Abstract
BackgroundIt is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations.MethodologyWe studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo.Principal FindingsWe calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo.Conclusion/SignificanceOur study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launched.
Highlights
Infections with the three major soil-transmitted helminth (STH) species, Ascaris lumbricoides, Trichuris trichiura and the hookworms Necator americanus and Ancylostoma duodenale are among the most common parasitic diseases in areas of rural poverty in developing countries [1]
We evaluated the activity of the ‘‘old’’, veterinary drug oxantel pamoate against T. muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo
We studied the activity of oxantel pamoate combinations with the four standard treatments for soil-transmitted helminthiasis
Summary
Infections with the three major soil-transmitted helminth (STH) species, Ascaris lumbricoides, Trichuris trichiura and the hookworms Necator americanus and Ancylostoma duodenale are among the most common parasitic diseases in areas of rural poverty in developing countries [1]. Two alternative drugs, pyrantel pamoate and levamisole are available but currently have a less prominent role since they require weight-based dosing [4]. Despite their excellent safety profile, these drugs have serious limitations with regard to their efficacy. When delivered as a single dose, as in preventive chemotherapy programs, all four compounds have a limited effect against infections with T. trichiura as shown in a recent metaanalysis [5]. It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations
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