Abstracts & Commentary
Synopsis: An American traveler returning from Amazonas, Brazil, died from yellow fever.
Sources: Centers for Disease Control and Prevention. Fatal yellow fever in a traveler returning from Amazonas, Brazil, 2002. MMWR Morb Mortal Wkly Rep. 2002;51(15):324-325. Monath TP, Cetron MS. Prevention of yellow fever in persons traveling to the tropics. Clin Infect Dis. 2002;34:1369-1378.
A healthy 47-year-old man from Texas traveled to Amazonas, Brazil, on a 6-day fishing trip in March 2002. He presented with abdominal pain, fever, and headache upon return, and subsequently developed intractable vomiting. His laboratory evaluation revealed leukopenia, anemia, thrombocytopenia, abnormal coagulation profile, renal failure, and liver failure. His IgM and IgG titers for yellow fever were negative. However, serum and postmortem liver samples tested positive for yellow fever by polymerase chain reaction.
The patient had not received pretravel evaluation, yellow fever vaccine, or malaria prophylaxis. He had slept on an air-conditioned fishing boat and used DEET. Among the 15 US travelers on the fishing trip, no one else became ill with fevers. Eight (53%) of the travelers had appropriate yellow fever vaccination within 10 years and at least 10 days before arriving in Manaus. One traveler had been immunized 11 years prior to the trip; one traveler had been vaccinated 5 days before arrival, and one may have been immunized more than 30 years ago in the military. Four travelers had never been vaccinated against yellow fever, and 12 travelers did not take malaria chemoprophylaxis. According to the CDC report, the travel agent and outfitter appear to have underestimated the health risk for the group.
Monath and Cetron reviewed many of the issues regarding yellow fever in travelers. First of all, there is an increase in travel to areas where yellow fever is endemic. Secondly, the epidemiology of yellow fever in endemic countries is continually changing. Next, new concerns regarding vaccine safety have been raised since the report of severe multiorgan systemic failure in yellow fever vaccine recipients. Moreover, certified yellow fever vaccination centers tend to be located in urban areas, which requires motivation for travelers residing in rural areas who seek the vaccine. Finally, shortages in vaccine supply can contribute to inadequate vaccination.
Monath and Cetron estimated the risks associated with unvaccinated travelers. For someone visiting an area with epidemic yellow fever for 2 weeks, the risk of developing yellow fever infection is 1:267, and the risk of death is 1:1333. For the visitor to Africa, the risk of developing yellow fever infection is estimated to be 1:2000 for a 2-week trip, and the risk of death is 1:10,000. For the visitor to South America, the risk of yellow fever infection is estimated to be 1:20,000 and the risk of death is estimated to be 1:100,000. The highest risk occurs during the rainy season. In West Africa, the peak risk occurs from July to October, whereas in Brazil, it occurs from January to March.
Serious vaccine adverse reactions were also reviewed. These include hypersensitivity reactions (1 per 58,000-131,000 vaccinees), postvaccinal encephalitis (< 1 per 1,000,000), and multiorgan systemic failure (MOSF, 1 per 400,000).
Two other American and 2 European travelers died of yellow fever in recent years, 1996-1999, and none had received yellow fever immunization prior to their travel. Using a mathematical model, Monath and Cetron calculated yellow fever vaccine coverage in travelers, and estimated that vaccine coverage decreased by more than 50% from 1992 to 1998.
Comment by Lin H. Chen, MD
Yellow fever has reemerged. Outbreaks were reported predominantly in Africa: Cameroon, Ghana, Liberia, Nigeria, Sierra Leone, Gabon, and Kenya, but yellow fever has also resurged in South America, in Peru and Brazil.1 Epidemics in Africa have affected the young, especially children younger than 15 years of age.2 It is estimated that more than 200,000 cases occur annually in Africa, and less than 50% of the 34 African countries at risk have been able to finance some form of vaccination program for yellow fever.2 Therefore, there are huge populations that are susceptible to the infection, and yellow fever epidemics can easily occur. Interestingly, 4 of the 5 American and European travelers who died of yellow fever since 1996 acquired their infections in South America.3-5 This perhaps indicates an under-appreciation of the risk of yellow fever to travelers who go there.
Recent reports of severe adverse events (MOSF) have renewed concerns regarding the yellow fever vaccine (See TMA Update 2001;11:35-36).6-8 The estimated incidence is 1 case per 400,000 vaccine recipients. On the other hand, Monath and Cetron noted that 190 million yellow fever vaccine doses have been distributed since the initial recognition of the syndrome in 1996, since which time 10 cases have been reported. Thus, the true incidence of the severe adverse events needs further elucidation.
Monath and Cetron suggest that the MOSF may probably develop only in patients who are receiving their primary vaccination. This may reassure the many patients who need repeat yellow fever vaccination. Monath and Cetron also report on a patient with chronic lymphocytic leukemia for whom IVIG was given, which contained protective levels of yellow fever neutralizing antibody. This passive protection may prove to be a good option for patients with contraindications to the yellow fever vaccine (ie, immunosuppression).
The case of fatal yellow fever in a traveler to Amazonas, Brazil, illustrates that some travel agents understate or underestimate potential health hazards. There is little motivation on the part of the travel agent to mention the need to see a travel medicine specialist. Nonetheless, the consequences of illnesses such as yellow fever and malaria in a traveler are severe. Travel medicine specialists should work with the travel agents to portray accurate risks to the travelers.
References
1. Robertson SE, et al. Yellow fever—a decade of reemergence. JAMA. 1996;276:1157-1162.
2. Tomori O. Impact of yellow fever on the developing world. Adv Virus Res. 1999;53:5-34.
3. McFarland JM, et al. Imported yellow fever in a United States citizen. Clin Infect Dis. 1997;25:1143-1147.
4. World Health Organization. Yellow fever, 1996-1997. Part I. Wkly Epidemiol Rec. 1998;73:354-359.
5. World Health Organization. Yellow fever, 1998-1999. Wkly Epidemiol Rec. 2000;75:322-328.
6. Martin M, et al. Fever and multisystem organ failure associated with 17D-204 yellow fever vaccinations: A report of four cases. Lancet. 2001;358:98-104.
7. Vasconcelos PFC, et al. Serious adverse events associated with yellow fever 17DD vaccine in Brazil: A report of two cases. Lancet. 2001;358:91-97.
8. Chan RC, et al. Hepatitis and death following vaccination with 17D-204 yellow fever vaccines. Lancet. 2001; 358:121-122.
9. Monath TP. Yellow fever. In: Plotkin SA, Orenstein WA, eds. Vaccines. 3rd ed. Philadelphia, Pa: WB Saunders; 1999:815-879.
Dr. Chen is Clinical Instructor, Harvard Medical School and Travel/Tropical Medicine Clinic, Lahey Clinic Medical Center, Cambridge, Mass.