Dengue and Yellow Fever

Teaching topics from the New England Journal of Medicine - Vol. 357, No. 22, November 29, 2007

NEJM Clinical Pearls

Dengue fever and yellow fever are important human viral diseases caused by single-stranded RNA viruses transmitted by insects. Although nearly half the world's population is at risk for infection of dengue fever, and as many as 100 million cases of infection occur annually, there are no antiviral drugs to treat dengue fever and no vaccines to prevent it. Conversely, yellow fever is now largely controlled by vaccination, but many regions are susceptible to a reemergence if the disease is introduced by travelers, and substantial, recent problems with vaccine safety may change vaccination policy.

Dengue Fever and Dengue Hemorrhagic Fever
In its classic form, dengue is an acute illness, characterized by fever, headache, muscle and joint pain, and rash. Immunity against a specific serotype is lifelong, but previous infection with one serotype is a risk factor for a more severe form of dengue — dengue hemorrhagic fever — upon subsequent infection with another serotype. Dengue hemorrhagic fever is characterized by the capillary-leak syndrome, thrombocytopenia, hemorrhage, hypotension, and shock. Approximately 500,000 cases of dengue hemorrhagic fever occur annually, with a case fatality rate ranging from 1 to 3% to as high as 10 to 20%, depending on the available fluid management and intensive care.

Dengue and Yellow Fever Mosquitoes
Dengue and yellow fever are endemic to and epidemic in tropical regions with the principal vector being Aedes aegypti mosquitoes. Infected humans have high blood levels of virus and can therefore infect vector mosquitoes. After an incubation period of about 10 days, during which the virus replicates in a person's salivary-gland tissues, blood-feeding aedes mosquitoes can become infected and transmit the virus to another person. A. aegypti mosquitoes are prevalent in the southern United States, which is therefore receptive to the introduction and spread of both dengue and yellow fever.

Q: What recent problems have occurred with the yellow fever vaccine?
A: Viscerotropic disease, a new syndrome, has been associated with the yellow fever vaccine, an extensive infection of vital organs by a 17D virus that is indistinguishable from wild-type yellow fever disease and has a 60% case fatality rate. Genetic factors of the host (possibly in genes involved in interferon responses) and acquired factors (advanced age and thymectomy) appear to underlie susceptibility to this condition. The overall incidence is about 1 case for every 200,000 to 400,000 vaccinations, but among persons over 60 years of age, the incidence is as high as 1 for every 50,000 vaccinations — which makes 17D one of the least safe vaccines in use.