Show Summary Details
Page of

Routine Vaccines for Vaccine-Preventable Diseases 

Routine Vaccines for Vaccine-Preventable Diseases
Chapter:
Routine Vaccines for Vaccine-Preventable Diseases
Author(s):

Tina Q. Tan

, John P. Flaherty

, and Melvin V. Gerbie

DOI:
10.1093/med/9780190604776.003.0003
Page of

PRINTED FROM OXFORD MEDICINE ONLINE (www.oxfordmedicine.com). © Oxford University Press, 2020. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy and Legal Notice).

date: 14 August 2020

Diphtheria

Did you know that:

  • Abraham Lincoln had 4 sons, 2 died from vaccine preventable infectious diseases. Eddie, Lincoln’s second son, died at the age of 2 from diphtheria. His third son, Willie, died at age 11 from typhoid fever.

  • The only son of Dr. Abraham Jacobi, who is often referred to as the “father of American Pediatrics,” died of diphtheria at age 8, a disease for his father was a recognized authority.

  • Historical descriptions of diphtheria (throat membrane, neck swelling, and suffocation) first appeared in ancient Egyptian writings from the second millennium bc.

  • In 1921 there were 206,000 cases of diphtheria in the United States, resulting in 15,520 deaths. 20% of children under 5 years of age died from diphtheria.

Diphtheria is caused by toxigenic strains of the gram-positive, non-spore forming, nonmotile, pleomorphic bacillus Corynebacterium diphtheriae. The disease can have a variety of manifestations including: respiratory tract diphtheria, which presents as membranous nasopharyngitis or obstructive laryngotracheitis. Onset of the disease is abrupt, with sore throat, mild pharyngeal injection, and the development of a gray membrane on one or both tonsils with extension to the tonsillar pillars, uvula, soft palate, oropharynx, and nasopharynx with a bloody nasal discharge. Involvement of the larynx and bronchi presents with symptoms of hoarseness, dyspnea, respiratory stridor, a brassy cough, cyanosis, retractions, and respiratory distress. Diphtheria may also present as cutaneous, vaginal, conjunctival, or otic disease; and as mycotic aneurysms, septic arthritis, and osteomyelitis. Local infections are associated with low-grade fever, malaise, and the gradual onset of manifestations over 1 to 2 days. Extensive neck swelling with cervical lymphadenitis (bull neck) is a sign of severe disease that occurs more often in persons who are unimmunized or inadequately immunized. Diphtheria remains endemic in the former Soviet Union, Africa, Latin America, Haiti, Asia, the Middle East, and parts of Europe where childhood immunization coverage with diphtheria toxoid-containing vaccines is suboptimal.

Life-threatening complications of respiratory diphtheria include upper airway obstruction caused by extensive membrane formation; myocarditis (detected in up to two-thirds of patients), which is often associated with varying degrees of heart block and myocardial dysfunction; cranial and peripheral neuropathies; and palatal palsy associated with pharyngeal diphtheria characterized by nasal speech.

Transmission

Humans are the sole reservoir of C. diphtheriae. Organisms are spread by intimate contact with airborne respiratory tract droplets from persons with active infection or carriers and by contact with exudates from infected skin lesions. People who travel to areas where diphtheria is endemic or people who come into contact with infected travelers from such areas are at increased risk of being infected with the organism.

Incubation period

2 to 7 days

Prevention

Postexposure

  1. a. Persons who have diphtheria disease and are in the convalescent stage of their disease should receive a dose of a diphtheria toxoid-containing vaccine because clinical infection does not always induce adequate levels of antitoxin.

  2. b. Close contacts of persons with diphtheria disease, regardless of their immunization status, should receive antibiotic prophylaxis with erythromycin or penicillin, and should receive a dose of a diphtheria toxoid-containing vaccine.

Preexposure

  1. a. Diphtheria toxoid-containing vaccines—type of vaccine varies by age

    1. i. For infants and children from 6 weeks up to 7 years of age—5 intramuscular doses of DTaP vaccines are recommended, beginning at 6 to 8 weeks of age. Recommended doses are given at 2 months, 4 months, 6 months, 12 to 18 months and 4 to 6 years of age.

    2. ii. For persons over 7 years of age—An intramuscular dose of Td vaccine should be administered if immunization against diphtheria or tetanus is indicated. A dose of Tdap vaccine (contains acellular pertussis) may also be given if a previous dose has not been received. Booster doses of Td are recommended every 10 years. Currently only a single dose of Tdap is recommended, however, discussions are underway regarding recommendation for booster doses.

Duration of immunity

approximately 10 years

Contraindications and precautions to diphtheria containing vaccines

Contraindications

  • Severe immediate allergic reaction (e.g., anaphylaxis) to a prior dose of tetanus and diphtheria toxoid-containing vaccines (e.g., DTaP, Tdap, Td) is a contraindication to further doses.

Precautions

  1. 1. Moderate or severe acute illness with or without fever

  2. 2. Guillain-Barré syndrome (GBS) within 6 weeks after a previous dose of tetanus-toxoid-containing vaccine

  3. 3. History of Arthus-type hypersensitivity reactions after a previous dose of tetanus or diphtheria toxoid-containing vaccine; defer vaccination until at least 10 years have elapsed since the last tetanus-toxoid-containing vaccine

Frequently asked questions

Diphtheria is rare in the United States, are there countries where diphtheria is still prevalent?

Yes, there are countries where diphtheria is still prevalent and poses a risk. These include countries in Asia (the Philippines, Nepal, Indonesia, Bangladesh, Vietnam), Africa, the Middle East (Pakistan, India, Afghanistan), the countries of the former Soviet Union (Russia, Ukraine, the Baltic States, and Georgia), South America, the South Pacific, Eastern Europe, Haiti, and the Dominican Republic. Persons traveling to these countries should ensure that they are up to date with their diphtheria toxoid vaccination status.

Who is at risk of acquiring diphtheria?

Persons, especially children who are not immunized or who did not receive adequate immunization are at the highest risk. Diphtheria is most common in areas where people live in crowded conditions with poor sanitation.

If a person is infected with diphtheria, how long are they contagious and able to spread disease to others?

Untreated people who are infected with the diphtheria organism can be contagious for up to two weeks but rarely more than four weeks. If treated with appropriate antibiotics, the contagious period can be limited to less than four days.

What are the potential consequences of not being treated for diphtheria?

If diphtheria goes untreated, serious complications such as paralysis, encephalitis, cerebral infarction, heart failure, and renal failure may occur. Death occurs in approximately 5% to 10% of all cases.

Does past infection with diphtheria make a person immune to the disease?

Unfortunately, a person who recovers from diphtheria does not reliably develop lasting immunity to the disease.

Tetanus

Did you know that:

  • John Augustus Roebling, the architect of the Brooklyn Bridge, died from tetanus after his leg was crushed by a ferryboat while working on the bridge.

  • John Thoreau, brother of famous American writer and Transcendentalist Henry David Thoreau, died from tetanus after cutting himself shaving.

  • Tetanus is called “lockjaw” because one of the first symptoms of the disease is severe muscle spasms of the jaw muscles preventing opening of the mouth.

Tetanus (lockjaw) occurs worldwide and is more common in warmer climates and during warmer months. It is caused by neurotoxin produced by the anaerobic, spore forming, gram positive bacterium Clostridium tetani, which is a normal inhabitant of soil, animal, and human intestines, and is ubiquitous in the environment. The organism multiplies in wounds and elaborates toxins in the presence of anaerobic conditions. Contaminated wounds, especially wounds with devitalized tissue and deep-puncture trauma, are at greatest risk (including frostbite). Neonatal tetanus is common in many developing countries where pregnant women are not immunized appropriately against tetanus and nonsterile umbilical cord-care practices are followed.

Tetanus has 4 clinical forms:

  1. 1. Generalized tetanus (lockjaw) is a neurologic disease manifesting as severe muscle spasms including trismus (jaw muscle spasms or lockjaw), risus sardonicus (facial muscle spasms resulting in a sardonic grin), and opisthotonus (severe spasm and hyperextension of the neck and spine). Onset is gradual, occurring over 1 to 7 days, and symptoms rapidly progress to severe generalized muscle spasms, which are made worse by any external stimuli. Severe spasms persist for 1 or more weeks and subside over several weeks in persons who survive. Other symptoms include fever, diaphoresis, tachycardia, and elevated blood pressure associated with sympathetic overactivity.

  2. 2. Local tetanus manifests as local muscle spasms in areas contiguous to a contaminated wound that very often progresses to generalized tetanus.

  3. 3. Neonatal tetanus is a form of generalized tetanus occurring in newborn infants who lack protective passive immunity because their mothers are not immunized. Neonates present with generalized weakness and failure to nurse followed by apnea, rigidity, and spasms. Mortality rate exceeds 90%, and developmental delays are common among survivors.

  4. 4. Cephalic tetanus is a dysfunction of cranial nerves associated with infected wounds on the head and neck. Cephalic tetanus can progress to generalized tetanus.

Transmission

Contamination of wounds. The vegetative form of C. tetani produces a potent plasmid-encoded exotoxin (tetanospasmin), which binds to gangliosides at the myoneuronal junction of skeletal muscle and on neuronal membranes in the spinal cord, blocking inhibitory impulses to motor neurons.

Incubation period

The incubation period is 3 to 21 days, with the majority of cases occurring within 8 days. Shorter incubation periods are associated with more heavily contaminated wounds, more severe disease, and a worse prognosis. For neonatal tetanus, symptoms appear on average 7 days after birth (range 4 to 14 days).

Prevention

Postexposure

  1. a. Tetanus toxoid-containing vaccine with or without human tetanus immunoglobulin (TIG) in the management of wounds depends on the type of wound and the immunization history with tetanus toxoid (Table 8). DTaP is used for children younger than 7 years of age. Tdap is preferred over Td for underimmunized persons over 7 years of age who have not received a prior dose of Tdap.

Table 8 Management of Wounds Depending on Wound Type and Tetanus Toxoid Immunization History

Number of Tetanus Toxoid Doses

Clean, Minor Wounds

All Other Wounds

DTaP/Tdap/Td

TIG

DTaP/Tdap/Td

TIG

≤ 3 or unknown

Yes

No

Yes

Yes

3 or more

No if <10 years since last tetanus containing vaccine

No

No if <5 years since last tetanus containing vaccine

No

Yes if >10 years since last tetanus containing vaccine

No

Yes if ≥5 years since last tetanus containing vaccine

No

When an infant is born outside the hospital and the umbilical cord is likely contaminated (e.g., cut with nonsterile equipment), the maternal history of tetanus immunization should be confirmed. If the mother’s tetanus immunization status is unknown and she is unlikely to have been immunized, TIG should be administered to the neonate unless the maternal tetanus serostatus can be confirmed quickly.

For infants younger than 6 months of age who have not received a full 3-dose primary series of tetanus-toxoid-containing vaccine, decisions on the need for TIG with wound care should be based on the mother’s tetanus toxoid immunization history at the time of delivery.

Preexposure

  1. a. Active immunization with tetanus toxoid containing vaccine is recommended for persons of all ages. Tetanus immunization is administered with diphtheria toxoid containing vaccines (e.g., Td) or with diphtheria toxoid and acellular pertussis containing vaccines (e.g., DTaP, Tdap)—type of vaccine varies by age. Vaccines are administered intramuscularly.

    1. i. For infants and children from 6 weeks up to 7 years of age—5 intramuscular doses of DTaP vaccines are recommended, beginning at 6 to 8 weeks of age. Recommended doses are given at 2 months, 4 months, 6 months, 12 to 18 months and 4 to 6 years of age.

    2. ii. For persons ≥ 7 years of age—an intramuscular dose of Td vaccine is given if immunization against diphtheria or tetanus is needed. A dose of Tdap vaccine (contains acellular pertussis) may also be given if a previous dose has not been received. Booster doses of Td are recommended every 10 years. Currently only a single dose of Tdap is recommended, however, discussions are underway regarding an appropriate interval for booster doses.

Duration of immunity

approximately 10 years

Contraindications and Precautions

Contraindications

  • Severe immediate allergic reaction (e.g., anaphylaxis) to a prior dose of tetanus and diphtheria toxoid-containing vaccines (e.g. DTaP, Tdap, Td) is a contraindication to further doses.

Precautions

  1. 1. Moderate or severe acute illness with or without fever

  2. 2. Guillain-Barré syndrome (GBS) within 6 weeks after a previous dose of tetanus-toxoid containing vaccine

  3. 3. History of Arthus-type hypersensitivity reactions after a previous dose of tetanus or diphtheria toxoid-containing vaccine; defer vaccination until at least 10 years have elapsed since the last tetanus-toxoid containing vaccine.

Frequently asked questions

If a person sustains a puncture wound or laceration that is tetanus prone (e.g., wounds contaminated with soil or fecal material), does the person need to receive tetanus wound management the day that the injury occurred or can this wait for 48 to 72 hours?

Puncture wounds should be attended to as soon as possible. The decision to delay a booster dose of tetanus-toxoid-containing vaccine following an injury should be based on the type of injury and likelihood that the person is susceptible to tetanus. The more likely the person is to be susceptible (e.g., unvaccinated or incompletely vaccinated against tetanus), the more quickly the tetanus prophylaxis (TIG and Tdap/Td) should be administered.

When should tetanus immue globulin (TIG) be administered as part of wound management?

TIG is recommended for any wound other than a clean minor wound if the person’s vaccination history is either unknown, or if they have had less than a complete series of 3 doses of Td vaccine. TIG should be given as soon as possible after the injury.

How long after a wound occurs is tetanus immune globulin (TIG) no longer recommended?

For a person who has been vaccinated but is not up to date, there is little benefit in giving TIG more than a week after the injury. For a person who is completely vaccinated, this interval can be increased to up to day 21 post-injury period.

If an adult patient states that he/she had tetanus infection as a child but does not know if he/she have ever received any tetanus-containing vaccines, should this patient be immunized with a tetanus containing vaccine as part of routine health maintenance?

A history of tetanus disease is not a reason to avoid using tetanus-containing vaccines. Tetanus disease does not produce immunity because only a very small amount of toxin is needed to produce disease. If the patient has no other contraindications, they should receive a tetanus-containing vaccine now. If they have no documentation of prior tetanus vaccination, they should complete a 3-dose series with Tdap, followed by a dose of Td 4 to 8 weeks later, and a dose of Td 6-12 months after the last Td dose.

Should an adult patient who previously received a Tdap vaccine, receive another Tdap vaccine after a bone marrow transplant?

Yes. A dose of Tdap vaccine 6 months after a bone marrow transplant is appropriate.

Can Tdap and RhoGam (anti-Rho[D]) immunoglobulin be given at the same prenatal visit?

Yes. Tdap is an inactivated vaccine and may be given at the same prenatal visit with RhoGam.

Pertussis

Did you know that:

  • George Washington Carver (American botanist and inventor), Dolly Madison (wife of US President James Madison), and Shah Mohammed Reza Pahlavi (the Shah of Iran) all suffered from bouts of pertussis.

  • Pertussis is also known as “whooping cough” because of the “whooping” sound that is made when gasping for air after a fit of coughing.

  • Coughing fits due to pertussis infection can last for up to 10 weeks or more; this disease has been called the “cough of 100 days.”

Pertussis (whooping cough) is caused by the Gram negative organism Bordetella pertussis. Humans are the only known hosts of the organism. It continues to be a major public health problem in all age groups and is the cause of major epidemics worldwide. Cases occur year round. The incidence of disease in the adolescent and adult populations has significantly increased over the last several decades primarily due to waning of both vaccine and naturally induced immunity and increased disease awareness. Neither natural infection nor immunization provides lifelong immunity. Older children, adolescents, and adults serve as the major reservoirs of pertussis disease in the community. Young infants, especially those under 3 months of age, are at the greatest risk for morbidity and mortality from disease. Since 1990, 93% to 100% of pertussis deaths in the United States have occurred in this very young infant population. The CDC, AAP, IOM, AAFP, and ACOG all strongly support immunization of pregnant women and a “cocoon strategy” to protect these young infants. This strategy focuses on the targeted immunization of older children, adolescents, and adults who either live in the household or who are close contacts of these young infants to prevent these individuals from getting pertussis disease and giving it to the young infants. This should include all adolescents and adults including persons over 65 years of age, grandparents, relatives, friends, nannies, babysitters, daycare providers, and housekeepers.

Pertussis disease consists of 3 stages and severity of disease ranges from very mild, atypical disease to severe classic pertussis (Table 9):

  1. Stage 1: Catarrhal stage—symptoms are mild and include rhinorrhea with no pharyngitis, mild conjunctival injection, low-grade fever or no fever and mild cough. This stage lasts for 2 weeks.

  2. Stage 2: Paroxysmal stage—symptoms include paroxysms of cough, posttussive emesis, inspiratory whooping, apnea, and cyanosis. Symptoms may be milder in individuals who have received immunization in the past and in the adolescent and adult populations. This stage lasts for 6 weeks.

  3. Stage 3: Convalescent stage—coughing paroxysms and other symptoms become less frequent and intense. This stage lasts for 4-6 weeks.

Table 9 Clinical Signs and Symptoms of Pertussis in Adolescents and Adults (based on a compilation of 8 different studies)

Clinical Characteristics

Age Group

  • Adolescents (%)

  • (10 to 19 years)

  • Adults (%)

  • (≥20 years)

Paroxysms of cough

82.5 (82–83)

87 (33–100)

Inspiratory whoop

50 (30–67)

74 (7–82)

Apnea

46 (19–86)

85 (29–87)

Cyanosis

6–15

9–12

Posttussive emesis

56 (45–71)

50 (17–70)

Hospitalization

1.4–7.5

3.5–5.7

Persons with pertussis may be ill for 3 to 4 months from onset of cough. Any intercurrent viral illness will exacerbate cough illness. Treatment with antibiotic therapy is effective in preventing transmission of the organism but does not have an impact on the duration of the cough. The illness has a significant negative impact on the quality of life of adolescent and adult patients with pertussis. The vast majority are unable to sleep, go to work, attend school, eat or drink normally during their illness.

Pertussis should be included in the differential diagnosis for all adolescents and adults presenting for evaluation of a persistent cough illness lasting 2 weeks or more.

Infants, especially those under 3 months of age, who are unimmunized or who have received only the first of their primary immunizations, are at the greatest risk for complications, hospitalizations, and death due to pertussis disease. Apnea alone or apnea associated with very mild cough may be the only presenting symptom of pertussis in this age group. Complications seen among infants include: pneumonia (22%), seizures (2%), encephalopathy (<0.5%), pulmonary hypertension, hernia, subdural bleeding, conjunctival bleeding and death.

Complications in children, adolescents, and adults

These complications include pneumonia (1.9% in patients <30 years of age, 5% to 9% in older patients), seizures (0.3%), encephalopathy (0.1%), urinary incontinence (4% of adults, 35% of women >50 years), pneumothorax, inguinal hernia, aspiration pneumonia, fractured ribs, hearing loss, syncope, subconjunctival hemorrhages, carotid artery dissection, and intracranial bleeding. Incidence of complications increases with age.

Table 10 Antibiotic Treatment and Chemoprophylaxis of Pertussis

Antibiotic

Dosage

Comments

Erythromycin estolate or erythromycin ethylsuccinate

40–50 mg/kg/day (max 2 g/day) PO divided q 6–8 hours X 14 days

Contraindicated in infants <6 weeks of age due to increased risk for pyloric stenosis

Azithromycin

10 mg/kg/day X 5 days (infants <6 mos); 10 mg/kg on day 1 (max 500 mg/day) then 5 mg/kg per day on days 2–5 (max 250 mg/day)

DRUG OF CHOICE FOR ALL AGE GROUPS

Clarithromycin

15–20 mg/kg/day (max 1 gram/day) q 8–12 hours X 7–10 days

___

Trimethoprim-sulfamethoxazole (TMP/SMX)

8 mg TMP/40 mg SMX per kg/day (max 320 mg TMP/1600 mg SMX/day) in 2 divided doses X 14 days

Drug of choice for patients who cannot tolerate the macrolide antibiotics or who are allergic to the macrolide antibiotics

Persons who should receive chemoprophylaxis include:

  • All household contacts regardless of age and immunization status

  • Other close contacts regardless of age and immunization status defined by the CDC as:

    • Anyone who has had face-to-face contact or shared a confined space for a prolonged period of time (>1 hour) with an infected individual

    • Persons who have direct contact with respiratory, oral, or nasal secretions from a symptomatic patient (e.g., cough, sneeze, sharing food and eating utensils, mouth-to-mouth resuscitation, or performing a medical examination of the mouth, nose, and throat)

Transmission

Close contact with cases via aerosolized respiratory droplets. Persons are infectious beginning with the first day of cough and if untreated can continue to transmit the organism for up to 3 weeks after onset of illness.

Prevention

Postexposure

  1. a. Antibiotic chemoprophylaxis for all household and close contacts as above in addition to pertussis containing vaccines.

  2. b. Pertussis containing vaccines are recommended for all underimmunized or incompletely immunized household and close contacts. Pertussis immunization is administered with diphtheria and tetanus-toxoid- containing vaccines (e.g., DTaP, Tdap)—type of vaccine varies by age. Vaccines are administered intramuscularly. DTaP is used for children younger than 7 years of age. Tdap is used for underimmunized persons over 7 years of age who have not received a prior dose of Tdap.

Preexposure

Pertussis containing vaccines

  1. i. For infants and children from 6 weeks up to 7 years of age—5 intramuscular doses of DTaP vaccines are recommended, beginning at 6 to 8 weeks of age. Recommended doses are given at 2 months, 4 months, 6 months, 12–18 months and 4 to 6 years of age.

  2. ii. For persons over 7 years of age—an intramuscular dose of Tdap vaccine is given if immunization against pertussis is needed and if a previous dose has not been received. Currently only a single dose of Tdap is recommended, except in the case of pregnant women, however, discussions are underway regarding interval for boosting.

  3. iii. It is recommended that pregnant women receive a dose of Tdap vaccine after 20 weeks’ gestation (during the late second or third trimesters of pregnancy) for each pregnancy, regardless of prior immunization status or time interval since previous Tdap dose.

  4. iv. If a woman is unable to receive a dose of Tdap during pregnancy, postpartum administration of a dose of Tdap is a viable option for those women who have not received a previous Tdap dose. The dose should be given as soon as possible after delivery but before hospital discharge.

  5. v. Tdap vaccine is recommended for all adolescents starting at 11 to 12 years of age and all adults regardless of the interval from the last dose of Td vaccine.

  6. vi. Tdap vaccine is strongly recommended for all health-care workers that have any direct patient contact either in a hospital or clinic setting regardless of the interval from the last dose of Td vaccine.

Duration of immunity

The duration is 3 to 5 years after last dose of pertussis containing vaccine. Immunity is at best 10 years after natural infection.

Contraindications and precautions

Contraindications

  1. 1. Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) not attributable to another identifiable cause within 7 days of administration of a previous dose of DTP or DTaP (for DTaP); or a previous dose of DTP, DTaP, or Tdap (Tdap).

  2. 2. Severe immediate allergic reaction (e.g., anaphylaxis) to a prior dose of vaccine or to a vaccine component

Precautions

  1. 1. Moderate or severe acute illness with or without fever

  2. 2. Guillain-Barré syndrome (GBS) within 6 weeks after a previous dose of tetanus-toxoid-containing vaccine

  3. 3. Progressive or unstable neurologic disorder (including infantile spasms for DTaP), uncontrolled seizures, or progressive encephalopathy until a treatment regimen has been established and the condition has stabilized.

  4. 4. For DTaP only:

    1. a. Temperature of 105˚F or higher (40.5˚C or higher) within 48 hours after vaccination with a previous dose of DTP/DTaP

    2. b. Collapse or shock-like state (i.e., hypotonic hyporesponsive episode) within 48 hours after receiving a previous dose of DTP/DTaP

    3. c. Seizure within 3 days after receiving a previous dose of DTP/DTaP

    4. d. Persistent, inconsolable crying lasting 3 or more hours within 48 hours after receiving a previous dose of DTP/DTaP

Frequently asked questions

If a person (infant, child, or adult) has had a documented case of pertussis, can they get the disease again?

Reinfection is uncommon but it does occur. Symptoms with reinfection may present as only a persistent cough with little else.

If a person (infant, child, adolescent, or adult) has had pertussis disease, should they still be vaccinated with a pertussis-containing vaccine?

Yes. All persons who have a history of pertussis disease generally should receive pertussis-containing vaccines (DTaP or Tdap) according to the routine schedule. This is recommended because the amount and duration of protection induced by pertussis disease is unknown and because the diagnosis of pertussis can be difficult to confirm.

Which HCWs should be vaccinated against pertussis with tetanus-diphtheria-acellular pertussis (Tdap) vaccine?

The CDC recommends that all HCWs, regardless of age, should receive a dose of Tdap as soon as feasible if they have not previously received Tdap and regardless of the time since their last Td vaccine.

If a health-care worker (HCW) has been vaccinated with tetanus-diphtheria-acellular pertussis (Tdap) vaccine and is then has a significant exposure to someone with pertussis, does the vaccinated HCW need to be treated with prophylactic antibiotics or are they considered immune to the disease?

All HCWs who have a significant exposure to pertussis disease should receive antibiotic prophylaxis regardless of their immunization status. Effectiveness of Tdap in preventing pertussis in the health-care setting is currently unknown. Until studies can be performed that define the optimal management of exposed vaccinated HCWs, the CDC’s post-exposure prophylaxis protocol for pertussis exposure should be followed.

How many doses of pediatric diphtheria-tetanus-acellular pertussis (DTaP) vaccine does an infant need before they are protected from pertussis?

Vaccine efficacy following 3 doses of pediatric DTaP vaccine is 80% to 85%. Information regarding efficacy after 1 or 2 doses is limited, but efficacy is most likely lower. In order to protect the infant against pertussis prior to them receiving their 3-dose primary DTaP vaccine series, it is important that all people who live in the household with the infant and all those who provide care to them (e.g., babysitters, nannies, au pairs, and daycare providers) be protected against pertussis. It is recommended that these individuals receive a dose of adolescent/adult tetanus-diphtheria-acellular pertussis vaccine (Tdap) if they have not already done so.

What should be done in the situation where a 4-month-old infant inadvertently received a dose of adolescent/adult Tdap instead of pediatric DTaP?

If Tdap is inadvertently administered to a child under 7 years of age, it should not be counted as valid for the first, second, or third dose of DTaP (primary vaccine series). The dose should be repeated with a dose of DTaP and the routine vaccination schedule should be followed. If the dose of Tdap was administered for the fourth or fifth booster dose, the Tdap dose can be counted as valid.

What should be done in the situation where a 10-year-old child inadvertently received a dose of DTaP instead of Tdap?

DTaP given to patients age 7 years or older can be counted as valid for the Tdap dose.

What should be done in the situation where a 12-year-old patient received only 2 doses of DTP (whole cell pertussis vaccine) at 2 months and 4 months of age after developing persistent crying and a temperature of 105˚F following the second dose of DTP vaccine. Is it safe to give this patient a dose of Tdap vaccine?

Yes, it is safe to give a dose of Tdap vaccine. Many of the precautions to DTP and DTaP (e.g., temperature of 105˚F or higher, persistent crying lasting 3 hours of longer, seizure with or without fever, and hyporesponsive or shock-like state) do not apply to the Tdap vaccine.

A 2-month old received her first dose of DTaP vaccine and then developed inconsolable crying for greater than 3 hours. Should the infant receive additional doses of DTaP or should they be given DT vaccine?

Persistent crying following DTaP has been observed much less frequently than it was following the use of DTP (whole cell pertussis) vaccine. When it occurs following DTaP, it is considered a precaution. If the benefit of the pertussis vaccine exceeds the risk of persistent crying (which in itself is benign), one can administer additional doses of DTaP. Many providers choose to administer pertussis-containing vaccine if this is the only precaution the infant has experienced. The health-care provider and the parent will need to make this judgement.

Is there an upper age limit for Tdap administration?

There is no upper age limit for Tdap vaccination. A single dose of Tdap is recommended for all adults regardless of age.

Which adults should be vaccinated with a Tdap vaccine?

The CDC recommends that all adults age 19 years and older receive a dose of Tdap vaccine regardless of the interval since the last tetanus or diphtheria-toxoid containing vaccine (e.g., Td).

What should be done in the situation where a patient remembers receiving a “tetanus booster” several years ago at a convenient care clinic but no vaccination record is available and the patient does not remember if he received Td or Tdap. The patient’s wife is 37 weeks pregnant. Can the patient receive a dose of Tdap vaccine as a way to protect their soon to be born child against pertussis?

Yes. If vaccination is indicated and there is a lack of vaccine documentation, a dose of Tdap can be given to the patient.

If a pregnant woman got a dose of Td during pregnancy, how soon can she get her dose of Tdap?

She should have been given Tdap rather than Td; however, she can receive her Tdap at any interval since the Td dose was given, preferably between 27 and 36 weeks gestation.

If a woman received a dose of Tdap early in her pregnancy (e.g., in her first trimester), should she get another dose in the third trimester?

No, it is not recommended to give another dose of Tdap. The optimal timing for Tdap administration in pregnancy is between 27 and 36 weeks’ gestation because of the favorable transplacental antibody kinetics. Tdap may be administered at any time during pregnancy, but vaccination during the third trimester would provide the highest concentration of maternal antibodies to be transferred.

Should fathers and other family members receive a Tdap booster each time there is a pregnancy in the family to boost the cocoon effect to protect the newborn from pertussis?

At this time the CDC does not recommend additional doses of Tdap vaccine for fathers, other family members or caregivers. The recommendation for a dose of Tdap with each pregnancy only applies to the pregnant woman.

Can Tdap vaccine be given to breastfeeding mothers?

Yes. Women who have never received Tdap and who did not receive it during pregnancy should receive it immediately postpartum or as soon as feasibly possible. Breastfeeding does not decrease the immune response to routine childhood vaccine.

My practice is seeing a number of patients who are refugees or who have immigrated from other countries. What vaccine schedule should be used to vaccinate children, adolescents, or adults who have never received the primary series of tetanus-toxoid-containing vaccines?

Children 7 years of age and older, adolescents and adults who have never received tetanus-containing vaccines, or whose vaccination history is unknown, should receive a 3-dose vaccine series. The CDC recommends Tdap at 0, and Td at 4 weeks and at least 6 months. Tdap can be substituted for only one of the 3 Td doses in the series, preferably the first. The amount of protection provided by a single dose of Tdap in a person who has not previously received pertussis vaccine is not known. Following the primary series, booster doses of Td should be given every 10 years.

If a child has already received 5 appropriately spaced doses of DTaP (6-month intervals between doses #3 and #4 and doses #4 and #5) by their fourth birthday, should a booster dose be given after the fourth birthday?

As a rule, a child should receive no more than 4 doses of DTaP before 4 years of age. The CDC recommends that a dose of DTaP be given at 4 to 6 years of age. Many states have school immunization laws which require that at least one dose of DTP/DTaP be given on or after the fourth birthday. This dose is important to boost immunity to pertussis.

Influenza

Did you know that:

  • The word “influenza” comes from the Italian influentia because it was believed that the influence of the planets, moon, and stars caused the flu—for only such universal influence could explain such sudden and widespread illness.

  • Martin van Buren, the eighth president of the United States; Benjamin Harrison, the twenty-third president of the United States; Juan Peron, the former president of Argentina; Shoghi Effendi, the Guardian and appointed head of the Baha’i faith; and Sir William Osler, physician, educator, and medical philosopher all died from severe influenza infections.

  • The Spanish influenza pandemic of 1918 killed between 20 to 40 million people, which is more than the number that were killed during World War I. More people died in one year from this pandemic than in 4 years of the Black Death Bubonic Plague from 1347 to 1351. The death rate for 15 to 34-year-olds of influenza and pneumonia were 20 times higher in 1918 than in previous years. People were struck with illness on the street and died rapid deaths—“people on their way to work suddenly developing the flu and dying within hours.”

Influenza causes annual epidemics during the winter months with up to 20% of the US population becoming ill with influenza A or B viruses. Children are the most likely to acquire and transmit infection given that they are able to shed virus at very high titers and for prolonged periods of time (≥10 days). Up to 40% of healthy children become ill with influenza each year. However, the populations with the highest rates of serious disease, complications and deaths are persons ≥65 years of age, children <2 years of age, pregnant women, and persons of any age with underlying medical conditions. Each year, complications from influenza are responsible for >200,000 hospitalizations and an average of 36,000 deaths, with greater than 50% of the hospitalizations and 90% of the deaths occurring in persons ≥65 years of age. On a societal level, influenza is an extraordinarily expensive disease with an average of $10 billion dollars being spent each year on health care and work-loss costs.

The clinical presentation of influenza differs by age. The typical symptoms of the sudden onset of fever accompanied by chills or rigors, headache, malaise, diffuse myalgia, non-productive cough, sore throat, nasal congestion, and rhinorrhea are seen most commonly in the adolescent and adult populations. Children more commonly have fever, non-productive cough, rhinitis, nasal congestion, nausea, vomiting, abdominal pain and diarrhea. Symptoms in the elderly population are very nonspecific with cough and malaise being the most common. Symptoms in all age groups usually resolve after 3 to 7 days; however, cough and malaise may persist for >2 weeks.

Persons at increased risk for influenza complications

  • Children 6 to 59 months of age

  • Adults ≥ 50 years of age (especially persons ≥65 years of age)

  • Pregnant women

  • Adults and children with chronic pulmonary, renal, cardiovascular, hepatic, neurologic, hematologic, or metabolic disorders

  • Immunosuppressed patients (immunosuppressive medications, HIV infection)

  • Residents in long-term care facilities (of any age)

  • Health-care personnel

  • Morbidly obese people, BMI ≥40 kg/m2

  • Household contacts and caregivers of children <5 years (especially <6 months of age) and adults ≥50 years

  • Children and adolescents (6 months to 18 years) receiving long-term aspirin therapy

  • Immunization rates for all these at risk populations are well below the levels recommended by the Healthy People 2020 Goals.

Complications of influenza in the adult population

These complications include primary influenza pneumonia and/or secondary bacterial pneumonia, which may be necrotizing and is most often due to Staphylococcus aureus and Streptococcus pneumoniae; pneumonia may be especially severe in pregnant women; exacerbation of underlying pulmonary or cardiac disease; encephalitis; myositis; myocarditis; pericarditis; transverse myelitis; Guillain-Barré syndrome. Complications of influenza in the pediatric population include: acute otitis media; bronchiolitis; laryngotracheobronchitis; bacterial pneumonia, which may be necrotizing and is most often due to Staphylococcus aureus and Streptococcus pneumoniae; encephalitis and encephalopathy, which may be necrotizing; dehydration with severe hypotension; respiratory failure; myositis; transverse myelitis.

Influenza can be particularly severe in pregnant women. The risk of hospitalization for heart and lung problems is more than 4X higher in pregnant women compared to non-pregnant women and the risk increases exponentially as pregnancy progresses. This risk is further increased in women with asthma who are pregnant. For example, pregnant women infected with the 2009 H1N1 influenza virus were at very high risk for severe or fatal illness and were at significantly increased risk for fetal death, spontaneous abortions, and preterm delivery. In 2009 pregnant women represented 1% of the US population but accounted for 5% of the US deaths from H1N1 disease. Over 91% of the deaths occurred in women in their second and third trimesters of pregnancy.

Transmission

Person to person by respiratory droplets or by direct contact with articles contaminated with nasopharyngeal secretions via coughing and sneezing

Incubation period

Incubation period is 1 to 4 days (average 2 days). Adults are infectious from the day before symptoms begin through 5 days after illness onset. Children are infectious for several days before onset of symptoms through ≥10 days after illness onset.

Prevention

Post-exposure

  1. a. Influenza vaccine is the primary means of protecting persons against influenza disease and its complications, and can be administered at any time during influenza season, even when the virus is circulating in the community. Vaccines may be trivalent or quadrivalent. The trivalent vaccines contain two influenza A strains and one influenza B strain—there are several different formulations of the vaccine and method of administration that are available. Quadrivalent influenza vaccine (containing two influenza A strains and two influenza B strains) became available beginning in the 2013–2014 influenza season. Injectable and intranasal formations are available for this vaccine.

  2. b. Chemoprophylaxis with influenza antiviral drugs is an adjunctive measure, not a substitute, for immunization. It may be used in certain situations in order to control and prevent influenza disease. Situations in which chemoprophylaxis may be considered include:

    • Protection of unimmunized high-risk children or adults or children or adults who were immunized less than 2 weeks before influenza circulation in the community

    • Protection of children and adults at increased risk of severe infection or complications, such as high-risk populations for whom the vaccine is contraindicated

    • Protection of unimmunized close contacts of persons at high risk

    • Protection of immunocompromised persons who may not respond to vaccine

    • Control of influenza outbreaks in a closed setting, such as an institution with unimmunized high-risk persons

    • Protection of immunized high-risk persons if the vaccine strain poorly matches circulating influenza strains

Oseltamivir (oral) or zanamivir (inhaled) are the recommended anti-viral agents.

Preexposure

  1. a. Influenza vaccine—there are several different formulations of the vaccine and methods of administration that are available.

Influenza vaccines—United States, 2015–2016 influenza season

  • Inactivated influenza vaccine, quadrivalent (IIV4), standard dose

    • Fluarix Quadrivalent

    • FluLaval Quadrivalent

    • Fluzone Quadrivalent

    • Fluzone Intradermal Quadrivalent

  • Inactivated influenza vaccine, trivalent (IIV3), standard dose

    • Afluria

    • Fluvirin

    • Fluzone

  • Inactivated influenza vaccine, trivalent (IIV3), high dose

    • Fluzone High-Dose

  • Inactivated influenza vaccine, cell-culture-based (ccIIV3), standard dose

    • Flucelvax

  • Recombinant influenza vaccine, trivalent (RIV3), standard dose

    • FluBlok

  • Live, attenuated influenza vaccine, quadrivalent (LAIV4)

    1. i. Quadrivalent inactivated influenza vaccine (IIV4)—given as IM injection to any person ≥ 6 months of age. The American Congress of Obstetrics and Gynecology (ACOG) strongly recommends that all women who will be pregnant during influenza season receive a dose of inactivated influenza vaccine—IIV4 or IIV3. The vaccine may be given during any trimester of pregnancy. Contraindication: severe anaphylactic reaction to any vaccine component, including egg protein, or after previous dose of any influenza vaccine. Precautions: Moderate to severe acute illness with or without fever; history of Guillain-Barré syndrome within 6 weeks of receipt of influenza vaccine.

    2. ii. Quadrivalent, intradermal influenza vaccine—given as an intradermal injection using a novel microinjection system. Vaccine is licensed for use in persons 18 to 64 years of age. Needle used is only 1.5 mm in length—injection system allows for reliable delivery of an accurate dose of antigen into dermal skin layer (2 mm). There is no need to alter the injection technique or needle length based on patient age, gender, muscle mass, or BMI. Contraindication: severe anaphylactic reaction to egg or egg products.

    3. iii. Trivalent inactivated influenza vaccine (IIV3)—given as IM injection to any person ≥6 months of age. Contraindications and precautions the same as those for IIV4.

    4. iv. Trivalent inactivated influenza vaccine (IIV3)—high-dose—given as IM injection—this vaccine that contains 4 times the amount of influenza antigen in standard dose influenza vaccine. It stimulates older individuals to produce higher levels of antibody and provides enhanced protection against influenza illness. It is associated with a higher risk of local injection site reactions but no higher risk of serious adverse events. This vaccine is recommended for persons aged ≥ 65 years.

    5. v. Trivalent inactivated influenza vaccine, cell-culture-based (ccIIV3)—contraindications and precautions are the same as those for IIV3 and IIV4. It is not licensed for use in children <18 years of age.

    6. vi. Trivalent recombinant influenza vaccine (RIV3)—this is the only influenza vaccine that is egg free. It is contraindicated in anyone with a history of a severe allergic reaction to any vaccine component, but safe for use in individuals with serious egg allergy. It is not licensed for use in children <18 years of age.

    7. vii. Trivalent, intradermal influenza vaccine—given as an intradermal injection using a novel microinjection system. Vaccine is licensed for use in persons 18 to 64 years of age. Needle used is only 1.5 mm in length—injection system allows for reliable delivery of an accurate dose of antigen into dermal skin layer (2mm). There is no need to alter the injection technique or needle length based on patient age, gender, muscle mass, or BMI.

    8. viii. Quadrivalent live attenuated, cold adapted influenza vaccine (LAIV)—given as a nasal spray. This vaccine is recommended only for healthy persons 2 to 49 years of age. Contraindications include: pregnancy, hives or anaphylaxis to egg or egg products, persons with known or suspected immunodeficiencies and children aged 2 through 4 years who have asthma or who have had a wheezing episode noted in the medical record within the past 12 months, or for whom parents report that a health-care provider stated that they had wheezing or asthma within the last 12 months.

Egg allergic patients

Egg allergy of any severity (including anaphylaxis) is no longer considered a contraindication or precaution to receiving injectable inactivated (IIV) or live, attenuated, intranasal (LAIV) influenza vaccines. Multiple published studies involving greater than 4,100 egg allergic patients (including those with severe anaphylactic reactions to egg) who have received IIV and over 1,200 egg allergic patients who have received LAIV have shown that these patients have tolerated the vaccines well with no hives or anaphylaxis. The CDC and the AAP Committee on Infectious Diseases have reviewed the data and feel that it supports that egg allergy does not impart an increased risk of anaphylactic reaction to immunization with either IIV or LAIV. Immediate hypersensitivity reactions such as urticarial or anaphylaxis may occur, however, these are no more common in egg-allergic than non-egg-allergic vaccine recipients. Anaphylactic reactions after influenza vaccine occur at the same rate as with other vaccines (about 1 per million persons vaccinated) whether the recipient is egg allergic or not and whether the vaccine contains egg or not. Special precautions regarding the medical setting and waiting period after administration of IIV or LAIV to egg allergic recipients beyond those recommended for any vaccine are not warranted. Persons with egg allergy of any severity can be safely vaccinated with IIV or LAIV in any setting.

Efficacy

The efficacy and effectiveness of influenza vaccines depend primarily on the age and immunocompetence of the vaccine recipients and the degree of similarity between the viruses in the vaccine and those circulating in the community. Efficacy in persons 2 years of age and older ranges from 50% to 95%. LAIV use was not recommended during the 2016–2017 influenza season because of low effectiveness during the 2013–2014 and 2014–2015 seasons.

Duration of protection

Duration of protection is 6 to 12 months—annual vaccination is critical to maintain protection against influenza in all populations.

Contraindications and precautions to influenza vaccines

Contraindications

  1. I. For inactivated, recombinant, and live, attenuated vaccines

    1. 1. Severe allergic reaction (e.g., anaphylaxis) after previous dose of any influenza vaccine; or to a vaccine component

  2. II. Additional contraindications for live, attenuated vaccine

    1. 1. Pregnant women

    2. 2. Immunosuppressed persons

    3. 3. Persons that have taken influenza antiviral medications (amantadine, rimantadine, zanamivir, or oseltamivir) within the previous 48 hours; avoid use of these antiviral drugs for 14 days after vaccination

    4. 4. Asthma or a wheezing episode noted in the medical record within the past 12 months in children ages 2 through 4 years of age

Precautions

  1. I. For inactivated, recombinant, and live, attenuated vaccines

    1. 1. Moderate or severe acute illness with or without fever

    2. 2. History of Guillain-Barré syndrome within 6 weeks of previous influenza vaccination

  2. II. Additional precautions for live, attenuated vaccine

    1. 1. Asthma in persons aged 5 years and older

    2. 2. Other chronic medical conditions such as other chronic lung disease, chronic cardiovascular disease (excluding isolated hypertension), diabetes, chronic renal or hepatic disease, hematologic disease, neurologic disease, and metabolic disorders

Frequently asked questions

What are the benefits of the flu vaccine?

Flu vaccination reduces the risk of influenza illness in recipients and protects those around recipients who may be more vulnerable to serious flu illness. Influenza vaccination also may make illness milder if someone does get sick and reduce the risk of more serious outcomes, like hospitalizations and deaths. Recent studies showed that flu vaccine reduced children’s risk of flu-related pediatric intensive care unit (PICU) admission by 74% and flu-related hospitalizations among adults by 71% during the 2011–2012 flu season. Vaccination has been associated with lower rates of some cardiac events among people with heart disease, especially among those who had had a cardiac event in the past year.

Does protection from seasonal influenza vaccine decline several months after vaccination? Should I wait until flu season starts to vaccinate my elderly or medically frail patients?

Antibody to seasonal inactivated influenza vaccine does decline in the months following vaccination, but it should still be high enough to provide protection through the end of the season. Because the onset of flu season is unpredictable, seasonal influenza vaccine should be administered ideally by October. To avoid missed opportunities, offer vaccination during routine health care visits and hospitalizations when vaccine is available.

How long does immunity from seasonal influenza vaccine last?

Protection from influenza vaccine usually persists for about a year, although antibody persistence may be shorter for persons aged 65 and older. Vaccination is recommended on an annual basis because of waning antibody titers and because of changes in the circulating influenza viruses from year to year.

When should I stop offering influenza vaccination?

Continue to offer flu vaccine as long as influenza viruses are circulating in the community. The peak of influenza activity usually occurs in January or February in the United States. It is recommended that providers continue to vaccinate persons into the spring (typically through May).

If an unvaccinated patient has just recovered from a confirmed case of influenza, should that person be vaccinated with influenza vaccine?

Yes. Influenza vaccines contain 3 or 4 influenza strains, two influenza A strains, and one or two influenza B strains. Infection with one virus type does not confer immunity to other virus types and it is not unusual to be exposed to more than one strain during a typical influenza season. So a person who recently had influenza will benefit from a vaccine containing additional influenza virus strains.

Is Guillain-Barré syndrome an important risk for patients receiving influenza vaccination?

A significantly increased risk of GBS was reported in association with the swine flu vaccine in 1976. The reasons for that are unclear but since that time, the risk of GBS following flu vaccination has been estimated to be about 1 in 1,000,000 flu vaccine recipients. GBS is a risk following stimulation of the immune system whether by immunization or illness. Influenza illness is associated with a significantly greater risk of GBS than influenza vaccination, and the overall benefits of influenza vaccination far outweigh the risk of GBS.

Is influenza vaccine safe to administer to patients with multiple sclerosis?

Yes. Multiple sclerosis is not a contraindication to receiving any vaccine, including influenza vaccine. These patients should receive the inactivated influenza vaccine and not the live, attenuated influenza vaccine.

What type of influenza vaccine is recommended for pregnant women?

Pregnant women can receive any of the inactivated injectable vaccines. They should not be given the live, attenuated intransal influenza vaccine. It is important to vaccinate pregnant women during any trimester because of the increased risk of influenza-related complications, hospitalizations, and death. Vaccinating pregnant women protects the woman, her unborn baby, and the baby following birth from influenza disease.

What vaccine if any should I offer a patient with a history of egg allergy?

Persons able to eat a lightly cooked (e.g., scrambled) egg are unlikely to be allergic to eggs. Persons with a history of only hives can be offered inactivated influenza vaccine (IIV) with observation for at least 30 minutes for a reaction following administration or the egg-free preparation recombinant influenza vaccine (RIV) (Flublok). Those with a history of angioedema, respiratory distress, lightheadedness or recurrent emesis should be offered RIV. Persons with history of severe allergic reaction to flu vaccine should not receive flu vaccine again, regardless of the component suspected to be responsible for the reaction.

What is the value of high-dose flu vaccine?

High dose flu vaccine has been associated with significantly higher antibody responses and better protection against laboratory-confirmed influenza illness (24% efficacy in one large study) in persons ≥65 years.

What is the value of quadrivalent over trivalent influenza vaccines?

Quadrivalent flu vaccines cover an additional influenza B strain and should offer broader protection.

Who should not receive the live, attenuated influenza vaccine?

The following persons should not receive LAIV:

  • children aged <2 years

  • adults aged ≥50 years

  • children aged 2 through 4 years with a wheezing episode during the preceding 12 months

  • persons with asthma

  • children and adults who have chronic pulmonary, cardiovascular (except isolated hypertension), renal, hepatic, neurologic/neuromuscular, hematologic, or metabolic disorders

  • immunosuppressed children and adults (including immunosuppression caused by medications or by HIV)

  • pregnant women.

Patients will refuse influenza vaccination because they insist they “got the flu” after receiving the injectable vaccine in the past. How can I respond?

This misconception persists for several reasons: 1) Less than 1% of persons vaccinated with the injectable inactivated influenza vaccine develop flulike symptoms, such as mild fever and muscle aches after vaccination. These side effects are not the same as having influenza infection, but people commonly confuse the symptoms as being the same. 2) Protective immunity does not develop until 1 to 2 weeks after vaccination. Some people vaccinated later in the season may be infected with influenza virus shortly after receiving the vaccine before immunity is established. 3) Many people believe that “the flu” is any illness with fever and cold symptoms. If they get any viral respiratory illness, they blame it on the vaccine or believe that got “the flu” despite being vaccinated. Influenza vaccine protects against certain influenza viruses, not all viruses. 4) The influenza vaccine is not 100% effective, especially in older adults.

Can high-dose influenza vaccine be administered to patients younger than 65 years of age with chronic underlying conditions (e.g., HIV, immunodeficiency)?

No. The high-dose influenza vaccine is only licensed for persons aged 65 and older and is not recommended for younger persons with underlying medical conditions.

Can a person aged 65 or older who has already received a standard-dose influenza vaccine also receive a dose of high-dose influenza vaccine in the same influenza season?

No. It is not recommended that anyone receive more than one dose of influenza vaccine in the same season except for infants and children age 6 months to 8 years who are receiving influenza vaccine for the first time and for whom two doses of vaccine are recommended.

How soon after a bone marrow transplant can patients be vaccinated against influenza?

Inactivated influenza vaccine should be administered beginning 6 months after bone marrow transplant and annually thereafter.

Which health-care providers should be vaccinated against influenza?

It is important to vaccinate all hospital, outpatient, nursing home and chronic care facility health-care personnel with influenza vaccine, especially those that have direct patient contact. Vaccine response is diminished in elderly and immunosuppressed persons and evidence suggests vaccinating health-care personnel may be even more effective than vaccinating the patients themselves.

Which health-care personnel can receive the live, attenuated influenza vaccine (LAIV)?

LAIV can be administered to all healthcare personnel for whom it is indicated based on age and health history except those who care for severely immunocompromised patients in a protected (reverse air flow) environment.

If a patient is allergic to chicken or duck feathers is this a contraindication to receiving an egg-based influenza vaccine?

No.

Can LAIV be administered to persons with a mild upper respiratory infection with or without fever?

Yes, unless it is clinically deemed that the patient’s nasal congestion would interfere with the delivery of the vaccine to the nasopharyngeal mucosa. In this case, administration of the vaccine should be deferred until the congestion resolves.

Can a woman who is breastfeeding receive LAIV?

Yes. Breastfeeding is not a contraindication for the receipt of any routine vaccine including LAIV. Postpartum maternal vaccination against influenza is associated with a significant reduction in illness, doctor visits and antibiotic prescriptions in infants during influenza season.

Can LAIV be given to contacts of immunosuppressed patients?

Household members, healthcare personnel and others with close contact to severely immunosuppressed individuals during periods in which the immunosuppressed person requires care in a protective environment should preferentially receive inactivated influenza vaccine.

What should be done in the situation when a young patient is only able to receive half the dose of the live attenuated intranasal vaccine (LAIV)?

A half dose of LAIV or any vaccine is a non-standard dose and should not be counted. If the second half of the dose is not administered at the same appointment, another full dose of influenza vaccine should be administered at another time. A dose of inactivated influenza vaccine can be administered at any time after the half dose of LAIV. If LAIV is given again, wait 4 weeks before administering another live vaccine.

What should be done is the situation when a patient believes they had a reaction to the influenza vaccine in the past and requests that the vaccine dose be split into 2 doses administered on different days?

This is not an acceptable practice. Doses of influenza vaccine or any other vaccine should not be split in half or partial doses. If a half or partial dose is administered, it is not counted as a valid dose and should be repeated as soon as possible with a full age-appropriate vaccine dose.

What should be done if a dose of intradermal influenza vaccine is administered to a patient that is not in the recommended age range of 18 to 64 years of age?

Persons younger than 12 years and older than 65 are more likely to have skin that is too thin for proper intradermal administration of the vaccine. A dose given to persons in these age ranges should be considered invalid and the patient should be revaccinated with an age appropriate dose of vaccine. For person age 12 to 17 years, the dose can be considered valid and does not have to be repeated if the health-care provider is certain that the dose was administered intradermally and not subcutaneously. If there is any doubt whether the dose was injected intradermally, the dose should be repeated with an age-appropriate vaccine.

If a patient has already received a dose of seasonal trivalent influenza vaccine, is it acceptable to administer an additional dose of the quadrivalent influenza vaccine to this patient?

No, the CDC does not recommend more than one dose of influenza vaccine in a season, except for certain children ages 6 months through 8 years of age for whom two doses are recommended if this is the first season they are receiving influenza vaccine.

Which persons who are traveling abroad should influenza vaccine be given?

Health-care providers should vaccinate any person who failed to get vaccinated during the influenza season and who wants to reduce their risk of acquiring influenza during their travels. This includes persons who are traveling to the tropics, traveling with organized tourist groups at any time of the year or in the Southern Hemisphere from April through September.

If a patient received a dose of influenza vaccine in May for international travel, how long should the patient wait before getting vaccinated with the next season’s influenza vaccine?

There should be a minimum of 4 weeks between the doses of influenza vaccine.

If a child needs 2 doses of influenza vaccine, can they receive 1 dose of injectable vaccine and 1 dose of the nasal spray vaccine?

Yes, as long as the child is eligible to receive nasal spray vaccine, it is acceptable to receive 1 dose of each type of influenza vaccine as long as the doses are spaced at least 4 weeks apart.

Can high dose influenza vaccine be administered to patients younger than 65 years of age with chronic underlying conditions (e.g., HIV, immunodeficiencies)?

No. The high dose influenza vaccine is only licensed for people age 65 years and older and is not recommended for younger persons with chronic underlying conditions.

Can a person age ≥65 years who has already received standard-dose influenza vaccine, also receive a dose of high dose influenza vaccine during the same influenza season?

No. It is not recommended that anyone receive more than one dose of influenza vaccine in the same season except for certain infants and children age 6 months through 8 years who are receiving influenza vaccine for the first time and for whom two doses are recommended.

If high dose influenza vaccine is not available, can 2 doses of standard-dose influenza vaccine be given to a person age ≥ 65 years in place of the high dose influenza vaccine?

No. This is not the same as high dose influenza vaccine and is not recommended.

References

Des Roches A, Paradis L, Gagmon R, et al. Egg-allergic patients can be safely vaccinated against influenza. J Allergy Clin Immunol 2012;130:1213–1216.Find this resource:

The Joint Task Force on Practice Parameters. Update on influenza vaccination of egg allergic patients. Ann Allergy, Asthma & Immunol 2013;111:301–302.Find this resource:

Des Roches A, Samaan K, Graham F et al. Safe vaccination of patients with egg allergy by using live attenuated influenza vaccine. J Allergy Clin Immunol Pract 2015;3:138–139.Find this resource:

Turner PJ, Southern J, Andrews NJ, et al. Safety of live, attenuated influenza vaccine in atopic children with egg allergy. J Allergy Clin Immunol 2015;136:376–381.Find this resource:

Turner PJ, Southern J, Andrews NJ, et al. Safety of live, attenuated influenza vaccine in young people with egg allergy: multicenter prospective cohort study. BMJ 2015;351:h6291.Find this resource:

Kelso JM. Administering influenza vaccine to egg-allergic persons. Expert Rev Vaccines 2014;13:1049–1057.Find this resource:

Hepatitis A

Did you know that:

  • In 1988 an epidemic of hepatitis A in Shanghai, China, attributed to the consumption of raw clams affected 300,000 persons in a two-month period.

  • Hepatitis A vaccination was first introduced in the United States in 1995, expanded to 17 “high-risk” states in 1999, and to all children aged 12 to 23 months of age in 2006. The incidence of hepatitis A has declined to an all-time low in recent years. The most susceptible population is now older adults in whom disease is typically more severe.

Hepatitis A virus is the cause of 20% to 40% of viral hepatitis cases in the Western world. The majority (over 70%) of cases in infants and children under 6 years of age are asymptomatic. Hepatitis A is the cause of an acute, self-limited illness associated with fever, malaise, jaundice, anorexia, and nausea that resolves in 2 months or less. Ten to 15% of symptomatic persons have prolonged or relapsing disease that may last as long as 6 months.

Hepatitis A infection in pregnancy may be associated with a high risk of maternal complications including: premature contractions, preterm labor, premature rupture of membranes, placental separation, vaginal bleeding, fetal distress and low birthweight infants.

Rates of hepatitis A in the United States are the lowest they have been in 40 years. The hepatitis A vaccine was introduced in 1995, and health professionals now routinely vaccinate all children, travelers to certain countries, and persons at risk for the disease. The use of hepatitis A vaccination has dramatically decreased rates of the disease in the United States (Figure 7).


Figure 7 Incidence of hepatitis A, by year, United States, 1980–2013

Figure 7 Incidence of hepatitis A, by year, United States, 1980–2013

Transmission:

  1. 1. Direct person to person contact via fecal-oral route

  2. 2. Ingestion of contaminated food or water

  3. 3. Oral or anal sex

Hepatitis A viruses persist in the environment and can withstand food-production processes routinely used to inactivate bacterial pathogens.

Incubation period

Incubation period is on average 28 days (range: 15 to 50 days).

Prevention

Post-exposure

  1. a. Administration of intramuscular immunoglobulin—if given within 2 weeks after exposure is greater than 85% effective in preventing symptomatic hepatitis A infection. Recommended to be administered to persons younger than 12 months of age, persons of any age who are immunocompromised or have chronic liver disease, and is preferred for persons 41 years of age and older.

  2. b. Hepatitis A vaccine—if given within 2 weeks after exposure is greater than 85% effective in preventing symptomatic Hepatitis A infection. Recommended to be administered to persons 12 months through 40 years of age. May be used in persons 41 years of age and older if immunoglobulin not available.

Preexposure

  1. a. Hepatitis A vaccine—licensed for persons 12 months of age and older

  2. b. Immunoglobulin—persons younger than 12 months of age

Vaccine: Given intramuscularly as a 2 dose series at 0 and 12-18 months. Vaccine should not be given to those persons with hypersensitivity to any of the vaccine components.

Immunogenicity

95% after 1 dose, >99% after 2 doses

Duration of protection

At least 10 years after 2-dose series, but felt to be lifelong.

Contraindications and precautions to hepatitis A vaccine

Contraindications

  • Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component

Precautions

  • Moderate or severe acute illness with or without fever

Frequently asked questions

How stable is hepatitis A virus (HAV) in the environment?

Depending on the environmental conditions, HAV can remain stable in the environment for months. Heating foods at temperatures greater than 185˚F (85˚C) for 1 minute or disinfecting surfaces with a 1:100 dilution of bleach in tap water will inactivate HAV.

Can people with HAV develop chronic disease?

Unlike hepatitis B and hepatitis C viruses, HAV does not cause chronic, long-term infection. Once you have had HAV infection and recover, you cannot get it again.

Should prevaccination testing be performed before administering Hepatitis A vaccine?

Prevaccination testing is recommended only in specific circumstances to reduce the costs of vaccinating people who are already immune to hepatitis A, including

  • Persons born in geographic areas with high prevalence of HAV infection

  • Older adolescents and adults in certain population groups (i.e., American Indians, Alaska Natives, and Hispanics)

  • Adults in groups that have a high prevalence of infection (e.g., injection drug users)

Prevaccination testing might also be warranted for all older adults. The decision to test should be based on (1) the expected prevalence of immunity, (2) the cost of vaccination compared with the cost of serologic testing, and (3) the likelihood that testing will not interfere with vaccination.

Should postvaccination HAV titers be performed after a person has received the 2-dose vaccine series?

No. Postvaccination testing is not indicated because of the high rate of vaccine response among vaccine recipients. Also, not all testing methods approved for diagnostic use in the United States have the sensitivity to detect low, but protective, anti-HAV concentrations after vaccination.

Should health-care workers (HCWs) be routinely vaccinated against hepatitis A?

No. Studies have shown that HCWs are not at increased risk of HAV infection due to their occupation. The only HCWs for whom hepatitis A vaccine is routinely recommended are those who work with live HAV or with primates.

Should daycare workers be routinely vaccinated against hepatitis A?

No. Child care centers may be the source of outbreaks of hepatitis A in certain communities, HAV disease in child care centers more commonly reflects transmission from the community.

Can a breastfeeding woman receive hepatitis A vaccine?

Yes. Hepatitis A vaccine is an inactivated vaccine that poses no harm to the breastfeeding infant.

What should be done in the situation in which an adult patient inadvertently receives a dose of pediatric hepatitis A vaccine?

As a general rule, if a patient is given a vaccine dose that is less than a full age-appropriate dose of any vaccine, the dose is invalid and the patient should be revaccinated with the age appropriate dose as soon as feasible. However, there are 2 exceptions to the general rule:

  1. 1. If a patient sneezes after receiving nasal spray live, attenuated influenza vaccine, the dose is counted as valid.

  2. 2. If an infant regurgitates, spits up, or vomits during or after receiving oral rotavirus vaccine, the dose is counted as valid.

If a patient receives more than an age-appropriate dose of a vaccine (e.g., infant receiving adult dose of HAV), the dose is counted as valid and caution must be taken not to repeat the error. Using larger than recommended doses can be hazardous because of excessive local or systemic concentrations of antigens or other vaccine constituents.

Can someone donate blood if they have had hepatitis A?

If a patient had hepatitis A before age 11 years of age, they may donate blood; if they were 11 years of age or older, they cannot donate blood.

When does protection from hepatitis A vaccine commence?

Protection begins approximately 2 to 4 weeks after the first vaccine dose. A second booster dose results in long-term protection.

Your patient is leaving for their trip abroad in a few days. Can they still get the hepatitis A vaccine?

The first dose of hepatitis A vaccine can be given at any time before departure and will provide some protection for most healthy people.

Who should receive post-exposure prophylaxis (PEP) after exposure to hepatitis A?

People who might benefit from PEP include those who:

  • Live with someone who has hepatitis A

  • Have recently had sexual contact with someone who has hepatitis A

  • Have recently shared injection or non-injection illegal drugs with someone who has hepatitis A

  • Have had ongoing, close personal contact with a person with hepatitis A, such as a regular babysitter or caregiver

  • Have been exposed to food or water known to be contaminated with HAV

Is it harmful to administer an extra dose(s) of hepatitis A vaccine or to repeat the entire vaccine series if documentation of vaccination history is unavailable?

No. If necessary, administering extra doses of hepatitis A vaccine is not harmful.

What are the current CDC guidelines for post-exposure protection against Hepatitis A?

Persons who have recently been exposed to HAV and who have not been vaccinated previously should be administered a single dose of hepatitis A vaccine or IG (0.02 mL/kg) as soon as possible and within 2 weeks after exposure.

  • For healthy persons aged 12 months to 40 years, hepatitis A vaccine is preferred to IG because of the vaccine’s advantages (long-term protection, ease of administration, and equivalent efficacy).

  • For persons aged 40 years and older, IG is preferred because of the absence of data regarding vaccine performance in this age group and because of the more severe manifestations of hepatitis A in older adults.

  • Vaccine can be used if IG cannot be obtained.

  • IG should be used for children aged less than 12 months, immunocompromised persons, persons with chronic liver disease, and persons who are allergic to the vaccine.

Hepatitis B

Did you know that:

  • Despite the availability of an effective vaccine, worldwide, hepatitis B virus (HBV) infection kills a person every 30 to 45 seconds.

  • HBV is 100 times more infectious than HIV.

  • An estimated 350 million people worldwide are chronically infected with HBV and 15% to 40% will develop severe serious sequelae (e.g., cirrhosis, liver failure, and hepatocellular carcinoma) during their lifetime.

There are an estimated 46,000 new cases of hepatitis B virus (HBV) infection reported each year in the United States; however, the CDC recognizes that this only accounts for 10% of the cases. Adults 30 to 49 years of age account for the majority of the new cases being reported. Hepatitis B infection accounts for 2,000 to 4,000 deaths each year primarily due to cirrhosis and liver cancer. The likelihood of developing symptoms of acute hepatitis is age dependent: <1% of infants younger than 1 year of age, 5% to 15% of children 1 to 5 years of age, and 30% to 50% of people older than 5 years of age are symptomatic. The spectrum of signs and symptoms includes subacute illness with nonspecific symptoms (e.g., anorexia, nausea, or malaise), clinical hepatitis with jaundice, or fulminant hepatitis, and extrahepatic manifestations such as arthralgia, arthritis, macular rashes, thrombocytopenia, polyarteritis nodosa, glomerulonephritis, or papular acrodermatitis (Gianotti-Crosti syndrome).

Risk factors for hepatitis B infection include:

  • Travelers to countries where HBV infection is highly endemic

  • Persons adopting or fostering children from countries where HBV infection is highly endemic

  • Household contacts and sexual partners of person with HBV acute infection or chronic carriers

  • Tattooing, piercing, or other forms of body modification

  • Health-care, public safety workers exposed to blood and other fluids

  • Staff and patients of institutions for the developmentally disabled, assisted-living facilities, and nursing homes

  • Correctional facilities

  • Persons with end-stage renal disease, chronic liver disease, DM, HIV, or hemodialysis patients

  • Men who have sex with men

  • Persons seeking evaluation or treatment for a sexually transmitted infection especially HIV and syphilis

  • Current or recent injection-drug users

  • Sexually active persons with multiple sexual partners

60% of persons infected with HBV do not have an identifiable risk factor.

Age at time of acute infection is the primary determinant of the risk of progression to chronic infection.

  • Risk is 5% if HBV infection is acquired as an adult.

  • Risk is 30% to 50% if the infection is acquired as a child <5 years of age.

  • Risk is >90% if infection is acquired as neonate.

Transmission

Hepatitis B is transmitted through percutaneous and permucosal exposure to infected blood and body fluids (including serum, semen, vaginal secretions, CSF, synovial, pleural, pericardial, peritoneal, and amniotic fluids) with serum, semen, vaginal secretions, and amniotic fluid being the most infectious. The most common modes of transmission are parenteral, sexual, and perinatal.

Incubation period

Incubation period is on average 90 days (range 45 to 160 days).

Hepatitis B and pregnancy

Women who are pregnant and have an acute hepatitis B infection are at increased risk for having a premature or low birthweight infant. Universal screening of all pregnant women for HBsAg, regardless of HBV vaccination history, is strongly recommended and should be performed during an early prenatal visit with every pregnancy. Perinatal transmission poses an extremely high risk to the infant for developing chronic disease and its complications. There are an estimated 20,000 infants each year born to women known to be infected with HBV infection (remember that only 10% of cases in adults are reported so that vast majority of cases are unrecognized). Perinatal transmission of HBV is highly efficient and usually occurs from blood exposure during labor and delivery. In the absence of post-exposure treatment, 6,000 of the 20,000 infants would develop chronic infection, and 25% will die prematurely from HBV-related hepatocellular carcinoma or cirrhosis.

If a mother is HBsAg positive at time of delivery, 20% of infants born to these mothers will be infected with HBV—in the absence of post-exposure treatment, 90% of these infants will go on to become chronic carriers.

If a mother is HBsAg positive and HBeAg positive (marker for transmissibility—very high viral loads) at the time of delivery, 70% to 90% of infants born to these mothers will be infected with HBV—in the absence of post-exposure treatment, >90% of these infants will go on to become chronic carriers.

Prevention

Postexposure

  1. a. Perinatal—hepatitis B immune globulin (HBIG) given within 12 hours of birth and a dose of HBV vaccine—use of this regimen is 95% effective in preventing transmission of HBV to infant. Standard immune globulin (IG) is not effective for postexposure prophylaxis against HBV infection because concentrations of hepatitis B antibodies are too low.

  2. b. Discrete exposure to an HBsAg-positive source (e.g., percutaneous—needlestick, bite, nonintact skin or mucosal exposure to HBsAg positive blood or body fluids; sexual contact or needle sharing with HBsAg positive person; victim of sexual assault/abuse by a person who is HBsAg positive)—HBIG and hepatitis B vaccine to complete series

  3. c. Household contact of HBsAg positive person or exposure to a source with unknown HBsAg status—administer hepatitis B vaccine series

Preexposure

  • Administer hepatitis B vaccine series—given intramuscularly as 3-dose series at 0, 1, and 6 month intervals.

Vaccine efficacy

Efficacy is 90% to 95% after 3 doses for preventing HBV infection and clinical HBV disease.

Duration of protection

At least 20 years but probably lifelong. Confers protection against clinical illness and chronic HBV infection.

Vaccine contraindications and precautions

Contraindications

  • Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component.

Precautions

  • Moderate or severe acute illness with or without fever

Frequently asked questions

Can hepatitis B virus (HBV) be transmitted in the daycare setting by the saliva of drooling infants?

HBV has been found in saliva, but there is no data indicating that saliva exposure alone can transmit a HBV infection. If a HBV-infected person bites another person, HBV can be transmitted; however, it is the blood in the infected person’s mouth from the bite that was the likely vehicle of transmission. HBV is not spread by casual contact, sneezing, kissing, coughing, sharing eating utensils or drinking containers, or by food or water.

Can a patient who had an acute hepatitis B infection that was completely resolved ever get hepatitis B infection again?

In general, the answer is no. However, it is possible for this person to acquire a different HBV variant or subtype as the cause of the second infection. This would be a very rare occurrence.

I run a clinic for patients who are chronic hepatitis B carriers. How stable is HBV in the environment, and what type of disinfectant should I use to clean my waiting room and exam rooms?

HBV is very stable in the environment and remains viable for 7 or more days on environmental surfaces at room temperature. It is capable of transmitting HBV infection despite the absence of visible blood. Any disinfectant that is tuberculocidal will kill HBV.

What screening blood test should be done in pregnant women to prevent perinatal HBV infection?

Screening should be done with the hepatitis B surface antigen (HBsAg) test only. This test will determine whether a woman currently has a HBV infection that she can transmit to her infant. Other HBV tests such as antibody to hepatitis B core antigen (anti-HBc) and hepatitis B surface antibody (anti-HBs) are not useful when screening to prevent perinatal HBV infections and should not be used in the screening process.

If a woman has been previously vaccinated against HBV infection does she still need to screened for HBV during pregnancy?

Yes. Women who have received hepatitis B vaccine should still be screened for HBsAg early in each pregnancy. Just because she is vaccinated does not mean that she is HBsAg negative.

Can a pregnant woman receive hepatitis B vaccine?

Yes. Current hepatitis B vaccines contain noninfectious HBsAg and pose no risk to the developing fetus.

How should an infant be managed if their mother’s HBsAg test result is not available at the time of birth?

  1. 1. Women without documentation of HBsAg test results at the time of admission for delivery should have blood drawn and tested as soon as possible after admission.

  2. 2. All infants born to women without documentation of HBsAg test results should receive the first dose of single-antigen hepatitis B vaccine (without HBIG) by 12 hours of age.

  3. 3. If the mother is found to be HBsAg positive, her infant should receive HBIG as soon as possible but no later than 7 days of age, and the HBV vaccine series should be completed according to the recommended schedule for infants born to HBsAg positive mothers.

  4. 4. If the mother is found to be HBsAg negative, the infant’s HBV vaccine series should be completed according to the recommended schedule.

Is it safe for an HBsAg positive mother to breastfeed her infant?

Yes. An HBsAg positive mother should be encouraged to breastfeed her infant if she wishes to do so. The infant should receive HBIG and hepatitis B vaccine within 12 hours of birth. Even though HBV can be detected in breast milk, studies have shown that breastfed infants born to HBsAg positive mothers do not have an increased rate of perinatal or early childhood HBV infection.

What should be done in the situation where an infant inadvertently receives a dose of the adult formulation of hepatitis B vaccine?

The adult formation of hepatitis B vaccine contains twice the amount of antigen compared to a dose of the infant/child formulation. If an infant receives an adult dose of the hepatitis B vaccine, the dose is counted as valid and does not need to be repeated. Hepatitis B vaccine is a very safe vaccine and no adverse events would be expected. The next age appropriate dose should be given on the routine schedule.

Is post-vaccination serologic testing recommended for adults who receive hepatitis B vaccine?

Testing is not necessary after routine vaccination of adults. Serologic testing for immunity after vaccination is recommended only for people whose subsequent clinical management depends on knowledge of their immune status. Post-vaccination testing is recommended for: health-care and public safety workers at increased risk for continued exposure to blood on the job; immune compromised individuals; and sex and needle sharing partners of HBsAg positive persons. Testing should be performed 1 to 2 months after the last dose of vaccine. However, CDC does not recommend routine testing of health-care personnel who were not tested within the 1- to 2-month postvaccination time period. Health-care personnel who are exposed to HBV can be tested as part of postexposure management.

What should be done in the situation where a person has received an appropriate 3-dose series of HBV vaccine but their anti-HBs (HBsAb) titer is negative (less than 10 mIU/mL)?

Repeat the 3-dose HBV vaccine series, and the person should be tested for anti-HBs 1 to 2 months after the third dose of the vaccine. If the anti-HBs test is still negative after the second vaccine series, the person should be tested for HBsAg and anti-HBc to determine their HBV infection status. People who test negative for HBsAg and anti-HBc should be considered vaccine non-responders and susceptible to HBV infection. These patients should be counseled about precautions to prevent HBV infection and the need to obtain hepatitis B immunoglobulin (HBIG) prophylaxis for any known or likely exposure to HBsAg-positive blood. Persons found to be HBsAg negative but anti-HBc positive were infected in the past and require no vaccination or treatment.

Measles

Did you know that:

  • The 7-year-old daughter of Roald Dahl, the British author of Charlie and the Chocolate Factory, died from a measles infection in 1962, the year before a measles vaccine became available. Dahl went on to become a strong supporter of vaccines: “In my opinion parents who now refuse to have their children immunized are putting the lives of those children at risk. In America, where measles immunization is compulsory, measles like smallpox, has been virtually wiped out. Here in Britain, because so many parents refuse, either out of obstinacy or ignorance or fear, to allow their children to be immunized, we still have a hundred thousand cases of measles every year.”

  • Currently on a worldwide basis, 13 people die from measles every hour; measles continues to kill 430 children each day.

Measles virus causes an acute viral illness characterized by fever, cough, conjunctivitis, coryza, pharyngitis, erythematous maculopapular rash (starts on forehead around hairline and spreads centrifugally from the head to the feet, becoming confluent), lymphadenopathy (cervical, suboccipital and postauricular), and Koplik spots (white lesions on an erythematous base on buccal mucosa opposite the lower molars). It is one of the most contagious viral infections with secondary attack rates of over 90% in susceptible household contacts.

Complications

Complications include otitis media; diarrhea; bronchopneumonia (responsible for 60% of deaths associated with measles disease and may be measles virus associated and/or a secondary bacterial superinfection with Streptococcus pneumoniae, group A Streptococcus, Staphylococcus aureus); acute encephalitis (more common in adults, associated with fever, headache, seizures, altered consciousness, permanent neurologic sequelae and brain damage); and subacute sclerosing panencephalitis (SSPE). SSPE is a rare degenerative central nervous disease that occurs 7 to 10 years after wild-type measles infection, especially in those who had measles before 2 years of age. It is caused by a persistent infection with a mutant measles related virus in the CNS. It is characterized by behavioral and intellectual deterioration and seizures.

Measles infection during pregnancy maybe associated with a risk of miscarriage and prematurity. Pneumonia (both measles virus associated and secondary bacterial superinfection) is a major complication in pregnant women with measles.

Significant declines in measles vaccination rates or lack of measles vaccination in various areas of the world have resulted in a major resurgence in endemic disease. In 2011, France had the highest number of measles cases in the world. Many countries in Europe, Asia, Africa, South America, and New Zealand are also experiencing large numbers of measles cases. The majority of the cases seen in the United States are brought in by infected persons from other countries or by unvaccinated persons who contract the disease while traveling to countries where measles is endemic.

Transmission

The disease is transmitted person to person by direct contact with droplets from infected respiratory secretions. Persons are contagious from 4 days before the rash to 4 days after appearance of the rash.

Incubation period

8 to 12 days.

Prevention

Post-exposure

  1. a. Administration of immunoglobulin can be given to prevent or modify measles in a susceptible person within 6 days of exposure. It is indicated for susceptible household or other close contacts of persons with measles, particularly contacts under 1 year of age, pregnant women, and immunocompromised people, for whom the risk of complications is highest, or in those persons in whom measles vaccine is contraindicated.

  2. b. MMR (measles, mumps, rubella) vaccine, if given within 72 hours of measles exposure, will provide protection in some cases.

Preexposure

  1. a. MMR vaccine—live, attenuated vaccine containing measles, mumps, and rubella viruses. Recommended for use in persons born in 1957 or later with first dose given to those 12 months of age and older.

  2. b. Given subcutaneously (SQ) as MMR vaccine as a 2-dose series with minimal interval of 28 days between doses. In infants first dose is given at 12 to 15 months of age with second dose given at 4 to 6 years of age.

  3. c. Inadvertent administration of MMR vaccine to a pregnant woman is not an indication for termination of the pregnancy.

Immunogenicity

95% after 1 dose, >99% after 2 doses

Duration of protection

Lifelong after 2 doses

Contraindications and precautions for MMR vaccine

Contraindications

  1. 1. History of severe (anaphylactic) reaction to neomycin (or other vaccine component) or following a previous dose of MMR

  2. 2. Pregnancy

  3. 3. Severe immunosuppression from either disease or therapy

Precautions

  1. 1. Receipt of an antibody-containing blood product in the previous 11 months

  2. 2. Moderate or severe acute illness with or without fever

  3. 3. History of thrombocytopenia or thrombocytopenic purpura

Frequently asked questions

Why does being born before 1957 confer immunity to measles?

People born before 1957 lived through a number of years of epidemic measles before the first measles vaccine was licensed in 1963. Because of this, these people are very likely to have had measles disease. Data from survey studies suggest that 95% to 98% of those born before 1957 are immune to measles. However, if serologic testing indicates that the person is not immune, at least 1 dose of MMR should be administered.

What are the current CDC criteria for evidence of immunity to measles, mumps, and rubella?

The current CDC criteria for evidence of immunity to measles, mumps, and rubella are:

  1. 1. Documented receipt to two appropriately timed doses of MMR vaccine, the first dose of which was given after 1 year of age

  2. 2. Laboratory confirmation of disease

  3. 3. Born before 1957

Physician diagnosis of disease has been removed as reliable evidence of immunity.

What should be done in the situation in which the MMR vaccine was given intramuscularly (IM) instead of subcutaneously (SC)?

It is recommended that all live injected vaccines (e.g., MMR, varicella, and yellow fever) be given SC; however, IM administration of these vaccines does not decrease immunogenicity and doses given IM do not need to be repeated.

What should be done in the situation in which MMRV vaccine was mistakenly given to an adult instead of MMR?

MMRV vaccine is licensed for use in persons 1 year to 12 years of age. If it is given to a patient 13 years of age and older it is considered to be off-label use. This dose may be counted as valid toward the completion of the MMR and varicella vaccine series and does not need to be repeated.

What are the current CDC recommendations for the administration of a dose of MMR vaccine to infants 6 to 11 months of age who will be traveling internationally?

CDC recommends that children who will be traveling or living abroad should be vaccinated with MMR vaccine at an earlier age than that recommended for children who live in the United States given that the risk for measles exposure can be high in both developed and developing countries. It is recommended that children age 6 to 11 months receive 1 dose of MMR vaccine before departure from the United States. This dose does not count toward the 2 recommended doses of MMR at 12 to 15 months and 4 to 6 years.

Can MMR vaccine be given to a child whose sibling is receiving chemotherapy?

Yes. MMR and varicella vaccines should be given to the healthy household contacts of immunosuppressed patients.

Is egg allergy considered a contraindication to receiving MMR vaccine?

No. Studies have documented the safety of giving MMR vaccine (which is grown in chick embryo tissue culture) to children with severe egg allergy. Egg allergy is not considered a contraindication to MMR vaccine, and the CDC and AAP recommend routine MMR vaccination of egg-allergic children without the use of special protocols or desensitization procedures.

Can MMR vaccine be given to a breastfeeding mother or to a breastfed infant?

Yes, breastfeeding does not interfere with the response to MMR vaccine and vaccination of a woman who is breastfeeding poses no risk to the infant being breastfed.

Mumps

Did you know that:

  • The clinical picture of mumps (swelling about one or both ears and, in some instances, painful swelling of one or both testes…) was first described by Hippocrates in the 5th century bc in Book 1 of his Book of Epidemics.

  • Orchitis, an inflammation of the testicles, occurs in approximately 25% of males that are infected with mumps after puberty, up to 50% of those affected develop testicular atrophy, and 10% will have a drop in their sperm count.

Mumps is a systemic disease characterized most commonly by swelling of one or more of the salivary glands, usually the parotid glands. About one-third of the infections do not have clinically apparent salivary gland swelling and may be asymptomatic or manifest primarily as a respiratory tract infection. Infection in adults is much more likely to result in complications.

Complications

Over 50% of people with mumps have cerebrospinal fluid pleocytosis, but less than 10% have symptoms of viral meningitis. Symptoms are most commonly seen in older children, adolescents, and adults. Epididymo-orchitis is a common complication reported in 15% to 40% of post-pubertal males, especially in persons in the second, third, and fourth decades of life. It is usually unilateral but may be bilateral in up to 30% of cases. Oophoritis occurs in 7% of post-pubertal females. The incidence of deafness as a complication is 0.5 to 5 per 100,000 cases; it is usually unilateral and permanent.

Mumps infection during pregnancy is associated with increased rates of fetal mortality in women who contract mumps during the first trimester of pregnancy (27.3% vs. 13% in healthy controls). Even though mumps virus can cross the placenta, this mortality is not associated with the development of fetal malformations. Other complications in pregnant women include: mastitis, aseptic meningitis, and glomerulonephritis.

Large outbreaks have been seen in recent years on college campuses, among the Hasidic Jewish communities in New York and New Jersey, and among professional sports teams.

Transmission

Contact with infectious respiratory tract secretions and saliva. The period of maximum communicability is several days before and after the onset of parotid swelling.

Incubation period

16 to 18 days

Prevention

Post-exposure

  1. a. Immunoglobulin preparations are not effective as post-exposure prophylaxis for mumps.

  2. b. MMR (measles, mumps, rubella) vaccine has not been demonstrated to be effective in preventing infection after exposure. MMR vaccine can be given after exposure, because immunization will provide protection against subsequent exposures.

Preexposure

  1. a. MMR vaccine—live, attenuated vaccine containing measles, mumps, and rubella viruses. Recommended for use in persons born in 1957 or later with first dose given to those 12 months of age and older.

  2. b. Given subcutaneously as MMR vaccine as a 2-dose series with minimal interval of 28 days between doses. In infants first dose is given at 12 to 15 months of age with second dose given at 4 to 6 years of age. Inadvertent administration of MMR vaccine to a pregnant woman is not an indication for termination of the pregnancy.

Immunogenicity

73% to 91% after 1 dose, 79% to 95% after 2 doses

Duration of protection

Lifelong after 2 doses

Contraindications and precautions for MMR vaccine

Contraindications

  1. 1. History of severe (anaphylactic) reaction to neomycin (or other vaccine component) or following a previous dose of MMR

  2. 2. Pregnancy

  3. 3. Severe immunosuppression from either disease or therapy. This includes people with conditions such as congenital immunodeficiency, AIDS, leukemia, lymphoma, generalized malignancy, and those receiving treatment for cancer with drugs, radiation, or large doses of corticosteroids.

Precautions

  1. 1. Receipt of an antibody-containing blood product in the previous 11 months

  2. 2. Moderate or severe acute illness with or without fever

  3. 3. History of thrombocytopenia or thrombocytopenic purpura

Frequently asked questions

How long is a person with mumps contagious?

People with mumps are considered most infectious from a few days before until 5 days after the onset of parotitis (facial swelling). The CDC recommends isolating mumps patients for 5 days after their glands begin to swell.

Can someone who had a laboratory confirmed case of mumps get mumps again?

People who have had mumps are usually protected for life against another mumps infection. However, second occurrences of mumps do rarely happen.

Which adult patients should receive 2 doses of MMR vaccine?

Certain adults are at higher risk of exposure to measles, mumps, and/or rubella and should receive a second dose of MMR unless they have other evidence of immunity; this includes adults who are

  • Students in postsecondary educational institutions

  • Health-care personnel

  • Living in a community experiencing an outbreak or recently exposed to the disease

  • Planning to travel internationally (for measles and mumps)

  • People who received inactivated (killed) measles vaccine or measles vaccine of unknown type during the period 1963 to 1967 should be revaccinated with two doses of MMR vaccine.

  • People vaccinated before 1979 with either killed mumps vaccine or mumps vaccine of unknown type who are at high risk for mumps infection (e.g., people who are working in a health-care facility) should be considered for revaccination with 2 doses of MMR vaccine.

Rubella

Did you know that:

  • Rubella, first described in the late 18th century as a mild exanthematous disease of children and young adults, exploded onto the world stage when it was recognized in 1941 that it was a prominent cause of congenital defects in the fetus after maternal infection during pregnancy.

  • The sweat of patients with rubella smells like freshly plucked chicken feathers.

Rubella (German measles) is caused by Rubella virus. The majority of postnatal rubella cases are subclinical and asymptomatic. Clinical disease is mild and characterized by a generalized erythematous maculopapular rash, lymphadenopathy, and low grade fever. The rash starts on the face, becomes generalized over 24 hours, and lasts a median of 3 days. Lymphadenopathy, which may precede the rash, often involves the posterior auricular or suboccipital lymph nodes but can be generalized, and lasts between 5 and 8 days. Transient polyarthralgia and polyarthritis are commonly seen in adolescents and adults, especially females. Due to the success of the vaccination program, the rubella cases seen in the United States occur in persons born in other countries who were never vaccinated or in underimmunized people.

Complications

Encephalitis (1 in 6,000 cases) and thrombocytopenia (1 in 3,000 cases).

Rubella during pregnancy is associated with a higher incidence of miscarriage, fetal death, or the congenital rubella syndrome (a constellation of congenital anomalies). The most common clinical manifestations seen in the infant at the time of birth include: “blueberry muffin” lesions (erythropoiesis in dermis and upper subcutaneous adipose tissue), growth restriction, interstitial pneumonitis, hepatosplenomegaly, thrombocytopenia, and radiolucent bone lesions. The most common anomalies associated with the congenital rubella syndrome are: ophthalmologic (cataracts, microphthalmia, and congenital glaucoma); cardiac (patent ductus arteriosus, peripheral pulmonary artery stenosis); auditory (sensorineural hearing loss); and neurologic (meningoencephalitis, microcephaly, mental retardation).

Congenital defects occur in up to 85% of cases if maternal infection occurs during the first 12 weeks of gestation, 50% during the first 13 to 16 weeks of gestation, and 25% during the end of the second trimester.

Transmission

Direct or droplet contact from infected nasopharyngeal secretions. The period of maximal communicability occurs from a few days before to 7 days after the onset of rash.

Incubation period

16 to 18 days

Prevention

Post-exposure

  1. a. Immunoglobulin preparations are not effective as post-exposure prophylaxis for rubella and is not recommended for routine post-exposure prophylaxis of rubella in early pregnancy or any other circumstance.

  2. b. MMR (measles, mumps, rubella) vaccine has not been demonstrated to be effective in preventing infection after exposure. MMR vaccine can be given after exposure, because immunization will provide protection against subsequent exposures.

Post-exposure evaluation of the pregnant woman includes:

  1. a. Obtaining a blood sample as soon as possible after exposure and testing for rubella IgM and IgG antibodies. An aliquot of frozen serum should be stored for possible repeated testing at a later time. The presence of rubella-specific IgG antibody at the time of exposure indicates that the person is most likely immune.

  2. b. If antibody is not detectable, a second blood specimen should be obtained 2 to 3 weeks later and tested concurrently with the first specimen.

  3. c. If the second test result is negative, another blood specimen should be obtained 6 weeks after the exposure and also tested concurrently with the first specimen.

  4. d. A negative test result in both the second and third specimens indicates that infection has not occurred.

  5. e. A positive test result in the second or third specimen but not the first indicates a recent infection.

Preexposure

  1. a. MMR vaccine—live, attenuated vaccine containing measles, mumps and rubella viruses. Recommended for use in persons born in 1957 or later with first dose given to those 12 months of age and older. Contraindictated in persons who are pregnant, persons with certain immunodeficiencies or those who had a previous anaphylactic reaction to the vaccine or any of its components.

Vaccine: Given subcutaneously as MMR vaccine as a 2-dose series with minimal interval of 28 days between doses. In infants first dose is given at 12 to 15 months of age with second dose given at 4 to 6 years of age. Inadvertent administration of MMR vaccine to a pregnant woman is not an indication for termination of the pregnancy.

Immunogenicity

73% to 91% after 1 dose, 79% to 95% after 2 doses

Duration of protection

Lifelong after 2 doses

Contraindications and precautions for MMR vaccine

Contraindications

  1. 1. History of severe (anaphylactic) reaction to neomycin (or other vaccine component) or following a previous dose of MMR.

  2. 2. Pregnancy

  3. 3. Severe immunosuppression from either disease or therapy

Precautions

  1. 1. Receipt of an antibody-containing blood product in the previous 11 months

  2. 2. Moderate or severe acute illness with or without fever

  3. 3. History of thrombocytopenia or thrombocytopenic purpura

Frequently asked questions

What is the recommended length of time a woman should wait after receiving MMR (rubella) vaccine before becoming pregnant?

CDC recommends deferring pregnancy for 4 weeks after receiving MMR vaccine.

What should be done in the situation in which a pregnant woman inadvertently was given an MMR vaccine?

MMR vaccination during pregnancy alone is not a reason to terminate the pregnancy. No specific action needs to be taken other than to reassure the woman that no adverse outcomes are expected as a result of this vaccination.

What should be done in the situation in which a pregnant woman’s rubella test result shows that she is “not immune” but she has documentation of receiving 2 appropriately timed doses of MMR vaccine?

It is now recommended that women of childbearing age who have received 1 or 2 doses of a rubella-containing vaccine and have serum rubella IgG titers that are not positive should be administered 1 additional dose of MMR vaccine (maximum 3 doses) and do not need to be retested for serologic evidence of rubella immunity. MMR vaccine should not be administered to a pregnant woman. The dose should be given after the baby is delivered.

How soon after delivery can MMR vaccine be given?

MMR vaccine may be administered any time after delivery. It should be administered before hospital discharge, even if the patient has received RhoGam during the hospital stay, is discharged in less than 24 hours, or is breastfeeding.

Is there any evidence that MMR vaccine or thimerosal are causes of autism spectrum disorder (ASD)?

NO. This is an issue that has been studied extensively, including several thorough reviews by the Institute of Medicine (IOM). A 2004 scientific review by the IOM concluded that “the evidence favors rejection of a causal relationship between thimerosal–containing vaccines and ASD.” Since 2003, there have been nine CDC-funded or conducted studies that have found no link between thimerosal-containing vaccines and ASD, as well as no link between the measles, mumps, and rubella (MMR) vaccine and ASD in children. In 2011 an IOM report on eight routinely used vaccines (MMR, hepatitis A, meningococcal, varicella zoster, influenza, hepatitis B, HPV, and tetanus-containing vaccines) given to children and adults found that these vaccines are very safe and that there is no link between receiving vaccines and developing ASD. A 2013 CDC study added to the research showing that vaccines do not cause ASD. The study looked at the number of antigens (substances in vaccines that cause the body’s immune system to produce disease-fighting antibodies) from vaccines during the first two years of life. The results showed that the total amount of antigen from vaccines received was the same between children with ASD and those that did not have ASD. All the extensive research performed to date shows absolutely no evidence of any link between receiving vaccines or those vaccines containing trace thimerosal and ASD.

How likely is it for a person to develop arthritis after receiving an MMR vaccine?

Joint pain or arthralgia and transient arthritis following MMR vaccination occurs only in people who were susceptible to rubella at the time of vaccination. About 25% of non-immune post-pubertal women report joint pain after receiving a rubella-containing vaccine, and about 10% to 30% report arthritis-like signs and symptoms. If joint symptoms occur, it is generally 1 to 3 weeks after vaccination, are mild and last about 2 days.

How soon must MMR vaccine be administered once it has been reconstituted with diluent?

Optimally MMR vaccine should be administered immediately after reconstitution. If reconstituted, MMR vaccine should be used within 8 hours. If it is not used within this time period it should be discarded. The dose should be refrigerated and should never be left at room temperature.

Varicella Zoster (chickenpox)

Did you know that:

  • In 2011 in a misguided attempt to expose their children to the chickenpox virus to build immunity later in life, a group of parents across the United States (Tennessee, Arizona, California) started trading chickenpox virus-laced lollipops by mail, which is a federal crime.

  • Prior to the introduction of varicella vaccine, varicella accounted for 10,600 hospitalizations and 100 to 150 deaths each year in the United States. That equates to 1 to 2 deaths each week!

  • Primary varicella infection (chicken pox) wasn’t differentiated from smallpox until the end of the 18th century.

Primary infection with varicella zoster virus (VZV) results in varicella (chickenpox). VZV establishes latency in the dorsal root ganglia after primary infection and reactivation at a later time results in herpes zoster (shingles). Varicella is a highly contagious disease with an 80% to 100% secondary household attack rate in unvaccinated persons. The appearance of the rash is preceded by a 1 to 2 day prodrome of fever, malaise, headache, and abdominal pain. The rash appears as crops of lesions that develop over several days. Each crop progresses within 24 hours from macules to papules to vesicles, and then pustules before crusting. All lesions are on an erythematous base and are pruritic. Lesions are in different stages of development at any given time and classically are described as “dew drops on a rose petal”. The rash usually starts on the face and trunk and then spreads to the extremities and all other areas of the body. Usually between 250 and 500 lesions develop and all lesions are usually crusted by 4 to 7 days after onset of the rash. Recovery from primary varicella usually results in lifetime immunity. In otherwise healthy persons a second occurrence of varicella is uncommon but it can happen.

Complications include secondary bacterial infections of the skin lesions most commonly caused by group A Streptococcusand Staphylococcus aureus (which may progress to necrotizing fasciitis); pneumonia(viral or bacterial) which occurs in 15% of adults and is the most common complication in this population; central nervous system manifestations (e.g., cerebellar ataxia, meningoencephalitis, encephalitis); hepatitis; thrombocytopenia; acute respiratory distress syndrome; and hemorrhagic complications.

Persons at the highest risk of complications of varicella include: healthy adults, pregnant women, developing fetuses, infants born to mothers who have varicella five days before and 2 days after the delivery, and immunocompromised persons of any age. The risk of varicella complications is 10 to 20 times higher in adults than in children.

Congenital varicella syndrome (fetal varicella syndrome) may occur in women with maternal varicella infection occurring during the first two trimesters of pregnancy. There is an estimated 2% incidence of congenital disease after maternal varicella infection when occurring in the first 20 weeks’ gestation. Characteristic features in affected infants include: low birthweight; skin lesions or scarring in a dermatomal distribution (76%); neurologic defects (e.g., microcephaly) (60% of cases); ophthalmologic disease (51%), and skeletal anomalies (e.g., hypoplasia of the extremities), muscle atrophy (50% of cases). 30% of infants born with congenital varicella syndrome die in the first month of life (Table 11).

Table 11 Timing of Maternal Varicella Infection and Potential Outcome in Fetus

Period of Gestation of Infected Mother

Potential Outcome in the Fetus

7 to 28 weeks

Fetal varicella syndrome

1 to 28 weeks

Neonatal/childhood herpes zoster

2 weeks before delivery

Neonatal chickenpox

*5 days before or after delivery

Neonatal disseminated chickenpox with septicemia and increased mortality of up to 30%

*potentially the most severe outcome for the fetus

Transmission

Person to person by direct contact, inhalation of aerosols from vesicular fluid of skin lesions of acute varicella and/or zoster, or aerosolized respiratory tract secretions.

Incubation period

Incubation period is 14 to 16 days after exposure to rash. The maximal period of contagiousness is 1 to 2 days before onset of the rash until all the lesions have crusted. In cases where there is only a maculopapular rash, person is contagious until the rash disappears.

Prevention

Post-exposure

  1. a. Varicella Zoster Immune Globulin (VariZIG) administered intramuscularly from 96 hours to 10 days after exposure. Recommended dose is based upon kg of body weight: 62.5 units (0.5 vial) for children weighing ≤2.0 kg; 125 units (1 vial) for children weighing 2.1 to 10 kg; 250 units (2 vials) for children weighing 10.1 to 20 kg; 375 units (3 vials) for children weighing 20.1 to 30 kg; 500 units (4 vials) for children weighing 30.1 to 40 kg; and 625 units (5 vials) for all people weighing >40 kg. If VariZIG not available, IVIG given intravenously may be used at a dose of 400 mg/kg.

  2. b. Prophylactic administration of oral acyclovir beginning 7 days after exposure may also prevent or attenuate varicella disease in healthy children. There is no information on whether prophylactic oral acyclovir is protective for adults or immunocompromised people. Prophylactic dosing of acyclovir is 20 mg/kg per dose, administered 4 times per day with a maximum daily dose of 3200 mg or valacyclovir 20 mg/kg per dose, administered 3 times per day with a maximum daily dose of 3000 mg. This should be continued for 7 days.

  3. c. Varicella vaccine administered ideally within 3 days but up to 5 days after exposure (followed by a second dose of vaccine at least 28 days after the first dose in persons 13 years of age and older) may prevent or modify disease.

  4. d. Because vaccine is contraindicated in pregnancy, a pregnant woman with no evidence of immunity (either prior infection or vaccine) with significant varicella exposure is a candidate for acyclovir prophylactic therapy.

Preexposure

  1. a. Varicella vaccine is a live, attenuated viral vaccine that is given subcutaneously as a 2 dose series. For persons 13 years of age and older, the second dose should be given at least 28 days after first dose. The vaccine should be stored in a frost-free freezer at an average temperature of –15˚C (+5˚F) or colder.

Effectiveness

Effectiveness is 86% against varicella infection and 95% against severe disease after one dose, and 98% after 2 doses.

Duration of protection

Appears to be long lasting after two doses (at least 25 years).

Precautions and contraindications to varicella vaccine

Contraindications

  1. 1. History of a serious reaction (e.g., anaphylaxis) after a previous dose of varicella vaccine or to a varicella vaccine component.

  2. 2. Pregnancy currently or in a patient that may become pregnant within 1 month.

  3. 3. Any malignant condition, including blood dyscrasia, leukemia, lymphoma, or any type, or other malignant neoplasm affecting the bone marrow or lymphatic system.

  4. 4. A patient receiving high-dose systemic immunosuppression therapy (e.g., two weeks or more of daily prednisone or equivalent of 20 mg or more [or 2 mg/kg or more for body weight]).

  5. 5. Family history of congenital or hereditary immunodeficiency in a first-degree relative (e.g., parents, siblings) when the immunocompetence of the potential vaccine recipient has not been clinically substantiated or verified by a laboratory.

  6. 6. A child age 1 year or older with CD4+ T-lymphocyte percentages less than 15% or a child, adolescent, or adult age 6 years or older with CD4+ T-lymphocyte count less than 200 cells per microliter.

  7. 7. For combination MMRV only (approved only for use in children 1 through 12 years of age), primary or acquired immunodeficiency, including immunosuppression associated with AIDS or other clinical manifestations of HIV infections, cellular immunodeficiency, hypogammaglobulinemia, and dysgammaglobulinemia.

Precautions

  1. 1. Receipt within the previous 11 months of antibody-containing blood products (specific interval depends on product).

  2. 2. Moderate to severe acute illness with or without fever.

Frequently asked questions

Can an infant younger than 12 months of age receive the varicella vaccine if they were exposed to the chickenpox or zoster virus?

The minimum age for varicella vaccine is 12 months. Vaccination is not recommended for infants younger than 12 months of age even as post-exposure prophylaxis. A healthy infant should receive no specific treatment or vaccination after exposure to VZV.

Should a dose of varicella vaccine be given to infants younger than 12 months of age if they are traveling internationally?

Varicella vaccine is neither approved nor recommended for children younger than 12 months of age in any situation.

If a child inadvertently receives zoster vaccine instead of varicella vaccine, does that vaccine dose count?

The administration of zoster vaccine instead of varicella vaccine is a serious vaccine administration error and procedures, and safeguards should be put in place to prevent this error from happening again. The dose of zoster vaccine can be counted as one dose of varicella vaccine, and if the error occurred for the first dose, the person should receive the second dose of varicella vaccine on schedule.

Should a child who had chickenpox prior to their first birthday get the first dose of varicella vaccine at age 1 year?

If the child had confirmed varicella disease or laboratory evidence of prior disease, it is not necessary to vaccinate regardless of age at infection. If there is any question that the illness was actually varicella, the child should be vaccinated.

Is it recommended that children who received one varicella dose 12 years ago at age 1 year, be vaccinated with a second dose at this time?

Yes. The current CDC recommendation is for two doses of the varicella vaccine regardless of age, for anyone school age and older without evidence of immunity. For everyone whose varicella immunity is based on vaccination, 2 doses of varicella vaccine are recommended.

If a child or adult has not had documented chickenpox but has had shingles, is varicella vaccination still recommended?

No. Shingles is caused by varicella zoster virus, the same virus that causes chickenpox. A history of shingles based on a health-care provider diagnosis is evidence of immunity to chickenpox. A person who has had shingles does not need to be vaccinated against varicella.

If a patient has a very mild case of chickenpox (less than 10 lesions), are they considered immune or should they receive the varicella vaccine?

A case of chickenpox, whether it is mild, moderate or severe, produces immunity to varicella. A patient with a reliable history of chickenpox does not need to receive the varicella vaccine. However, if there is any doubt about the diagnosis, it is best to vaccinate the patient. There is no harm in vaccinating a patient who may already be immune.

Should an infant receive the varicella vaccine if they are living in a household with a person who is pregnant or someone who is immunocompromised?

Yes. Based on available data, healthy children are unlikely to transmit the vaccine virus and transmission of vaccine virus to household contacts has rarely been documented. Transmission of the vaccine virus occurs almost exclusively when the vaccinated person develops a rash following vaccination.

What are the recommendations for the use of varicella vaccine in children with HIV or other immunodeficiencies?

The CDC recommends the use of varicella vaccine in children with humoral but not cellular immunodeficiencies. Single antigen varicella vaccine should be considered for HIV-infected children age 1 through 8 years with CD4+ T-lymphocyte percentages greater than or equal to 15% or for children age 9 years and older with CD4+ T-lymphocyte counts greater than or equal to 200 cells per microliter. Eligible children should receive two doses of varicella vaccine with a 3-month interval between doses.

Should healthcare personnel avoid contact with immunocompromised patients after receiving varicella vaccine?

No. This is not necessary unless the person who was vaccinated develops a rash. If the vaccinated person develops a rash 7 to 21 days following vaccination, they should avoid prolonged close contact with a pregnant or immunosuppressed household contact or patient that is known to be susceptible to varicella, until the rash resolves.

What should be done in the situation in which hospital employees claim that they have had chickenpox; however, their varicella antibody titers show no antibodies?

If the health-care employee’s history of chickenpox cannot be verified, the employee should receive two doses of varicella vaccine at least 4 weeks apart.

A health professions student (e.g., medical, nursing, dental, physical therapy, etc.) received 2 valid, appropriately spaced, documented doses of varicella vaccine. Subsequently a titer was drawn for whatever reason and the titer was negative. Is it recommended to revaccinate this individual with 2 doses of varicella vaccine?

No. Documented receipt of two doses of varicella vaccine supersedes results of subsequent serologic testing. Most commercially available tests for varicella antibody are not sensitive enough to detect vaccine-induced antibody, which is why it is not recommended to perform post-vaccination testing.

Is receipt of a single documented dose of zoster vaccine proof of varicella immunity in a health-care employee who has no other evidence of immunity?

No. Receipt of zoster vaccine is not proof of prior varicella disease. Per the CDC, acceptable evidence of varicella immunity in healthcare personnel includes: (1) documentation of two doses of varicella vaccine given at least 28 days apart, (2) history of varicella or herpes zoster based on physician diagnosis, (3) laboratory evidence of immunity, or (4) laboratory confirmation of disease. If a health-care employee has already received a dose of zoster vaccine but has no evidence of immunity to varicella, the zoster dose can be considered the first dose of the two dose varicella vaccine series.

How soon after varicella exposure does the varicella vaccine need to be administered if it is used in a postexposure setting?

Varicella vaccine is effective in preventing chickenpox or reducing the severity of the disease if used within 72 hours (3 days), and possibly up to 5 days, after exposure. Not every exposure to varicella leads to infection, so for future immunity, varicella vaccine should be given, even if more than 5 days have passed since the exposure.

What are the circumstances in which a varicella titer should be obtained after vaccination?

Obtaining postvaccination serologic testing is not recommended in any group, including healthcare personnel.

Should all pregnant women have serology screening for varicella?

No. Serologic testing for varicella should only be considered for women who do not have evidence of immunity (either a reliable history or chickenpox or documented vaccination). Once a person has been found to be seropositive, it is not necessary to test them again in the future.

What should be done in the situation where a full-term, healthy, 2-month-old infant was exposed to their mother and another household contact with varicella for the last week?

There is no evidence that healthy full-term infants born to women in whom varicella occurs more than 48 hours after delivery are at increased risk for serious complications from the disease. Varicella zoster immune globulin (VariZIG) can be given up to 10 days after exposure, but it is only recommended for newborn infants whose mothers have signs and symptoms of varicella around the time of delivery (5 days before to 2 days after), hospitalized premature infants born at 28 or more weeks gestation whose mothers do not have evidence of immunity to varicella, or hospitalized premature infants born at less than 28 weeks of gestation or who weigh 1,000 grams or less at birth regardless of their mothers’ evidence of immunity to varicella. In the above situation, VariZIG would not be recommended. If the infant develops varicella, it would be managed as it would be for any healthy child.

Herpes Zoster (shingles)

Did you know that:

  • The term herpes zoster is derived from the Greek word herpes meaning creeping and zoster meaning a beltlike binding or girdle and describes a herpes zoster rash encircling the waist.

  • Otto von Bismarck (“Iron Chancellor” and architect of the unification of Germany), James H. Doolittle (American aviation pioneer), Golda Meir (fourth prime minister of Israel), and Charles Lindbergh (“Lucky Lindy,” aviator and explorer) all suffered from severe bouts of herpes zoster (shingles).

Herpes zoster is caused by the reactivation of the varicella zoster (chickenpox) virus and may occur years or decades after primary illness with chickenpox. It is generally associated with normal aging and with anything that causes reduced immunocompetence (e.g., bone marrow and solid organ transplants, hematologic malignancies and solid tumors, HIV, immunosuppressive medications). Other risk factors include: female gender, white race, trauma, surgery and persons with early varicella (e.g., varicella in utero or early infancy). One in three persons will develop herpes zoster sometime during their lifetime with an estimated 1 million cases occurring annually in the United States.

Clinical features include a prodromal illness of headache, photophobia, malaise, fever, and abnormal skin sensation or pain in the affected area. This is followed by the development of the zoster rash that is unilateral involving 1 to 3 adjacent dermatomes. Thoracic, cervical, and ophthalmic areas are most commonly involved. The rash initially starts as erythematous and maculopapular and then evolves into vesicles over several days before crusting. Full resolution of the rash may take 2 to 4 weeks. Occasionally the rash does not develop but patient continues with abnormal skin sensation and pain in the affected area.

Complications of herpes zoster include:

  1. a. Postherpetic neuralgia, the most common complication, develops in 10% to 34% of people. It ranges from mild-to-excruciating constant or intermittent pain occurring after the resolution of the rash. The pain may persist for weeks, months, or even years and may be completely debilitating. Risk factors include age ≥50 years and severe zoster disease.

  2. b. Herpes zoster ophthalmicus occurs in up to 15% of cases and can lead to reduced vision and even blindness. If untreated, 50% to 70% develop acute ocular complications.

  3. c. Secondary infection of the herpes zoster rash, which may lead to permanent scarring or changes in skin pigmentation.

  4. d. Neurologic complications including encephalitis, ventriculitis, cranial nerve palsies, meningoencephalitis, myelitis and ischemic stroke syndrome.

  5. e. Rarely varicella zoster virus viremia can lead to pneumonia, hepatitis, DIC.

Transmission

Transmission is person to person via direct contact with zoster lesions, however, airborne transmission may occur in certain settings. A person is contagious from the time the rash erupts until the lesions are crusted. Transmission may be decreased by covering the lesions and preventing contact.

Prevention

  1. a. Herpes Zoster Vaccine which is a live, attenuated varicella vaccine that contains 14 times the amount of virus compared to regular varicella vaccine. It is administered subcutaneously as a single dose and must be stored in a freezer at all times. It is recommended for all adults ≥60 years of age whether or not they have reported a prior episode of shingles. Persons with chronic medical conditions may be vaccinated unless a contraindication or precaution exists. Contraindications for vaccination include severe allergic reaction after exposure to any component of the vaccine, primary or acquired immunodeficiency and immunosuppressive therapy.

Contraindications and Precautions with Herpes zoster vaccine

Contraindications

  1. 1. Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component.

  2. 2. Known severe immunodeficiency (e.g., hematologic and solid tumors, receipt of chemotherapy, or long-term immunosuppressive therapy, patients with HIV who are severely immunocompromised).

  3. 3. Pregnancy. Women should not become pregnant for at least 4 weeks after receiving the zoster vaccine.

Precautions

  1. 1. Moderate or severe acute illness with or without fever.

  2. 2. Receipt of specific antiviral agents (e.g., acyclovir, famciclovir, or valacyclovir) 24 hours before vaccination. The use of these antiviral agents should be avoided for 14 days after receiving the vaccine as it will reduce the immune response to the vaccine.

Effectiveness

Reduces risk for developing zoster by 51%, post-herpetic neuralgia by 66.5% and overall severity and duration of disease by 61%.

Duration of protection

Unknown. No booster dose of vaccine is recommended at this time.

Frequently asked questions

Zoster vaccine is approved by the FDA for people age 50 years and older. Does the CDC recommend that health-care providers vaccinate people in their 50s?

CDC does not currently recommend the use of zoster vaccine in people 50 to 59 years of age. The reasons for not vaccinating this population include: (1) even though the burden of herpes zoster disease increases after age 50, disease rates are lower in this age group than they are in persons 60 years of age and older; (2) there is insufficient evidence for long-term protection provided by the vaccine; and (3) persons vaccinated at younger than age 60 years may not be protected when the incidence of zoster and its complication are highest. Zoster vaccine is approved by the FDA for persons aged 50 through 59 years and health-care providers may choose to vaccinate persons in this age group despite the absence of a CDC recommendation.

Is there an upper age limit for receipt of the zoster vaccine?

There is no upper age limit for zoster vaccine. The incidence of herpes zoster increases with increasing age; an estimated 50% of persons living until age 85 years will develop zoster. CDC recommends the vaccine for everyone age 60 years and older, even though vaccine efficacy decreases with an increase in the age of the vaccine recipient. With increasing age at vaccination, the vaccine is more effective in reducing the severity of zoster and post-herpetic neuralgia than in reducing the occurrence of disease.

Is it necessary to ask when a person has ever had chickenpox or shingles prior to administering zoster vaccine?

No. All persons aged 60 years of age and older, whether or not they have a history of chickenpox or shingles, should receive zoster vaccine unless they have a medical contraindication to vaccination. Serologic studies show that almost everyone born in the United States before 1980 has had chickenpox. It is also not recommended or necessary to test for varicella antibody prior to administering the vaccine.

How soon after a case of shingles can a person receive the zoster vaccine?

The general rule for any vaccine is to wait until the patient is over the acute stage of the illness and symptoms have resolved. A recent case of shingles is expected to boost the immunity of the person to varicella and administering zoster vaccine to a person whose immunity was recently boosted by a case of shingles might reduce the effectiveness of the vaccine. CDC does not have specific recommendations for this issue, however, it may be wise to defer zoster vaccination for 6 to 12 months after the shingles has resolved so that the vaccine can produce a more effective boost to immunity.

What should be done in the situation where a child received zoster vaccine instead of varicella vaccine?

This is a serious vaccine administration error and the event needs to be documented and procedures put in place to prevent this from occurring again. Zoster vaccine contains 14 times as much varicella vaccine virus as varicella vaccine; however, no specific action needs to be taken in response to this error. If this was the child’s first dose of varicella-containing vaccine, they will still need the second dose of varicella-containing vaccine given as per the recommended schedule.

What should be done in the situation where a 60-year-old patient was inadvertently given varicella vaccine instead of zoster vaccine?

If a provider inadvertently administers varicella vaccine to a person for whom zoster vaccine is indicated, the dose should not be considered valid and the patient should be administered a dose of zoster vaccine during the same visit. If the error is not immediately detected, a dose of zoster vaccine should be administered 4 weeks after the varicella vaccine dose to prevent potential blunting of the immune response to 2 doses of live, attenuated viral vaccine.

If a 65-year-old patient has an underlying condition that requires monthly treatment with intravenous immune globulin (IVIG), can they receive the zoster vaccine?

Yes. The concern about interference by circulating antibody in the IVIG, applies to varicella and MMR vaccines but not to zoster vaccine. The amount of antigen in zoster vaccine is so substantial that it offsets any effect of any circulating herpes zoster antibody that may be in the IVIG.

When can a patient who is receiving immunosuppressive chemotherapy receive zoster vaccine?

If a patient is receiving or has recently received cancer chemotherapy, it is recommended to wait 3 months after the therapy is discontinued before administering zoster vaccine. If the patient was receiving high-dose steroids, isoantibodies, immune mediators, or immunomodulators, it is recommended to wait 1 month after the therapy is discontinued before administering zoster vaccine. If the person was receiving low doses of methotrexate, azathioprine, or 6-mercaptopurine, it is not necessary to wait as these therapies are not considered immunosuppressive.

Is there any reason to delay administration of zoster vaccination in a healthy person 60 years of age and older who has frequent contact with an unvaccinated infant or an immunocompromised person?

Neither one of these situation is a reason to delay administration of zoster vaccine. There are no special contact precautions that are needed if a person who receives zoster vaccine has close household or occupational contact with persons who are at risk for developing severe varicella or zoster infection. The only exception is in the rare instance when a person develops a varicella-like rash after receiving zoster vaccine. If a rash develops, the vaccinated person should restrict contact with an immunocompromised person if the immunocompromised person is susceptible to varicella.

Pneumococcal Disease

Did you know that:

  • Charles Bronson, actor; James Brown, the “Godfather of Soul”; Leo Tolstoy, author of War and Peace; Rene Descartes, French philosopher, mathematician, and scientist; and horror film actor Boris Karloff all died from pneumococcal pneumonia.

  • The organism, Streptococcus pneumoniae, was first identified concurrently in 1881 in France by Louis Pasteur and in the United States by George Sternberg.

  • Adults 65 years and older comprise about 15% of the population of the United States but account for one third of all the cases of invasive pneumococcal disease.

  • In 1911, Sir Almroth Wright, a scientist renowned for his work developing an effective vaccine for typhoid fever, was sent to South Africa to develop and test a pneumococcal vaccine in order to alleviate the burden of epidemic disease in gold miners. Despite vaccinating over 50,000 miners and claiming his results showed that the vaccine worked, his data did not hold up well to scrutiny. This left him with the unfortunate nickname “Sir Almost Right.”

Capsular polysaccharides are an important determinant of pathogenicity and form the basis for classifying pneumococci by serotypes. Ninety-four different serotypes have been identified to date.

Since the introduction of routine infant PCV-7 vaccine in 2000, indirect vaccine effects have reduced invasive pneumococcal infections among unvaccinated persons of all ages, including those aged ≥65 years. Among persons 18 to 49 years, 50 to 64 years, and ≥65 years, rates of IPD decreased 40%, 18%, and 37%, respectively. However, IPD remains an important cause of illness and death with an estimated 43,500 cases and 5,000 deaths occurring among persons of all ages; 36,540 cases of IPD (e.g., pneumonia, bacteremia, meningitis) and 4,900 deaths (98%) are seen in persons >50 years of age. The highest mortality rates are seen among the elderly (17.4% for those ≥65 years of age and 20.6% for those >80 years of age) with persons ≥65 years of age accounting for more than 50% of all deaths from IPD.

The conjugate pneumococcal vaccine has had a major impact on the incidence of invasive disease among young children, resulting in a 99% decrease in disease caused by the seven serotypes in PCV7 and serotype 6A, a serotype against which PCV7 provides some cross-protection. These decreases have been offset partially by increases in invasive disease caused by serotypes not included in PCV7. Indirect effects of the conjugate vaccine have reduced invasive pneumococcal infections among unvaccinated persons of all ages. However, pneumococcal pneumonia and IPD remain important causes of illness and death with an estimated 400,000 hospitalizations annually for pneumococcal pneumonia; 12,000 cases of bacteremia with a case-fatality rate of 20% (and up to 60% in the elderly); and 3,000-6,000 cases of meningitis with a case-fatality rate of 22% in adults and 8% in children.

Transmission

Person to person by respiratory droplet contact. Viral upper respiratory infections, including influenza, can predispose to pneumococcal infection and transmission.

Incubation period

Varies by type of infection but can be as short as 1 to 3 days.

Persons at Increased Risk for Pneumococcal Disease

Individuals at increased risk for pneumococcal disease include: those with chronic heart disease (especially those with cyanotic heart disease and cardiac failure), chronic lung disease (including asthma especially if treated with prolonged high-dose oral steroids), diabetes mellitus, cerebrospinal fluid leaks, cochlear implant, sickle cell disease and other hemoglobinopathies, chronic or acquired asplenia or splenic dysfunction, HIV infection, diseases associated with treatment with immunosuppressive drugs or radiation therapy (e.g., malignant neoplasms, leukemias, lymphomas, and Hodgkin disease, or solid organ transplantation), congenital immunodeficiency (e.g. B and T lymphocyte deficiency, complement deficiencies [especially C1, C2, C3, and C4 deficiency], phagocyte disorders, alcoholism, chronic liver disease, cigarette smokers).

Prevention

Pneumococcal vaccine—2 types of pneumococcal vaccine available

  1. a. 23-valent polysaccharide vaccine (PPSV23)

  2. b. 13-valent protein conjugate vaccine (PCV13)—each capsular polysaccharide is individually conjugated to a nontoxic variant of diphtheria toxin carrier protein, CRM197.

PPSV23 contains 23 pneumococcal serotypes that account for 85% to 90% of invasive disease in persons >2 years of age. PPSV23 is effective in preventing bacteremia, bacteremic pneumonia, and meningitis with an efficacy of 56% to 81%. The vaccine does not prevent non-bacteremic pneumonia.

PCV13 contains 13 pneumococcal serotypes that account for 92% of invasive disease. PCV13 has been proven effective in preventing bacteremia, pneumonia (with and without bacteremia), meningitis, otitis media with an efficacy of 90% to 100% against the various pneumococcal serotypes contained in the vaccine. This is a routinely recommended vaccine of childhood given as a 4 dose series at 2, 4, 6, and 15 to 18 months. Doses routinely may be given up to 5 years of age. Persons between 6 and 18 years of age who are at increased risk for IPD because of functional or anatomic asplenia, sickle cell disease, HIV or other immunocompromising conditions, cochlear implant, or CSF leak should receive a single dose of PCV13 regardless of whether they have received PPSV23 or PCV7 in the past. Conjugate vaccines like PCV13 also decrease nasopharyngeal colonization and indirectly reduce the risk of invasive pneumococcal disease in unvaccinated contacts.

The CDC has expanded recommendations for use of PCV13 vaccine in adults 19 years and older with certain immunocompromising conditions. In these situations vaccine is given as a single dose.

The CDC recommends both PCV13 and PPSV23 for

  • All adults age 65 years and older

  • Adults age 19 to 64 years with:

    • Conditions or treatments that affect the immune system (such as: HIV, lymphoma, leukemia, or Hodgkin disease, chronic kidney disease, radiation therapy, or certain long-term corticosteroid use, multiple myeloma

    • Functional or anatomic asplenia

    • Cochlear implants or cerebrospinal fluid (CSF) leaks

    • Organ transplant

    • Congenital or acquired immune deficiencies

If a patient has received at least one dose of PPSV23, a single dose of PCV13 is recommended at least 1 year after the last PPSV23 dose. If needed, a second PPSV23 dose is recommended for immunosuppressed and asplenic persons at least 8 weeks after PCV13 and five years after the first PPSV23.

If the patient has not previously been immunized with PPSV23, a dose of PCV13 should be given followed 1 year later by a dose of PPSV23.

CDC recommends only PPSV23 for the following adults age 19 to 64 years:

  • Those with chronic conditions such as asthma, diabetes, lung, heart, or liver disease, or alcoholism

  • Cigarette smokers

  • Residents of nursing homes or other long-term care facilities

These individuals should receive a dose of PCV13 when they reach age 65 years.

Vaccine efficacy

PPSV23 in older adults has an efficacy of about 75% against invasive pneumococcal disease. In the US, PCV13 in children ≤5 years of age has an effectiveness of 86% against IPD.

Contraindications and precautions for pneumococcal vaccines

Contraindications

  1. 1. For PCV13—Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component, including to any vaccine containing diphtheria toxoid.

  2. 2. For PPSV23—Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component.

Precautions

  • For both PCV13 and PPSV23—moderate or severe acute illness with or without fever

Frequently asked questions

What should be done in the situation where a 2-month-old was mistakenly given PPSV23 instead of PCV13?

PPSV23 is not effective in infants and children less than 24 months of age. PPSV23 given at this age should not be considered to be part of the pneumococcal vaccination series. PCV13 should be administered as soon as possible after the error was discovered.

Which children should receive PPSV23 vaccine (in addition to PCV13)? At what age should they receive PPSV23?

PPSV23 is recommended for children with an immunocompromising condition, functional or anatomic asplenia, and for immunocompetent children with chronic heart disease, chronic lung disease, diabetes mellitus, CSF leaks, or cochlear implants. One dose of PPSV23 should be administered to children age 2 years and older at least 8 weeks after the child has received the final dose of PCV13. Children with an immunocompromising condition, or functional or anatomic asplenia should receive a second dose of PPSV23 five years after the first PPSV23 dose.

Can PPSV23 be given to a pregnant woman with asthma?

Yes. PPSV23 is recommended in pregnancy if some other risk factor is present (e.g., on the basis of medical, occupational, lifestyle, or other indications).

Given that PPSV23 is indicated for smokers age 19 through 64 years, should adults who use smokeless tobacco products (e.g., chewing tobacco) also be vaccinated?

No. The CDC does not identify people who use smokeless tobacco products as being at increased risk for pneumococcal disease or as being in a risk group for vaccination.

Is PCV13 recommended for adults age 19 through 64 years who smoke?

No. PCV13 is only recommended for adults 19 through 64 years at increased risk for invasive pneumococcal disease because of an immunocompromising condition, asplenia, cerebrospinal fluid leak or cochlear implant.

Is obstructive sleep apnea (OSA) considered a chronic pulmonary disease which would require PPSV23 vaccination for adults under 65 years of age?

OSA alone is not an indication for vaccination with PPSV23 for persons 2 through 64 years of age. Persons with OSA often have other pulmonary conditions (e.g., chronic obstructive pulmonary disease) that would put them at increased risk for invasive pneumococcal disease, for which they should be vaccinated.

Can PPSV23 and PCV13 be administered at the same office visit?

No. PCV13 and PPSV23 should not be given at the same visit. If PCV13 is indicated, administer it if at least 1 year has passed since the previous dose of PPSV23 or if no doses of PPSV23 have previously been received. Then wait at least 8 weeks for adults with immune compromise and at least 1 year for all other adults to administer PPSV23.

If an adult who is 19 through 64 years of age has already gotten one or more doses of PPSV23, when should they get PCV13, if indicated?

PCV13 should be administered at least 1 year after the previous dose of PPSV23 was administered. For those who require additional doses of PPSV23, the first such dose should be given at least 8 weeks after PCV13 and at least 5 years since the most recent dose of PPSV23.

If a patient has had laboratory confirmed pneumococcal pneumonia or other invasive pneumococcal disease, do they still need to be vaccinated with PCV13 and/or PPSV23?

Yes. There are more than 90 known serotypes of pneumococcus. PCV13 contains 13 serotypes and PPSV23 contains 23 different serotypes. Infection with one serotype does not necessarily produce immunity to other serotypes. Therefore, if a person is a candidate for vaccination, they should receive it even after one or more episodes of invasive pneumococcal disease.

Do patients who were vaccinated with one or two doses of PPSV23 before age 65 years need an additional dose of PPSV23 at age 65 or later?

Yes. Patients who received one or two doses of PPSV23 for any indication at age 64 years of younger should receive an additional dose of PPSV23 vaccine at age 65 years or older if at least 5 years have elapsed since their previous PPSV23 dose.

If an adult age 65 years or older has already received one dose of PCV13 before age 65 for an appropriate indication, should another dose of PCV13 be given at age 65?

No. If a dose of PCV13 was already received before age 65 for an appropriate indication, no additional PCV13 doses are needed. A dose of PPSV23 should be administered at age 65 and at least 1 year following the PCV13 dose.

If patient over 65 years of age and has recently received one dose of PPSV23 is diagnosed with a medical condition that places them at increased risk for pneumococcal disease and its complications, should a second dose of PPSV23 be given in 5 years because of the underlying medical condition?

No. Individuals who are first vaccinated with PPSV23 at age 65 years or older should receive only one dose, regardless of any underlying medical condition that they may have developed.

Should the dose of PCV13 be repeated if given less than 1 year after a dose of PPSV23? If yes, what is the interval between doses?

No, if inadvertently administered sooner than the recommended interval, no repeat dose is recommended. The two vaccines should never be given during the same visit.

If I inadvertently administer PPSV23 less than 8 weeks after PCV13, do I need to repeat the dose of either vaccine?

No. Administration of PPSV23 less than 8 weeks after PCV13 may increase risk for localized reaction at the injection site but remains a valid vaccination and should not be repeated; the PCV13 dose also remains valid and should not be repeated.

How many doses of PPSV23 can an adult get in a lifetime?

Some adults may be recommended to receive up to 3 doses of PPSV23 in a lifetime. Two doses of PPSV23, given 5 years apart, are indicated for adults with functional or anatomic asplenia and immunocompromising conditions before age 65 years. Those adults should then receive a third dose of PPSV23 at or after 65 years, as long as it’s been at least 5 years since the previous dose.

How many doses of PCV13 can an adult get in a lifetime? Who/when?

All adults are recommended to receive 1 dose of PCV13 in a lifetime. If they received a dose of PCV13 prior to turning 65 years of age (due to a medical indication), they are not recommended an additional dose of PCV13 as part of the routine recommendation to administer PCV13 to all adults 65 years of age or older.

Can either PPSV23 and/or PCV13 be administered to patients with multiple sclerosis?

Yes. Multiple sclerosis is not a contraindication to any vaccine, including either of the pneumococcal vaccines.

When should patients (either children or adults) be vaccinated if they are scheduled to have either cochlear implant placement or an elective splenectomy?

It is preferable that the person planning to have the procedure have antibodies to pneumococcus at the time of the surgery. If possible, the appropriate vaccine should be administered prior to the cochlea implant or splenectomy. Infants and children 2 through 71 months of age should continue to receive PCV13 vaccine according to the recommended vaccine schedule.

Meningococcal Disease

Did you know that:

  • The “meningitis belt” refers to a region stretching across sub-Saharan Africa, which has seen recurring epidemics of meningococcal meningitis. An estimated 250,000 people developed meningitis and 25,000 died when the largest epidemic in recorded history spread through the region in 1996 and 1997. The Meningitis Vaccine Project has provided widespread vaccination with a low-cost conjugate meningococcal type A vaccine resulting in an 89% decrease in disease and an 83% decrease in deaths from 2009 to 2013.

  • In the pre-antibiotic era, the case fatality rate from meningococcal disease was 70% to 85%. Today, despite effective antimicrobial therapy and state-of-the-art intensive care, the overall case fatality rate remains 10% to 15%.

  • Many patients with severe meningococcal sepsis respond poorly to treatment with antimicrobial agents, steroids, or vasopressor agents, and death may occur within hours of onset.

Meningococcal disease is caused by the organism Neisseria meningitidis (encapsulated gram-negative diplococcus), which is strictly a human pathogen. Asymptomatic carriage is common with 10% of the general population and 25% to 30% of the adolescent/young adult population being carriers. Less than 1% of carriers will become symptomatic with disease. Most common clinical presentations of disease are meningitis accounting for about 50% of the cases with a 3% to 10% fatality rate and meningococcal sepsis (meningococcemia) accounting for 10% to 40% of cases with up to a 40% fatality rate. Both presentations may be associated with serious permanent sequelae. Fatality rates and rates of serious outcomes are significantly higher in the adolescent and young adult populations compared to general population (23% vs. 13%). Other clinical presentations that are less common include pneumonia, occult bacteremia, septic arthritis and otitis media.

Onset of disease can be nonspecific but often is abrupt and may progress rapidly over several hours. Patients develop fever, chills, sore throat, nausea and/or vomiting, general aches, diarrhea, headache, malaise, limb pain, abnormal skin color, cold hands and feet, and a rash that initially can be macular, maculopapular, petechial, or purpuric. In fulminant cases, purpura, limb ischemia, coagulopathy, pulmonary edema, shock with poor peripheral perfusion, hypotension, confusion, tachycardia, tachypnea and oliguria, coma, and death may occur in hours despite appropriate therapy. The signs and symptoms of meningococcal meningitis are indistinguishable from other causes of meningitis.

Complications and sequelae

  1. a. Meningococcemia includes: skin scars from necrosis, limb loss from gangrene, renal insufficiency, septic arthritis, pneumonia, epiglottis, pericarditis

  2. b. Meningitis includes: hearing loss, seizures, hemiparesis, spastic quadriplegia, cerebral infarction, cranial nerve palsies, cortical venous thrombophlebitis, mental retardation

Risk factors for disease include: impaired immunity (e.g., terminal complement component deficiency, properidin deficiency), functional or anatomic asplenia, nasopharyngeal irritation and disruption of the mucous membranes, social behaviors that predispose to exposure to secretions. Also persons traveling to or residing in countries where N. meningitidis is endemic; military recruits; persons attending summer camps and colleges who will be living in dormitory setting; microbiologists, laboratory personnel, and other healthcare workers who are routinely exposed to N. meningitidis.

Most common serogroups causing disease include: serogroup A, serogroup B, serogroup C, serogroup Y, serogroup X, and serogroup W-135. Serogroup distribution varies over time and geographically. Most common serogroups in US are B, C, Y, and W135; in Europe serogroup B, in African meningitis belt serogroup A, in Saudi Arabia serogroup W-135 and in New Zealand serogroup B.

Transmission

Person to person through contact with droplets from the respiratory tract. Transmission requires close contact. Close contact defined as:

  1. a. Household contact, especially children younger than 2 years of age

  2. b. Child-care or preschool contact at any time during 7 days before onset of illness

  3. c. Direct exposure to index patient’s secretions through kissing or through sharing toothbrushes or eating utensils, markers of close social contact, at any time during 7 days before onset of illness

  4. d. Mouth-to-mouth resuscitation, unprotected contact during endotracheal intubation at any time 7 days before onset of illness

  5. e. Frequently sleeping in same dwelling as index patient during 7 days before onset of illness

  6. f. Passengers seated directly next to the index case during airline flights lasting more than 8 hours

Incubation period

Incubation period is 1 to 10 days but usually less than 4 days.

Prevention

Postexposure

  1. a. Antibiotic chemoprophylaxis—regardless of immunization status, close contacts of all persons with invasive meningococcal disease are at high risk and should receive post-exposure chemoprophylaxis (Table 12). Chemoprophylaxis ideally should be initiated within 24 hours after the index patient is diagnosed; prophylaxis given more than 2 weeks after exposure has little value.

Table 12 Antibiotic Chemoprophylaxis Agents for Close Contacts of Patients with Invasive Meningococcal Disease

Antibiotic

Dose

Duration

Cautions

Rifampin

10 mg/kg PO q 12 hours (max 600 mg)

2 days

Can interfere with efficacy of oral contraceptives and some seizure and anticoagulant medications. Not recommended to be used in pregnant women

Ceftriaxone

<15 years of age

125 mg IM

Single dose

≥15 years of age

250 mg IM

Single dose

Ciprofloxacin

20 mg/kg PO (max 500 mg)

Single dose

Not recommended to be used in pregnant women

Azithromycin

10 mg/kg PO (max 500 mg)

Single dose

Not routinely recommended

  1. b. Quadrivalent meningococcal conjugate vaccine (MenACWY) should be given in addition to antibiotic chemoprophylaxis to those persons who have not previously been immunized. Vaccine is given intramuscularly.

Preexposure

Table 15 shows the available meningococcal vaccines against meningococcal serotypes A, C, W, Y.

  1. a. Quadrivalent meningococcal conjugate vaccine (MenACWY)—routinely recommended vaccination for all adolescents 11 to 18 years of age (Table 13), persons with HIV ≥2 months of age, and persons 2 to 54 years of age with persistent complement component deficiency or functional or anatomic asplenia. Vaccine should also be given to other persons at increased risk for meningococcal disease (see above risk factors for disease).

Table 15 Currently Available Meningococcal Vaccines

Trade Name

Type of Vaccine

Meningococcal Serogroups covered

MPSV4

Menomune®

Polysaccharide

A, C, W, Y

MenACWY

Menactra®

Conjugate

A, C, W, Y

MenACWY-CRM

Menveo®

Conjugate

A, C, W, Y

Hib-MenCY-TT

MenHibrix®

Conjugate

C, Y (and Haemophilus influenzae type b [Hib])

Table 13 Schedule for routine dosing of adolescents

Initial (primary) dose

Booster dose

11–12 years (preferred timing)

16 years

13–15 years

16–18 years

≥ 16 years

No booster needed

All persons ≥2 months of age with HIV should routinely receive meningococcal vaccine. The number of doses and dosing schedule are shown in the Table 14.

Table 14 Meningococcal vaccine schedule in patients with HIV

Primary vaccination

<2 years

4 doses of Menveo (MenACWY-CRM) at 2,4,6 and 12–15 months

2 doses of Menatra (MenACWY) at 9–23 months, 12 weeks apart

≥2 years

2 doses of Menveo or Menactra, 8 to 12 weeks apart

Booster dose

<7 years at previous dose

Additional dose of Menveo or Menactra 3 years after primary series; boosters should be repeated every 5 years thereafter

≥7 years at previous dose

Additional dose of Menveo or Menactra 5 years after primary series; boosters should be repeated every 5 years thereafter

Routine 2-dose primary series administered 2 months apart for: persons 2 to 54 years of age with persistent complement component deficiency, functional or anatomic asplenia and adolescents with HIV infection.

A dose should be given to persons traveling to or residing in countries where N. meningitidis is endemic; military recruits; persons attending summer camps and colleges who will be living in dormitory setting; microbiologists, laboratory personnel, and other health-care workers who are routinely exposed to N. meningitidis. Booster dose may be given 5 years after initial dose if the person continues to be in a situation of increased risk.

Vaccination with a meningococcal conjugate vaccine is recommended for infants aged 2 through 23 months at increased risk for meningococcal disease. Infants at increased risk for meningococcal disease are:

  • those with persistent complement component deficiencies (C3, C5–C9, properdin, factor D, and factor H),

  • those with functional or anatomic asplenia (including sickle cell disease),

  • healthy infants in communities with a meningococcal disease outbreak for which vaccination is recommended, and

  • those traveling to or residing in areas where meningococcal disease is hyperendemic or epidemic.

  1. b. Meningococcal serogroup B vaccine (MenB)—currently has a category B recommendation which means that the MenB vaccine series may be administered to adolescents and young adults aged 16 to 23 years to provide short term protection against most strains of serogroup B meningococcal disease based on the clinical judgment of the health-care provider for the individual patient (weighing the risk and benefits). The preferred age for MenB vaccination is 16 to 18 years.

There are two MenB vaccines that are licensed in the U.S. MenB vaccine should either be administered as a 2-dose or a 3-dose series of MenB-FHbp (Trumenba) or a 2-dose series of MenB-4C (Bexsero). The two MenB vaccines are not interchangeable; the same vaccine product must be used for all doses. Both vaccines may be administered concomitantly with other vaccines indicated for this age group.

  • MenB-FHbp (Trumenba)—2 dose series at 0 and 6 months 3 dose series given at 0, 1–2, and 6 months.

  • MenB-4C (Bexsero)—2-dose series given at least 1 month apart.

Efficacy

MenACYW—80% to 100% for the serotypes contained in the vaccine.

Duration of immunity

For MCV4 vaccines, probably 3 years. Duration of immunity for MenB vaccines unknown.

Contraindications and precautions for meningococcal vaccines

Contraindications

  • Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component.

Precautions

  • Moderate or severe acute illness with or without fever

Frequently asked questions

Is meningococcal polysaccharide vaccine appropriate for adolescents?

Only the quadrivalent meningococcal conjugate vaccine (MCV4) is recommended for adolescents. However, an initial dose of meningococcal vaccine administered as polysaccharide vaccine can be counted as valid. The booster dose of meningococcal vaccine should always be quadrivalent meningococcal conjugate vaccine. If polysaccharide vaccine is inadvertently administered as the booster dose, revaccination with conjugate vaccine is recommended 8 weeks later.

Who is recommended to be vaccinated against meningococcal disease?

MCV4 is recommended for:

  • All children and teens, aged 11 through 18 years of age

  • People younger than 22 years of age if they are or will be a first-year college student living in a residential hall

  • People aged 2 months and older with functional or anatomic asplenia (MenHibrix may be used for children age 6 weeks through 18 months in this group—vaccine only contains meningococcal serogroups C and Y)

  • People aged 2 months and older who reside in or travel to certain countries in sub-Saharan Africa as well as to other countries for which meningococcal vaccine is recommended (e.g., travel to Mecca, Saudi Arabia, for the annual Hajj)

  • Microbiologists who work with meningococcus bacteria in the laboratory

MenB is recommended for:

  • People 10 years of age and older who have functional or anatomic asplenia

  • People 10 years of age and older who have persistent complement component deficiency, or are at risk during an outbreak caused by a vaccine serogroup

  • Microbiologists who work with meningococcus bacteria in the laboratory

Can adolescents receive quadrivalent meningococcal vaccine and serogroup B meningococcal vaccine at the same time?

Yes. Meningococcal and other vaccines may be administered during the same visit but at a different anatomic site if feasible.

Is meningococcal vaccination recommended for adolescents during outbreaks?

Yes. If a meningococcal disease outbreak is serogroup A, C, W, or Y, vaccination with quadrivalent meningococcal vaccine is recommended for adolescents identified as being at increased risk. If the meningococcal disease outbreak is serogroup B, adolescents identified as being at increased risk because of the outbreak should be vaccinated with serogroup B meningococcal vaccine.

Why isn’t it recommended to administer the serogroup B meningococcal vaccine to all adolescents?

Administration of the serogroup B meningococcal vaccine to patients 16 through 23 years of age is left to the discretion of the clinician. Detailed efficacy and safety data for making policy recommendations are not yet available because these vaccines were licensed for use in the United States under an accelerated approval process. And the current burden of disease with this serotype is low. In the setting of an outbreak of serogroup B disease, vaccination would be appropriate.

How many doses of serogroup B meningococcal vaccine are necessary?

Both serogroup B meningococcal vaccines require more than one dose for maximum protection: two doses for Bexsero (0, ≥1 month after first dose) and two or three doses for Trumenba (0, 6 months after 1st dose or 0, 1–2 after 1st dose and 6 months after 1st dose). The same vaccine product must be used for all doses.

Are there any groups for whom a booster dose of MenB vaccine is recommended after completion of the primary series?

No. There is currently no recommended booster dose of MenB vaccine for any group.

Should persons with continued high risk of meningococcal disease receive additional doses of meningococcal vaccine beyond the 3- or 5-year booster?

Yes, people should receive additional booster doses (every 5 years) if they continue to be at highest risk for meningococcal infection.

Human Papillomavirus

Did you know that:

  • Infection with human papillomavirus (HPV) is universal among humans (both females and males).

  • The vast majority of US teenagers are not aware that a single sexual contact with an infected partner with or without a visible lesion can spread HPV.

  • Every 20 minutes in the United States a person acquires an infection with HPV.

  • In the USA, among girls 14 to 19 years old, HPV incidence dropped by nearly two-thirds from 11.5% to 4.3% since the introduction of HPV vaccines in 2006. For women 20 to 24 the rate was down slightly more than one-third from 18.5% to 12.1%.

In the United States, HPV will infect 80% of sexually active males and females in their lifetime. According to the CDC, there are approximately 14 million new genital HPV infections in the United States each year, half of which occur in people ages 15 to 24 years. For most people, HPV clears spontaneously, but for those who do not clear the virus, infection can lead to significant cancers and other diseases in men and women. There is no way to predict who in the population will clear the virus, although, the oncogenic types are more likely to persist and lead to the development of malignancy than the benign types.

Human papillomavirus (HPV) causes a range of disease manifestations including: cutaneous non-genital warts of the skin (e.g., common skin warts, plantar warts, flat warts, filiform warts), mucous membranes (e.g., anogenital, oral, nasal, and conjunctival areas), and the respiratory tract (e.g., respiratory papillomatosis). It also is associated with cervical, anogenital, and oropharyngeal dysplasias (precancers) and cancers. There are over 100 different serotypes of HPV that have been identified. These serotypes are subdivided into high-risk, oncogenic, serotypes and low-risk, non-oncogenic serotypes. The most common high-risk serotypes include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 73, 82, which account for 98% of all cervical cancers. Serotypes 16 and 18 account for 70% of all cervical cancers and the vast majority of other anogenital cancers. The most common low-risk serotypes include types 6, 11, 40, 42, 43, 44, 54, with serotypes 6 and 11 accounting for 90% of all external anogenital warts.

Transmission

Transmission takes place person to person by close contact. Nongenital warts are acquired through contact with HPV and minor trauma to the skin. Anogenital HPV infection is the most common sexually transmitted infection in the United States. Most infections are subclinical and resolve spontaneously within 2 years. Persistent infection with high-risk types of HPV is associated with development of cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers. In the case of respiratory papillomatosis, infection is transmitted to an infant through the birth canal during delivery by aspiration of infectious secretions. The finding of genital warts or laryngeal lesions in young children should raise the suspicion of child abuse.

Incubation period

Incubation period is unknown but is estimated to range from 3 months to 10 years.

Prevention

Condoms, both male and female provide some protection but as the male condom only covers the shaft of the penis, there is still the potential for contact and spread from the anogenital area. Female condoms that cover much of the anogenital area and the entire vagina should provide more protection; however, the usage of female condoms is not widespread or even advertised significantly.

The best protection is provided by HPV vaccines.

Postexposure

  1. a. HPV vaccine—there are three vaccines currently licensed in United States:

    1. i. HPV4 (contains serotypes 6/11/16/18)—licensed for use in both girls and boys 9 through 26 years of age for the prevention of cervical intraepithelial neoplasia (CINs), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), cervical, vulvar, vaginal cancers, anal intraepithelial neoplasia (AIN), anal cancers, and genital warts. It is given as a 3-dose intramuscular series at 0, 1 to 2, and 6 months.

    2. ii. HPV2 (contains serotypes 16/18)—licensed for use in girls 10 through 25 years of age for the prevention of CIN1, 2, 3; cervical AIS; and cervical cancer. It is given as a 3-dose intramuscular series at 0, 1, and 6 months.

    3. iii. HPV9 (contains the 4 serotypes in HPV4 6/11/16/18 plus 5 additional serotypes 31, 33, 45, 52, 58). It is licensed for use in both females and males ages 9–25, and is replacing HPV-4. It is given as a 3 dose intramuscular series at 0, 1–2, and 6 months or 2 dose intramuscular series at 0 and 6 months for adolescents 11 to 14 years of age. Effectiveness is expected to be over 90% worldwide.

    4. iv. HPV vaccine is still recommended to be given even after onset of sexual activity and if HPV positive since very unlikely to be infected with more than one serotype.

    5. v. These vaccines are not therapeutic vaccines and are not useful in treating any specific HPV-related conditions.

Preexposure

  1. a. HPV vaccines—the best time to administer is prior to the onset of sexual activity. It is not prudent to give the vaccine based on perceived risk, since it is not possible to predict onset of sexual activity in any patient. In multiple studies in New Zealand, Australia, and the United States, there was no increased sexual activity related to immunizing adolescents with HPV vaccine.

    1. i. HPV4 (contains serotypes 6/11/16/18)—licensed for use in both girls and boys 9 through 26 years of age for the prevention of cervical CINs, vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), anal cancers, and genital warts. It is given as a 3-dose intramuscular series at 0, 1 to 2, and 6 months.

    2. ii. HPV2 (contains serotypes 16/18)—licensed for use in girls 10 through 25 years of age for the prevention of CIN 1, 2, 3; cervical AIS; and cervical cancer. It is given as a 3-dose intramuscular series at 0, 1, and 6 months.

    3. iii. HPV9 (contains the 4 serotypes in HPV4 6/11/16/18 plus 5 additional serotypes 31, 33, 45, 52, 58). Licensed for use in both females and males ages 9–25, and is replacing HPV-4. It is given as a 3-dose intramuscular series at 0, 1–2, and 6 months or 0 and 6 months for the 2 dose series in adolescents 11 to 14 years of age.

    4. iv. Vaccines are not to be used as therapeutic vaccines.

Immunogenicity

  1. a. All HPV vaccines are 98% to 100% effective for the prevention of cervical precancers due to vaccine serotypes.

  2. b. HPV4 and HPV9 are 98% to 100% effective for the prevention of VIN and VAIN.

  3. c. HPV4 and HPV9 are 90% effective for the prevention of genital warts and anal cancers.

Vaccination rates in females and males 13 to 17 years of age in the United States remain around 39.7% and 21.6% respectively for receiving all 3 doses. Young patients are strongly encouraged to be vaccinated and parents should be strongly encouraged to have their children vaccinated. The emphasis must be “this is a cancer vaccine,” not a “sexual activity” vaccine. The recommendation of the health-care provider is the most important factor in a patient or parent’s acceptance of the vaccination.

Duration of immunity

Duration is at least 12 years.

Contraindications and precautions to HPV vaccine

Contraindications

  1. 1. Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component

  2. 2. HPV4 and HPV9—severe allergic reaction (e.g., anaphylaxis) to yeast

  3. 3. HPV2—severe allergic reaction (e.g., anaphylaxis) to latex

Precautions

  1. 1. Moderate or severe acute illness with or without fever

  2. 2. Pregnancy

Frequently asked questions

If a person was vaccinated at age 11 years and completed the 3-dose series, and is now aged 20 years and sexually active, should she receive a booster dose of vaccine?

NO. Long-term studies have shown no loss of efficacy at least 13 years after the first series of vaccinations.

Should individuals who have completed a 3-dose series of HPV2 or HPV4 receive a booster dose or be revaccinated with a 3-dose series of HPV9?

At this time, there are no recommendations for a booster dose of vaccine or revaccination with HPV9. There are data that indicate revaccination with HPV9 after a series of HPV4 is safe. Clinicians should decide if the benefit of immunity against 5 additional oncogenic strains of HPV is justified for their patients.

If a patient received 1 or 2 doses and has not completed the 3-dose series, should the series be restarted?

NO. Even if a long period of time has passed since the last vaccine dose, the series should not be restarted but should be resumed where it was left off and can be completed at any time. However, if multiple doses are needed, the timing between doses cannot be shortened.

Should HPV9 be used in males ages 16 to 26 years, given that current FDA licensure is for males 9 to 15 years of age?

Although HPV9 vaccine was initially licensed for use in males aged 9 to 15 years, the CDC ACIP and the AAP recommend that this vaccine be used in males through age 21 years routinely and in high-risk males age 21 to 26 years old. To arrive at this off-label male recommendation, the CDC ACIP reviewed data that was not yet available during the FDA licensure process. This has now been submitted for FDA review.

Will giving HPV vaccination encourage sexual activity in my teenage child?

No. Multiple studies have shown no difference in the initiation of sexual activity in adolescents who have or not received the HPV vaccine. These studies used STD incidence, use of contraception, pregnancy and abortion rates in determining the lack of differences in the 2 groups.

If a woman becomes pregnant and has received only 1 or 2 doses of HPV vaccine can she complete the series during the pregnancy?

No. Even though HPV vaccine poses no risk to the fetus, the doses should be delayed until after the pregnancy. She may receive the vaccine even if she is breast feeding.

Is HPV vaccine effective for patients over the age of 26 years?

HPV vaccine has been tested in patients up to age 45 years, and although there is an immune response, it is less robust than what occurs in younger patients. Patients could receive the vaccine off label, however, insurance would probably not pay for the vaccine.

If a patient has received 1 or 2 doses of HPV2 or HPV4 vaccine, can the patient complete the series with HPV9?

Yes. Any available HPV vaccine may be used to continue to complete the series for females. HPV4 or HPV9 can be used to continue or complete the series for males. However, receiving fewer than 3 doses of HPV4 or HPV9 may provide less protection against genital warts caused by HPV types 6 and 11 than the usual 3-dose series. There are no data on the efficacy of the 5 additional HPV types included in HPV9 if the person receives fewer than 3 doses.

Can the HPV vaccine damage a woman’s ovaries?

No. The CDC and FDA have found no evidence that HPV vaccine is associated with premature ovarian failure. There has also been no evidence of amenorrhea or irregular menses in women who have received the vaccine.

Why is HPV vaccine recommended if Pap tests can detect cervical cancer?

Pap tests are effective screening tests and can detect precancerous changes before progression to cancer. But the vaccine actually prevents cancer in the first place, and Pap tests are not perfect (overall 50% sensitivity), and not all women get tested as often as recommended.

Should women still have Pap tests done after receiving HPV vaccine?

Yes. Although the HPV9 vaccine protects against over 90% of the cancer producing HPV viruses, many women have received either the HPV2 or HPV4 vaccines which protect against approximately 70% of oncogenic virus types. Pap screening recommendations may well change as a higher percentage of women are vaccinated.

Do women and men whose sexual orientation is same sex need HPV vaccine?

Yes. HPV vaccine is recommended for females and males regardless of their sexual orientation.

Is there an accelerated vaccination schedule to complete the HPV vaccine series?

No. There is no accelerated schedule for completing the HPV vaccine series. The recommended schedule of 0, 1–2, and 6 months or 0 and 6 months (adolescents 11 to 14 years of age) should be followed.

If HPV vaccine is inadvertently given subcutaneously instead of intramuscularly, does the dose need to be repeated?

Yes. No data exist on the efficacy or safety of HPV vaccine given by the subcutaneous route, therefore, the CDC and the manufacturers recommend that a dose of HPV vaccine given by any route other than intramuscular should be repeated. There is no minimum interval between the invalid subcutaneous dose and the repeat dose.

Haemophilus Influenzae Type B (Hib) Disease

Did you know that:

  • Before the availability of Hib conjugate vaccine, each year in the United States about 20,000 children under 5 years of age got Hib disease, and 3% to 6% died from their disease.

  • The bacteria was first isolated by Pfeiffer from the sputum of patients in 1892 during an outbreak of influenza, and it was proposed that there was a causal association between the bacteria and the clinical syndrome of influenza.

Haemophilus influenzae type b (Hib) is a pleomorphic gram-negative coccobacillus. It may cause a variety of different infections including pneumonia, bacteremia, meningitis, epiglottis, septic arthritis, osteomyelitis, cellulitis, otitis media, purulent pericarditis, endocarditis, endophthalmitis, peritonitis and gangrene. Before the introduction of effective Hib conjugate vaccines (before 1990), Hib was the most common cause of bacterial meningitis in children in the United States. There were 20,000 cases a year of invasive disease with the peak age of infections occurring in infants between 6 and 18 months of age. Non-type b encapsulated strains cause disease similar to type b infections. Nontypeable strains commonly cause infections of the respiratory tract (e.g., otitis media, sinusitis, pneumonia, and conjunctivitis). Less commonly, these strains may be the cause of bacteremia, meningitis, chorioamnionitis, and neonatal sepsis.

Unimmunized children ≤4 years of age are at increased risk of invasive Hib disease. Other risk factors that predispose to invasive disease in all ages include: sickle cell disease, asplenia, human immunodeficiency virus (HIV) infection, certain immunodeficiency syndromes and malignant neoplasms. Historically, invasive Hib disease was more common in boys; black, Alaskan Native, Apache, and Navajo children; daycare attendees; children living in crowded conditions; and children who were not breastfed. Since the introduction of Hib conjugate vaccines in the United States, the incidence of invasive Hib disease has decreased by 99%. Currently, invasive disease occurs primarily in underimmunized children and among infants too young to have completed the primary immunization series. Hib remains a major pathogen in many resource-limited countries where Hib vaccine is not routinely available. In the United States, non-typeable H. influenzae now causes the majority of invasive disease in all age groups.

Transmission

The major reservoir of Hib is young infants and toddlers who carry the organism in the upper respiratory tract, which is the nature habitat of H. influenzae in humans. Transmission is person-to-person by inhalation of respiratory tract droplets or by direct contact with infected respiratory tract secretions. In neonates, infection is acquired intrapartum by aspiration of amniotic fluid or by contact with genital tract secretions containing the organism. Pharyngeal colonization by H. influenzae is common, especially with nontypeable and non-type b capsular types.

Incubation period

Unknown

Prevention is available only for Hib

Post-exposure

Careful observation of exposed, unimmunized, or incompletely immunized children who are household, childcare, or nursery school contacts of patients with invasive Hib disease is essential.

  1. a. Chemoprophylaxis—the risk of invasive Hib disease is increased among unimmunized, or incompletely immunized household contacts younger than 4 years of age. Rifampin (20 mg/kg, max dose 600 mg—given once a day for 4 days) eradicates Hib from the pharynx in about 95% of carriers and decreases the risk of secondary invasive infection in exposed household contacts. Nursery and childcare center contacts under 4 years of age may also be at increased risk of secondary disease. The following are indications for rifampin chemoprophylaxis for contacts of index cases of invasive Hib disease.

    • For all household contacts (defined as people living with the index patient or nonresidents who spend 4 or more hours with the index patient for at least 5 of the 7 days preceding the day of hospital admission) in the following circumstances:

      • household with at least 1 contact younger that 4 years of age who is unimmunized or incompletely immunized

      • household with a child younger than 12 months of age who has not completed the primary Hib series

      • household with a contact who is an immunocompromised child, regardless of that child’s Hib immunization status

    • for preschool and childcare contacts when 2 or more cases of Hib invasive disease have occurred within 60 days

    • for index patient, if younger than 2 years of age or member of household with a susceptible contact and treated with a regimen other than ceftriaxone or cefotaxime, chemoprophylaxis is provided just before hospital discharge

  2. b. Hib vaccine—in addition to chemoprophylaxis, unimmunized or incompletely immunized children should receive a dose of Hib vaccine and should be scheduled for completion of the recommended age-specific immunization schedule.

Preexposure

  1. a. Hib vaccine—vaccine is given intramuscularly

    1. i. Primary series—depending on the vaccine used, the recommended primary series consists of 3 doses given at 2, 4, and 6 months of age (DTaP-IPV/PRP-T), or 2 doses given at 2 and 4 months of age (PRP-OMP, PRP-OMP-HepB). If PRP-OMP vaccine is not administered as both doses in the primary series, a third dose of Hib conjugate vaccine is needed to complete the primary series.

    2. ii. Booster dose—recommended to be given at 12 through 15 months of age.

Contraindications and Precautions for Hib vaccine

Contraindications

  1. 1. Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component.

  2. 2. Age younger than 6 weeks.

Precautions

  • Moderate or severe acute illness with or without fever

Efficacy

Efficacy is 98% to 100% against Hib.

Frequently asked questions

Can all the licensed Hib-containing vaccines be used interchangeably?

Yes, but there is one exception. The GSK monovalent product (Hiberix) is only licensed for the booster dose of vaccine.

If Hiberix is inadvertently given as some or all of the doses of the primary Hib vaccine series, do the doses need to be repeated?

No, the administered doses count and do not need to be re-administered with another Hib vaccine.

If an infant received one dose of Hib at 4 months of age, and another at 16 months of age, do they need any additional doses of Hib vaccine?

No, if an infant receives a dose of Hib vaccine at 15 months of age or older, they do not need any further Hib vaccine doses regardless of the number of doses received before 15 months of age.

If a 4-year-old patient received dose #3 of Hib vaccine at 6 months of age, does the child need a fourth dose of Hib?

Yes, all children less than 5 years of age need at least one dose of Hib vaccine on or after the first birthday. The last dose should be separated from the previous dose by at least 2 months.

The booster dose of Hib vaccine is recommended to be given at 12 to 15 months of age. If a patient received their first dose of Hib vaccine at 12 months of age, is it necessary to administer the booster dose 2 months later?

If the child received a primary series (2 or 3 doses) of Hib vaccine in the first year of life, then the final (booster) dose of the series may be given as early as 12 months, provided at least 2 months have passed since the last dose. An unvaccinated 12- to 14-month-old child should receive one dose of Hib vaccine as the primary series, and a booster dose 2 months later. Unvaccinated children 15 to 59 months of age need only a single dose of any licensed conjugate Hib vaccine.

Does an 8-year old who does not have a record of ever receiving Hib vaccine need a dose?

The CDC does not recommend routine Hib vaccination of healthy children 59 months or older, even if they have no prior history of receiving Hib vaccination.

Which adults should receive a dose of Hib vaccine?

Hib vaccine is recommended for adults with sickle cell disease, leukemia, HIV infection, and persons with functional or anatomic asplenia if they have not previously received Hib vaccine. A standard pediatric dose of any Hib vaccine may be used. Hib vaccine is not routinely recommended for healthy adults 19 years of age and older.

When should Hib vaccine be administered to a person having a splenectomy?

When elective splenectomy is planned, vaccination with pneumococcal, meningococcal, and Hib vaccines should be administered at least 2 weeks prior to the surgery, if possible. If the vaccines are not administered before surgery, they should be administered as soon as the person’s condition stabilizes post-operatively.

Poliovirus Infections

Did you know that:

  • None of the 3 strains of wild poliovirus can survive outside the human body for very long and will die out if the virus can’t find an unvaccinated person to infect.

  • Franklin D. Roosevelt, the thirty-second president of the United States, contracted paralytic polio at the age of 39, resulting in partial paralysis of his legs and the inability to walk without the aid of crutches, leg braces, or a wheelchair.

  • In addition to Franklin Delano Roosevelt, a well-known polio survivor; others include science fiction writer Arthur C. Clarke, artist Frida Kahlo, golfer Jack Nicklaus, swimmer (and actor) Johnny Weissmuller, actors Mia Farrow and Alan Alda, and singer/songwriters Neil Young and Joni Mitchell.

  • Poliomyelitis has affected humankind since ancient times. An Egyptian stele from the 18th dynasty (1403 to 1365 bc) depicts a crippled young man with a withered and shortened right leg, with his foot held in a typical equinus position characteristic of flaccid paralysis.

  • In the prevaccine era, poliomyelitis was the leading cause of permanent disability. It was a feared disease because it could strike anyone, and no means existed to protect oneself or one’s children.

  • Epidemic poliomyelitis in the early 20th century was associated with a case fatality rate of 27.1%.

  • The first iron lung was constructed in 1928 and its widespread use in the 1930s and 1940s rapidly decreased the case fatality rate of bulbar forms of poliomyelitis.

  • The game Candy Land was invented in 1948 by a patient trying to cheer up kids in a polio ward.

  • Polio can be completely eradicated.

Polioviruses are group C enteroviruses that consist of serotypes 1, 2, and 3. Poliovirus infections occur only in humans. About 72% of poliovirus infections in susceptible children are asymptomatic. A non-specific febrile illness with low-grade fever and sore throat occurs in 24% of people who become infected. Aseptic meningitis (pleocytosis with a lymphocytic predominance), sometimes with paresthesias occurs in 1% to 5% of patients a few days after the minor illness has resolved. Paralytic polio occurs in less than 1% of infected persons. There is the rapid onset of asymmetric acute flaccid paralysis with areflexia of the involved limb and residual paralytic disease involving the motor neurons that occurs in approximately two-thirds of people with acute motor neuron disease. Cranial nerve involvement and paralysis of respiratory tract muscles can occur.

Adults who contracted paralytic poliomyelitis during childhood may develop the non-infectious post-polio syndrome 15 to 40 years later. Post-polio syndrome is characterized by slow and irreversible exacerbation of weakness most likely occurring in those muscle groups involved during the original infection. Muscle and joint pain are common. Studies estimate the risk of post-polio syndrome in poliomyelitis survivors to be 25% to 40%.

No cases of polio have originated in the United States since 1979; the last case of wild-type polio in a US resident traveling abroad occurred in 1986, and the last imported case of polio in the United States occurred in 1993. Globally, polio cases have decreased by over 99% since 1988 due to a concerted global effort to eradicate the disease. In 1994 the World Health Organization (WHO) Region of the Americas was certified polio-free, followed by the WHO Western Pacific Region in 2000, the WHO European Region in June 2002, and the WHO South East Asian Region in 2014. Of the three types of wild poliovirus, type 2 wild poliovirus transmission has been successfully eradicated since 1999. In 2016 only 2 countries in the world continue to have endemic circulating wildtype poliovirus—Afghanistan, and Pakistan, down from 125 in 1988. However, as long as wildtype poliovirus continues to circulate, children in all countries are at risk of contracting polio.

Transmission

Spread is by the fecal, oral, and respiratory routes. Infection is more common in infants and young children and occurs at an earlier age among children living in poor hygienic conditions. Communicability of poliovirus is greatest shortly before and after the onset of clinical disease, when the virus is present in the throat and is excreted in high concentration in the feces. Virus persists in the throat for approximately 2 weeks after onset of illness and is excreted in the feces for 3 to 6 weeks. Patients are potentially contagious as long as fecal excretion persists.

Incubation period

For nonparalytic polio, the incubation period is 3 to 6 days. For the onset of paralysis in paralytic poliomyelitis, the incubation period is usually 7 to 21 days.

Prevention

Preexposure prophylaxis

  1. a. Inactivated polio vaccine (IPV)—four doses of IPV vaccine are recommended for routine immunization of all infants and children.

    1. i. The first 2 doses of the 4-dose vaccine series should be given at 2-month intervals beginning at 2 months of age (2 mo, 4 mo). The third dose is recommended to be given at 6 through 18 months of age. A fourth and final dose in the series should be administered at 4 years of age or older regardless of the number of previous doses and at a minimum interval of 6 months from the third dose. If a child misses an IPV dose at 4 through 6 years of age, the child should receive a booster dose as soon as feasible.

    2. ii. Most adults living in the United States are presumed to be immune as a result of previous immunization. However, immunization is recommended for certain adults who are a greater risk of exposure to wild-type polioviruses than the general population, including the following:

      • travelers to areas or countries where poliomyelitis is or may be epidemic or endemic

      • laboratory workers handling specimens that may contain wild-type polioviruses

      • health-care personnel in close contact with patients who may be excreting wild-type polioviruses

For unimmunized or incompletely immunized adults, primary immunization with IPV vaccine is recommended as a series of 3 doses. Two doses of IPV vaccine should be given at intervals of 1 to 2 months (4 to 8 weeks); a third dose is given 6 to 12 months after the second dose. If 3 doses of IPV cannot be administered within the recommended intervals before protection is needed, the following alternatives are recommended:

  • If >8 weeks are available before protection is needed, 3 doses of IPV should be administered ≥4 weeks apart.

  • If <8 weeks but >4 weeks are available before protection is needed, 2 doses of IPV should be administered ≥4 weeks apart.

  • If <4 weeks are available before protection is needed, a single dose of IPV is recommended.

Vaccine efficacy

Both inactivated polio vaccine (IPV) and oral live, attenuated polio vaccine (OPV) are highly immunogenic and effective in preventing poliomyelitis. IPV is the only polio vaccine available in the United States. After 2 doses of IPV, greater than 95% of recipients seroconvert to the 3 polio serotypes contained in the vaccine. After 3 doses, seroconversion is seen in 99% to 100% of vaccine recipients.

Duration of immunity

At least 18 years after a 3-dose series of vaccine.

Contraindications and precautions for polio vaccine

Contraindications

  • Vaccine is contraindicated for people who have experienced an anaphylactic reaction after a previous dose of IPV vaccine or to streptomycin, neomycin, or polymyxin B.

Precautions

  1. 1. Moderate or severe acute illness with or without fever

  2. 2. Pregnancy

Frequently asked questions

If there is no longer any polio in the Western Hemisphere, why do we still recommend universal polio vaccination?

If polio vaccination were discontinued in the United States, there would be millions of susceptible children within a year. Since wild polio infection still occurs in the world, the virus could be imported and an epidemic could result.

After what age is routine polio vaccine no longer recommended?

Routine polio vaccination is not recommended for persons 18 years of age and older who reside in the United States.

Exceptions would include adults at risk for coming into contact with polio virus: traveling in polio-endemic areas of the world (currently Afghanistan or Pakistan), working in a laboratory and handling specimens that might contain polioviruses, and those who may have close contact with someone who could be infected with poliovirus.

Is vaccine-derived poliovirus a risk in the United States?

Vaccine-derived poliovirus (VDPV) is a strain of poliovirus that was initially contained in OPV and that has mutated over time and behaves more like the wild-type virus. These strains may be transmitted to unvaccinated persons and cause illness, including paralytic poliomyelitis—indistinguishable from the illness caused by wild-type poliovirus. VDPV can cause outbreaks in countries where vaccine coverage with OPV is low. Because OPV has not been used in the United States since 2000 and vaccine coverage with IPV is high, the risk of VDPV in the United States is very low. It would be possible for an unvaccinated person to acquire VDPV from some who recently received live oral vaccine in another country.

How long is oral polio vaccine virus shed in the stool after the dose?

OPV may be shed in the stool for up to 6 weeks, but can be longer in immunosuppressed individuals. Viral shedding in the stool is generally longest following the first dose and is generally shorter with each subsequent dose.

A 4-year-old who is entering pre-K has a vaccination record that shows that they received 4 doses of IPV given at 2 months, 4 months, 6 months, and 2 years of age. Does this child need a booster dose of vaccine?

Yes. The current recommendations are that a child receive 4 doses of IPV vaccine with the last dose being given on or after the fourth birthday.

If a 10-year-old child adopted from another country received three doses of oral polio vaccine (OPV) before their first birthday, should they receive an additional dose of inactivated poliovirus vaccine (IPV)?

Yes. The patient should receive a dose of IPV now. The final dose of the polio vaccine series should be received on or after the fourth birthday, regardless of the number of doses received prior to the fourth birthday.

What polio vaccination schedule should be used for older children who have not completed their IPV series?

The schedule for polio vaccination for unvaccinated or under-vaccinated older children through age 17 years is a total of 3 doses of IPV: 2 doses of IPV separated by 4 to 8 weeks, and a third dose 6 to 12 months after the second dose. Polio vaccine is not routinely administered to persons 18 years of age and older.

Should adults get vaccinated against polio if they are traveling to a high-risk area where polio still occurs?

If an adult at increased risk previously received only one or two doses or polio vaccine (either OPV or IPV), they should receive the remaining dose(s) of IPV regardless of the interval since the last polio vaccine dose. If the at risk adult previously completed a primary course of polio vaccine (three of more doses of OPV or IPV), they may be given another dose of IPV to ensure protection. Only “one” booster dose of polio vaccine in a person’s lifetime is recommended. It is not necessary to administer a booster dose each time a person travels to an area where polio may be occurring.

Should an adult, who was diagnosed with polio as a child with some residual effects that now will be traveling to a high-risk area where polio still occurs, be vaccinated with polio vaccine even though they had polio in the past?

Immunity to one of the serotypes of polio does not produce significant immunity to the other serotypes. A history of having recovered from polio disease should not be considered evidence of immunity to polio. In this situation it is appropriate to vaccinate this person with a dose of IPV if they are traveling to a high-risk area.

A 22-year-old patient has been accepted to a medical school that requires polio vaccine for all the students. The patient has 2 documented doses of OPV vaccine as a child, then received a dose of IPV upon college entry at age 18 years. How many additional doses of IPV should this patient receive to complete the series and on what schedule?

Persons who receive a mixed series of OPV and IPV should receive a total of 4 doses of vaccine. The dose of IPV can be counted as the third dose in the primary series. The minimum interval between the third and last doses in the polio vaccination series is 6 months; therefore, the final dose in the series should be administered 6 months or greater after the last IPV dose.

Rotavirus Infections

Did you know that:

  • Worldwide, rotavirus is estimated to cause 450,000 to 600,000 deaths in children each year, which is approximately 20 to 25% of the estimated 1.9 million annual deaths from diarrhea.

  • Rotavirus diarrheal illness causes 1,200 to 1,600 deaths per day in developing countries.

  • Fluid loss from severe rotavirus diarrhea in an infant can be as much as 20 ml/Kg per hour.

Rotaviruses are segmented, double-stranded RNA viruses with at least 7 distinct antigenic groups (A through G). Group A viruses are the major causes of rotavirus diarrhea worldwide. Serotyping is based on the 2 surface proteins, VP7 glycoprotein (G) and VP4 protease-cleaved hemagglutinin (P). Prior to introduction of the rotavirus vaccine, G types 1 through 4 and 9 and P types 1A and 1B were the most common in the United States. Rotavirus infection is the leading cause of severe acute diarrhea among young children worldwide. In the United States, prior to the introduction of rotavirus vaccine in 2006, rotavirus caused an estimated 20 to 60 deaths, 55,000 to 70,000 hospitalizations, 205,000 to 272,000 emergency department visits, and 410,000 outpatient visits annually. Nearly every child in the United States was infected with rotavirus by 5 years of age and most developed gastroenteritis. Rotavirus was responsible for 5%–10% of all gastroenteritis episodes among children less than 5 years of age in the United States.

Infection begins with the acute onset of fever and vomiting followed 24 to 48 hours later by watery diarrhea. Symptoms generally persists for 3 to 8 days. In moderate to severe cases, dehydration, electrolyte abnormalities, and acidosis may occur. The epidemiology of rotavirus disease in the United States has changed dramatically since rotavirus vaccines became available in 2006. The overall burden of rotavirus disease has significantly declined. In the first 2 years after the RV5 vaccine became available, ER visits and hospitalizations for rotavirus decreased by 85% (estimated 40,000 to 60,000 fewer gastroenteritis hospitalizations among children younger than 5 years of age.) There were also substantial reductions in office visits for gastroenteritis during this time period.

Transmission

Believed to be by the fecal-oral route. Rotavirus can be found on toys and hard surfaces in child-care centers, indicating that fomites may also serve as a mechanism of transmission. Respiratory transmission may play a minor role in disease transmission.

Incubation period

1 to 3 days

Prevention

Preexposure

  1. a. Rotavirus vaccine—there are 2 rotavirus vaccines licensed for use among infants in the United States (Table 16). In February 2006, a live, oral human-bovine reassortant pentavalent rotavirus vaccine (RV5) was licensed as a 3-dose series for use among infants in the United States. In April 2008, a live, oral human attenuated monovalent rotavirus vaccine (RV1) was licensed as a 2-dose series for infants in the United States. Vaccine is administered orally.

Table 16 Oral Rotavirus Vaccines

Recommendation for Use

RV5 (RotaTeq—Merck)

RV1 (Rotarix—GSK)

Number of doses in the series

3

2

Recommended ages for doses

2, 4, and 6 months of age

2 and 4 months of age

Minimum age for first dose

6 weeks of age

6 weeks of age

Maximum age for first dose

14 weeks, 6 days of age

14 weeks, 6 days of age

Minimum interval between doses

4 weeks

4 weeks

Maximum age for last dose

8 months, 0 days of age

8 months, 0 days of age

  1. i. Rotavirus vaccine can be administered concurrently with other childhood vaccines.

  2. ii. Preterm infants may be immunized if at least 6 weeks of postnatal age and are clinically stable. They should be immunized on the same schedule and with the same precautions recommended for full-term infants. The first dose of the vaccine should be given at the time of discharge or after the infant has been discharged from the nursery.

  3. iii. Breastfeeding infants should be immunized according to the same schedule as non-breastfed infants.

  4. iv. Infants who have had rotavirus gastroenteritis before receiving the full series of rotavirus immunization should begin or complete the schedule following the standard age and interval recommendations.

Vaccine contraindications

  1. 1. Rotavirus vaccine should not be given to infants who have a history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose of rotavirus vaccine or to a vaccine component. Latex rubber is contained in the RV1 vaccine oral applicator, so infants with a severe allergy to latex (e.g., anaphylaxis) should not receive RV1.

  2. 2. Severe combined immunodeficiency (SCID) and a history of intussusception are contraindications for use of both RV1 and RV5 rotavirus vaccines.

Vaccine efficacy

  1. a. RV5—effectiveness after 3-dose series ranges from 96% to 100% against severe rotavirus disease, 78% to 100% against disease requiring hospitalization and 96% in preventing disease requiring an outpatient visit

  2. b. RV1—effectiveness after 2-dose series ranges from 76% to 89% against rotavirus disease requiring hospitalization and 50% in preventing disease requiring an outpatient visit

Frequently asked questions

How long is a person with rotavirus diarrhea contagious?

Infected persons shed large quantities of virus in their stool beginning 2 days before the onset of diarrhea and for up to 10 days after onset of symptoms. Rotavirus may be detected in the stool of persons with immune deficiency for more than 30 days after infection.

Can a person get rotavirus disease more than once?

Yes. A person may develop rotavirus disease more than once because there are many different rotavirus types, but second infections tend to be less severe than the first infections. After a single natural infection, 40% of children are protected against a subsequent rotavirus illness. Persons of all ages can get repeated rotavirus infections, but symptoms may be mild or not occur at all in repeat infections.

Can adults be infected with rotavirus?

Yes. Rotavirus infection of adults is usually asymptomatic but may cause diarrheal illness. Outbreaks of diarrheal illness caused by rotavirus have been reported, especially among elderly persons living in retirement communities and nursing homes.

Should an infant who has already been infected with rotavirus still be vaccinated?

Yes. Infants who have recovered from a rotavirus infection may not be immune to all of the virus types present in the vaccine. So infants who have previously had rotavirus disease should still complete the vaccine series if they can do so by age 8 months.

If it is unknown which rotavirus vaccine an infant previously received, how should the vaccine schedule be completed?

If the product used for a previous dose is unknown, and the infant is at an age when the vaccine can still be administered, a total of 3 doses of rotavirus vaccine should be given. All doses of vaccine should be administered by age 8 months and 0 days.

If the first dose of rotavirus vaccine is inadvertently given to an infant age 15 weeks and older, should the vaccine series be continued?

Infants for whom the first dose of rotavirus vaccine was inadvertently administered at age 15 weeks or older should receive the remaining doses of the series at the routinely recommended intervals. The timing of the first dose should not affect the safety and efficacy of the remaining doses. Rotavirus vaccine should not be given after 8 months 0 days even if the series is incomplete.

In the situation where an infant received the first dose of rotavirus vaccine but got laboratory confirmed rotavirus disease prior to the second vaccine dose, should the infant complete the vaccine series?

CDC recommends that infants who have had rotavirus gastroenteritis before receiving the full series of rotavirus vaccination should still start or complete the schedule according to the age and interval recommendations since the initial rotavirus infection might provide only partial protection against subsequent rotavirus disease.

If an infant regurgitates or vomits during or after rotavirus vaccine administration, should the dose be repeated?

No—if an infant spits, regurgitates, or vomits during or after rotavirus vaccine has been administered, the dose should not be repeated. The next dose of vaccine should be administered at the appropriate interval.

Can an infant receive rotavirus vaccine if there are pregnant or immunocompromised individuals that live in the same household?

Infants living in households with pregnant women or immunocompromised people can be immunized with rotavirus vaccine. Transmission of vaccine virus strains from vaccines to unimmunized contacts is uncommon.

Table 17 Contradictions and Precautions for Commonly Used Vaccines

Vaccine

Contraindications

Precautions

For all vaccines

Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component

Moderate or severe acute illness with or without fever

In addition to the above, addition contraindications and precautions for specific vaccines

  • Diphtheria, tetanus, pertussis (DTaP, DTP)

  • Tetanus, diphtheria, pertussis (Tdap)

  • Tetanus, diphtheria (DT, Td)

For pertussis containing vaccines: encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) not attributable to another identifiable cause within 7 days of administration of a previous dose of DTP, DTaP, or Tdap

  • Guillain-Barré Syndrome (GBS) within 6 weeks after a previous dose of tetanus toxoid-containing vaccine

  • History of Arthus-type hypersensitivity reactions after a previous dose of tetanus or diphtheria toxoid-containing vaccine; defer vaccination until at least 10 years have elapsed since the last tetanus-toxoid-containing vaccine

  • For pertussis-containing vaccines: progressive or unstable neurologic disorder (including infantile spasms for DTaP), uncontrolled seizures, or progressive encephalopathy until a treatment regimen has been established and the condition has stabilized

For DTaP/DTP only:

  • Temperature of 105˚F or higher (40.5˚C or higher) within 48 hours after vaccination with a previous dose of DTP/DTaP

  • Collapse or shocklike state (i.e., hypotonic hyporesponsive episode) within 48 hours after receiving a previous dose of DTP/DTaP

  • Seizure within 3 days after receiving a previous dose of DTP/DTaP

  • Persistent, inconsolable crying lasting 3 or more hours within 48 hours after receiving a previous dose of DTP/DTaP

Haemophilus influenzae Type b (Hib)

Age younger than 6 weeks

Hepatitis B

Infants weighing less than 2000 grams (4 lbs, 6.4 oz)

Human papillomavirus (HPV)

  • Severe allergic reaction (e.g. anaphylaxis) to yeast—HPV4, HPV9

  • Severe allergic reaction (e.g. anaphylaxis) to latex—HPV2

Pregnancy

Inactivated poliovirus vaccine (IPV)

Pregnancy

Influenza, inactivated injectable (IIV)

Severe allergic reaction (e.g., anaphylaxis) to prior dose of vaccine or to vaccine component

  • History of Guillain-Barré syndrome (GBS) within 6 weeks of previous influenza vaccination

  • Persons who experience only hives with exposure to eggs may receive recombinant influenza vaccine (RIV) or, with additional safety precautions, IIV.

Influenza, recombinant (RIV)—Flublok

Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component, RIV does not contain any egg protein, thimerosal, antibiotics, latex, gelatin, or formaldehyde

History of GBS within 6 weeks of previous influenza vaccination

Influenza, live, attenuated (LAIV)

  • People younger than 2 years or older than 49 years

  • Concomitant use of aspirin or aspirin-containing medication in children or adolescents through age 17 years

  • Specific populations: pregnant women; immunosuppressed people; children ages 2 through 4 years who have asthma or had wheezing within the past 12 months; people who have taken influenza antiviral medications (amantadine, rimantadine, zanamivir, or oseltamivir) within the previous 48 hours; avoid using these antiviral agents for 14 days after vaccination

  • History of GBS within 6 weeks of previous influenza vaccination

  • Asthma in persons aged 5 years and older

  • Other chronic medical conditions (other chronic lung diseases; chronic cardiovascular diseases excluding isolated hypertension; diabetes; chronic renal or hepatitis disease; hematologic disease; neurologic disease; and metabolic disorders

Measles, mumps, rubella (MMR)—live

  • Known severe immunodeficiency (e.g., from hematologic and solid tumors, receipt of chemotherapy, congenital immunodeficiency, or long-term immunosuppressive therapy, or patients with HIV infection who are severely immunocompromised

  • Pregnancy

  • Recent (within 11 months) receipt of antibody-containing blood product (specific interval depends on product)

  • History of thrombocytopenia or thrombocytopenia purpura

  • Need for tuberculin skin testing (Measles vaccine may suppress tuberculin reactivity temporarily. MMR may be administered on the same day as tuberculin skin testing; however, if testing cannot be performed at the same time, the test should be postponed for at least 4 weeks after MMR vaccination.)

Pneumococcal conjugate (PCV13)

Severe allergic reaction (e.g., anaphylaxis) to any vaccine containing diphtheria toxoid

---

  • Rotavirus—live, attenuated oral

  • RV5—RotaTeq

  • RV1—Rotarix

  • Severe combined immunodeficiency (SCID)

  • History of intussusception

  • Immunodeficiency other than SCID

  • Chronic gastrointestinal disease##

  • Spina bifida or bladder extrophy##

Varicella (VZV)—live

  • Known severe immunodeficiency (e.g., from hematologic and solid tumors, receipt of chemotherapy, congenital immunodeficiency, or long-term immunosuppressive therapy, or patients with HIV infection who are severely immunocompromised)

  • Pregnancy

  • Recent (within 11 months) receipt of antibody-containing blood product (specific interval depends on product)#

  • Receipt of specific antivirals (e.g., acyclovir, famiciclovir, or valacyclovir) 24 hours before vaccination; avoid use of these antiviral drugs for 14 days after vaccination

Zoster (HZV)—live

  • Known severe cellular immunodeficiency (e.g., from hematologic and solid tumors, receipt of chemotherapy, congenital immunodeficiency, or long-term immunosuppressive therapy, or patients with HIV infection who are severely immunocompromised)

  • Pregnancy

  • Receipt of specific antivirals (e.g., acyclovir, famiciclovir, or valacyclovir) 24 hours before vaccination; avoid use of these antiviral drugs for 14 days after vaccination