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Investigating emerging infectious diseases 

Investigating emerging infectious diseases
Chapter:
Investigating emerging infectious diseases
Author(s):

Ibrahim Abubakar

, Molebogeng X. Rangaka

, and Marc Lipman

DOI:
10.1093/med/9780198719830.003.0006
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date: 24 October 2020

Introduction to investigating emerging infectious diseases

On 13 June 2012, a 60-year-old Saudi man was admitted to a private hospital in Jeddah, Saudi Arabia, with a 7-day history of fever, dyspnoea, and productive cough. The patient’s symptoms, signs, and laboratory and radiological investigations were consistent with an infectious cause. He was severely ill, requiring management in intensive care, and died 11 days later. Serological tests and WGS identified the cause of this fatal illness as a previously unrecognized virus, which is now known as Middle East respiratory syndrome coronavirus (MERS-CoV).1

Since then, the epidemiology and clinical features of the infection caused by this pathogen have been identified, and a putative zoonotic source determined. The high mortality observed in the MERS-CoV outbreak illustrates the potential for emerging pathogens to cause human illness and challenge public health systems globally.

Newly identified infectious agents, such as MERS-CoV, are constantly being detected. Emerging and re-emerging infectious diseases thus pose an ongoing threat to global health security. It is not a question of if, but when, the next pathogen that will lead to a local outbreak or pandemic will arise. The study of emerging infections and how to detect and contain them is therefore an essential component of public health practice globally.

What are emerging and re-emerging infections?

No consensus definition exists for emerging or re-emerging infectious diseases. Similarly, the timescale within which a particular infection may be considered existing or re-emerging has not been defined. Emerging infectious diseases is thus a broad term coined to describe the occurrence of infections whose incidence is increasing due to new pathogens appearing in a population, or as a result of previously known organisms rapidly increasing in incidence or geographic range.2 Figure 6.1 shows select examples of recent emerging/re-emerging pathogens.3 Infectious diseases may emerge or re-emerge due to:

  • a new species of pathogen arising, such as HIV or the coronaviruses responsible for SARS and Middle East respiratory syndrome (MERS)

  • organisms that were previously unrecognized as human pathogens such as Helicobacter pylori (which is now known to be associated with chronic gastric ulcers)

  • an altered form of a previously known pathogen, such as new strains of the influenza virus, including avian and swine forms that have acquired the ability to cause severe disease in humans and can be transmitted from person to person. Emergence of drug-resistant pathogens and their widespread distribution, such as drug-resistant Mycobacterium tuberculosis, Escherichia coli, Neisseria gonorrhoeae, Pneumococcus spp., Shigella spp., Plasmodium falciparum, and Staphylococcus aureus, which have turned previously manageable microbes into new threats to global health. A recent review commissioned by the government in the UK estimated that drug-resistant pathogens could cost the global economy trillions of dollars by 2050 if action is not taken.

Figure 6.1 (a) Emerging and re-emerging infectious diseases, 2005–15. The map shows countries (shaded) with at least one case of a newly recorded emerging or re-emerging infectious disease in the Global Outbreak Alert and Response Network (GOARN) database between 2005 and 2015 (data accessed in February 2015); (b) Timeline for emergence of new pathogens.
Figure 6.1 (a) Emerging and re-emerging infectious diseases, 2005–15. The map shows countries (shaded) with at least one case of a newly recorded emerging or re-emerging infectious disease in the Global Outbreak Alert and Response Network (GOARN) database between 2005 and 2015 (data accessed in February 2015); (b) Timeline for emergence of new pathogens.

Figure 6.1 (a) Emerging and re-emerging infectious diseases, 2005–15. The map shows countries (shaded) with at least one case of a newly recorded emerging or re-emerging infectious disease in the Global Outbreak Alert and Response Network (GOARN) database between 2005 and 2015 (data accessed in February 2015); (b) Timeline for emergence of new pathogens.

(a) Made with Natural Earth. Free vector and raster map data @ naturalearthdata.com.

Source: data from Global Outbreak Alert and Response Network (GOARN), World Health Organization, Geneva, Switzerland, Copyright © WHO 2015, available from Investigating emerging infectious diseases http://www.who.int/ihr/alert_and_response/outbreak-network/en/.

Re-emerging diseases are known diseases that have reappeared after a significant decline in incidence. Such infections are not caused by new pathogens but result from the re-emergence of microbes or diseases that had previously been controlled successfully. Moreover, many important infectious diseases have never been controlled adequately on either the national or international level, so infectious diseases that have posed ongoing health problems in developing countries may re-emerge in more developed countries (e.g. TB, poliomyelitis, food- and waterborne infections, Ebola virus, West Nile virus infection).

Factors involved in the emergence or re-emergence of infectious diseases

Many factors contribute to the (re-)emergence of new infectious diseases. The concept of the epidemiological triangle provides a useful model for understanding disease emergence. The complex interplay of factors in the human host, factors within microbes (the infectious agent), the genomes of both, interactions with other organisms, and the environment determines the emergence and re-emergence of pathogens. Table 6.1 summarizes widely recognized factors involved in the emergence of infectious diseases.4 These factors include ecological and environmental changes, human demographic and behavioural issues, technological advances, poverty and inequality, factors altering the immunity of the human host, and population movement and mixing such as at mass gatherings.

Table 6.1 Factors involved in the emergence of infectious diseases

Factor

Description (with examples)

Environment

Ecological changes (voluntary or involuntary; includes land use)

  • Environmental factors such as climate change

    • Global warming caused by human activities may influence emergence of viral and bacterial vector-borne diseases

  • Farming practices that change the habitat of vectors

    • Factors affecting animal density, antibiotic use in animals, and changes in animal diet

    • Dams

    • Irrigation

    • De/reforestation

    • Flood/drought

Human demographics (include economic development)

  • Economic and cultural drivers

    • Increased population growth

    • Overcrowding

    • Changing levels of poverty

    • Poor housing

    • Poor sanitation

    • Increased mobility

    • Intercontinental transport of cargo

Human behaviour (includes intent to harm)

  • Human behaviour plays an important role in re-emergence

    • Overuse of pesticides and antibiotics, as well as poor stewardship of commonly prescribed antibiotics, may result in emergence of drug-resistant pathogens, allowing many diseases that were formerly treatable with drugs to make a comeback (e.g. tuberculosis, malaria, and nosocomial and food-borne infections)

    • Recently, decreased compliance with vaccination policy has led to re-emergence of previously controlled diseases such as measles and pertussis

    • Increased risk of exposure to zoonotic agents through animal or human displacement (voluntary or involuntary)

    • Changes in activity period of wild animals (under pressure of hunting)

    • Increased contact between human and livestock/wild animals or other reservoirs (may be associated with outdoor activities such as hunting or may expose humans to bacteria excreted by healthy animal carriers)

    • Bioterrorism, in which previously controlled microbes are considered for deliberate release into general population; use of deadly pathogens, such as smallpox and anthrax, as agents of bioterrorism is an increasingly acknowledged threat

International travel, commerce, and mass gatherings

  • Population movement and mixing is a key determinant of subsequent spread of infections (Table 6.2)

    • Air travel has revolutionized the rate at which human populations move between regions of the world and so also the potential for spread of infections

    • Mass gatherings provide unique contexts within which infections can be spread and novel strains transferred to new populations

Technology and industry

  • Although technological development and industry has mostly contributed to better living conditions and reduced global burden of infections, some aspects of technology and industry have played a role in emergence and re-emergence of infections

    • Medical technologies such as transfusion and hypodermic needles

    • Rapid mechanization of farming leading to deforestation and spread of vector-borne and other infections such as Lassa fever

    • Dams and waterborne diseases

    • Globalization of food supply

    • Iatrogenic immunosuppression

Breakdown in public health measures (includes lack of will, war, and famine)

  • Poor public health infrastructure, which may result from poor governance and conflicts

  • Lack of coordination or harmonization of control systems between neighbouring countries

Poverty and social inequality

  • Many infections are spread more effectively within context of poverty through overcrowding in urban slums and malnutrition, which increases susceptibility

Human host

Increased susceptibility

  • Healthy immune systems are required to protect against infection or disease, and changes in human immunity may arise from infectious diseases such as HIV, iatrogenic reasons such as treatment for cancers, and as a consequence of age and even poor nutrition

Microbe (infectious agent)

Microbial adaptation and change

  • Evolution of pathogens through acquisition of new genes by mutations or exchange between organisms (e.g. New Delhi metallo-β‎-lactamase gene), which could result in response to selection in an environment

  • Natural genetic variations, recombinations, and adaptations could allow emergence of new strains of known pathogens to which the human immune system has not been previously exposed and that it is therefore not primed to recognize (e.g. influenza)

HIV, human immunodeficiency virus.

Source: data from Morse SS and Schluederberg A., From the National Institute of Allergy and Infectious Diseases, the Fogarty International Center of the National Institutes of Health, and the Rockefeller University. Emerging viruses: the evolution of viruses and viral diseases, Journal of Infectious Diseases, Volume 162, Issue 1, pp. 1–7, Copyright © 1990, Oxford University Press.

The zoonotic origin of many emerging infections deserves special consideration. Some emerging infections are caused by microbes that originate in non-human vertebrates. Examples of recently emerging viruses that probably originated in non-human vertebrate hosts are HIV, SARS, MERS-CoV, and several viruses that cause haemorrhagic fever, including Ebola virus and Lassa virus. The most well-known of these is HIV—the virus that causes AIDS—which most likely arose from interspecies transmission between non-human primates, such as the central chimpanzee Pan troglodytes troglodytes, and humans. Subsequent population movement—such as migration of populations between countries and different world regions, travel for economic and other reasons, and mass gatherings (Box 6.1)—provides avenues for the spread of zoonotic or other pathogens that have emerged in one part of the world, leading to the potential for a pandemic.

Surveillance and control of emerging infections

The detection of, and subsequent response to, an emerging or re-emerging infection depends on the pathogen concerned, the disease syndrome caused, how and when it was detected, existing infrastructure for surveillance and public health action available at the site of detection, and the local, national, and global context within which it has emerged. Infections with high morbidity/mortality and potential for spread that emerge over a relatively short period of time require an appropriate initial response, including risk assessments, and measures designed to tackle acute public health emergencies, which will differ depending on the suspected aetiology of the disease. The US CDC’s response to the SARS coronavirus (SARS-CoV) outbreak is provided as an exemplary case study in Table 6.2.7

Table 6.2 Centers for Disease Prevention and Control (CDC)’s response to outbreak of severe acute respiratory syndrome (SARS)

Year

Month

Day

Description

2002

November

16

  • First case of atypical pneumonia reported in Guangdong province of southern China

2003

March

12

  • WHO issued global alert for severe form of pneumonia of unknown origin in people from China, Vietnam, and Hong Kong

14

  • CDC activated its EOC

15

  • CDC issued first health alert and hosts media telebriefing about atypical pneumonia, which had been named severe acute respiratory syndrome (SARS)

  • CDC issued interim guidelines for state and local health departments on SARS

  • CDC issued ‘health alert notice’ for travellers to USA from Hong Kong, Guangdong Province, China

20

  • CDC issued infection control precautions for aerosol-generating procedures in patients suspected of having SARS

22

  • CDC issued interim laboratory biosafety guidelines for handling and processing specimens associated with SARS

24

  • CDC laboratory analysis suggested new coronavirus may be cause of SARS

  • 39 suspected cases identified in USA to date, 32 of which had travelled to countries where SARS was reported

27

  • CDC issued interim domestic guidelines for management of exposures to SARS for healthcare and other institutional settings

28

  • SARS outbreak had become more widespread

  • CDC began utilizing pandemic planning for SARS

29

  • CDC extended travel advisory for SARS to include all of mainland China and Singapore

  • CDC quarantine staff began meeting planes, cargo ships, and cruise ships coming directly or indirectly to USA from China, Singapore, and Vietnam and began distributing health alert notice to travellers

April

4

  • 115 suspected cases of SARS reported from 29 states in USA; no deaths among these suspected cases

5

  • CDC established community outreach team to address stigmatization associated with SARS

10

  • CDC issued specific guidance for students exposed to SARS

14

  • CDC published sequence of virus believed to be responsible for global epidemic of SARS, as identifying genetic sequence of new virus is important to treatment and prevention efforts; results came just 12 days after team of scientists and technicians began working around clock to grow cells taken from throat culture of one patient with SARS

22

  • CDC issued health alert notice for travellers to Toronto, Ontario, Canada

May

6

  • In USA, no new probable cases had been reported in past 24 hours, and there had been no evidence of ongoing transmission beyond initial case reports in travellers for more than 20 days; containment in USA had been successful

20

  • CDC lifted travel alert on Toronto because more than 30 days (or three SARS incubation periods) had elapsed since date of onset of symptoms for last reported case

23

  • CDC reinstated travel alert for Toronto, because Canadian health officials reported cluster of five new probable SARS cases on 22 May

June

4

  • CDC removed travel alert for Singapore and downgraded traveller notification for Hong Kong from travel advisory to travel alert

July

3

  • CDC removed travel alert for mainland China

5

  • WHO announced global SARS outbreak was contained

10–15

  • CDC removed travel alert for Hong Kong, Toronto, and Taiwan

17

  • CDC updated SARS case definition, excluding cases in which blood specimens collected more than 21 days after onset of illness tested negative, which halved number of cases in USA

December

31

  • WHO had received reports of SARS from 29 countries and regions globally; this comprised 8096 people with probable SARS and 774 deaths

  • Eight SARS infections in USA were documented by laboratory testing and additional 19 probable SARS infections were reported

2004

January

13

  • CDC issues 'Notice of embargo of civets’, which banned importation of civets, after SARS-like virus was isolated from civets captured in areas of China where SARS outbreak originated

2012

October

5

  • National Select Agent Registry Program declared SARS coronavirus a select agent (defined as a bacterium, virus, or toxin that has potential to pose severe threat to public health and safety)

CDC, Centers for Disease Control and Prevention; EOC, emergency operations centre; SARS, severe acute respiratory syndrome; USA, United States of America; WHO, World Health Organization.

Reproduced from Centres for Disease Control and Prevention (CDC), CDC SARS response timeline, CDC, Atlanta, GA, USA, available from Investigating emerging infectious diseases http://www.cdc.gov/about/history/sars/timeline.htm.

Control measures for less acute conditions are just as challenging, and successful implementation may take several years or decades. This is illustrated by several ongoing epidemics in poor settings, including those caused by HIV and TB, where global action has been essential to the control of these infections.

For all infections, irrespective of how fast or slow the epidemic evolves, the following are essential:

  • local, national, and global surveillance systems to detect new infections and monitor control efforts (see Investigating emerging infectious diseases Chapter 2)

  • disease control systems

  • a programme of applied research, including field epidemiology and applied microbiology

  • an infrastructure that allows a rapid response to emergencies and is robust enough to sustain the control of longer-lasting epidemics.

Initial clinical response and assessment of risk

Health personnel are often the first to respond to a potential threat of a new pathogen. This places them at direct risk, sometimes leading to significant illness and possibly death. Health personnel accounted for a substantial proportion of deaths in the 2014 Ebola outbreak in West Africa.5 Transmission within the healthcare setting and beyond is also possible if the infectious nature of the new pathogen is not realized quickly and dealt with systematically. Both SARS and MERS spread successfully in healthcare settings.6,8 An early systematic assessment of risk therefore is essential to trigger the correct epidemic response and deal with public concern.

Initial patient assessment includes, in the first instance, attending to the patient and providing rapid medical attention. Patients should be asked about potential risk factors and details of their contacts and recent travel history. In the case of a newly emerging pathogen, working case definitions may not exist yet. If an infectious nature is suspected, immediate actions should include isolating the patient and introducing infection prevention and control measures, while a detailed risk assessment is carried out. Local standard operating procedures on conducting initial risk assessment of a potential threat should exist and would be helpful. Examples of such frameworks include the Advisory Committee on Dangerous Pathogens (ACDP)’s risk assessment guidance and algorithm on VHF,9 which is issued by the government in the UK, and the ECDC’s rapid risk assessment tools.10

In resource-rich contexts, an early consultation with a local infection specialist may be possible. Local hotlines, such as the UK’s 24-hour imported fever service and rare and imported pathogens laboratory, may offer further advice on testing and clinical management. In the case of a suspected zoonosis, it is essential to assess the risk of transmission to humans. A qualitative risk assessment tool that assigns levels of confidence of risk of zoonotic transmission of animal diseases is available in the UK.11 Once a risk assessment has been completed and a substantial threat is identified, the public will need to be informed.

Informing the public

Concern is fuelled by the public’s perception of their own risk of exposure and infection, the availability of treatment for themselves and their dependents, and local efforts to mitigate the new threat. The media has an important role to play in conveying correct, up-to-date information as part of an organized public health response to the emerging infection.

Managing an acute public health emergency

The public health response to a newly emerged pathogen with potential to cause an outbreak or pandemic usually requires the prompt institution of measures to contain its spread, including the following actions:

  • Identify the problem: use descriptive epidemiology, ‘soft’ intelligence gathering, desktop review of available information, sentinel surveillance (if necessary), and outbreak investigation measures, including microbiological investigations, as summarized in Box 6.2 and outlined in Investigating emerging infectious diseases Chapter 3.

  • Set up the required structure and organization: this includes an emergency operating centre and relevant command-and-control infrastructure and assigning roles and responsibilities. In an emergency, this may be the critical factor that determines whether there is chaos or successful disease control.

  • Conduct rapid hazard and health risk assessment: tools developed by governmental and non-governmental bodies for rapid assessment of the hazards and risk should be utilized, and the information gathered analysed to inform subsequent actions.

  • Establish related surveillance and emergency information systems for ongoing monitoring: this may initially include sentinel surveillance and clinical criteria for establishing the diagnosis; it is essential to establish laboratory surveillance as soon as this is feasible.

  • Set up communications systems for healthcare workers and the general population: messages communicated in the early phase of an emerging infection may determine population behaviour and may be essential to prevent nosocomial spread among health workers; provided information should include what to expect, how the disease might be prevented, and how to seek care.

  • Plan interventions based on findings of rapid review, surveillance, and aetiology of the outbreak: this may include environmental and occupational health; infection control; and behavioural, medical, and other measures.

  • Target specific vulnerable populations, core groups, and other drivers of spread: for many outbreaks and epidemics, the focus of spread is a particular core group or vulnerable population, so tackling the disease in such subpopulations may be the key to disease control; until such a reservoir is addressed, efforts to control and possibly eliminate the outbreak as a public health problem may not be possible.

  • Plan for recovery and reconstruction while managing the outbreak: it is never too early to set up plans for recovery, and this is particularly critical for outbreaks or epidemics that have been detected after they have caused considerable morbidity and mortality in the population.

  • Set up systems to evaluate the response and learn lessons to prevent future public health emergencies.

National or regional surveillance systems

The organization of national or regional systems for emerging infections is based on the analysis and synthesis of information collected by official public health institutions of health such as Public Health England in the UK and the US CDC. Data are often provided to health officials through partnerships and networks involving medical practitioners and veterinary agencies.

Global mechanisms

At the global level, a number of recognized systems aid the detection of emerging infections.

World Health Organization systems

The IHR12 are an agreed set of policies, and WHO member states that have signed up to these obligations are required to implement them. This includes a range of measures, implementation of which may require new or modified legislation in some countries. Implementation of IHR began in 2007 and has led to a framework within which the WHO has established an international advisory committee. All member states are expected to foster global partnerships; strengthen national disease prevention, surveillance, control, and response systems; improve public health security in travel and transport; support the WHO global alert and response systems; ensure the management of specific risks; sustain rights, obligations, and procedures; conduct studies; and monitor progress towards implementation of the measures. The WHO runs the Global Outbreak Alert and Response Network (GOARN) which effectively provides global intelligence on emerging infections.

Early Warning and Response System

The Early Warning and Response System (EWRS) is a mechanism established by the EU to allow the competent public health authorities of the EU member states to exchange information on public health incidents promptly, allowing public health actions to be taken to contain threats across the EU.

Programme for Monitoring Emerging Diseases

Programme for Monitoring Emerging Diseases (Pro-Med) is an Internet-based system that allows the rapid global dissemination of information on outbreaks of infectious diseases and acute exposures to toxins that affect human health. It is less formal than GOARN and EWRS and operates as a programme of the International Society for Infectious Disease.

GeoSentinel and European Travel Medicine Network

GeoSentinel (Investigating emerging infectious diseases http://www.istm.org/geosentinel) is a worldwide communication and data collection network for the surveillance of travel-related morbidity. It was initiated in 1995 by the International Society of Travel Medicine (ISTM) and the US CDC as a network of ISTM member travel/tropical medicine clinics. GeoSentinel is based on the concept that these clinics are ideally situated to detect geographic and temporal trends in morbidity among travellers, immigrants, and refugees.

The ISTM also initiated the European Travel Medicine Network (EuroTravNet; Investigating emerging infectious diseases http://www.istm.org/eurotravnet) to create a network of clinical experts in tropical and travel medicine to support the detection, verification, assessment, and communication of infectious diseases that can be associated with travelling, specifically tropical diseases. The goal of EuroTravNet is to build, maintain, and strengthen a multidisciplinary network of highly qualified experts with demonstrated competence in diseases of interest, ideally in the fields of travel advice; tropical medicine; clinical diagnosis of the returned traveller; and detection, identification, and management of imported infections. The founding core sites and members of EuroTravNet belong to the GeoSentinel surveillance network.

Future priorities

The current approach, in which we wait for new pathogens to emerge before responding, needs to be replaced by a more proactive system that includes prevention of such outbreaks, rapid detection and response by a well-resourced system, and resilience to tackle the longer-term consequence of such outbreaks. Heymann et al.13 have described a model that should help achieve this, based on the ‘OneHealth’ approach, which depends on collaboration between local, national, and international experts to address human, animal, and environmental health issues.

The response to the threat of emerging and re-emerging infectious diseases requires a global plan that builds on current mechanisms, such as GOARN, and that relies on existing agreements, such as the IHR, to create robust systems to support research, training, surveillance, and control. One element of this plan is the need to strengthen developing countries’ health systems, especially those that are weak due to previous conflict or underdevelopment. The contrast between Nigeria and other West African states in containing the outbreak of Ebola fever in 2014 illustrates the importance of health infrastructure and manpower in limiting the spread of emerging infectious diseases.

Consistent with the ‘OneHealth’ approach, wider determinants of emerging infections would also need to be addressed, including antimicrobial resistance, zoonotic origin of new and re-emerging infections, and changing environmental and population-level factors that determine the emergence and spread of pathogens.

Finally, the development of an applied research infrastructure—including generic protocols that are pre-approved by ethics governance committees, funding agreements, and the formation of international consortia such as the International Severe Acute Respiratory and Emerging Infection Consortium—and of an inclusive global clinical trials programme would be essential to prevent or, if that fails, to contain the next pandemic.

References

1. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier RAM (2012). Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med, 2012, 367, 1814–20.Find this resource:

2. Morse SS, Schluederberg A (1990). From the National Institute of Allergy and Infectious Diseases, the Fogarty International Center of the National Institutes of Health, and the Rockefeller University. Emerging viruses: the evolution of viruses and viral diseases. J Infect Dis,162, 1–7.Find this resource:

3. Koenig KL, Schultz CH. The 2014 Ebola virus outbreak and other emerging infectious diseases. In: Koenig and Schultz’s disaster medicine: comprehensive principles and practices, 2nd edn, p. 10. Available at: Investigating emerging infectious diseases http://www.acep.org/uploadedFiles/ACEP/practiceResources/issuesByCategory/publichealth/The%202014%20Ebola%20Virus%20Outbreak.pdf, Oct 21, 2014, (accessed 25 June 25 2015).

4. Morse SS (1995). Factors in the emergence of infectious diseases. Emerg Infect Dis, 1, 7–15.Find this resource:

5. WHO Ebola Response Team (2014). Ebola virus disease in West Africa—the first 9 months of the epidemic and forward projections. N Engl J Med, 371, 1481–95.Find this resource:

6. Seto WH, Tsang D, Yung RWH, et al. (2003). Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet, 361, 1519–20.Find this resource:

7. Centers for Disease Control and Prevention (CDC). CDC SARS response timeline. CDC, Atlanta. Available at: Investigating emerging infectious diseases http://www.cdc.gov/about/history/sars/timeline.htm (accessed 18 February 2015).

8. Assiri A, McGeer A, Perl TM, et al. (2013). Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med, 369, 407–16.Find this resource:

9. Public Health England, Department of Health (2014). Viral haemorrhagic fever: ACDP algorithm and guidance on management of patients. Public Health England and Department of Health, London. Available at: Investigating emerging infectious diseases https://www.gov.uk/government/publications/viral-haemorrhagic-fever-algorithm-and-guidance-on-management-of-patients (accessed 18 February 2015).Find this resource:

10. European Centre for Disease Prevention and Control (ECDC) (2014). Rapid risk assessment: outbreak of Ebola virus disease in West Africa. ECDC, Stockholm. Available at: Investigating emerging infectious diseases http://www.ecdc.europa.eu/en/publications/Publications/Ebola-Sierra%20Leone-Liberia-Guinea-Nigeria-23-09-2014-rapid-risk-assessment.pdf (accessed 18 February 2015).Find this resource:

11. Palmer S, Brown D, Morgan D (2005). Early qualitative risk assessment of the emerging zoonotic potential of animal diseases. BMJ, 331, 1256–60.Find this resource:

12. World Health Assembly (2005). Revision of the International Health Regulations, WHA58.3. 2005. Available at: Investigating emerging infectious diseases http://apps.who.int/gb/ebwha/pdf_files/WHA58-REC1/english/Resolutions.pdf (accessed 19 January 2015).

13. Heymann DL, Dar OA (2014). Prevention is better than cure for emerging infectious diseases. BMJ, 348, g1499.Find this resource: