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VENEZUELAN HEMORRHAGIC FEVER (VHF)In September 1989, physicians in the state of Portuguesa, Venezuela, became aware of an outbreak of a severe febrile illness, mainly among rural inhabitants of the southern part of the state, which was characterized by fever, headache, myalgia, sore throat, weakness, anorexia, nausea, vomiting and occasionally convulsions. The duration of the illness in nonfatal cases ranged from about 10-14 days. Many of the patients where hospitalized because of unremitting fever, weakness, dehydration and hemorrhagic manifestations (epistaxis, bleeding gums, hematemesis, melena and menorrhagia). All age groups and both sexes were affected, but the highest incidence was in persons 15-44 years of age. Many of the cases were initially diagnosed as dengue hemorrhagic fever or classical dengue. A new arenavirus, designated Guanarito virus, was eventually identified as etiologic agent of the disease, now described as Venezuelan hemorrhagic fever (VHF). Guanarito virus is antigenically related to Junin, Machupo and Lassa viruses, the causative agents of Argentine hemorrhagic fever, Bolivian hemorrhagic fever and Lassa fever, respectively. Phylogenetic studies of the viral S-RNA indicate 30% divergence of Guanarito virus from other arenaviruses. During the period from September 1989 until May 1995 a total of 105 confirmed or probable cases of VHF were reported to the Venezuelan Ministry of Health and Social Assistance. About 34% of the cases were fatal. Most of the recognized cases have been in persons living or working in rural areas in the municipality of Guanarito, Protuguesa State; however, the surveillance activities have been focused mainly in this region, it is possible that additional VHF cases have occurred in neighboring municipalities or in other states. Without laboratory confirmation, VHF can easily be confused clinically with dengue, yellow fever, idiopathic thrombocytopenic purpura and a number of other prolonged febrile illnesses with leucopenia and hemorrhagic manifestations. As shown in Figure 1, the largest concentration of VHF cases occurred between October 1989 and February 1992. Cases have been sporadic and have occurred in all months of the year, although more that half of the reported VHF cases have been during the dry season (December to March). During this period of the year there is considerable agricultural and land clearing activity in the affected region. Epidemiologic field studies in the VHF-endemic region have implicated the cotton rat Sigmodon alstoni and the cane mouse Zygodontomys brevicauda as reservoirs of Guanarito virus. Laboratory studies with experimentally infected Z. brevicauda have demonstrated that these rodents develop a chronic infection and shed Guanarito virus in their urine and saliva for up to five months. During the past 2 years, several thousand wild rodents have been trapped in the states of Portuguesa, Barinas, Apure, Guarico and Cojedes in the central plains (llanos) of Venezuela in an attempt to determine the geographic range of Guanarito virus. Naturally infected S. alstoni and/or Z. brevicauda have been found at almost every site sampled in these five states. Guanarito virus isolation rates among S. alstoni at the different sample sites have ranged from 10 to 55%, indicating that the virus has a fairly wide geographic distribution. In contrast, serologic studies among humans living in the states of Portuguesa indicate the <2% of the population has antibodies to Guanarito virus. These data and the sporadic occurrence of the recognized cases of VHF suggest that the human infection with Guanarito virus is relatively infrequent and that transmission must occur under special circumstances that are not yet well understood. Like other arenavirus infections, transmission of Guanarito virus to people is though to be by aerosol from the excreta of infected rodents. To date, there are no confirmed reports of secondary VHF cases among attending hospital personnel or close family members. Epidemiologic studies are continuing in the VHF endemic area to identify the full distribution of the disease in Venezuela, risk factors for human infection, methods for early detection and treatment of VHF cases, and the pathogenesis of Guanarito virus in its presumed rodent reservoirs. This work is a collaborative effort between scientists: Rosalba Salas, D.V.M., M.S., Instituto Nacional de Higiene "Rafael Rangel", Caracas, the Venezuelan Ministry of Health and Social Assistance; Nuris de Manzione, M.D., Universidad Nacional Experimental de los Llanos Ezequíel Zamora, Guanare; Robert B. Tesh, M.D., The University of Texas Medical Branch, Galveston, and Charles Fullhorst, D.V.M., Dr.P.H. at The Centers for Disease Control and Prevention, Atlanta.
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