Yellow outbreaks continue in South America and Subsaharan Africa

February 2006

WASHINGTON — Yellow fever epidemiology is generally centralized to South America and Africa. Outbreaks have been continuing in these locations sometimes moving to new areas as well, according to Martin S. Cetron, MD, director of the division of global migration and quarantine at the CDC.

In Sudan, a large outbreak is ongoing, in which 565 cases have officially been reported, according to Cetron. Although yellow fever is a major public health threat, the live-attenuated yellow fever vaccine offers long–term protection. The vaccine is associated with multisystem adverse events, but they are rare.

“In the vast majority of situations of travelers to endemic and epidemic-prone areas, vaccine is still strongly recommend, the key is to clearly understand and define the risk factors for exposure to yellow fever virus in particular populations and locations,” he said. “It is important to weigh the risks and benefits of vaccine particularly in the elderly population.”

Yellow fever outbreaks

Yellow fever typically occurs in sub–Saharan Africa, where it is endemic in 33 countries, and tropical South America, where it is endemic in 11 countries. WHO estimates that 200,000 yellow fever–attributable cases and 30,000 deaths occur each year, most of them in sub–Saharan Africa. In Africa, the case–fatality rate is greater than 20%, and infants and children are at increased risk for acquiring the disease, according to the CDC’s Yellow Book.

Recently, the Ministry of Health of Guinea reported 114 cases of suspected yellow fever, with 26 deaths since the beginning of 2005, according to a WHO report. Of these cases, 23 were laboratory confirmed. Boké is the most affected region of Guinea. WHO is currently assisting the Ministry of Health in investigating the outbreak.

A mass vaccination campaign is slated for the four high–risk regions of Guinea: Boké, Boffa, Gaoual and Koundara. As part of the campaign, the Global Alliance for Vaccines and Immunization Emergency Stockpile will provide about 800,000 vaccine doses and the Ministry of Health’s stockpile will provide 100,000 doses.

In November 2005, WHO received reports of 53 suspected yellow fever cases and 23 deaths in the region of Kayes, Mali, primarily in the Bafoulabè district. The month before, the Ministry of Health of Senegal reported two laboratory–confirmed cases from the district of Goudirij. Other yellow fever outbreaks in West Africa occurred in September 2005 in Burkina Faso and Côte d’Ivoire. All five countries are in the yellow fever endemic zone of Africa. In the Sudan region, the Federal Ministry of Health reported to WHO a total of 565 cases of yellow fever including 143 deaths, with a case fatality of 25.3% in South Kordofan State.

In South America — specifically the yellow fever–endemic areas of Bolivia, Brazil, Colombia, Ecuador, Venezuela, Guyana, French Guiana and Peru — cases occur more frequently in young men with occupational exposure to forest–dwelling mosquito vectors. Travelers within Brazil to endemic areas are also at risk. There have been outbreaks in the transition zone between epidemic and endemic areas of Brazil since 2000.

Risk of acquiring the disease depends on the duration of exposure, occupational and recreational activities while traveling, the rate of yellow fever virus transmission at the time, immunization status, location of travel and season.

Yellow fever is transmitted through the bite of infected mosquitoes. Illness ranges in severity from influenzalike syndrome to severe hepatitis and hemorrhagic fever.

Controlling yellow fever

The main strategies for controlling yellow fever are based on a combination of immunization and surveillance, according to WHO. Prevention can be done by administering the yellow fever vaccine as part of routine infant immunization and preventing outbreaks in high–risk areas through mass prevention campaigns and control of Aedes aegypti, the vector mosquito, in urban centers. Instituting a surveillance system with laboratory capacity to analyze samples, confirm suspected cases and respond to outbreaks through mass campaigns are other ways to try to control yellow fever.

“In the last five years there has been a major effort to enhance surveillance, of yellow fever vaccine associated adverse events. I think that the United States has been very successful in the formulation of a yellow fever vaccine working group to review serious adverse events, review surveillance data, and plan a research agenda to better understand these rare but serious adverse events,” Cetron said. “We’re also beginning to see a tune-up of yellow fever adverse events surveillance in both Europe and Brazil.”

The CDC recommends yellow fever vaccination for most travelers to yellow fever endemic countries. The vaccine is a live–attenuated virus preparation made from the 17D yellow fever virus strain, according to the CDC. Vaccine type 17D–204 (Stamaril, YF–VAX, Sanofi Pasteur) is used in the United States, Europe and Australia, whereas vaccine type 17DD is used in Brazil.

Vaccine adverse events have been associated with viscerotropic disease, formerly reported as febrile multiple organ system failure, and neurotropic disease, formerly known as postvaccinal encephalitis, according to Cetron. In 2001, the CDC began an enhanced, surveillance system to more accurately detect these events and put risk estimates around adverse event surveillance rates.

In 2002, the Advisory Committee on Immunization Practices updated its vaccine recommendations, which highlighted vaccine–associated viscerotropic disease, and risk factors associated with the vaccine’s use in pregnant women and people with HIV.

Most adverse reactions to the vaccine are generally mild, consisting of headaches, myalgia, low–grade fevers or other minor symptoms.

During the early pilots in the 1940s, before standardization of the vaccine seed lots, yellow fever vaccine–associated encephalitis was the most serious adverse event among young infants and led to contradictions for vaccinating children younger than 12 months of age. Characteristically, this adverse event occurs between four days and one month after vaccination, according to Cetron. Recently, yellow fever vaccine–associated neurotropic disease has reemerged in adults. Since 1996, a new syndrome of yellow fever vaccine–associated viscerotropic disease, has been described. Cetron explained that this adverse event generally targets the visceral organs especially the liver and onset occurs two to five days after vaccination among primary vacinees only.

The CDC recommends physicians advise patients traveling to endemic areas to take precautions against mosquito exposure, such as wearing long–sleeves, applying permethrin-containing repellants to clothes and spraying DEET on exposed skin.

For more information:

• Cetron MS. Clinical update on yellow fever vaccine adverse effects. Symposium 87. Presented at: 54th Annual Meeting of the American Society of Tropical Medicine and Hygiene; Dec. 11-15, 2005; Washington.
• Cetron MS, Marfin AA, Julian KG, et al. Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices, (ACIP), 2002. MMWR. 2002;51(RR17):1-11.
• Visit the CDC’s Travelers’ Health’s Yellow Book Health Information for International Travel, 2005-2006 at www.cdc.gov.
• For current WHO disease outbreak information, visit www.who.int.