Yellow fever is endemic in the tropical areas of 45 African and Latin America countries with a total population of over 900 million. In jungles and forests in Africa, yellow fever virus is transmitted by Aedes africanus
mosquitoes; in South America, it is transmitted by Haemagogus
species, with monkeys as the primary host and forest dwellers, loggers, and construction workers as the infected groups. In savannah areas in Africa, Aedes
species transmit the virus to monkeys or humans as the intermediate hosts, and in urban areas, Ae. aegyptii
transmits infection between humans. It is the urban cycle that is particularly capable of generating rapidly increasing epidemics.1
The majority of yellow fever virus infections are asymptomatic.1
Monath and others2
estimate that 15% of those people infected with yellow fever virus develop moderate or severe disease with jaundice, that reported case fatality rates vary widely, and in one series of West Africans with jaundice, that the fatality rate approximated 20%. The number of yellow fever cases proven by clinical examination and detailed laboratory investigations is small, and it certainly underenumerates the true number of cases.
An outbreak of yellow fever can go undetected, because the signs and symptoms of yellow fever are similar to viral hepatitis, malaria, leptospirosis, typhus, Ebola hemorrhagic fever, and other hemorrhagic fevers. It is difficult for health workers to make a definitive diagnosis based on the signs and symptoms alone. Additionally, mild cases may go undetected, because the patient is likely to be treated at home and not seek care in a health facility.3
In 1992, the World Health Organization (WHO) estimated that yellow fever virus caused 200,000 cases of clinical disease and 30,000 deaths annually,4
and the survey by Rogers and others5
of the literature in 2006 repeated and did not update these estimates.
Yellow fever vaccination very rarely causes severe adverse neurologic, multisystem, or anaphylaxis reactions. The neurologic syndromes (encephalitis, myelitis, or encephalomyelitis) can be difficult to distinguish from bacterial encephalitis/meningitis or malaria, and the viscerotropic syndrome (which can result in multiorgan failure of the liver, kidneys, heart, and circulation) can be difficult to distinguish from hemorrhagic fevers, viral hepatitis, and many other causes of multisystem failure.6
There are no effective medications for these adverse effects of vaccination, and treatment consists of supportive care, including the intensive care unit (ICU). The number of these serious adverse events attributable to yellow fever vaccination that have been proven by clinical examination and detailed laboratory investigations is very small.
17D vaccines using the substrains 17DD and 17D-204 have very low interlot variability and high genetic stability levels; they are highly immunogenic (91–100%)6,7
and provide an estimated more than 40 years of protection. More than 600 million doses of yellow fever (YF) vaccines (YFVs) have been distributed worldwide.
The WHO advises vaccination for all individuals ≥ 9 months living in countries or areas at risk, except pregnant females and breastfeeding mothers, who may be vaccinated during epidemics or if unavoidably traveling to high-risk areas. Similarly, the WHO advises that individuals 60 years and older are at risk for severe adverse events after vaccination, and the risk and benefits need to be weighed.8
The US Advisory Committee on Immunization Practices (ACIP) indicates that YF vaccine is contraindicated in those people with sensitivity to eggs or chicken, infants < 6 months, individuals with thymus disorders or who have had a thymectomy, individuals with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), and individuals on immunosuppressive therapies. ACIP advises precaution in vaccinating infants 6–8 months, individuals ≥ 60 years, individuals with asymptomatic HIV infection and moderate immune suppression (CD4 count = 200–499/mm3
for persons ≥ 6 years or 15–24% of total lymphocytes for children < 6 years), pregnant women, and breastfeeding women. The ACIP notes the limited database for these recommendations.1
The most complete description of the etiology, pathology, and vaccines for YF is in the work by Monath and others.2
A description of the symptoms of YFV-associated neurotropic disease (YEL-AND) and YFV-associated viscerotropic disease (YEL-AVD) and the Centers for Disease Control and Prevention (CDC) Working Group’s definitions are provided in the work by Staples and others.1
The Brighton Collaboration’s case definitions and guidelines for encephalitis, myelitis, and acute disseminated encephalomyelitis are presented in the work by Sejvar and others,9
and the Brighton Collaboration’s case definitions and guidelines for anaphylaxis are presented in the work by Rüggeberg and others.10
The Brighton Collaboration website (accessed October 10, 2011) indicates that the viscerotropic case definitions and guidelines are in progress. The mild reactions in vaccine-naïve subjects are usually low-grade fever, mild headache, arthralgias, and myalgias, and 15–20% of vaccinees may experience these reactions.11
We wished to ascertain the rate of serious adverse events in vulnerable populations which may be at greater risk of experiencing a serious YFV-related adverse events (AEs). These vulnerable populations include children, pregnant women, individuals with HIV, cancer, transplants, or immunosuppressive medication regimens, and older patients