Towards Novel Antifilarial Drugs: Challenges and Recent Developments

Abstract

Filariasis is caused by thread-like nematode worms, classified according to their presence in the vertebrate host. The cutaneous group includes Onchocerca volvulus, Loa loa and Mansonella streptocerca; the lymphatic group includes Wuchereria bancrofti, Brugia malayi and Brugia timori and the body cavity group includes Mansonella perstans and Mansonella ozzardi. Lymphatic filariasis, a mosquito-borne disease, is one of the most prevalent diseases in tropical and subtropical countries and is accompanied by a number of pathological conditions. In recent years, there has been rapid progress in filariasis research, which has provided new insights into the pathogenesis of filarial disease, diagnosis, chemotherapy, the host-parasite relationship and the genomics of the parasite. Together, these insights are assisting the identification of novel drug targets and the discovery of antifilarial agents and candidate vaccine molecules. This review discusses the antifilarial activity of various chemical entities, the merits and demerits of antifilarial drugs currently in use, their mechanisms of action, in addition to antifilarial drug targets and their validation.

Recombinant trehalose-6-phosphate phosphatase of Brugia malayi cross-reacts with human Wuchereria bancrofti immune sera and engenders a robust protective outcome in mice

“…The current antifilarial chemotherapy is based on Diethylcarbamazine and Ivermectin which are administered alone or in combination with Albendazole [2]. Yearly or half yearly treatment needs to be continuously repeated for many years to block the transmission of infection.…”

Validation of onchocerciasis biomarker N -acetyltyramine- O -glucuronide (NATOG)

“…First, a simple and robust point-of-care diagnostic test to replace the highly invasive and painful skin snip diagnostic test must be developed, which, if correctly designed, could also be used to monitor mass drug treatment progression 5, 6. Second, new drugs must be developed for macrofilarial elimination 5, 6. Currently, the skin snip remains the gold standard for diagnosing O. volvulus infections in the field.…”

Progress and challenges in the discovery of macrofilaricidal drugs

“…The field has recently been reviewed [74,75]. The primary problem in this area is the difficulty in translating in vitro actives to in vivo actives, as discussed later.…”

“…Thus, in the Review judgment of the authors, it is not useful to re-review them here. Indeed, many series first identified in the 1990s remain described as potential leads, but have not fostered additional work [75].…”