Yellow Fever                             

• Introduction
• Epidemiology
• Risk for Travellers
• Transmission
• Signs and Symptoms
• Treatment
• Prevention
• Vaccine Information
• International Health Regulations
• References

Introduction

Yellow fever (YF) virus is an arthropod borne virus of the Flaviviridae family within the genus flavivirus. Other flaviviruses include dengue fever and Japanese encephalitis viruses. YF is considered to be one of the most lethal viral diseases. The endemic zones for the disease are in tropical regions of Africa and South America.

Epidemiology

(Information collated by the Travel Health Surveillance Section of the Health Protection Agency, Communicable Disease Surveillance Centre).

Global Epidemiology

YF is endemic in tropical parts of Africa and South America. Endemic regions include countries (or areas within countries) where there is the potential for human infection because of the presence of the mosquito vector and of the YF virus in non-human primates. In endemic areas human cases may be occurring but are below the level of surveillance detection and are not reported to the World Health Organization (WHO).

To date YF has not appeared in Asia or the Pacific region. The World Health Organization (WHO) estimates that there are approximately 200,000 cases of YF every year with 30,000 deaths. Under International Health Regulations (IHRs) [1] cases of YF should be reported to the WHO. Countries that are reporting human cases are termed infected countries. However, as stated earlier, human cases of YF may be occurring below the level of surveillance detection. Therefore the distinction between endemic and infected areas is no longer being made, and the term endemic zone, area or country is used to describe both infected and endemic areas.

In addition, YF is under reported, especially in Africa where the disease is most prevalent. As an example of underreporting, in 1999, only 208 cases (including 101 deaths) of YF were officially notified to the WHO and all but one of the reports originated from the Americas.

In consultation with WHO and the Pan American Health Organization (PAHO), scientists at the US Centers for Disease Control and Prevention (CDC) have undertaken to more clearly define the endemic zones based on up-to-date epidemiological data. This has resulted in the revision of their yellow fever maps.

                         

Yellow fever endemic zones CDC 2005

This map is reproduced with acknowledgement to the US Centers for Disease Control and Prevention

Outbreaks of Yellow Fever

In recent years, outbreaks of YF have been reported to the WHO most commonly from West Africa (http://www.who.int/disease-outbreak-news/disease/A95.htm). Since the year 2000 there have been outbreaks in Liberia, Côte D'Ivoire, Nigeria, Guinea, Peru and Brazil. In 2002, an outbreak reported in Senegal involved 60 cases including 11 deaths; most cases occurred in the central area north of The Gambia but one case occurred in the capital Dakar. In 2003, there were five outbreaks reported; three in West Africa (Guinea, Sierra Leone and Burkina Faso) and one in Sudan where there were 178 cases and 27 deaths. In February 2003, an outbreak of sylvatic YF was reported in Brazil in which there were 24 cases and five deaths all reported from Minas Gerais state.

Epidemiology of Yellow Fever in UK Travellers

Since 1982 there have been two Statutory Notifications of YF in England and Wales, but no laboratory reports to the Centre for Infections. Statutory Notifications are made on the grounds of clinical suspicion and/or diagnosis therefore notified cases may not have been laboratory confirmed or reported through the laboratory network. The last known case occurring in the UK was in a laboratory worker who contracted the disease whilst working with the yellow fever virus at the Hospital for Tropical Diseases in London [2].

There have been other cases in European and American travellers. In 1996 two tourists died from YF following trips to the Amazon Basin in Brazil [3,4]. A further two travellers died in 1999 after contracting the virus in Venezuela and Cote d'Ivoire [5,6], and in 2001 a traveller died in a Belgian hospital after contracting YF whilst on holiday near the Gambia/Senegal border [7]. In 2002, an American died of YF after returning from a fishing trip on the Amazon near Manaus, Brazil [8].

Risk for Travellers

The risk of contracting YF is determined by the following factors:

• Travel destination
• Intensity of YF transmission in area to be visited
• Season of travel
• Duration of travel
• Activities allowing exposure to mosquitoes
• Immunisation status

Although ongoing cases and outbreaks of YF are occurring in Africa and South America, the disease is preventable by vaccination and remains a very rare cause of illness in travellers. In recent years there have been six recorded deaths from YF in non-vaccinated travellers.

Transmission

Jungle primates and humans are the vertebrate hosts for the YF virus. The female Aedes sp. or Haemogogus sp. (South America only) mosquito is the vector and a bite from an infected female of these species may transmit the virus.

Transmission of yellow fever occurs in two main cycles:

Sylvatic (jungle): occurring in tropical rainforests of Africa and South America. The transmission cycle occurs between monkeys and wild mosquitoes (i.e. those breeding in the jungle). Humans may become infected when they live or work in areas where this cycle occurs.

Urban: following infection during the sylvatic cycle, humans import the virus to urban areas where there is a high population density. Virus transmission occurs between humans in areas where the domesticated mosquito vector (i.e. those that breed around houses) is present (exclusively Aedes aegypti).

The Aedes mosquito is active during daylight hours and bites from dawn to dusk. Once infected with the virus, the mosquito remains infectious for life (2-3 months). Whilst the mosquito is killed by extremes of heat and cold, the virus can survive from season to season in mosquito eggs. This makes eradication of the disease difficult.

Signs & Symptoms

Yellow fever varies in severity. The infection has an incubation period of 3 to 6 days. Initial symptoms include myalgia, pyrexia, headache, anorexia, nausea and vomiting. In many patients there will be improvement in symptoms and gradual recovery occurring three to four days after the onset of symptoms. However, within 24 hours of an apparent recovery, 15% to 25% of patients progress to a more serious illness. This takes the form of an acute haemorrhagic fever, in which there may be bleeding from the mouth, eyes, ears and stomach, pronounced jaundice (from which the disease gets its name) and renal damage. The patient develops shock and there is deterioration of major organ function. Twenty to 50% of patients who develop this form of the disease die within 7-10 days after the onset [9].

Infection confers lifelong immunity in those who recover.

Treatment

There is no specific antiviral treatment. Supportive nursing care and symptomatic management are the standard.

Prevention

There are two methods to prevent YF: mosquito bite avoidance and control, and immunisation. A highly effective live attenuated yellow fever vaccine has been available for more than 50 years. In general, vaccination is recommended for all persons visiting countries where there is a risk of YF virus transmission. These usually are countries that lie in the endemic zones for YF.

Persons who insist on travelling to countries where YF is a risk without the benefit of vaccination, should be advised of the risk of contracting YF and the potential for quarantine, depending on certificate requirements. Meticulous mosquito bite avoidance should be advised.

International Health Regulations

The IHRs [1] adopted by the World Health Assembly were formulated to help prevent the international spread of disease, and in the context of international travel, to do so with minimum disruption to trade and travel. The IHRs were designed primarily as a public health measure for the receiving country rather than for the protection of the individual. Currently YF is the only disease for which an International Certificate of Vaccination or Prophylaxis may be required for entry into a country. In the future, proof of protection against other diseases could be required depending upon global health events.

A proportion of mandatory vaccination against YF is carried out with the aim of preventing yellow fever virus from being imported into vulnerable or receptive countries. These are countries where YF does not occur but where the mosquito vector and often non-human primate hosts are present. Importation of the virus could lead to YF in the local population. In these cases, vaccination may be an entry requirement for all travellers (occasionally including airport transit) arriving from countries where there is a risk of YF transmission. Failure to provide a valid certificate to the port health authorities could, in some circumstances, result in a traveller being quarantined, immunised or denied entry.

If YF vaccination is contraindicated for medical reasons (including infants < 9 months of age), a medical waiver letter can be issued.

Information on country requirements for yellow fever is published annually by the WHO in International Travel and Health. Information regarding becoming a Yellow Fever Vaccination Centre is on the NaTHNaC Website.

The absence of a requirement for vaccination (refer to WHO International Travel and Health) does not imply that there is no risk of yellow fever in the country, and yellow fever immunisation may be recommended for the protection of the individual traveller (see Health Information for Overseas Travel for yellow fever recommendations for individual countries).

References

1. World Health Organization. International Health Regulations (2005). Geneva: World Health Organization, 2005:1-60. http://www.who.int/csr/ihr/en/

2. Cook GC. Fatal yellow fever contracted at the Hospital for Tropical Diseases, London, UK, in 1930. Trans Roy Soc Trop Med Hyg 1994; 88 (6): 712-3

3. Barros MLB, Boecken G., Jungle yellow fever in the central Amazon. Lancet. 1996; 348:969-70

4. McFarland J, Baddour LM, Nelson JE et al., Imported yellow fever in a United States citizen. Clin Infect Dis.1997; 25:1143-7

5. Centers for Disease Control and Prevention. Fatal Yellow Fever in a traveller returning from Venezuela. MMWR 2000; 49:303-5.

6. Teichmann D, Grobusch MP, Wesselmann H et al. A haemorrhagic fever from the Cote d'Ivoire. Lancet 1999; 354:1608-9.

7. Colebunders R. Imported case of confirmed yellow fever detected in Belgium. Eurosurv Wkly 2001; 5 - http://www.eurosurveillance.org/ew/2001/011122.asp (accessed 20.8.2003).

8. Centres for Disease Control and Prevention, Fatal yellow fever in a traveller returning from Amazonas. Brazil, MMWR 2002; 51:324

9. Monath TP, Yellow Fever: an update. The Lancet Infect Dis. 2001; 1:11-20.

Reading list

Broom AK, Smith DW, Hall RA, Johansen CA, Mackenzie JS. 2002, Arbovirus Infections, In: Manson's Tropical Diseases, Eds. Cook G, Zumla A, London WB Saunders

International Travel and Health, 2003 (http://www.who.int/ith/) (accessed 19.08.2003)

Monath T, Cetron M. Prevention of yellow fever in persons travelling to the tropics. Clin Infect Dis. 2002; 24:1369-1378.

Monath TP. Yellow fever vaccine. In: Plotkin SA, Orenstein WA, eds. Vaccines. Philadelphia: Saunders, 2004:1095-1176.

World Health Organization, Yellow fever vaccine. Weekly Epidemiological Record 2003; 78, 349-360

World Health Organization, Information: Yellow Fever factsheet, http://www.who.int/mediacentre/factsheets/fs100/en/index.html (accessed 19.08.2003)