A new approach to the treatment of filariasis

Abstract

The symbiosis of filarial nematodes and intracellular Wolbachia bacteria has recently been exploited as a target for antibiotic therapy of filariasis. Antibiotic treatment of filarial nematodes results in sterility and inhibits larval development and adult worm viability. In the first trial on human onchocerciasis depletion of bacteria following treatment with doxycycline resulted in a complete and long-term block of embryogenesis. Bacteria are unable to repopulate nematode tissues up to 18 months after depletion, suggesting these effects may be permanent. Following ivermectin treatment, individuals given antibiotic therapy showed sustained reductions in skin microfilariae, with the majority of people remaining microfilarial negative 12-18 months after treatment. Since Wolbachia also contribute to the inflammatory pathogenesis of filarial disease, antibiotic therapy could, in addition to effects on worm fertility or viability, prevent the onset or development of filarial pathology.

Identifying sub-optimal responses to ivermectin in the treatment of River Blindness

“…This is important as the lack of heterogeneity observed in ivermectin's microfilaricidal effect reduces the chance of this type of drug resistance developing as there is little variability within the parasite population for selection to act upon. This should, however, not create complacency and efforts should be made to contain the spread of the suboptimal responses identified in Ghana by, for instance, vector control and anti-Wolbachia therapy (34). Mathematical models can be used to investigate how changing from annual to biannual mass ivermectin distribution could compensate for faster rates of skin repopulation and help national programs achieve their objectives of morbidity control, sustained reductions in transmission, or elimination of the parasite reservoir.…”

Mapping the presence of Wolbachia pipientis on the phylogeny of filarial nematodes: evidence for symbiont loss during evolution

“…W. pipientis) is implicated in these pathological outcomes. Some experimental evidence for the presence of W. pipientis in L. loa specimens have apparently been obtained (Taylor and Hoerauf, 2001), even though this evidence for positivity has not yet been published. The contrary evidence that samples of L. loa do not harbor W.…”

Culture and Phenotypic Characterization of a Wolbachia pipientis Isolate

“…A variant strain detected in Drosophila melanogaster was demonstrated to proliferate massively in adults, leading to widespread degeneration of tissues followed by early death of the insect (17). The bacteria may be associated with nematodes and thus may be indirectly responsible for pathogenesis in human filariasis (27,32). Wolbachia is extremely widespread and has been found in up to 16% of insect species, including each of the major insect orders.…”