Yellow fever virus is the prototype of the family Flaviviridae, V which includes approximately 70 single-stranded RNA viruses, _JL the majority of which are transmitted by mosquitoes or ticks.
Yellow fever virus is transmitted principally by insects (mosquitoes), but ticks (Amblyomma variegatum) may play a secondary and minor role in Africa.
DISEASE AND MEDICAL IMPACT
The disease caused by the yellow fever virus is a severe hemor-rhagic fever, characterized by high viremia (virus in the blood), hepatic, renal, and myocardial injury, hemorrhage, and case-fatality rates of 20-50%. Today, the disease occurs in tropical Africa and South America. It is estimated that up to 200,000 cases occur annually but far fewer are reported officially. Between 1990 and 1999, 11,297 cases and 2648 deaths were reported; 83% of these cases occurred in Africa. The highest incidence was in Nigeria, where epidemics occurred between 1986 and 1994. Recent epidemics have affected Cameroon (1990), Kenya (1992), Ghana (1993-1994, 1996), Liberia (1995, 1998, 2000), Guinea (2000), Gabon (1994), Senegal (1995, 1996), and Benin (1996). In South America, 1939 cases and 941 deaths were reported between 1990 and 1999, an average of about 200 cases per year. Bolivia and Peru had the highest incidence, reflecting low vaccination coverage. In Brazil, an increase in yellow fever activity occurred over a wide area between 1998 and 2000.
ROLE OF INSECTS IN TRANSMISSION
The enzootic transmission cycle involves tree-hole-breeding mosquitoes such as Aemagogus janthinomys (South America) and Aedes africanus (Africa), and nonhuman primates. Infection of mosquitoes begins after ingestion of blood containing a threshold concentration of virus (~3.5 log10inlresulting in infection of the midgut epithelium. The virus is released from the midgut into the hemolymph and spreads to other tissues, notably the reproductive tract and salivary glands. A period of 7-10 days is required between ingestion of virus and virus secretion in saliva (the extrinsic incubation period), after which the female mosquito is capable of transmitting virus to a susceptible host. Vertical transmission of virus occurs from the female mosquito to her progeny and from congenitally infected males to females during copulation. Virus in the egg stage provides a mechanism for virus survival over the dry season when adult mosquito activity and horizontal transmission abate.
In tropical South America, the virus is transmitted by Haemagogus mosquitoes (principally Hg. janthinomys) between monkeys in the rain forest canopy and from monkeys to humans. Transmission peaks during months of high rainfall, humidity, and temperature (January-March), corresponding to the activity of Haemagogus mosquitoes. It is during occupational activities, such as forest clearing, lumbering, and road construction that humans acquire the infection (“jungle” yellow fever) from mosquitoes that previously had fed on viremic monkeys; most patients are young adult males. The density of Haemagogus and risk of human exposure are relatively low, and human cases occur in a sporadic fashion. Other mosquitoes involved in jungle yellow fever in South America include Hg. leucocalaenus and Sabethes chloropterus. In the early 1950s an epizootic extended to Central America, where other species were implicated (Hg. lucifer, Hg. equinus, Hg. iridicolor, Hg. mesodentatus). Prior to the 1940s, epidemics of yellow fever due to bites from Ae. aegypti occurred in the Americas. Ae. aegypti breeds in and around houses, principally in artificial containers, and is responsible for direct interhuman transmission of virus (“urban” yellow fever). Age and sex distributions are different from jungle yellow fever, because children and females are affected. Most areas of South America had effectively eliminated Ae. aegypti during eradication efforts (1930s-1960s), but the continent was reinvaded in the 1970s, and the vector is now widespread. The first outbreak of urban yellow fever since 1954 occurred in Santa Cruz, Bolivia, during 1997-1998. The wide distribution of Ae. aegypti (including areas juxtaposed to the yellow fever endemic zone) and the rise in air travel have increased the risk of reemergence of urban yellow fever in the Americas.
In Africa, the enzootic cycle involves tree-hole-breeding Aedes mosquitoes, which transmit virus between monkeys, from monkeys to humans, and between humans. In West Africa, cases appear during the middle of the rainy season (August) and peak during the early dry season (October), the period of maximum vector longevity. The principal enzootic vector is Ae. africanus; this species is responsible for transmission between monkeys in the forest zone and in gallery forests. During the rainy season, Ae. africanus and other vector species [Ae. furcifer, Ae. taylori, Ae. luteocephalus, Ae. metallicus, Ae. vittatus, and (in many parts of East Africa) Ae. simpsoni] reach high densities in the humid savanna zone (the “zone of emergence” of yellow fever). The prevalence of immunity in the human population accumulates rapidly with age, and children are at highest risk of infection and illness. The domestic vector Ae. aegypti breeds in receptacles widely used by humans for water storage where piped water supplies are unavailable. Where this mosquito is involved in virus transmission, the disease may occur in the dry season in both rural and urban areas. Ae. aegypti has been the principal vector in many recent human epidemics in West Africa. Because the density and biting rates of Ae. aegypti and sylvatic Aedes vectors are high, human infection rates during epidemics may reach 20-30%.
Rainfall and temperature influence vector abundance and transmission rates and the potential for yellow fever epidemics. Prolongation of the rainy season, reflected by vegetational indices in satellite images, predicts a risk of yellow fever epidemics. Increasing temperature shortens the extrinsic incubation period of yellow fever virus in the mosquito, resulting in a significantly increased rate of transmission. Even brief exposure to high temperatures (e.g., in a sunlit forest clearing) can have this effect. Warm temperature also increases biting and reproductive rates of Ae. aegypti.
Ae. aegypti populations differ genetically in vector competence for yellow fever virus. High vector densities may be required for virus transmission by relatively insusceptible populations, such as those occurring in West Africa.
CONTROL STRATEGIES
The principal method for prevention and control is human vaccination. A safe and effective live, attenuated vaccine (yellow fever 17D vaccine) has been in wide use since World War II. The vaccine is incorporated into routine childhood vaccination programs in South America and some parts of Africa. The occurrence of human disease reflects incomplete coverage of the population, because vaccine immunity is probably lifelong after a single dose.
In the Americas, control of Ae. aegypti through larval source reduction was successful in reducing urban yellow fever in the early decades of the 20th century. The increasing size and complexity of urban areas, the proliferation of detritus and objects such as automobile tires that collect rainwater and breed mosquitoes, and increasing costs and competition with other health care priorities have limited the impact of mosquito control efforts. Emergency vector control using space sprays to kill infected female vectors could undoubtedly be used to contain urban yellow fever outbreaks, but the measure has never been evaluated specifically for this purpose. Spraying of large areas of forest and around villages by air- or ground-operated equipment to contain sylvatic yellow fever has been evaluated, with mixed success.
