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Crimean-Congo hemorrhagic fever (CCHF) virus is becoming increasingly recognized as an important human pathogen in southern Africa. In order to determine the role of wild mammals in the natural ecology of the virus, sera from 3,772 wild mammals of 87 species and from 1,978 domestic dogs collected in South Africa and Zimbabwe between 1964 and 1985 were tested for antibody to CCHF virus by reversed passive hemagglutination inhibition (RPHI) and by indirect immunofluorescence (IF). Antibody was found to be highly prevalent in large mammals in the Orders Artiodactyla and Perissodactyla such as giraffe, Giraffa camelopardalis (3/3 positive), rhinoceros, Ceratotherium simium and Diceros bicornis (7/13), eland, Taurotragus oryx (59/127), buffalo, Syncerus caffer (56/287), kudu, Tragelaphus strepsiceros (17/78), and zebra, Equus burchelli (16/93). In small mammals antibody was found in the sera of 40/293 hares, 22/1,305 rodents, and 1/74 wild carnivores, but not in 522 primates, 176 insectivores, or 19 hyrax. Antibody was also found in the sera of 118/1,978 domestic dogs. The species of wild mammal in which antibody was distributed (with highest antibody prevalence in hares and large herbivores) reflects the feeding preference of immature and adult ticks of the genus Hyalomma, suggesting that Hyalomma sp. are the principal CCHF vectors in the wild.