Albendazole for lymphatic filariasis

Addiss, David G.; Critchley, Julia; Ejere, Henry OD; Garner, Paul; Gelband, Hellen

doi:10.1002/14651858.cd003753.pub2

Cited by 5 publications

(2 citation statements)

References 39 publications

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“…Albendazole (ALB) is a carbamate benzimidazole, broad-spectrum anthelminthic drug against flatworms, nematodes and cestodes that inhibits the polymerization of worm β-tubulin and microtubule formation [ 10 ]. Whether ALB has demonstrable antifilarial effects is still unclear [ 11 ]. But it has been reported to increase compliance of mass drug administration (MDA) program because of its direct effect on other gastrointestinal helminths.…”

Section: Introductionmentioning

confidence: 99%

Killing filarial nematode parasites: role of treatment options and host immune response

2016

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BackgroundThere is compelling evidence that not only do anti-filarials significantly reduce larval forms, but that host immune responses also contribute to the clearance of filarial parasites; however, the underlying mechanisms have not been fully elucidated.Main textFilarial infections caused by Wuchereria bancrofti and Brugia species (lymphatic filariasis) and Onchocerca volvulus (onchocerciasis) affect almost 200 million individuals worldwide and pose major public health challenges in endemic regions. Indeed, the collective disability-adjusted life years for both infections is 3.3 million. Infections with these thread-like nematodes are chronic and, although most individuals develop a regulated state, a portion develop severe forms of pathology. Mass drug administration (MDA) programmes on endemic populations focus on reducing prevalence of people with microfilariae, the worm's offspring in the blood, to less than 1 %. Although this has been successful in some areas, studies show that MDA will be required for longer than initially conceived.ConclusionThis paper highlights the mode of action of the various antifilarial treatment strategies and role of host immune response.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0183-0) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Killing filarial nematode parasites: role of treatment options and host immune response

2016

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“…The development of a macrofilaricidal compound has long been a goal of the World Health Organization (WHO), but attempts to develop appropriate compounds have yet to be successful [3]. Meanwhile the ongoing campaign for the global elimination of LF is based on the use of DEC, or ivermectin in sub-Saharan Africa where LF overlaps with onchocerciasis, together with albendazole, a drug with known efficacy against gastro-intestinal nematodes but with limited efficacy against filariae [4]. The availability of a macrofilaricidal drug would obviate the need for continued treatment with microfilaricidal drugs.…”

Section: Introductionmentioning

confidence: 99%

Assay Strategies for the Discovery and Validation of Therapeutics Targeting Brugia pahangi Hsp90

et al. 2010

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The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target.

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