Fatal Yellow Fever in a U.S. Traveler to Venezuela

Abstract & Commentary

Synopsis: An unvaccinated traveler acquired fatal yellow fever in the Venezuelan Amazon region.

Source: CDC. Fatal yellow fever in a traveler returning from Venezuela, 1999. MMWR Morb Mortal Wkly Rep 1999;49: 303-305.

On sept. 26, 1999, a man returned to marin County, Calif., after a 10-day trip to the rainforests of the Amazon region of Venezuela. He presented to a local emergency room on Sept. 28 with a two-day history of fever, chills, headache, photophobia, myalgias and arthralgias, nausea, vomiting, and upper abdominal discomfort. He was found to be icteric (bilirubin 5.9 mg/dL) and to have upper abdominal tenderness. His ALT was more than 5000 U/L, WBC 3400/mm3, platelet count 77,000/mm3, and creatinine 5.9 mg/dL. He worsened and died on Oct. 4. Postmortem examination revealed hepatic necrosis with numerous Councilman bodies, as well as disseminated aspergillosis. Yellow fever viral antigen was detected in the liver by immunohistochemistry and yellow fever genome by PCR. His serum IgG antibody titer to this flavivirus increased from undetectable on presentation to 1:128 subsequently.

The patient had received multiple vaccinations, but not against yellow fever, prior to travel. Five of six travel companions had received yellow fever vaccine; all were healthy on follow-up.

Comment by Stan Deresinski, MD, FACP

This was only the second case of imported infection with this flavivirus in the United States since 1924. A fatal case in an unvaccinated American traveler to the jungles of Brazil along the Rio Negro and Amazon rivers occurred in 1996.1 The current case occurs in the face of a resurgence of yellow fever over the last two decades.2 Yellow fever is currently endemic in sub-Saharan Africa and tropical South America, with transmission occurring in Bolivia, Brazil, Colombia, Ecuador, French Guiana, Peru, and Venezuela. There has been a recent increase in yellow fever activity in Brazil, as well as Bolivia, where it is occurring in urban areas.3,4 On May 2, 2000, the 26th fatality among 51 cases in the previous 12 months in Goias State occurred. The patient had been offered vaccination 10 days earlier during a door-to-door program designed to arrest yellow fever activity, but refused.

Sylvatic yellow fever is the result of a transmission cycle involving non-human primates, mosquitoes, and humans, while the urban cycle involves only humans and mosquitoes. The latter, Aedes aegypti, breed in manmade containers. After an incubation period of 3-6 days, the onset of illness is abrupt, with fever, chills, headache, and myalgia. Conjunctival injection is common, as is relative bradycardia and leukopenia. Illness may progess, with the development of vomiting, abdominal pain, jaundice, renal dysfunction, and bleeding. Management is supportive.

Administration of yellow fever 17D vaccine is recommended, but not required, for travelers to Venezuela coming directly from the United States.5 This live attenuated viral vaccine is safe, with a low rate of significant adverse reactions, although the incidence of anaphylaxis has been estimated to be approximately one in 131,000.6 A single dose provides protective long-lasting immunity in more than 95% of recipients. As with other live viral vaccines, its administration is contraindicated in significantly immunocompromised individuals and best avoided in pregnancy. Its use may, however, be considered (and is recommended by the CDC) in pregnant individuals traveling to highly endemic areas. The vaccine is also contraindicated in infants younger than 4 months of age and in individuals with severe egg allergy.


1. McFarland JM, et al. Imported yellow fever in a United States citizen. Clin Infect Dis 1997;25:1143-1147.

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

3. Promed Mail Archives. http://www.promedmail.org

4. Van der Stuyft P, et al. Urbanisation of yellow fever in Santa Cruz, Bolivia. Lancet 1999;353:1558-1562.

5. CDC. Health information for international travel 1999-2000. Atlanta, Ga: US Department of Health and Human Services, 1999. Available at http://www.cdc.gov/travel.

6. Kelso JM, Mootrey GT, Tsai TF. Anaphylaxis from yellow fever vaccine. J Allergy Clin Immunol 1999; 103:698-701.

Which of the following is correct?

a. The yellow fever virus is a retrovirus.

b. Aedes aegypti is a competent vector of yellow fever virus.

c. Relative tachycardia is a common clinical finding in patients with yellow fever.

d. The yellow fever vaccine in common use in the United States is a killed whole virus vaccine.