Health Information Sheets
August 2011
Yellow Fever
Epidemiology of yellow fever in UK travellers
International Health Regulations (IHR (2005))
Introduction
Yellow fever (YF) virus is an arthropod borne virus of the Flaviviridae family. Other flaviviruses include dengue and Japanese encephalitis viruses. The areas at risk for transmission of YF are in tropical regions of Africa and South America. Vaccination against YF is available and should be recorded in an International Certificate of Vaccination or Prophylaxis. YF carries a high mortality rate.
Epidemiology
Global epidemiology
YF is a risk in tropical parts of Africa and South America, as well as eastern Panama in Central America and Trinidad in the Caribbean. Areas with a risk of YF transmission are countries (or areas within countries) where infection occurs in humans and/or primates and there is a competent mosquito vector. The annual number of confirmed cases reported to the World Health Organization (WHO) for the years 2008 to 2010 were 730, 134 and 392 cases respectively [1]. This is likely to be a gross underestimate of the true number of cases as there is under-reporting and human cases often occur below the level of surveillance detection [2].
Following a Consultation on Yellow Fever and International Travel convened by the WHO in 2008 [3], an expert working group considered the evidence for risk of YF transmission on a country by country basis [4]. The results from this were used to develop vaccination recommendation maps that were first published in April 2011. These new vaccination recommendations result from an entirely new approach to protection of travellers against YF, and require healthcare providers to consider carefully the traveller’s potential exposure to YF and the safety of the vaccine [5].
Reproduced with acknowledgement to the World Health Organization.
Yellow fever activity
In late 2007 and early 2008, the WHO region of the Americas experienced an increase in YF activity. In particular, an outbreak of jungle YF occurred in the monkey population (epizootic) in the south eastern regions of Brazil including the state of Rio Grande do Sul (the first outbreak of jungle YF in the state since 1966). This outbreak spread to Paraguay (the first monkey and human cases since 1974) and in the provinces of Misiones and Corrientes, Argentina (the first human cases in Corrientes since 1966). Yellow fever virus was also identified in monkeys in Trinidad and Venezuela during this epizootic [6].A total of 102 human cases including 52 deaths were reported by Argentina, Bolivia, Brazil, Colombia, Paraguay and Peru in 2008 [7].
During 2009, 55 cases with 18 deaths were reported from Brazil, Colombia and Peru, the majority from Brazil (42 cases with 11 deaths). There were no cases reported from Argentina, Bolivia or Paraguay in 2009 [7].
In 2010, there were only two confirmed cases of YF reported in Brazil, one each from the states of Para and Mato Grosso do Sul [8]. No other countries in the Americas region reported YF outbreaks to the WHO in 2010 [9].
Intense YF virus circulation occurred in West Africa in 2008 and 2009 with outbreaks reported from Burkina Faso, Cameroon, Central African Republic, Chad, Congo, Côte d’Ivoire, Guinea, Liberia and Sierra Leone [7].
Between January 2010 and March 2011, outbreaks of YF were reported to the WHO by Cameroon, Côte d’Ivoire, Democratic Republic of Congo, Sierra Leone, Senegal and Uganda [9]. The YF outbreak in Uganda was the first time YF had been recognised in humans since 1975 [10]. Cases were reported in three northern districts of Abim, Agago and Kitgum near the border with South Sudan [9].
Reporting systems and the level of information that is sent to the WHO differs between countries and case numbers and outbreaks may not accurately represent YF activity [2].
Further information on recent outbreaks of YF can be found in the Outbreak Surveillance Database and the Clinical Updates pages.
Epidemiology of yellow fever in UK travellers
There have been no confirmed YF cases reported in the UK since 1930, when a laboratory worker contracted YF while working with the virus at the Hospital for Tropical Diseases in London [11].
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 occur in Africa and South America, the disease is preventable by vaccination and remains a very rare cause of illness in travellers. There have been six recorded deaths from YF in non-vaccinated European and American travellers between 1996 and 2010. In 1996, two tourists died from YF following trips to the Amazon Basin in Brazil [12,13]. A further two travellers died in 1999 after contracting the virus in Venezuela and Côte d'Ivoire [14,15], and in 2001, a traveller died in a Belgian hospital after contracting YF whilst on holiday near the Gambia/Senegal border [16]. In 2002, an American died of YF after returning from a fishing trip on the Amazon near Manaus, Brazil [17]. None of these travellers were vaccinated against YF.
Transmission
Jungle primates and humans are the vertebrate hosts for the YF virus. The virus is transmitted via the bite of infected Aedes spp. or Haemogogus spp. (South America only) mosquitoes. Only females of these mosquito species transmit the virus.
Transmission of YF occurs in three cycles:
- Jungle: occurring in tropical rainforests of Africa and South America. The transmission cycle occurs between monkeys and jungle breeding mosquitoes. Humans can become infected when they live or work in areas where this cycle occurs.
- Savannah (Africa only): occurs in the moist savannah regions of Africa where humans live and work in close proximity to the monkey population. The transmission cycle occurs between monkeys and humans, with spread via Aedes spp. mosquitoes.
- Urban: following infection during the jungle cycle, infected humans can introduce the virus to urban areas where there is a high population density. Virus transmission occurs between humans in areas where the domesticated mosquito vector, Aedes aegypti (i.e. those that breed around human habitation) is present.
Aedes spp. mosquitoes are active during daylight hours, and bite from dawn to dusk. Haemagogous spp. mosquitoes that breed in the forest canopy in South America are also daytime biters.
Once infected with the virus, the mosquito remains infectious for life (two to three months). Although the mosquito is killed by extremes of heat and cold, the virus can survive from season to season in mosquito eggs, making disease eradication difficult.
Signs and symptoms
YF varies in severity. The infection has an incubation period of three to six days. Initial symptoms include myalgia, pyrexia, headache, anorexia, nausea, and vomiting. In many patients there will be improvement in symptoms and gradual recovery three to four days after the onset of symptoms. 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; 20% to 50% of patients who develop this form of the disease do not survive [18].
Infection confers lifelong immunity in those who recover.
Treatment
There is no specific antiviral treatment. Intensive supportive nursing care and symptomatic management are the standard.
Prevention
There are two methods to prevent YF: mosquito control and bite avoidance, and immunisation. A highly effective live, attenuated YF vaccine has been available for more than 60 years. In general, vaccination is recommended for all persons visiting countries where there is a risk of YF virus transmission. Persons who travel to YF risk countries, without the benefit of vaccination should be advised of the risk of contracting YF and the potential for quarantine at the port of entry, depending on the country requirements for vaccination. They should also practise meticulous mosquito bite avoidance.
International Health Regulations (IHR (2005))
IHR (2005) [19] which were revised and adopted by the World Health Assembly in 2005, were formulated to help prevent the international spread of disease, and in the context of international travel, 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 (ICVP), used to record YF vaccination, may be required for entry into a country.
A proportion of mandatory vaccination against YF is carried out with the aim of preventing YF virus from being imported into vulnerable or receptive countries. These are countries where YF does not occur but where the mosquito vector and often the non-human primate hosts are present and 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. When YF vaccine is required under IHR (2005), failure to provide a valid ICVP to the port health authorities could result in a traveller being quarantined, put under surveillance, or denied entry.
If YF vaccination is contraindicated for medical reasons (including infants under 6 months of age), a letter of medical exemption from vaccination can be issued by an authorised health worker (e.g. UKYFVC designated physician, nurse or pharmacist working at that centre, or a licensed health care professional otherwise supervising the medical care of the traveller). Guidance on the issue of letters of medical exemption is available as an FAQ on the NaTHNaC website. The current ICVP now has a page to record a medical exemption.
Information on country requirements for YF is published annually by the WHO in International Travel and Health and can be found on the NaTHNaC Country Information Pages.
Information regarding becoming a Yellow Fever Vaccination Centre (YFVC) is on the NaTHNaC website.
The absence of a requirement for YF vaccination does not necessarily mean that there is no risk of YF in the country, and YF immunisation may still be recommended for the protection of the individual traveller. The requirements and recommendations for YF vaccine should be reviewed on the NaTHNaC Country Information Pages.
Yellow Fever Vaccine
Country recommendations for yellow fever vaccination
Map of yellow fever vaccination recommendations for Africa
Map of yellow fever vaccination recommendations for the Americas
Indication for use of vaccine
♦ Yellow fever vaccine is indicated for susceptible adults and children aged nine months or older who need primary immunisation or booster vaccination against YF for personal protection, in order to comply with IHR (2005), or both (the requirement for vaccination against YF is not always related to the risk of exposure to disease)
♦ Laboratory workers handling infective material
A careful assessment that balances the risk of disease with requirements for vaccination, taking into account the age and health status of traveller, needs to be performed prior to vaccination.
YF vaccine should be administered under a Patient Group Direction (PGD) in the private sector and under a Patient Specific Direction (PSD) in the NHS setting. Guidance is available in the NaTHNaC FAQ: PSD and PGDs. Model PGD and PSD +are available to registered UK YFVCs (login required).
Availability
There is currently one licensed YF vaccine in the UK, Stamaril® (Sanofi Pasteur MSD). This contains an attenuated 17D strain of YF virus that protects against all strains of YF.
The Summary of Product Characteristics (SPC) for the vaccine should be consulted for specific information relating to the product.
Vaccine |
Manufacturer/ |
Schedule |
Length of protection |
Age range |
|---|---|---|---|---|
Stamaril® |
Sanofi Pasteur MSD |
1 dose |
10 years |
Minimum age 9 months. Seek medical advice for infants 6-8 months who are travelling to high risk area |
The vaccine induces a rapid immune response with 90% of recipients achieving protective levels of antibody within 10 days. Immunity following vaccination has been shown to be long lasting and possibly life-long. However, IHR (2005) require re-vaccination at 10-year intervals if indicated, in order to retain a valid ICVP.
Contraindications
Specific contraindications should be reviewed in the SPC.
- Infants age five months and younger
- Persons with a history of a severe allergic reaction to any component of the vaccine including anaphylaxis to egg protein
- Immunocompromised hosts
- History of thymus dysfunction, e.g. including thymoma, thymectomy secondary to a thymus disorder, myasthenia gravis and DiGeorge syndrome [20]
Precautions
Expert advice should be sought prior to immunising individuals in these groups.
- Infants age six to eight months
- Febrile illness
- HIV-infected individuals
- Pregnant women
- Breast feeding women
- Individuals age 60 years and older
Adverse events
The 17D strain virus YF vaccine has been in use for more than 60 years. It is estimated that 300 to 400 million doses of the vaccine have been administered worldwide [21]. Reactions to YF vaccine are usually mild and short lived. They include myalgia, headache, and low-grade fever, typically occurring during the first five to ten days post vaccination, and will affect 10-30% of recipients.
Serious adverse events are rare and fall into three main categories: hypersensitivity reactions, vaccine-associated neurologic disease (YEL-AND) and vaccine-associated viscerotropic disease (YEL-AVD).
Hypersensitivity reactions
The vaccine is propagated in chick embryos. The SPC for Stamaril® (the only YF vaccine used in the UK) lists sorbitol and lactose as excipients. Anaphylaxis and urticaria as a result of sensitivity to either egg or other vaccine components, occurs at an incidence between 0.8 to 1.8 cases/100,000 doses administered [22].
Yellow Fever Vaccine-Associated Neurologic Disease (YEL-AND)
Post-vaccine encephalitis has been recognised as a rare event since the early use of the vaccine. It was usually seen in infants; early reports documented an incidence of 0.5 to 4 cases per 1,000 infants under the age of six months [23]. Since 2001, a new pattern of neurologic adverse events has been recognized [24-26]. These events have been termed YF vaccine-associated neurologic disease (YEL-AND), and they occur in the range of 0.4 to 0.8 cases per 100,000 doses administered [27, 28]. The clinical presentation of neurologic events begins four to 23 days (median 14 days) following receipt of vaccine, with fever and headache that can progress to encephalitis, or an autoimmune demyelinating disease with peripheral or central nervous involvement. Most patients will completely recover. All cases have occurred in primary vaccinees with no underlying YF immunity.
Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD)
YF vaccine-associated viscerotropic disease (YEL-AVD) is a syndrome of fever and multi-organ failure that resembles severe YF disease; it was first described in 2001 [29-31]. As of February 2010, 57 cases of YEL-AVD had been reported from 14 countries; of the 57 cases, 37 (65%) died [21]. Three cases have been reported in the United Kingdom, one in 1998 and two in 2000; all the UK cases survived [32].
Two to eight days (median four days) following vaccination, patients with YEL-AVD develop fever, malaise, headache, and myalgias that progress to hepatitis, hypotension, and multi-organ failure. Death has occurred in more than 60% of reported cases. Thymus disorders and thymectomy are documented risk factors and all patients with thymus disorders should not receive vaccine. As with neurologic disease, all cases have occurred in first-time vaccine recipients.
Viscerotropic severe adverse events occur in the range of 0.3 to 0.4 cases per 100,000 doses [21, 27]. For individuals who are aged 60 years and older, the current risk for neurologic and viscerotropic adverse events, increases by several fold to approximately 2 cases per 100,000 doses [21].
There is no evidence that YEL-AVD is related to reversion of the vaccine virus to a more virulent form [33]. Rather, these patterns of serious adverse events appear to be host related. Host risk factors such as genetic control of inflammation, are being actively investigated, but it is clear that those with existing thymus disease and older adults are at more risk [20-23, 34-36].
Pregnancy and breast-feeding
The safety of YF vaccine in pregnancy has not been systematically evaluated; a prospective study in Brazil, where women were inadvertently vaccinated in early pregnancy (mean gestational age of 6 weeks) during a YF outbreak, found no increase in foetal malformations, complications to the central nervous system, premature delivery or perinatal deaths [37].
YF vaccination should be avoided, on theoretical grounds, particularly in the first trimester of pregnancy. However, if the risk of YF during travel is considered sufficiently high, pregnant women may be vaccinated. Infants should be monitored after birth for adverse events and evidence of YF infection.
The first case of YEL-AND and transmission of YF vaccine virus through breastfeeding was reported in a 23 day old infant in 2009 [38]. Two other probable cases in infants aged 10 days and five weeks have since been reported [39,40]. Vaccination of breastfeeding women should be avoided where possible. However, if the risk of YF during travel is considered sufficiently high they may be vaccinated.
Where an infant less than 9 months of age is breastfeeding, and the mother needs YF vaccination for personal protection, one option is to discontinue breastfeeding and replace feeds with formula on the day of vaccination and for a further two to three weeks (expressing and disposing of breast milk during that time). Breast feeding can be recommenced after this time.
References
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29. Chan RC, Penney DJ, Little D, et al. Hepatitis and death following vaccination with 17D-204 yellow fever vaccine. Lancet 2001; 358:121-122.
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37. Suzano CES, Amaral E, Sato HK et al. The effects of yellow fever immunization (17DD) inadvertently used in early pregnancy during a mass campaign in Brazil. Vaccine 2006;24(9): 1421-1426
38. Centers for Disease Control and Prevention. Transmission of yellow fever vaccine virus through breast feeding – Brazil, 2009. MMWR 2010:59(05); 130-132. [Accessed 31 February 2011]. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5905a2.htm
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Links
World Health Organization, Position paper: Yellow fever vaccine. 2003
World Health Organization, Information: Yellow Fever
World Health Organization, International Travel and Health, 2011
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