humans by other mosquitoes (e.g., Aedes aegypti) that have adapted to living in cities. It is generally believed that the movement of people through the slave trade and maritime commerce disseminated yellow fever, dengue, and chikungunya viruses, as well as Ae. aegypti , from Africa to other tropical areas. Ae. aegypti is still widespread in many urban areas of the southeastern United States, although the last yellow fever epidemic in a major U.S. city was in New Orleans in 1905.

Although the odds are low that a randomly chosen organism will become a successful human pathogen, the great variety of microorganisms in nature increases those odds. For example, field sampling and disease surveillance efforts have now identified more than 520 arthropod-borne viruses, or arboviruses (Karabatsos, 1985). The disease potential of most of these viruses is unknown, but nearly 100 have been shown to cause human disease (Benenson, 1990). In spite of the demise of the Rockefeller Foundation arbovirus program in 1971, and although only a few laboratories are actively searching for new pathogens in animals and arthropods, new viruses are being discovered every year (see Box 2-2).

One example of a recently discovered zoonotic virus is Guanarito, the cause of Venezuelan hemorrhagic fever. In the fall of 1989, an outbreak of an unusually severe and sometimes fatal disease was detected in the state of Portuguesa in central Venezuela. Patients presented for treatment with prolonged fever, headache, arthralgia, diarrhea, cough, sore throat, prostration, leucopenia, thrombocytopenia, and hemorrhagic manifestations. Physicians in the region initially diagnosed the disease as dengue hemorrhagic fever (DHF). During one period, from early May 1990 through late March 1991, 104 cases of the disease were recorded. Slightly more than a quarter of these patients, most of them adults, died (Salas et al., 1991).

All of the cases of the DHF-like illness occurred in the Municipio of Guanarito in Portuguesa State, or in adjoining areas in Barinas State. The Municipio of Guanarito, population 20,000, is located in the central plains of Venezuela, a major food-producing region. The outbreak was confined to the municipio's roughly 12,000 rural inhabitants, who either farm or raise cattle (Salas et al., 1991).

In the fall of 1990, a virologist from the Venezuelan Ministry of Health sent serum samples from several patients who were suspected to have DHF to the Yale Arbovirus Research Unit (YARU) at Yale University School of Medicine. No virus could be isolated after routine culture of the sera in mosquito cells (the standard method for recovery of dengue viruses).

In early 1991, a member of the YARU staff visited Venezuela while on a trip to South America collecting dengue virus isolates for an ongoing research project. In Caracas, the YARU staff member was given spleen cultures from two fatal cases of suspected DHF from the Guanarito area. Upon inoculation into newborn mice and Vero (monkey kidney) cell cultures at

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