Filarial nematodes are important and widespread parasites of animals and humans. We have been using the African bovine parasite Onchocerca ochengi as a chemotherapeutic model for O. volvulus, the causal organism of`river blindness' in humans, for which there is no safe and e¡ective drug lethal to adult worms. Here we report that the antibiotic, oxytetracycline is macro¢laricidal against O. ochengi. In a controlled trial in Cameroon, all adult worms (as well as micro¢lariae) were killed, and O. ochengi intradermal nodules resolved, by nine months' post-treatment in cattle treated intermittently for six months. Adult worms removed from concurrent controls remained fully viable and reproductively active. By serial electron-microscopic examination, the macro¢laricidal e¡ects were related to the elimination of intracellular micro-organisms, initially abundant. Analysis of a fragment of the 16S rRNA gene from the O. ochengi micro-organisms con¢rmed them to be Wolbachia organisms of the order Rickettsiales, and showed that the sequence di¡ered in only one nucleotide in 858 from the homologous sequence of the Wolbachia organisms of O. volvulus. These data are, to our knowledge, the ¢rst to show that antibiotic therapy can be lethal to adult ¢lariae. They suggest that tetracycline therapy is likely to be macro¢lari-cidal against O. volvulus infections in humans and, since similar Wolbachia organisms occur in a number of other ¢larial nematodes, against those infections too. In that the elimination of Wolbachia preceded the resolution of the ¢larial infections, they suggest that in O. ochengi at least, the Wolbachia organisms play an essential role in the biology and metabolism of the ¢larial worm.

Here we analyze patterns of human infection with Onchocerca volvulus (the cause of river blindness) in different continents and ecologies. In contrast with some geohelminths and schistosome parasites whose worm burdens typically exhibit a humped pattern with host age, patterns of O. volvulus infection vary markedly with locality. To test the hypothesis that such differences are partly due to heterogeneity in exposure to vector bites, we develop an ageand sex-structured model for intensity of infection, with parasite regulation within humans and vectors. The model is fitted to microfilarial data from savannah villages of northern Cameroon, coffee fincas of central Guatemala, and forest-dwelling communities of southern Venezuela that were recorded before introducing ivermectin treatment. Estimates of transmission and infection loads are compared with entomological and epidemiological field data. Host age-and sex-heterogeneous exposure largely explains locale-specific infection patterns in onchocerciasis (whereas acquired protective immunity has been invoked for other helminth infections). The basic reproductive number,R 0, ranges from 5 to 8, which is slightly above estimates for other helminth parasites but well below previously presented values.age ͉ sex ͉ helminth ͉ mathematical model ͉ onchocerciasis

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Development of a drug lethal to adult Onchocerca volvulus (i.e., macrofilaricide) is a research priority for the control of human onchocerciasis. Using bovine O. ochengi infections, we investigated the effects of oxytetracycline administered in a short intensive regimen (SIR; 10 mg/kg daily for 14 days), compared with a prolonged intermittent regimen (PIR; 20 mg/kg monthly for 6 months) or a combination of both (COM), on the viability of adult worms and their endosymbiotic bacteria (Wolbachia species). The long-term treatments eliminated >80% (COM) or >60% (PIR) of adult female worms (P<.001), and the COM regimen effected a sustained depletion of Wolbachia organisms. Conversely, SIR was not macrofilaricidal and only transiently depleted Wolbachia densities, which repopulated worm tissues by 24 weeks after treatment. These results unequivocally demonstrate the macrofilaricidal potential of tetracyclines against Onchocerca infection and suggest that intermittent, protracted administration will be more effective than continuous shorter term treatment.