Special Feature

Re-Emergence of Yellow Fever

By David R. Hill, MD, DTM&H

The recent deaths from yellow fever of two tourists who traveled to the Brazilian Amazon,1 and the publication of a review of the World Health Organization on the global status of yellow fever2 highlight the ongoing importance of this historic viral infection. In April 1996, a Swiss tourist on a river trip to Manaus, Brazil, became ill shortly before he returned to Europe. He died of yellow fever six days after exposure. He had not been vaccinated. In August 1996, an American spent 10 days on the River Negro near Manaus on a fishing and outdoor trip. A day after return to the United States, he became ill with fever, severe myalgias, and headache. Although he sought medical care for what he thought was dengue fever, he was not admitted to the hospital until five days later. He died eight days after admission. Yellow fever virus was cultured from serum and tissue samples. He also had not been vaccinated against yellow fever.

The review article that appeared in JAMA covers the diagnosis and management, global epidemiology, and vaccine efficacy of yellow fever, and makes recommendations on vaccine policy. The last decade has seen a dramatic increase in the number of cases of yellow fever, particularly in Africa, where, from 1987 to 1991, 18,735 cases were reported with 4522 deaths (CFR 24%). However, this is likely to grossly underestimate the actual number of infections by 10- to 500-fold. Most cases of yellow fever in Africa have occurred in the sub-Saharan region between 15° north and 10° south of the equator. Nigeria, which has historically had some of the greatest activity, continues to have outbreaks.3,4 But, infection has expanded into new areas such as Kenya beginning in late 1992, and recent outbreaks have occurred in Senegal, Gabon, Liberia, Benin, Ghana, and Sierra Leon. Transmission in Africa has followed the pattern of both jungle and urban transmission. In jungle transmission, man becomes an incidental host, and infection is maintained among non-human primates, with several Aedes species transmitting the virus. In the urban cycle, transmission is between susceptible humans by Aedes aegypti mosquitoes, which breed efficiently in household containers and refuse. Epidemics may occur when an individual returns to the urban environment following jungle exposure and is fed upon by the Aedes mosquito. The establishment of Aedes aegypti throughout urban areas of the yellow fever region (and also the southeastern United States) raises concern about continued outbreaks.

The Amazon basin of South America (Bolivia, Brazil, Colombia, Ecuador, Peru) has had lower levels of infection, about 150 cases per year, and the transmission cycle is primarily jungle. However, in 1995, Peru had 492 cases with a CFR of 39%.4 Most cases in South America occur in rural workers who could have been protected by adequate immunization.

The authors then discuss the potential for control of yellow fever by expanding immunization programs. Most cases in endemic areas of Africa occur in children under the age of 15 years. Thus, inclusion of yellow fever vaccine in the Expanded Programme on Immunization (EPI) could be an effective control strategy. In one country where this has been done, the Gambia, outbreaks have been entirely eliminated. There are 33 countries in Africa at risk for yellow fever. Of these, 16 have a national policy of including the vaccine in their childhood immunization programs, but only four of these have ever achieved 50% coverage (Burkina Faso, the Gambia, Central African Republic, and Senegal). The authors appropriately state that a major effort is needed to provide for vaccination in each of the countries at risk. The financial need for such a campaign is $70 million, but a successful program could result in control of yellow fever in sub-Saharan Africa within five years. An appeal has been launched by the WHO for these funds.

Similar to other viral hemorrhagic fevers such as Ebola and Lassa fever, yellow fever carries a high mortality rate. But, unlike the others, yellow fever is an entirely preventable illness by vaccination. The vaccine is safe, highly effective, and has a duration of efficacy of at least 10 years.

A recent outbreak (27 cases and 5 deaths) of yellow fever in the Upper East Region of Ghana illustrates the value of trying to integrate this vaccine into the EPI (ProMED Electronic Network, 12/6/96). In order to halt the epidemic, it is estimated that 90,000 doses of vaccine are required, and a further 1.4 million are needed to protect the at-risk population. An emergency response to an outbreak such as this requires personnel, health care and diagnostic expertise, and vaccine. This results in tremendous financial and human resources compared with a strategic program of childhood vaccination—a difference of $7.84 per person vaccinated emergently vs. $0.65 per person if included in the EPI (1991 dollars).5

International travelers going to countries in the yellow fever endemic zones should be properly immunized according to the recommendations of the Centers for Disease Control6,7 and the WHO.8 The deaths of two travelers to the Amazon indicate that even "limited risk" trips should be covered by vaccination. Physicians can determine countries in the endemic zone by referring to the CDC and WHO documents7,8 and can find out actual areas infected with yellow fever by using the Summary of Health Information for International Travel, also known as the "Blue Sheet."9 With proper awareness of risk and receipt of vaccine by travelers, and implementation of the WHO strategy, it may be possible to control human infection with yellow fever.


1. World Health Organization. Yellow fever in a traveller: United States of America. Wkly Epidemiol Rec 1996;71:342-343.

2. Robertson SE, Hull BP, Tomori O, et al. Yellow fever. A decade of reemergence. JAMA 1996;276:1157-1162.

3. Monath TP. Yellow fever: Victor, Victoria? Conquerer, conquest? Epidemics and research in the last forty years and prospects for the future. Am J Trop Med Hyg 1991;45:1-43.

4. World Health Organization. Yellow fever in 1994 and 1995. Wkly Epidemiol Rec 1996;71:313-318.

5. Monath TP, Nasidi A. Should yellow fever vaccine be included in the Expanded Program of Immunization in Africa? A cost-effective analysis for Nigeria. Am J Trop Med Hyg 1993;48:274-299.

6. Centers for Disease Control. Yellow fever vaccine: Recommendations of the immunization practices advisory committee (ACIP). MMWR Morb Mortal Wkly Rep 1990;39 (No. RR-6):1-6.

7. Centers for Disease Control and Prevention. Health Information for International Travel, 1995. (HHS publication no [CDC] 94-8280). Atlanta: U.S. Department of Health and Human Services, Public Health Service; 1995.

8. World Health Organization. International Travel and Health. Vaccination Requirements and Health Advice. Geneva: World Health Organization; 1996.

9. Centers for Disease Control and Prevention. Summary of Health Information for International Travel (HHS publication no. 396). Atlanta: U.S. Department of Health and Human Services, Public Health Service; 1996.