itinerary is limited to the city of Asunción.

Malaria

  • No malaria transmission.

Peru

Yellow Fever

  • Requirements: None

  • Recommendations:

  • Recommended for all travelers ≥9 months of age going to areas at elevations <2,300 m (7,546 ft) in the regions of Amazonas, Loreto, Madre de Dios, San Martin, Ucayali, Puno, Cusco, Junín, Pasco, and Huánuco, and designated areas (Map 2-23) of the following regions: far north of Apurimac, far northern Huancavelica, far northeastern Ancash, eastern La Libertad, northern and eastern Cajamarca, northern and northeastern Ayacucho, and eastern Piura.

  • Generally not recommended for travelers whose itineraries are limited to the following areas west of the Andes: regions of Lambayeque and Tumbes and the designated areas (Map 2-23) of western Piura and south, west, and central Cajamarca.

  • Not recommended for travelers whose itineraries are limited to the following areas: all areas >2,300 m (7,546 ft) in elevation, areas west of the Andes not listed above, the city of Cusco, the capital city of Lima, Machu Picchu, and the Inca Trail (Map 2-23).

Map 2-23. Yellow fever vaccine recommendations in Peru1

Map 2-23. Yellow fever vaccine recommendations in Peru1

1,2See footnotes on page 101

Malaria

  • Areas with malaria: All departments <2,000 m (6,562 ft), including the cities of Iquitos and Puerto Maldonado and only the remote eastern regions of La Libertad and Lambayeque. None in the following areas: Lima Province; the cities of Arequipa, Ica, Moquegua, Nazca, Puno, and Tacna; the highland tourist areas (Cusco, Machu Picchu, and Lake Titicaca); and along the Pacific Coast (Map 2-24).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 85%, P. falciparum 15%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Philippines

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present in Palawan and Mindanao Islands. None in metropolitan Manila and other urban areas.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 70%–80%, P. vivax 20%–30%, P. knowlesi rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Pitcairn Islands (UK)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Poland

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Portugal

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Puerto Rico (US)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Qatar

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Romania

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Russia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Rwanda

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.

  • Recommendations: Generally not recommended for travelers to Rwanda.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. vivax 5%, P. ovale 5%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

RéUnion (France)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Saba

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Saint Barthelemy

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Saint Helena (UK)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Saint Kitts (Saint Christopher) and Nevis (UK)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Saint Lucia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Saint Martin

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Saint Pierre and Miquelon (France)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Saint Vincent and the Grenadines

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Samoa (Formerly Western Somoa)

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

  • Malaria

  • No malaria transmission.

San Marino

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

SãO Tomé and Príncipe

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: Generally not recommended for travelers to São Tomé and Príncipe.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 85%; P. malariae, P. ovale, P. vivax 15% combined.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Saudi Arabia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Asir and Jizan emirates by border with Yemen. None in the cities of Jeddah, Mecca, Medina, Riyadh, and Ta’if.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum predominantly.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Senegal

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Serbia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Seychelles

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Sierra Leone

Yellow Fever

  • Requirements: Required for arriving travelers from all countries.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale 5%–10%, P. malariae and P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Singapore

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YFV transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YFV transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Sint Eustatius

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥6 months of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Sint Maarten

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥6 months of age.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Slovakia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Slovenia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Solomon Islands

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 60%, P. vivax 35%–40%, P. ovale <1%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Somalia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations:

  • Generally not recommended for travelers going to the following regions: Bakool, Banaadir, Bay, Galguduud, Gedo, Hiiraan, Lower Juba, Lower Shabelle, Middle Juba, and Middle Shabelle (Map 4-13).

  • Not recommended for all other areas not listed above.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. vivax 5%–10%, P. malariae and P. ovale rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

South Africa

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present along the border with Zimbabwe and Mozambique. Specifically in Mopani, Vhembe, and Waterberg district municipalities of Limpopo Province; Ehlanzeni district municipality in Mpumalanga Province; and Umknanyakude in Kwazulu-Natal Province. Present in Kruger National Park (Map 2-25)

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. vivax 5%, P. ovale 5%.

  • Recommended chemoprophylaxis: Areas in Limpopo, Mpumalanga, and Kwazulu-Natal Provinces with malaria: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

South Georgia and the South Sandwich Islands

Yellow Fever

  • Requirements: This country has not stated its yellow fever vaccination certificate requirements.

  • Recommendations: None

Malaria

  • No malaria transmission.

South Korea

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: Limited to the months of March–December in rural areas in the northern parts of Incheon, Kangwon-do, and Kyônggi-do Provinces, including the demilitarized zone (DMZ).

  • Drug resistance3: None.

  • Malaria species: P. vivax 100%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, chloroquine, doxycycline, mefloquine, primaquine,4 or tafenoquine.4

South Sudan, Republic Of

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. vivax 5%–10%, P. malariae and P. ovale rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Spain

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Sri Lanka

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • No malaria transmission.

Sudan

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1 A certificate may be required for travelers departing Sudan.

  • Recommendations:

  • Recommended for all travelers ≥9 months of age traveling to areas south of the Sahara Desert (Map 4-13).

  • Not recommended for travelers whose itineraries are limited to areas in the Sahara Desert and the city of Khartoum (Map 4-13).

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 90%, P. vivax 5%–10%, P. malariae and P. ovale rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Suriname

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: Present in the municipality of Tapanahony in Sipaliwini Province. Rare cases in Brokopondo Province, Marowijne Province, and Boven Saramacca municipality in Sipaliwini Province. No malaria in Paramaribo.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 70%, P. vivax 15%–20%.

  • Recommended chemoprophylaxis: Tapanahony municipality in Sipaliwini Province: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4 Other areas with malaria: None (practice mosquito avoidance).

Sweden

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Switzerland

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Syria

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Taiwan

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Tajikistan

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: Rare indigenous cases.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 90%, P. falciparum 10%.

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Tanzania

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: Generally not recommended for travelers to Tanzania.

Malaria

  • Areas with malaria: All areas <1,800 m (5,906 ft).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%, P. ovale >10%, P. malariae and P. vivax rare.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Thailand

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Primarily in provinces that border Burma (Myanmar), Cambodia, and Laos and the provinces of Kalasin, Krabi (Plai Phraya district), Nakhon Si Thammarat, Narathiwat, Pattani, Phang Nga (including Phang Nga City), Rayong, Sakon Nakhon, Songkhla, Surat Thani, and Yala, especially the rural forest and forest fringe areas of these provinces. Rare to few cases in other parts of Thailand, including other parts of Krabi Province and the cities of Bangkok, Chiang Mai, Chiang Rai, Koh Phangan, Koh Samui, and Phuket. None in the islands of Krabi Province (Koh Phi, Koh Yao Noi, Koh Yao Yai, and Ko Lanta) and Pattaya City (Map 2-26).

  • Drug resistance3: Chloroquine and mefloquine.

  • Malaria species: P. falciparum 50% (up to 75% in some areas), P. vivax 50% (up to 60% in some areas), P. ovale and P. knowlesi rare.

  • Recommended chemoprophylaxis: Provinces that border Burma (Myanmar), Cambodia, and Laos, the provinces of Kalasin, Plai Phraya district of Krabi, Nakhon Si Thammarat, Narathiwat, Pattani, Phang Nga (including Phang Nga City), Rayong, Sakon Nakhon, Songkhla, Surat Thani, and Yala: Atovaquone-proguanil, doxycycline, or tafenoquine.4 All other areas of Thailand with malaria including the cities of Bangkok, Chiang Mai, Chiang Rai, Koh Phangan, Koh Samui, and Phuket: None (practice mosquito avoidance).

Timor-Leste

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: Present in Oecusse District. Rare cases in other districts.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 50%, P. vivax 50%, P. ovale <1%, P. malariae <1%.

  • Recommended chemoprophylaxis: Oecusse District: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4 Other districts: None (practice mosquito avoidance).

Togo

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥9 months of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 85%, P. ovale 5%–10%, remainder P. vivax.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Tokelau (New Zealand)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Tonga

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Trinidad and Tobago

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit in an airport located in a country with risk of YF virus transmission.1

  • Recommendations:

  • Recommended for all travelers ≥9 months of age traveling to densely-forested areas on the island of Trinidad.

  • Not recommended for cruise ship passengers and airplane passengers in transit, or travelers whose itineraries are limited to the island of Tobago.

Malaria

Tunisia

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Turkey

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Turkmenistan

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Turks and Caicos Islands (UK)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Tuvalu

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Uganda

Yellow Fever

  • Requirements: Required for arriving travelers from all countries if traveler is ≥1 year of age.

  • Recommendations: Recommended for all travelers ≥9 months of age.

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >85%; remainder P. malariae, P. ovale, and P. vivax.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Ukraine

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

United Arab Emirates

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

United Kingdom (With Channel Islands and Isle of Man)

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

United States

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Uruguay

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Uzbekistan

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Vanuatu

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 60%, P. vivax 35%–40%, P. ovale <1%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Venezuela

Yellow Fever

  • Requirements: Required if traveling from Brazil and ≥1 year of age, including transit >12 hours in an airport located in Brazil.

  • Recommendations:

  • Recommended for all travelers ≥9 months of age, except as mentioned below.

  • Generally not recommended for travelers whose itineraries are limited to the following areas: the states of Aragua, Carabobo, Miranda, Vargas, and Yaracuy, and the Distrito Capital (Map 2-27).

  • Not recommended for travelers whose itineraries are limited to the following areas: all areas >2,300m (7,546 ft) in elevation in the states of Merida, Tachira, and Trujillo; the states of Falcón and Lara; Margarita Island; the capital city of Caracas; and the city of Valencia (Map 2-27).

Map 2-27. Yellow fever vaccine recommendations in Venezuela1

Map 2-27. Yellow fever vaccine recommendations in Venezuela1

1,2See footnotes on page 101

Malaria

  • Areas with malaria: All areas <1,700m (5.577 ft). Present in Angel Falls (Map 2-28).

  • Drug resistance3: Chloroquine.

  • Malaria species: P. vivax 83%, P. falciparum 17%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Vietnam

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: Rural areas only. Rare cases in the Mekong and Red River Deltas. None in the cities of Da Nang, Haiphong, Hanoi, Ho Chi Minh (Saigon), Nha Trang, and Qui Nhon.

  • Drug resistance3: Chloroquine and mefloquine.

  • Malaria species: P. falciparum 50%–90%, P. vivax. 10%–50%, P. knowlesi rare.

  • Recommended chemoprophylaxis: Southern part of the country in the provinces of Dac Lac, Gia Lai, Khanh Hoa, Kon Tum, Lam Dong, Ninh Thuan, Song Be, Tay Ninh: Atovaquone-proguanil doxycycline, or tafenoquine.5 Other areas with malaria except Mekong and Red River Deltas: Atovaquone-proguanil, doxycycline, omefloquine, or tafenoquine.4 Mekong and Red River Deltas: None (practice mosquito avoidance).

Virgin Islands, British

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Virgin Islands, Us

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Wake Island, Us

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • No malaria transmission.

Western Sahara

Yellow Fever

  • Requirements: This territory has not stated its yellow fever vaccination certificate requirements.

  • Recommendations: None

Malaria

  • Areas with malaria: Rare cases.

  • Drug resistance3: Chloroquine.

  • Malaria species: Unknown.

  • Recommended chemoprophylaxis: None (practice mosquito avoidance).

Yemen

Yellow Fever

  • Requirements: None

  • Recommendations: None

Malaria

  • Areas with malaria: All areas <2,000 m (6,562 ft). None in Sana’a.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum 95%; P. malariae, P. vivax, and P. ovale 5% combined.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Zambia

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥1 year of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations:

  • Generally not recommended for travelers going to the North West and Western Provinces (Map 2-29).

  • Not recommended in all other areas not listed above.

Map 2-29. Yellow fever vaccine recommendations in Zambia1

Map 2-29. Yellow fever vaccine recommendations in Zambia1

1,2See footnotes on page 101

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >90%, P. vivax up to 5%, P. ovale up to 5%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Zimbabwe

Yellow Fever

  • Requirements: Required if traveling from a country with risk of YF virus transmission and ≥9 months of age, including transit >12 hours in an airport located in a country with risk of YF virus transmission.1

  • Recommendations: None

Malaria

  • Areas with malaria: All.

  • Drug resistance3: Chloroquine.

  • Malaria species: P. falciparum >90%, P. vivax up to 5%, P. ovale up to 5%.

  • Recommended chemoprophylaxis: Atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.4

Footnotes

Yellow Fever

1 The official WHO list of countries with risk of YF virus transmission can be found in Table 4-23. Proof of yellow fever vaccination should be required only if traveling from a country on the WHO list, unless otherwise specified. The following countries, containing only areas with low potential for exposure to YF virus, are not on the WHO list: Eritrea, Rwanda, São Tomé and Príncipe, Somalia, Tanzania, Zambia.

2 An elevation of 2,300 m is equivalent to 7,546 ft.

Malaria

3 Refers to P. falciparum malaria unless otherwise noted.

4 Primaquine and tafenoquine can cause hemolytic anemia in people with G6PD deficiency. Patients must be screened for G6PD deficiency before starting primaquine or tafenoquine.

Yellow Fever Maps

1 Current as of August 2018. This map is an updated version of the 2010 map created by the Informal WHO Working Group on the Geographic Risk of Yellow Fever.

2 Yellow fever (YF) vaccination is generally not recommended in areas where there is low potential for YF virus exposure. However, vaccination might be considered for a small subset of travelers to these areas who are at increased risk for exposure to YF virus because of prolonged travel, heavy exposure to mosquitoes, or inability to avoid mosquito bites. Consideration for vaccination of any traveler must take into account the traveler’s risk of being infected with YF virus, country entry requirements, and individual risk factors for serious vaccine-associated adverse events (such as age or immune status).

3 In 2017, CDC expanded yellow fever vaccination recommendations for travelers to Brazil because of a large outbreak of yellow fever in multiple states in that country. Please refer to the CDC Travelers' Health website (www.cdc.gov/travel) for more information and updated recommendations.

Food & Water Precautions

Contaminated food and water often pose a risk for travelers. Many of the infectious diseases associated with contaminated food and water are caused by pathogens transmitted via the fecal–oral route. Swallowing, inhaling aerosols of, or coming in contact with contaminated water—including natural freshwater, marine water, or the water in inadequately treated swimming pools, water playgrounds (splash parks or splash pads), or hot tubs and spas—can transmit pathogens that can cause diarrhea, vomiting, or infection of the ears, eyes, skin, or the respiratory or nervous system.

Food

Advise travelers to select food with care. Raw food is especially likely to be contaminated. Raw or undercooked meat, fish, and shellfish can carry various intestinal and systemic pathogens. (Some fish harvested from tropical waters can transmit toxins that survive cooking; see Food Poisoning from Marine Toxins in this chapter.) In areas where hygiene and sanitation are inadequate or unknown, travelers should avoid consuming salads; uncooked vegetables; raw, unpeeled fruits; and unpasteurized fruit juices. Fruits that can be peeled are safest when peeled by the person who eats them. Produce should be rinsed with safe water (see Water Disinfection in this chapter). Foods of animal origin, including meat and eggs, should be thoroughly cooked; milk and milk products, including milk used in soft cheese, should be pasteurized. In restaurants, inadequate refrigeration and lack of food safety training among staff can result in transmission of pathogens. Consumption of food and beverages obtained from street vendors has been associated with an increased risk of illness. In general, foods that are fully cooked and served hot are safest, as are foods people carefully prepare themselves.

Travelers should wash their hands with soap and water before preparing food, before eating, after using the bathroom or changing diapers, before and after caring for someone who is ill, and after contact with animals or their environments. If soap and water are not available, use an alcohol-based hand sanitizer (with ≥60% alcohol) and wash hands with soap and water as soon as they become available. Hand sanitizer is not very effective against Cryptosporidium or norovirus and does not work well when hands are visibly dirty or greasy.

The safest way to feed an infant aged <6 months is to breastfeed exclusively. If the infant is fed formula prepared from commercial powder, the powder should be reconstituted with hot water at a temperature of ≥158°F (≥70°C). This precaution will kill most pathogens with which the infant formula may have been contaminated during manufacturing or through handling after opening. To ensure that the water is hot enough, travelers should prepare formula within 30 minutes after boiling the water (see Water Disinfection in this chapter). The prepared formula should be cooled to a safe temperature for feeding (for example, by placing the bottle upright in a bath of safe water and safe ice [see below], keeping the bath water below the nipple ring) and used within 2 hours of preparation. Bottles and nipples should be washed and then sterilized (in boiling water or in an electric sterilizer). Travelers may wish to pack enough formula for their trip, because manufacturing standards vary widely around the world.

Tell travelers not to bring perishable food from high-risk areas back to their home country without refrigeration. Moreover, travelers should exercise the same cautions about food and water served on flights that they do for restaurants.

Water

Drinking Water and Other Beverages

In many parts of the world, particularly where water treatment, sanitation, and hygiene are inadequate, tap water may contain disease-causing agents, including viruses, bacteria, and parasites, or chemical contaminants. As a result, tap water in some places may be unsafe for drinking, preparing food and beverages, making ice, cooking, and brushing teeth. Infants, young children, pregnant women, the elderly, and people whose immune systems are compromised (for example, because of HIV, chemotherapy, or transplant medications) may be especially susceptible to illness.

Travelers should avoid drinking or putting into their mouths tap water unless they are reasonably certain it is safe. Many people choose to disinfect or filter their water when traveling to destinations where safe tap water may not be available. Tap water that is safe for drinking is still not sterile and should not be used for sinus or nasal irrigation or rinsing, including use in neti pots and for ritual ablution unless it is further disinfected by the traveler. Tap water should never be used to clean or rinse contact lenses. Water that looks cloudy or colored may be contaminated with chemicals and will not be made safe by boiling or disinfection. In these situations, travelers should use bottled water if it is available.

In areas where tap water may be unsafe, only commercially bottled water from an unopened, factory-sealed container or water that has been adequately disinfected should be used for drinking, preparing food and beverages, making ice, cooking, and brushing teeth. (See Water Disinfection in this chapter for proper disinfection techniques.)

Beverages made with water that has just been boiled, such as tea and coffee, are generally safe to drink. When served in unopened, factory-sealed cans or bottles, carbonated beverages, commercially prepared fruit drinks, water, alcoholic beverages, and pasteurized drinks generally can be considered safe. Because water on the outside of cans and bottles may be contaminated, they should be wiped clean and dried before opening or drinking directly from the container.

Beverages that may not be safe for consumption include fountain drinks or other drinks made with tap water and iced drinks. Because ice might be made from contaminated water, travelers in areas with unsafe tap water should request that beverages be served without ice.

Recreational Water

Pathogens that cause gastrointestinal, respiratory, skin, ear, eye, and neurologic illnesses can be transmitted by contaminated recreational water in inadequately treated pools, water playgrounds (splash pads or spray parks) or hot tubs/spas, or in freshwater or marine water. Recreational water contaminated by human feces from swimmers, sewage, animal waste, or wastewater runoff can appear clear but still contain disease-causing infectious or chemical agents. Ingesting even small amounts of such water can cause illness. To protect other people, children and adults with diarrhea should not enter recreational water. Infectious pathogens, such as Cryptosporidium, can survive for days even in well-maintained pools, water playgrounds, and hot tubs/spas.

Maintaining proper pH and free chlorine or bromine concentration is necessary to prevent transmission of most infectious pathogens in water in pools, water playgrounds, and hot tubs/spas. If travelers would like to test recreational water before use, CDC recommends pH 7.2–7.8 and a free available chlorine concentration of 2–4 ppm in hot tubs/spas (4–6 ppm if bromine is used) and 1–3 ppm in pools and water playgrounds. Test strips may be purchased at most superstores, hardware stores, and pool supply stores. Pseudomonas, which can cause “hot tub rash” or “swimmer’s ear,” and Legionella (see Chapter 4, Legionellosis) can multiply in hot tubs and spas in which chlorine or bromine concentrations are not adequately maintained. Travelers at increased risk for legionellosis, such as the elderly and those with immunocompromising conditions, may choose to avoid entering or walking near higher-risk areas such as hot tubs/spas. Travelers should avoid pools, water playgrounds, and hot tubs/spas where bather limits are not enforced or where the water is cloudy. Additional guidance can be found at www.cdc.gov/healthywater/swimming.

Travelers should not swim or wade 1) near storm drains; 2) in water that may be contaminated with sewage, human or animal feces, or wastewater runoff; 3) in lakes or rivers after heavy rainfall; 4) in freshwater streams, canals, and lakes in schistosomiasis-endemic areas of the Caribbean, South America, Africa, and Asia (see Chapter 4, Schistosomiasis); 5) in water that might be contaminated with urine from animals infected with Leptospira (see Chapter 4, Leptospirosis); or 6) in warm seawater or brackish water (mixture of fresh and sea water) when they have wounds.

A traveler with an open wound should consider staying out of the water or covering the wound with a water-repellent bandage (often labeled “waterproof”), as seawater and brackish water can contain germs, such as Vibrio spp., that can cause wound infections. If a sore or open wound comes into contact with untreated recreational water, it should be washed thoroughly with soap and water to reduce the chance of infection.

Naegleria fowleri (www.cdc.gov/parasites/naegleria) is a parasite found in warm freshwater around the world. To help prevent a rare but fatal infection caused by this parasite, travelers should hold their nose shut or wear a nose clip when swimming, diving, or participating in similar activities in warm freshwater (including lakes, rivers, ponds, hot springs, or locations with water warmed by discharge from power plants and industrial complexes). They should also avoid digging in or stirring up sediment, especially in warm water. This infection has also been linked to use of contaminated tap water for sinus and nasal irrigation.

Bibliography

1. CDC. Notes from the field: primary amebic meningoencephalitis associated with ritual nasal rinsing—St. Thomas, US Virgin Islands, 2012. MMWR Morb Mortal Wkly Rep. 2013 Nov 15;62(45):903.Find this resource:

2. Drinking Water: Camping, Hiking, Travel. CDC; 2016. [cited 2016 Apr 15]. Available from: www.cdc.gov/healthywater/drinking/travel/index.html.

3. Eberhart-Phillips J, Besser RE, Tormey MP, Koo D, Feikin D, Araneta MR, et al. An outbreak of cholera from food served on an international aircraft. Epidemiol Infect. 1996 Feb;116(1):9–13.Find this resource:

4. Food Safety. CDC; 2018. [cited 2018 Mar 4]. Available from: www.cdc.gov/foodsafety/index.html.

5. Healthy Swimming: Ear Infections. CDC; 2016. [cited 2016 Apr 15]. Available from: www.cdc.gov/healthywater/swimming/swimmers/rwi/ear-infections.html.

6. Healthy Swimming: Rashes. CDC; 2016. [cited 2016 Apr 15]. Available from: www.cdc.gov/healthywater/swimming/swimmers/rwi/rashes.html.

7. Legionella (Legionnaires’ Disease and Pontiac Fever). CDC; 2017. [cited 2018 Mar 4]. Available from: www.cdc.gov/legionella/index.html.

8. Parasites—Naegleria fowleri—Primary amebic meningoencephalitis (PAM) - Amebic Encephalitis. CDC; 2017. [cited 2016 Apr 15]. Available from: www.cdc.gov/parasites/naegleria/index.html.

9. Traveler’s Health: Food and Water Safety. CDC; 2018. [cited 2018 Mar 4]. Available from: wwwnc.cdc.gov/travel/page/food-water-safety.

10. Yoder JS, Straif-Bourgeois S, Roy SL, Moore TA, Visvesvara GS, Ratard RC, et al. Primary amebic meningoencephalitis deaths associated with sinus irrigation using contaminated tap water. Clin Infect Dis. 2012 Nov;55(9):e79–85.Find this resource:

Water Disinfection

Risk for Travelers

Waterborne disease is a risk for international travelers who visit countries that have poor hygiene and inadequate sanitation, and for wilderness visitors who rely on surface water in any country, including the United States. The list of potential waterborne pathogens is extensive and includes bacteria, viruses, protozoa, and parasitic helminths. Most of the organisms that can cause travelers’ diarrhea can be waterborne. Many types of bacteria and viruses can cause intestinal (enteric) infection through drinking water. Protozoa that are commonly waterborne include Cryptosporidium, Giardia, and Entameba histolytica (the cause of amebic dysentery). Parasitic worms are not commonly transmitted through drinking water, but it is a potential means of transmission for some.

Where treated tap water is available, aging or inadequate water treatment infrastructure may not effectively disinfect water or maintain water quality during distribution. Some larger hotels and resorts may provide additional onsite water treatment to provide potable water. Travelers can ask the facility manager about safety of their water; however, if there is concern, it may be easiest for travelers to treat the water themselves. Where untreated surface or well water is used and there is no sanitation infrastructure, the risk of waterborne infection is high.

Bottled water has become the convenient solution for most travelers, but in some places it may not be superior to tap water. Moreover, the plastic bottles create an ecological problem, since most developing countries do not recycle plastic bottles. All international travelers, especially long-term travelers or expatriates, should become familiar with and use simple methods to ensure safe drinking water. Several methods are scalable and some can be improvised from local resources, allowing adaptation to disaster relief and refugee situations. Table 2-7 compares benefits and limitations of different methods. Additional information on water treatment and disinfections methods can be found at www.cdc.gov/healthywater/drinking/travel.

Table 2-7. Comparison of water disinfection techniques

Technique

Advantages

Disadvantages

Heat

  • Does not impart additional taste or color

  • Single step that inactivates all enteric pathogens

  • Efficacy is not compromised by contaminants or particles in the water as for chemical disinfection and filtration

  • Does not improve taste, smell, or appearance of source water

  • Fuel sources may be scarce, expensive, or unavailable

  • Does not prevent recontamination during storage

Filtration

  • Simple to operate

  • Requires no holding time for treatment

  • Large choice of commercial product designs

  • Adds no unpleasant taste and often improves taste and appearance of water

  • Can be combined with chemical disinfection to increase microbe removal

  • Adds bulk and weight to baggage

  • Many filters do not reliably remove viruses

  • More expensive than chemical treatment

  • Eventually clogs from suspended particulate matter and may require some field maintenance or repair

  • Does not prevent recontamination during storage

Chlorine, iodine, electrolytic solutions

  • Inexpensive and widely available in liquid or tablet form

  • Taste can be removed by simple techniques

  • Flexible dosing

  • Equally easy to treat large and small volumes

  • Will preserve microbiologic quality of stored water

  • Impart taste and odor to water

  • Flexible dosing requires understanding of principles

  • Iodine is physiologically active, with potential adverse effects

  • Not readily effective against Cryptosporidium oocysts

  • Efficacy decreases with cloudy water

  • Corrosive and stains clothing

Chlorine dioxide

  • Low doses have no taste or color

  • Simple to use and available in liquid or tablet form

  • More potent than equivalent doses of chlorine

  • Effective against all waterborne pathogens, including Cryptosporidium

  • Volatile and sensitive to sunlight: do not expose tablets to air, and use generated solutions rapidly

  • No persistent residual concentration, so does not prevent recontamination during storage

Ultraviolet (UV)

  • Imparts no taste

  • Portable battery-operated devices now available

  • Effective against all waterborne pathogens

  • Extra doses of UV can be used for added assurance and with no side effects

  • Requires clear water

  • Does not improve taste or appearance of water

  • Relatively expensive (except solar disinfection [SODIS])

  • Requires batteries or power source (except SODIS)

  • Cannot know if devices are delivering required UV doses

  • No persistent residual concentration, so does not prevent recontamination during storage

Field Techniques for Water Treatment

Heat

Common intestinal pathogens are readily inactivated by heat. Microorganisms are killed in a shorter time at higher temperatures, whereas temperatures as low as 140°F (60°C) are effective with a longer contact time. Pasteurization uses this principle to kill foodborne enteric pathogens and spoilage-causing organisms at temperatures between 140°F (60°C) and 158°F (70°C), well below the boiling point of water (212°F [100°C]).

Although boiling is not necessary to kill common intestinal pathogens, it is the only easily recognizable end point that does not require a thermometer. All organisms except bacterial spores, which are rarely waterborne enteric pathogens, are killed in seconds at boiling temperature. In addition, the time required to heat the water from 60°C to boiling works toward heat disinfection. Any water that is brought to a boil should be adequately disinfected; however, if fuel supplies are adequate, travelers should consider boiling for 1 minute to allow for a margin of safety. Although the boiling point decreases with altitude, at common terrestrial travel elevations it is still well above the temperature required to inactivate enteric pathogens (for example, at 16,000 ft [4,877 m] the boiling temperature of water is 182°F [84°C]). In hot climates with sunshine, a water container placed in a simple reflective solar oven can reach pasteurization temperature of 65°C. Travelers with access to electricity can bring a small electric heating coil or a lightweight beverage warmer to boil water.

Filtration and Clarification

Portable hand-pump or gravity-drip filters with various designs and types of filter media are commercially available to international travelers. Filter pore size is the primary determinant of a filter’s effectiveness, unless the filter is designed to remove microbes by electrochemical attachment to filter media. Filter pore size will be described as being “absolute” or “nominal”: absolute pore size filters will remove all microbes of the identified pore size or larger, whereas nominal pore size filters allow 20%–30% of particles or microorganisms of the pore size to pass through. Progressively smaller pore size filters require higher pressure to push water through the filter, often at a slower rate and higher cost. Filters that claim Environmental Protection Agency (EPA) designation of water “purifier” undergo company-sponsored testing to demonstrate removal of at least 106 bacteria (99.9999%), 104 viruses (99.99%), and 103 Cryptosporidium oocysts or Giardia cysts (99.9%). (EPA does not independently test the validity of these claims.)

Filters with absolute pore size of 1 μ‎m or smaller should effectively remove protozoan parasites like Cryptosporidium and Giardia. Microfilters with “absolute” pore sizes of 0.1–0.4 µm are usually effective at removing bacteria as well as cysts but may not adequately remove enteric viruses, like norovirus (Table 2-8). Water in remote alpine areas with little human and animal activity generally has little contamination with enteric pathogens, so microfilters with ceramic, synthetic fiber, compressed carbon, or large-pore hollow-fiber filter elements are sufficient to remove bacteria and protozoan cysts, the primary pathogens.

Table 2-8. Microorganism size and susceptibility to filtration

Organism

Average Size (μ‎M)

Maximum Recommended Filter Rating (μ‎M ABSOLUTE)

Viruses

0.03

Not specified (optimally 0.01, ultrafiltration)

Enteric bacteria (such as Escherichia coli)

0.5 × 2–8

0.2–0.4 (microfiltration)

Cryptosporidium oocyst

4–6

1 (microfiltration)

Giardia cyst

8 × 19

3.0–5.0 (microfiltration)

Helminth eggs

30 × 60

Not specified; any microfilter

Schistosome larvae

50 × 100

Not specified; any microfilter

For areas with high levels of human and animal activity in the watershed or developing areas with poor sanitation, higher levels of filtration discussed below or other techniques to remove viruses are preferred. If using a microfilter, one option to remove viruses is pretreatment with chlorine. Progressively finer levels of filtration known as ultrafiltration, nanofiltration, and reverse osmosis can remove particles of 0.01, 0.001, and 0.0001 µm, respectively. All of these filters can remove viruses. Portable ultrafilters are the most commonly available “purifying” filters and may operate by gravity, hand-pump, or drink-through. Ultrafilter-based filters will have a rated pore size of 0.01 μ‎m, and should be effective for removing viruses, bacteria, and parasites. All are effective, although drink-through is least practical because of the negative pressure required to draw water through the filter.

Nanofilters will have rated pore sizes of 0.001 μ‎m and thus will remove chemicals and organic molecules. Reverse osmosis filters (having pore sizes of 0.0001 μ‎m [0.1 nm] and smaller) will remove monovalent salts and dissolved metals, thus achieving desalination. The high price and slow output of small hand-pump reverse osmosis units prohibit use by land-based travelers; however, they are survival aids for ocean voyagers, and larger powered devices are used for military and refugee situations.

In resource-limited international settings, filters may be used in the communities and households that are made from ceramic clay or simple sand and gravel (slow sand or biosand). Gravel and sand filters can be improvised in remote or austere situations when no other means of disinfection is available.

Water can be clarified by using chemical products that coagulate and flocculate (clump together) suspended particles that cause a cloudy appearance and bad taste and do not settle by gravity. This process removes many but not all microorganisms, unless the product also contains a disinfectant. Alum, an aluminum salt that is widely used in food, cosmetic, and medical applications, is the principal agent for coagulation/flocculation, but many other natural substances are used throughout the world. When using alum, a one-fourth teaspoon of alum powder can be added to a quart of cloudy water and the water stirred frequently for a few minutes. The process can be repeated, if necessary, until clumps form. The clumped material is allowed to settle, and then the water is poured through a coffee filter or clean, fine cloth to remove the sediment. Most microbes are removed, but not all, so a second disinfection step is necessary. Tablets or packets of powder that combine flocculant and a chemical disinfectant are available commercially (for example, Chlor-floc and P&G Purifier of Water).

Granular-activated carbon (GAC) treats water by adsorbing organic and inorganic chemicals (including chlorine or iodine compounds) and most heavy metals, thereby improving odor, taste, and safety. GAC is a common component of household and field filters. It may trap microorganisms, but GAC filters are generally not designed or rated for microbe removal and do not kill microorganisms.

Chemical Disinfection

Liquid and Tablet Products

Chemical disinfectants for drinking water treatment, including chlorine compounds, iodine, and chlorine dioxide, are commonly available as commercial products. Sodium hypochlorite, the active ingredient in common household bleach, is the primary disinfectant promoted by CDC and the World Health Organization. Other chlorine-containing compounds such as calcium hypochlorite and sodium dichloroisocyanurate, available in granular or tablet formulation, are equally effective for water treatment. An advantage of chemical water disinfection products is flexible dosing that allows use by individual travelers, small or large groups, or communities. In emergency situations, or when other commercial chemical disinfection water treatment products are not available, household bleach can be used for flexible dosing based on water volume and clarity. Refer to CDC guidelines at www.cdc.gov/healthywater/emergency/drinking/making-water-safe.html.

Given adequate concentrations and length of exposure (contact time), chlorine and iodine have similar activity and are effective against bacteria and viruses (www.cdc.gov/safewater/effectiveness-on-pathogens.html). Giardia cysts are more resistant to chemical disinfection; however, field-level concentrations are effective with longer contact times. For this reason, dosing and concentrations of chemical disinfection products are generally targeted to the cysts. Some common waterborne parasites, such as Cryptosporidium and possibly Cyclospora, are poorly inactivated by chlorine- and iodine-based disinfection at practical concentrations, even with extended contact times.

Chemical disinfection may be supplemented with filtration to remove resistant oocysts from drinking water. Cloudy water contains substances that will neutralize disinfectant, so it will require higher concentrations or contact times or, preferably, clarification through settling, coagulation/flocculation, or filtration before disinfectant is added.

Because iodine has physiologic activity, WHO recommends limiting iodine water disinfection to a few weeks. Iodine use is not recommended for people with unstable thyroid disease or known iodine allergy. In addition, pregnant women should not use iodine to disinfect water over the long term because of the potential effect on the fetal thyroid. Pregnant travelers who have other options should use an alternative means such as heat, chlorine, or filtration.

Some prefer the taste of iodine to chlorine, but neither is appealing in doses often recommended for field use. The taste of halogens in water can be improved by running water through a filter containing activated carbon or adding a 25-mg tablet of vitamin C, a tiny pinch of powdered ascorbic acid, or a small amount of hydrogen peroxide (5–10 drops of 3% peroxide per quart), then stir or shake. Repeat until taste of chlorine or iodine is gone.

Chlorine Dioxide

Chlorine dioxide (ClO2) can kill most waterborne pathogens, including Cryptosporidium oocysts, at practical doses and contact times. Tablets and liquid formulations are commercially available to generate chlorine dioxide in the field for personal use.

Salt (Sodium Chloride) Electrolysis

Electrolytic water purifiers generate a mixture of oxidants, including hypochlorite, by passing an electrical current through a simple brine salt solution. Purifier products sold for personal and group travel use produce an oxidant solution that can be added to water to kill microorganisms. This technique has been engineered into portable, battery-powered products that are commercially available.

Ultraviolet (UV) Light

UV light kills bacteria, viruses, and Cryptosporidium oocysts in water. The effect depends on UV dose and exposure time. Portable battery-operated units that deliver a metered, timed dose of UV are an effective way to disinfect small quantities of clear water in the field. Larger units with higher output are available where a power source is available. These units have limited effectiveness in water with high levels of suspended solids and turbidity, because suspended particles can shield microorganisms from UV light.

Solar Irradiation and Heating

UV irradiation of water using sunlight (solar disinfection or SODIS) can improve the microbiologic quality of water and may be used in austere emergency situations. Solar disinfection is not effective on turbid water. If the headlines in a newspaper cannot be read through the bottle of water, then the water must be clarified before solar irradiation is used. Under cloudy weather conditions, water must be placed in the sun for 2 consecutive days. (See www.sodis.ch/index_EN for further information.)

Silver and Other Products

Silver ion has bactericidal effects in low doses, and some attractive features include lack of color, taste, and odor, and the ability of a thin coating on the container to maintain a steady, low concentration in water. Silver is widely used by European travelers as a primary drinking water disinfectant. In the United States, silver is approved only for maintaining microbiologic quality of stored water because its concentration can be strongly affected by adsorption onto the surface of the container, and there has been limited testing on viruses and cysts. Silver is available alone or in combination with chlorine in tablet formulation.

Several other common products, including hydrogen peroxide, citrus juice, and potassium permanganate, have antibacterial effects in water and are marketed in commercial products for travelers. None have sufficient data to recommend them for primary water disinfection at low doses in the field.

Photocatalytic Disinfection

Advanced oxidation processes use UV light or natural sunlight to catalyze the production of potent disinfectants for microorganisms and can break down complex organic contaminants and even most heavy metals into nontoxic forms. Titanium dioxide (TiO2) is the most effective substance, but other metal oxides, chitins, and nanoparticles also have oxidative potential. A TiO2-impregnated membrane incorporated into a portable bag is available commercially.

Choosing a Disinfection Technique

Table 2-9 summarizes advantages and disadvantages of field water disinfection techniques and their microbicidal efficacy. It is advisable to test a method before travel.

Table 2-9. Summary of field water disinfection techniques

Bacteria

Viruses

Protozoan Cysts (GiardiaAmebas)

Cryptosporidia

Helminths/Schistosomes

Heat

+

+

+

+

+

Filtration

+

+/–1

+

+

+

Halogens

+

+

+2

+/–3

Chlorine dioxide

+

+

+

+

+

1 Most filters make no claims for viruses. Hollow-fiber filters with ultrafiltration pore size and reverse osmosis are effective.

2 Require higher concentrations and contact time than for bacteria or viruses.

3 Eggs are not very susceptible to chlorine or iodine, but risk of waterborne transmission is very low.

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10. World Health Organization. Boil water. Technical Brief. WHO; 2015 [cited 2016 Mar 13]. Available from: http://apps.who.int/iris/bitstream/10665/155821/1/WHO_FWC_WSH_15.02_eng.pdf?ua=1.

11. World Health Organization. Guidelines for drinking-water quality. WHO; 2011 [cited 2016 Mar 13]. Available from: http://apps.who.int/iris/bitstream/10665/44584/1/9789241548151_eng.pdf.

Food Poisoning from Marine Toxins

Poisoning from ingested marine toxins is an underrecognized hazard for travelers, particularly in the tropics and subtropics. Furthermore, the risk is increasing because of climate change, coral reef damage, and spread of toxic algal blooms (Map 2-30).

Map 2-30. Areas reporting select harmful algal blooms

Map 2-30. Areas reporting select harmful algal blooms

Harmful algal blooms occur widely and contribute to seafood toxicity. Risk of poisoning in humans depends on the particular seafood consumed, where it was caught or harvested, and—in some instances—the exposure of that seafood to a harmful algal bloom.

Harmful algal bloom data from Woods Hole Oceanographic Institution, Woods Hole, MA: 2015. [cited 2018 Aug 28]. Available from: www.whoi.edu/redtide/regions/world-distribution.

Ciguatera Fish Poisoning

Ciguatera fish poisoning occurs after eating reef fish contaminated with toxins such as ciguatoxin or maitotoxin. These potent toxins originate from Gambierdiscus toxicus, a small marine organism (dinoflagellate) that grows on and around coral reefs. Dinoflagellates are ingested by herbivorous fish. The toxins produced by G. toxicus are then modified and concentrated as they pass up the marine food chain to carnivorous fish and finally to humans. Ciguatoxins are concentrated in fish liver, intestines, roe, and heads.

G. toxicus may proliferate on dead coral reefs more effectively than other dinoflagellates. The risk of ciguatera poisoning is likely to increase as coral reefs deteriorate because of climate change, ocean acidification, offshore construction, and nutrient runoff.

Risk for Travelers

Up to 50,000 cases of ciguatera poisoning get reported annually worldwide. Because the disease is underrecognized and underreported, this is likely a significant underestimate. The incidence in travelers to highly endemic areas has been estimated as high as 3 per 100. Ciguatera is widespread in tropical and subtropical waters, usually between the latitudes of 35°N and 35°S; it is particularly common in the Pacific and Indian Oceans and the Caribbean Sea. The incidence and geographic distribution of ciguatera poisoning are increasing. Newly recognized areas of risk include the Canary Islands, the eastern Mediterranean, and the western Gulf of Mexico. Medical practitioners must be aware that cases of ciguatera fish poisoning acquired by travelers in endemic areas may present in nonendemic (temperate) areas. In addition, cases of ciguatera fish poisoning are seen with increasing frequency in nonendemic areas as a result of the increasing global trade in seafood products.

Fish that are most likely to cause ciguatera poisoning are large carnivorous reef fish, such as barracuda, grouper, moray eel, amberjack, sea bass, or sturgeon. Omnivorous and herbivorous fish such as parrot fish, surgeonfish, and red snapper can also be a risk.

Clinical Presentation

Ciguatera poisoning may cause gastrointestinal, cardiovascular, neurologic, and neuropsychiatric illness. The first symptoms usually develop within 3–6 hours after eating contaminated fish but may be delayed for up to 30 hours. Adverse health effects referable to the above-named organ systems include:

  • Diarrhea, nausea, vomiting, and abdominal pain

  • Bradycardia, heart block, hypotension

  • Paresthesias, weakness, pain in the teeth or a sensation that the teeth are loose, burning or metallic taste in the mouth, generalized itching, sweating, and blurred vision. Cold allodynia (abnormal sensation when touching cold water or objects) has been reported as characteristic, but there can be acute sensitivity to both hot and cold. Neurologic symptoms usually last a few days to several weeks but may persist for months or even years.

  • Fatigue, general malaise, insomnia

The overall death rate from ciguatera poisoning is <0.1% but varies according to the toxin dose and availability of medical care to deal with complications. The diagnosis of ciguatera poisoning is based on the characteristic signs and symptoms and a history of eating fish species known to carry ciguatera toxin. Fish testing can be done by the US Food and Drug Administration (FDA) in their laboratory at Dauphin Island. There is no readily available test for ciguatera toxins in human clinical specimens.

Prevention

Travelers can take the following precautions to prevent ciguatera fish poisoning:

  • Avoid or limit consumption of reef fish.

  • Never eat high-risk fish such as barracuda or moray eel.

  • Avoid eating the parts of the fish that concentrate ciguatera toxin: liver, intestines, roe, and head.

Ciguatera toxins do not affect the texture, taste, or smell of fish, nor are they destroyed by gastric acid, cooking, smoking, freezing, canning, salting, or pickling.

Treatment

There is no specific antidote for ciguatoxin or maitotoxin poisonings. Symptomatic treatment may include gabapentin or pregabalin (neuropathic symptoms), amitriptyline (chronic paresthesias, depression, and pruritus), fluoxetine (chronic fatigue), and nifedipine or acetaminophen (headaches). Intravenous mannitol has been reported in uncontrolled studies to reduce the severity and duration of neurologic symptoms, particularly if given within 48 hours of the appearance of symptoms. It should only be given to hemodynamically stable, well-hydrated patients.

After recovering from ciguatera poisoning, patients may want to avoid consuming fish, nuts, alcohol, or caffeine for at least 6 months, as they may cause a relapse in symptoms.

Scombroid

Scombroid occurs worldwide in both temperate and tropical waters. One of the most common fish poisonings, it occurs after eating improperly refrigerated or preserved fish containing high levels of histamine and often resembles a moderate to severe allergic reaction.

Fish typically associated with scombroid have naturally high levels of histidine in the flesh and include tuna, mackerel, mahi mahi (dolphin fish), sardine, anchovy, herring, bluefish, amberjack, and marlin. Histidine is converted to histamine by bacterial overgrowth in fish improperly stored after capture. Histamine and other scombrotoxins are resistant to cooking, smoking, canning, or freezing.

Clinical Presentation

Scombroid poisoning resembles an acute allergic reaction, usually appearing 10–60 minutes after eating contaminated fish. Symptoms include flushing of the face and upper body (resembling sunburn), severe headache, palpitations, itching, blurred vision, abdominal cramps, and diarrhea. Untreated, symptoms usually resolve within 12 hours but may last up to 48 hours. Rarely, there may be respiratory compromise, malignant arrhythmias, and hypotension requiring hospitalization. There are no long-term sequelae. Diagnosis is usually clinical. Clustering of cases helps exclude the possibility of true fish allergy.

Prevention

Fish contaminated with histamine may have a peppery, sharp, salty, taste or “bubbly” feel but will usually look, smell, and taste normal. The key to prevention is to make sure that the fish is properly iced or refrigerated at temperatures <38°F (<3.3°C) or immediately frozen after being caught. Cooking, smoking, canning, or freezing will not destroy histamine in contaminated fish.

Treatment

Scombroid poisoning usually responds well to antihistamines (H1-receptor blockers, although H2-receptor blockers may also provide some benefit).

Shellfish Poisoning

Several forms of poisoning may occur after ingesting toxin-containing shellfish, including filter-feeding bivalve mollusks (mussels, oysters, clams, scallops, and cockles), gastropod mollusks (abalone, whelks, and moon snails), or crustaceans (Dungeness crab, shrimp, and lobster). Toxins originate in small marine organisms (dinoflagellates or diatoms) that are ingested and are concentrated by shellfish.

Risk for Travelers

Contaminated (toxic) shellfish may be found in temperate and tropical waters, typically during or after phytoplankton blooms, also called harmful algal blooms (HABs). One example of a HAB is the Florida red tide caused by Karenia brevis.

Clinical Presentation

Poisoning results in gastrointestinal and neurologic illness of varying severity. Symptoms typically appear 30–60 minutes after ingesting toxic shellfish but can be delayed for several hours. Diagnosis is usually one of exclusion and typically is made clinically in patients who have recently eaten shellfish.

Paralytic Shellfish Poisoning

Paralytic shellfish poisoning (PSP) is the most common and most severe form of shellfish poisoning. PSP is caused by eating shellfish contaminated with saxitoxins. These potent neurotoxins are produced by various dinoflagellates. A wide range of shellfish may cause PSP, but most cases occur after eating mussels or clams.

PSP occurs worldwide but is most common in temperate waters, especially off the Pacific and Atlantic Coasts of North America, including Alaska. The Philippines, China, Chile, Scotland, Ireland, New Zealand, and Australia have all reported cases.

Symptoms usually appear 30–60 minutes after eating toxic shellfish and include numbness and tingling of the face, lips, tongue, arms, and legs. There may be headache, nausea, vomiting, and diarrhea. Severe cases are associated with ingestion of large doses of toxin and clinical features such as ataxia, dysphagia, mental status changes, flaccid paralysis, and respiratory failure. The case-fatality ratio is dependent on the availability of modern medical care, including mechanical ventilation. The death rate may be particularly high in children.

Neurotoxic Shellfish Poisoning

Neurotoxic shellfish poisoning (NSP) is caused by eating shellfish contaminated with brevetoxins produced by the dinoflagellate K. brevis. Predominately an illness of the Western Hemisphere (southeastern coast of the United States, the Gulf of Mexico, and the Caribbean), there are also reports of the disease from New Zealand.

NSP usually presents as a gastroenteritis accompanied by neurologic symptoms resembling mild ciguatera or paralytic shellfish poisoning, 30 minutes to 3 hours after a shellfish meal. A syndrome known as aerosolized red tide respiratory irritation (ARTRI) occurs when aerosolized brevetoxins are inhaled in sea spray. This has been reported in association with a red tide (K. brevis HAB) in Florida. It can induce bronchoconstriction and may cause acute, temporary respiratory discomfort in healthy people. People with asthma may experience more severe and prolonged respiratory effects.

Diarrheic Shellfish Poisoning

Diarrheic shellfish poisoning (DSP) is caused by eating shellfish contaminated with toxins such as okadaic acid. It occurs worldwide, with outbreaks reported from China, Japan, Scandinavia, France, Belgium, Spain, Chile, Uruguay, Ireland, the United States, and Canada.

Most cases result from eating toxic bivalve mollusks such as mussels and scallops. Symptoms usually occur within 2 hours of eating contaminated shellfish and include chills, diarrhea, nausea, vomiting, and abdominal pain. Symptoms usually resolve within 2–3 days. No deaths have been reported.

Amnesic Shellfish Poisoning

Amnesic shellfish poisoning (ASP) is a rare form of shellfish poisoning caused by eating shellfish contaminated with domoic acid, produced by the diatom Pseudonitzchia spp. Outbreaks of ASP have been reported in Canada, Scotland, Ireland, France, Belgium, Spain, Portugal, New Zealand, Australia, and Chile. Implicated shellfish include mussels, scallops, razor clams, and other crustaceans.

In most cases, gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain develop within 24 hours of eating toxic shellfish, followed by headache, memory loss, and cognitive impairment. In severe cases there may be hypotension, arrhythmias, ophthalmoplegia, coma, and death. Survivors may have severe anterograde, short-term memory deficits.

Prevention

Shellfish poisoning can be prevented by avoiding potentially contaminated shellfish. This is particularly important in areas during or shortly after algal blooms, which may be locally referred to as “red tides” or “brown tides.” Shellfish also carry a significant risk of infection from various viral and bacterial infections, for example hepatitis A virus, norovirus, Vibrio vulnificus, Vibrio parahaemolyticus, and several Salmonella and Shigella species. Ideally, travelers to developing countries should avoid eating all shellfish. Marine shellfish toxins cannot be destroyed by cooking or freezing.

Treatment

Treatment is symptomatic and supportive. Severe cases of paralytic shellfish poisoning may require mechanical ventilation.

Bibliography

1. Chan TY. Ciguatera fish poisoning in East Asia and Southeast Asia. Mar Drugs. 2015 Jun 2;13(6):3466–78.Find this resource:

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3. Hungerford JM. Scombroid poisoning: a review. Toxicon. 2010 Aug 15;56(2):231–43.Find this resource:

4. Isbister GK, Kiernan MC. Neurotoxic marine poisoning. Lancet Neurol. 2005 Apr;4(4):219–28.Find this resource:

5. Palafox NA, Buenoconsejo-Lum LE. Ciguatera fish poisoning: review of clinical manifestations. J Toxicol Toxin Rev. 2001 May;20(2):141–60.Find this resource:

6. Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy. Neurology. 2002 Mar 26;58(6):873–80.Find this resource:

7. Sobel J, Painter J. Illnesses caused by marine toxins. Clin Infect Dis. 2005 Nov 1;41(9):1290–6.Find this resource:

Travelers’ Diarrhea

Travelers’ diarrhea (TD) is the most predictable travel-related illness. Attack rates range from 30% to 70% of travelers, depending on the destination and season of travel. Traditionally, it was thought that TD could be prevented by following simple recommendations such as “boil it, cook it, peel it, or forget it,” but studies have found that people who follow these rules may still become ill. Poor hygiene practice in local restaurants is likely the largest contributor to the risk for TD.

TD is a clinical syndrome that can result from a variety of intestinal pathogens. Bacterial pathogens are the predominant risk, thought to account for up to 80%–90% of TD. Intestinal viruses may account for at least 5%–15% of illnesses, although multiplex molecular diagnostic assays increase their detection. Infections with protozoal pathogens are slower to manifest symptoms and collectively account for approximately 10% of diagnoses in longer-term travelers. What is commonly known as “food poisoning” involves the ingestion of preformed toxins in food. In this syndrome, vomiting and diarrhea may both be present, but symptoms usually resolve spontaneously within 12 hours.

Infectious Agents

Bacteria are the most common cause of TD. Overall, the most common pathogen identified is enterotoxigenic Escherichia coli, followed by Campylobacter jejuni, Shigella spp., and Salmonella spp. Enteroaggregative and other E. coli pathotypes are also commonly found in cases of TD. There is increasing discussion of Aeromonas spp., Plesiomonas spp., and newly recognized pathogens (Acrobacter, Larobacter, enterotoxigenic Bacteroides fragilis) as potential causes of TD as well. Viral diarrhea can be caused by a number of pathogens, including norovirus, rotavirus, and astrovirus.

Giardia is the main protozoal pathogen found in TD. Entamoeba histolytica is a relatively uncommon cause of TD, and Cryptosporidium is also relatively uncommon. The risk for Cyclospora is highly geographic and seasonal: the most well-known risks are in Nepal, Peru, Haiti, and Guatemala. Dientamoeba fragilis is a flagellate occasionally associated with diarrhea in travelers. Most of the individual pathogens are discussed in their own sections in Chapter 4, and diarrhea in returned travelers is discussed in Chapter 11.

Risk for Travelers

TD occurs equally in male and female travelers and is more common in young adult travelers than in older travelers. In short-term travelers, bouts of TD do not appear to protect against future attacks, and >1 episode of TD may occur during a single trip. A cohort of expatriates residing in Kathmandu, Nepal, experienced an average of 3.2 episodes of TD per person in their first year. In more temperate regions, there may be seasonal variations in diarrhea risk. In south Asia, for example, much higher TD attack rates are reported during the hot months preceding the monsoon.

In environments in warmer climates where large numbers of people do not have access to plumbing or latrines, the amount of stool contamination in the environment will be higher and more accessible to flies. Inadequate electrical capacity may lead to frequent blackouts or poorly functioning refrigeration, which can result in unsafe food storage and an increased risk for disease. Lack of safe water may lead to contaminated foods and drinks prepared with such water; inadequate water supply may lead to shortcuts in cleaning hands, surfaces, utensils, and foods such as fruits and vegetables. In addition, handwashing may not be a social norm and could be an extra expense; thus there may be no handwashing stations in food preparation areas. In destinations in which effective food handling courses have been provided, the risk for TD has been demonstrated to decrease. However, even in developed countries, pathogens such as Shigella sonnei have caused TD linked to handling and preparation of food in restaurants.

Clinical Presentation

Bacterial and viral TD presents with the sudden onset of bothersome symptoms that can range from mild cramps and urgent loose stools to severe abdominal pain, fever, vomiting, and bloody diarrhea, although with norovirus vomiting may be more prominent. Protozoal diarrhea, such as that caused by Giardia intestinalis or E. histolytica, generally has a more gradual onset of low-grade symptoms, with 2–5 loose stools per day. The incubation period between exposure and clinical presentation can be a clue to the etiology:

  • Bacterial toxins generally cause symptoms within a few hours.

  • Bacterial and viral pathogens have an incubation period of 6–72 hours.

  • Protozoal pathogens generally have an incubation period of 1–2 weeks and rarely present in the first few days of travel. An exception can be Cyclospora cayetanensis, which can present quickly in areas of high risk.

Untreated bacterial diarrhea usually lasts 3–7 days. Viral diarrhea generally lasts 2–3 days. Protozoal diarrhea can persist for weeks to months without treatment. An acute bout of gastroenteritis can lead to persistent gastrointestinal symptoms, even in the absence of continued infection (see Chapter 11, Persistent Diarrhea in Returned Travelers). This presentation is commonly referred to as postinfectious irritable bowel syndrome. Other postinfectious sequelae may include reactive arthritis and Guillain-Barré syndrome.

Prevention

For travelers to high-risk areas, several approaches may be recommended that can reduce, but never completely eliminate, the risk for TD. These include following instructions regarding food and beverage selection, using agents other than antimicrobial drugs for prophylaxis, using prophylactic antibiotics, and carefully washing hands with soap where available. Carrying small containers of alcohol-based hand sanitizers (containing ≥60% alcohol) may make it easier for travelers to clean their hands before eating when handwashing is not possible. No vaccines are available for most pathogens that cause TD, but travelers should refer to the Cholera, Hepatitis A, and Typhoid & Paratyphoid Fever sections in Chapter 4 regarding vaccines that can prevent other foodborne or waterborne infections to which travelers are susceptible.

Food and Beverage Selection

Care in selecting food and beverages can minimize the risk for acquiring TD. See the Food & Water Precautions section in this chapter for CDC’s detailed food and beverage recommendations. Although food and water precautions continue to be recommended, travelers may not always be able to adhere to the advice. Furthermore, many of the factors that ensure food safety, such as restaurant hygiene, are out of the traveler’s control.

Nonantimicrobial Drugs for Prophylaxis

The primary agent studied for prevention of TD, other than antimicrobial drugs, is bismuth subsalicylate (BSS), which is the active ingredient in adult formulations of Pepto-Bismol and Kaopectate. Studies from Mexico have shown that this agent (taken daily as either 2 oz. of liquid or 2 chewable tablets 4 times per day) reduces the incidence of TD by approximately 50%. BSS commonly causes blackening of the tongue and stool and may cause nausea, constipation, and rarely tinnitus.

Travelers with aspirin allergy, renal insufficiency, and gout, and those taking anticoagulants, probenecid, or methotrexate should not take BSS. In travelers taking aspirin or salicylates for other reasons, the use of BSS may result in salicylate toxicity. BSS is not generally recommended for children aged <12 years; however, some clinicians use it off-label with caution to avoid administering BSS to children aged ≤18 years with viral infections, such as varicella or influenza, because of the risk for Reye syndrome. BSS is not recommended for children aged <3 years or pregnant women. Studies have not established the safety of BSS use for periods >3 weeks. Because of the number of tablets required and the inconvenient dosing, BSS is not commonly used as prophylaxis for TD.

The use of probiotics, such as Lactobacillus GG and Saccharomyces boulardii, has been studied in the prevention of TD in small numbers of people. Results are inconclusive, partially because standardized preparations of these bacteria are not reliably available. Studies are ongoing with prebiotics to prevent TD, but data are insufficient to recommend their use. There have been anecdotal reports of beneficial outcomes after using bovine colostrum as a daily prophylaxis agent for TD. However, commercially sold preparations of bovine colostrum are marketed as dietary supplements that are not Food and Drug Administration (FDA) approved for medical indications. Because no data from rigorous clinical trials demonstrate efficacy, there is insufficient information to recommend the use of bovine colostrum to prevent TD.

Prophylactic Antibiotics

Although prophylactic antibiotics can prevent some TD, the emergence of antimicrobial resistance has made the decision of how and when to use antibiotic prophylaxis for TD difficult. Controlled studies have shown that use of antibiotics reduces diarrhea attack rates by 90% or more. The prophylactic antibiotic of choice has changed over the past few decades as resistance patterns have evolved. Fluoroquinolones have been the most effective antibiotics for the prophylaxis and treatment of bacterial TD pathogens, but increasing resistance to these agents among Campylobacter and Shigella species globally limits their potential use. In addition fluoroquinolones are associated with tendinitis and an increased risk of Clostridioides difficile infection, and current guidelines discourage their use for prophylaxis. Alternative considerations include azithromycin, rifaximin, and rifamycin SV.

At this time, prophylactic antibiotics should not be recommended for most travelers. Prophylactic antibiotics afford no protection against nonbacterial pathogens and can remove normally protective microflora from the bowel, increasing the risk of infection with resistant bacterial pathogens. Travelers may become colonized with extended-spectrum β‎-lactamase (ESBL)–producing bacteria, and this risk is increased by exposure to antibiotics while abroad. Additionally, the use of antibiotics may be associated with allergic or adverse reactions, and prophylactic antibiotics limit the therapeutic options if TD occurs; a traveler relying on prophylactic antibiotics will need to carry an alternative antibiotic to use if severe diarrhea develops despite prophylaxis.

The risks associated with the use of prophylactic antibiotics should be weighed against the benefit of using prompt, early self-treatment with antibiotics when moderate to severe TD occurs, shortening the duration of illness to 6–24 hours in most cases. Prophylactic antibiotics may be considered for short-term travelers who are high-risk hosts (such as those who are immunosuppressed or with significant medical comorbidities) or those who are taking critical trips (such as engaging in a sporting event) without the opportunity for time off in the event of sickness.

Treatment

Oral Rehydration Therapy

Fluids and electrolytes are lost during TD, and replenishment is important, especially in young children or adults with chronic medical illness. In adult travelers who are otherwise healthy, severe dehydration resulting from TD is unusual unless vomiting is prolonged. Nonetheless, replacement of fluid losses remains an adjunct to other therapy and helps the traveler feel better more quickly. Travelers should remember to use only beverages that are sealed, treated with chlorine, boiled, or are otherwise known to be purified.

For severe fluid loss, replacement is best accomplished with oral rehydration solution (ORS) prepared from packaged oral rehydration salts, such as those provided by the World Health Organization. ORS is widely available at stores and pharmacies in most developing countries. ORS is prepared by adding 1 packet to the indicated volume of boiled or treated water—generally 1 liter. Travelers may find most ORS formulations to be relatively unpalatable due to their saltiness. In mild cases, rehydration can be maintained with any palatable liquid (including sports drinks), although overly sweet drinks, such as sodas, can cause osmotic diarrhea if consumed in quantity.

Antimotility Agents

Antimotility agents provide symptomatic relief and are useful therapy in TD. Synthetic opiates, such as loperamide and diphenoxylate, can reduce frequency of bowel movements and therefore enable travelers to ride on an airplane or bus. Loperamide appears to have antisecretory properties as well. The safety of loperamide when used along with an antibiotic has been well established, even in cases of invasive pathogens; however, acquisition of ESBL-producing pathogens may be more common when loperamide and antibiotics are coadministered. Antimotility agents alone are not recommended for patients with bloody diarrhea or those who have diarrhea and fever. Loperamide can be used in children, and liquid formulations are available. In practice, however, these drugs are rarely given to small children (aged <6 years).

Antibiotics

Antibiotics are effective in reducing the duration of diarrhea by about a day in cases caused by bacterial pathogens that are susceptible to the particular antibiotic prescribed. However, there are concerns about adverse consequences of using antibiotics to treat TD. Travelers who take antibiotics may acquire resistant organisms such as ESBL-producing organisms, resulting in potential harm to travelers—particularly those who are immunosuppressed or women who may be prone to urinary tract infections—and the possibility of introducing these resistant bacteria into the community. In addition, there is concern about the effects of antibiotic use on travelers’ microbiota and the potential for adverse consequences such as Clostridioides difficile infection as a result. These concerns have to be weighed against the consequences of TD and the role of antibiotics in shortening the acute illness and possibly preventing postinfectious sequelae (see Chapter 11, Persistent Diarrhea in Returned Travelers).

Primarily because of these concerns, an expert advisory panel was convened in 2016 to prepare consensus guidelines on the prevention and treatment of TD. A classification of TD using functional impact for defining severity (Box 2-3) was suggested rather than the frequency-based algorithm that has traditionally been used. The guidelines suggest an approach that matches therapeutic intervention with severity of illness, in terms of both safety and effectiveness (Table 2-10).

Table 2-10. Travelers’ diarrhea treatment recommendations

Therapy of mild travelers’ diarrhea

  • Antibiotic treatment is not recommended in patients with mild travelers’ diarrhea.

  • Loperamide or BSS may be considered in the treatment of mild travelers’ diarrhea.

Therapy of moderate travelers’ diarrhea

  • Antibiotics may be used to treat cases of moderate travelers’ diarrhea.

  • Fluoroquinolones may be used to treat moderate travelers’ diarrhea.

  • Azithromycin may be used to treat moderate travelers’ diarrhea.

  • Rifaximin may be used to treat moderate, noninvasive travelers’ diarrhea.

  • Loperamide may be used as adjunctive therapy for moderate to severe travelers’ diarrhea. Antimotility agents alone are not recommended for patients with bloody diarrhea or those who have diarrhea and fever.

  • Loperamide may be considered for use as monotherapy in moderate travelers’ diarrhea.

Therapy of severe travelers’ diarrhea

  • Antibiotics should be used to treat severe travelers’ diarrhea.

  • Azithromycin is preferred to treat severe travelers’ diarrhea.

  • Fluoroquinolones may be used to treat severe, nondysenteric travelers’ diarrhea.

  • Rifaximin may be used to treat severe, nondysenteric travelers’ diarrhea.1

  • Single-dose antibiotic regimens may be used to treat travelers’ diarrhea.

1 These treatment recommendations were developed prior to the approval of rifamycin SV in the United States. Because it is in the same category of antimicrobial drug as rifaximin and because they have the same mechanism of action, rifamycin SV can be considered as an alternative to rifaximin.

The effectiveness of a particular antimicrobial drug depends on the etiologic agent and its antibiotic sensitivity (Table 2-11). As empiric therapy or to treat a specific bacterial pathogen, first-line antibiotics have traditionally been the fluoroquinolones, such as ciprofloxacin or levofloxacin. Increasing microbial resistance to the fluoroquinolones, especially among Campylobacter isolates, may limit their usefulness in many destinations, particularly South and Southeast Asia, where both Campylobacter infection and fluoroquinolone resistance is prevalent. Increasing fluoroquinolone resistance has been reported from other destinations and in other bacterial pathogens, including in Shigella and Salmonella. In addition, the use of fluoroquinolones has been associated with tendinopathies and the development of C. difficile infection. FDA warns that the potentially serious side effects of fluoroquinolones may outweigh their benefit in treating uncomplicated respiratory and urinary tract infections; however, because of the short duration of therapy for TD, these side effects are not believed to be a significant risk.

Table 2-11. Acute diarrhea antibiotic treatment recommendations

Antibiotic1

Dose

Duration

Azithromycin2,3

1,000 mg

Single or divided dose4

500 mg daily

3 days

Levofloxacin

500 mg daily

1–3 days4

Ciprofloxacin

750 mg

Single dose4

500 mg bid

3 days

Ofloxacin

400 mg bid

1–3 days4

Rifamycin SV5

388 mg bid

3 days

Rifaximin5

200 mg tid

3 days

1 Antibiotic regimens may be combined with loperamide 4 mg initially followed by 2 mg after each loose stool, not to exceed 16 mg in a 24-hour period.

2 Use empirically as first-line in Southeast Asia or other areas if fluoroquinolone-resistant bacteria are suspected.

3 Preferred regimen for dysentery or febrile diarrhea.

4 If symptoms are not resolved after 24 hours, continue daily dosing for up to 3 days.

5 Do not use if clinical suspicion for Campylobacter, Salmonella, Shigella, or other causes of invasive diarrhea. Use may be reserved for patients unable to receive fluoroquinolones or azithromycin.

A potential alternative to fluoroquinolones is azithromycin, although enteropathogens with decreased azithromycin susceptibility have been documented in several countries. Rifaximin has been approved to treat TD caused by noninvasive strains of E. coli. However, since it is often difficult for travelers to distinguish between invasive and noninvasive diarrhea, and since they would have to carry a backup drug in the event of invasive diarrhea, the overall usefulness of rifaximin as empiric self-treatment remains to be determined.

Single-dose regimens are equivalent to multidose regimens and may be more convenient for the traveler. Single-dose therapy with a fluoroquinolone is well established, both by clinical trials and clinical experience. The best regimen for azithromycin treatment may also be a single dose of 1,000 mg, but side effects (mainly nausea) may limit the acceptability of this large dose. Giving azithromycin as 2 divided doses on the same day may limit this adverse event.

Treatment of TD Caused by Protozoa

The most common parasitic cause of TD is Giardia intestinalis, and treatment options include metronidazole, tinidazole, and nitazoxanide (see Chapter 4, Giardiasis). Although cryptosporidiosis is usually a self-limited illness in immunocompetent people, nitazoxanide can be considered as a treatment option. Cyclosporiasis is treated with trimethoprim-sulfamethoxazole. Treatment of amebiasis is with metronidazole or tinidazole, followed by treatment with a luminal agent such as iodoquinol or paromomycin.

A new therapeutic option is rifamycin SV, which was approved by FDA in November 2018 to treat TD caused by noninvasive strains of E. coli in adults. Rifamycin SV is a nonabsorbable antibiotic in the ansamycin class of antibacterial drugs formulated with an enteric coating that targets delivery of the drug to the distal small bowel and colon. Two randomized clinical trials showed that rifamycin SV was superior to placebo and noninferior to ciprofloxacin in the treatment of TD.

Treatment for Children

Children who accompany their parents on trips to high-risk destinations can contract TD as well, with elevated risk if they are visiting friends and family. Causative organisms include bacteria responsible for TD in adults, as well as viruses including norovirus and rotavirus. The main treatment for TD in children is ORS. Infants and younger children with TD are at higher risk for dehydration, which is best prevented by the early initiation of oral rehydration. Empiric antibiotic therapy should be considered if there is bloody or severe watery diarrhea or evidence of systemic infection. In older children and teenagers, treatment recommendations for TD follow those for adults, with possible adjustments in the dose of medication. Among younger children, macrolides such as azithromycin are considered first-line antibiotic therapy, although some experts now use short-course fluoroquinolone therapy (despite its not being FDA-approved for this indication in children) for travelers aged <18 years. Rifaximin is approved for use in children aged ≥12 years. Rifamycin SV is approved for use only in adults.

Breastfed infants should continue to nurse on demand, and bottle-fed infants can continue to drink formula. Older infants and children should be encouraged to eat and may consume a regular diet. Children in diapers are at risk for developing diaper rash on their buttocks in response to the liquid stool. Barrier creams, such as zinc oxide or petrolatum, could be applied at the onset of diarrhea to help prevent and treat rash. Hydrocortisone cream is the best treatment for an established rash. More information about diarrhea and dehydration is discussed in Chapter 7, Traveling Safely with Infants & Children.

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3. DuPont HL, Ericsson CD, Farthing MJ, Gorbach S, Pickering LK, Rombo L, et al. Expert review of the evidence base for prevention of travelers’ diarrhea. J Travel Med. 2009 May–Jun;16(3):149–60.Find this resource:

4. Farthing M, Salam MA, Lindberg G, Dite P, Khalif I, Salazar-Lindo E, et al. Acute diarrhea in adults and children: a global perspective. J Clin Gastroenterol. 2013 Jan;47(1):12–20.Find this resource:

5. Kantele A, Lääveri T, Mero S, Vilkman K, Pakkanen S, Ollgren J, et al. Antimicrobials increase travelers’ risk of colonization by extended-spectrum betalactamase producing Enterobacteriaceae. Clin Infect Dis. 2015 Mar 15;60(6):837–46.Find this resource:

6. Kendall ME, Crim S, Fullerton K, Han PV, Cronquist AB, Shiferaw B, et al. Travel-associated enteric infections diagnosed after return to the United States, Foodborne Diseases Active Surveillance Network (FoodNet), 2004–2009. Clin Infect Dis. 2012 Jun;54(Suppl 5):S480–7.Find this resource:

7. Mcfarland LV. Meta-analysis of probiotics for the prevention of travelers’ diarrhea. Cochrane Database Syst Rev 2010;Cd003048.Find this resource:

8. Raja MK, Ghosh AR. Laribacter hongkongensis: an emerging pathogen of infectious diarrhea. Folia Microbiol. (Praha) 2014 Jul;59 (4):341–7.Find this resource:

9. Riddle MS, Connor BA, Beeching NJ, DuPont HL, Hamer DH, Kozarsky PE et al. Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report. J Travel Med. 2017;24(Suppl 1):S2–S19.Find this resource:

10. Riddle MS, DuPont HL, Connor BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016 May;111(5):602–22.Find this resource:

11. Shlim DR. Looking for evidence that personal hygiene precautions prevent travelers’ diarrhea. Clin Infect Dis. 2005 Dec 1;41(Suppl 8):S531–5.Find this resource:

12. Steffen R, Hill DR, DuPont HL. Traveler’s diarrhea: a clinical review. JAMA. 2015 Jan 6;313(1):71–80.Find this resource:

13. Zboromyrska Y, Hurtado JC, Salvador P, Alvarez-Martinez MJ, Valls ME, Marcos MA, et al. Aetiology of travelers’ diarrhea: evaluation of a multiplex PCR tool to detect different enteropathogens. Clin Microbiol Infect. 2014;20:O753–9.Find this resource:

…perspectives Antibiotics in Travelers’ Diarrhea—Balancing the Risks & Benefits

For the past 30 years, randomized controlled trials have consistently and clearly demonstrated that antibiotics shorten the duration of illness and alleviate the disability associated with travelers’ diarrhea (TD). Treatment with an effective antibiotic shortens the average duration of a TD episode by about a day, and if the traveler combines an antibiotic with an antimotility agent such as loperamide, the duration of illness is shortened even further. Emerging data on the potential long-term health consequences of TD, such as irritable bowel syndrome, dyspepsia, and chronic constipation, might suggest a benefit of early antibiotic therapy given the association between more severe and longer disease and risk of postinfectious consequences.

Although these clinical results are impressive, antibiotics, like any drug, are not without consequences. Each of the antibiotics commonly used to treat TD have side effects, but these are generally mild and self-limiting, and the benefits appear to outweigh the risks. More recently, however, there has been concern that antibiotics used by travelers might result in significant changes in the host microbiome as well as the acquisition of multidrug-resistant bacteria. Multiple observational studies have found that those people who travel (in particular to regions of Asia), develop TD, and take antibiotics are at incrementally increasing risk for colonization with extended-spectrum β‎-lactamase–producing Enterobacteriaceae (ESBL-PE). The direct effects of colonization on the average traveler appears limited; carriage is most often transient but does persist in a small percentage of those who are colonized. However, international travel by a household member is associated with ESBL-PE colonization among close-living contacts, which suggests potential larger public health consequences from acquiring ESBL-PE during travel.

The challenge that we face as providers and travelers is how to balance the risk of colonization and the global spread of resistance with the health benefits of antibiotic treatment of TD. Although the role of travelers in the translocation of infectious disease and resistance cannot be ignored, the ecology of ESBL-PE infections is complex and includes environmental, diet, immigration, and local nosocomial transmission dynamics. ESBL-PE infections are an emerging health threat, and addressing this complex problem will require multiple strategies.

How, then, to prepare a traveler with a prescription for empiric self-treatment before a trip? There needs to be a conversation with the traveler about the multilevel (individual, community, global) risks of travel, travelers’ diarrhea, preventing TD through hand hygiene and careful selection of foods and beverages, and antibiotic treatment. Reserving antibiotics for moderate to severe TD should be emphasized strongly, and using antimotility agents alone may be suggested for mild TD. Elderly travelers (because of the serious consequences of bloodstream infections in this population) or those with recurrent urinary tract infections (because Escherichia coli is a common cause) may be at higher risk of health consequences as a result of ESBL-PE colonization. At a minimum these travelers should be made aware of this risk, and should be counseled to convey their travel exposure history to their treating providers if they become ill after travel. Though further studies are needed (and many are underway), a rational approach is advised to decrease exposure by using single-dose regimens and selecting an antibiotic agent that minimizes microbiome disruption and risk of colonization. Additionally, as travel and untreated TD independently increase the risk of ESBL-PE colonization, nonantibiotic chemoprophylactic strategies, such as the use of bismuth subsalicylate, may decrease both the acute and posttravel risk concerns. Strengthening the resilience of the host microbiota to prevent infection and unwanted colonization, as with the use of prebiotics or probiotics, are promising potential strategies but need further investigation.

Finally, we must be cognizant of the fact that we expect the traveler to be the diagnostician, practitioner, and patient when it comes to managing TD. For even the most astute traveler, making such learned decisions can be challenged by the anxiety-provoking onset of that first abdominal cramp in sometimes austere and inconvenient settings. Providing prospective travelers with clear written guidance about TD prevention and step-by-step instructions about how and when to use medications for TD is crucial.

Bibliography

1. Arcilla MS, van Hattem JM, Haverkate MR, Bootsma MCJ, van Genderen PJJ, Goorhuis A, et al. Import and spread of extended-spectrum β‎-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study. Lancet Infect Dis. 2017 Jan;17(1):78–85.Find this resource:

2. Riddle MS, Connor BA, Beeching NJ, DuPont HL, Hamer DH, Kozarsky P, et al. Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report. J Travel Med. 2017 Apr 1;24(Suppl 1):S57–S74.Find this resource:

Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official recommendations contained in the book. The views and opinions expressed in this section are those of the author and do not necessarily represent the official position of CDC.

Notes:

1 The official WHO list of countries with risk of YF virus transmission can be found in Table 4-23. Proof of yellow fever vaccination should be required only if traveling from a country on the WHO list, unless otherwise specified. The following countries, containing only areas with low potential for exposure to YF virus, are not on the WHO list: Eritrea, Rwanda, São Tomé and Príncipe, Somalia, Tanzania, Zambia.

3 Refers to P. falciparum malaria unless otherwise noted.

4 Primaquine and tafenoquine can cause hemolytic anemia in people with G6PD deficiency. Patients must be screened for G6PD deficiency before starting primaquine or tafenoquine.

1 Current as of August 2018. This map is an updated version of the 2010 map created by the Informal WHO Working Group on the Geographic Risk of Yellow Fever.

2 An elevation of 2,300 m is equivalent to 7,546 ft.

3 In 2017, CDC expanded yellow fever vaccination recommendations for travelers to Brazil because of a large outbreak of yellow fever in multiple states in that country. Please refer to the CDC Travelers' Health website (www.cdc.gov/travel) for more information and updated recommendations.

2 Yellow fever (YF) vaccination is generally not recommended in areas where there is low potential for YF virus exposure. However, vaccination might be considered for a small subset of travelers to these areas who are at increased risk for exposure to YF virus because of prolonged travel, heavy exposure to mosquitoes, or inability to avoid mosquito bites. Consideration for vaccination of any traveler must take into account the traveler’s risk of being infected with YF virus, country entry requirements, and individual risk factors for serious vaccine-associated adverse events (such as age or immune status).