Onchocerca ochengi is a nodule-forming filarial nematode parasite of cattle. It is the closest known relative of the human parasite Onchocerca volvulus, with which it shares the black fly vector Simulium damnosum. Onchocerca sp. BSiisa^ was described in black flies and in cattle and, based on limited mitochondrial sequence information, appeared to be about equally phylogenetically distant from O. ochengi and O. volvulus. Based on molecular genetic markers and apparent interbreeding, we later proposed that O. sp. BSiisa^ belongs to the species O. ochengi. However, we did not demonstrate directly that the hybrids were fertile, and we were still unable to resolve the phylogenetic relationship of O. ochengi, O. sp. BSiisa,^ and O. volvulus, leaving some concerns with the conclusion mentioned above. Here, we present fully assembled, manually curated mitochondrial genomes of O. ochengi and O. sp. BSiisa,^ and we compare multiple individuals of these two taxa with respect to their whole mitochondrial and nuclear genomes. Based on the mitochondrial genomes, O. ochengi and O. sp. BSiisa^ are phylogenetically much closer to each other than to O. volvulus. The differences between them are well within the range of what is expected for within-species variation. The nuclear genome comparison provided no indication of genetic separation of O. ochengi and O. sp. BSiisa.^ From this, in combination with the earlier literature, we conclude that O. ochengi and O. sp. BSiisa^ should be considered one species.

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SummaryWe studied the effect of 10 annual distributions of ivermectin for control of human onchocerciasis on the reduction of Onchocerca volvulus transmission by Simulium vector¯ies. Prevalence and infection load in the human population decreased, whilst the annual biting rates (ABR) of the vector remained unchanged. The annual transmission potential of infective larvae of O. volvulus fell to 40% of the preintervention level, but was still suf®cient to maintain endemicity. However, recent immigration of herds of nomadic cattle into the study area has diverted the¯ies from man to cattle, creating an additional zooprophylactic effect. The predominant transmission of the bovine ®laria O. ochengi to man also provides some concomitant cross-protective immunity against further infestations with O. volvulus. The effects of ivermectin on O. volvulus, combined with the zooprophylactic effects of the increased cattle population, have produced a complex bene®cial in¯uence on the transmission of human onchocerciasis.

Onchocerciasis (river blindness), caused by the filarial worm Onchocerca volvulus, is a neglected tropical disease mostly affecting sub-Saharan Africa and is responsible for >1.3 million years lived with disability. Current control relies almost entirely on ivermectin, which suppresses symptoms caused by the first-stage larvae (microfilariae) but does not kill the long-lived adults. Here, we evaluated emodepside, a semi-synthetic cyclooctadepsipeptide registered for deworming applications in companion animals, for activity against adult filariae (i.e., as a macrofilaricide). We demonstrate the equivalence of emodepside activity on SLO-1 potassium channels in Onchocerca volvulus and Onchocerca ochengi, its sister species from cattle. Evaluation of emodepside in cattle as single or 7-day treatments at two doses (0.15 and 0.75 mg/kg) revealed rapid activity against microfilariae, prolonged suppression of female worm fecundity, and macrofilaricidal effects by 18 months post treatment. The drug was well tolerated, causing only transiently increased blood glucose. Female adult worms were mostly paralyzed; however, some retained metabolic activity even in the multiple high-dose group. These data support ongoing clinical development of emodepside to treat river blindness.

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