Abstract
Several issues have been identified with the current programs for the elimination of onchocerciasis that target only transmission by using mass drug administration (MDA) of the drug ivermectin. Alternative and/or complementary treatment regimens as part of a more comprehensive strategy to eliminate onchocerciasis are needed. We posit that the addition of “prophylactic” drugs or therapeutic drugs that can be utilized in a prophylactic strategy to the toolbox of present microfilaricidal drugs and/or future macrofilaricidal treatment regimens will not only improve the chances of meeting the elimination goals but may hasten the time to elimination and also will support achieving a sustained elimination of onchocerciasis. These “prophylactic” drugs will target the infective third- (L3) and fourth-stage (L4) larvae of Onchocerca volvulus and consequently prevent the establishment of new infections not only in uninfected individuals but also in already infected individuals and thus reduce the overall adult worm burden and transmission. Importantly, an effective prophylactic treatment regimen can utilize drugs that are already part of the onchocerciasis elimination program (ivermectin), those being considered for MDA (moxidectin), and/or the potential macrofilaricidal drugs (oxfendazole and emodepside) currently under clinical development. Prophylaxis of onchocerciasis is not a new concept. We present new data showing that these drugs can inhibit L3 molting and/or inhibit motility of L4 at IC50 and IC90 that are covered by the concentration of these drugs in plasma based on the corresponding pharmacological profiles obtained in human clinical trials when these drugs were tested using various doses for the therapeutic treatments of various helminth infections.
Highlights
Initiate control programs that were first focused on reducing onchocerciasis as a public health problem, and since 2012, the ultimate goal is to eliminate it by 2030 [2]
An effective prophylactic treatment regimen can utilize drugs that are already part of the onchocerciasis elimination program, those being considered for mass drug administration (MDA) [19,20], and/or the potential macrofilaricidal drugs currently under clinical development [21]
When ivermectin and moxidectin were evaluated, we found that both drugs were highly effective as inhibitors of molting: IC50 of 1.048 μM [918.86 ng/ml] and IC90 of 3.73 μM [2,949.1 ng/ml] for ivermectin and IC50 of 0.654 μM [418.43 ng/ml] and IC90 of 1.535 μM [985.3 ng/ml] for moxidectin (Table 1 and S1 Fig), with moxidectin being more effective than ivermectin
Summary
Citation: Jawahar S, Tricoche N, Bulman CA, Sakanari J, Lustigman S (2021) Drugs that target early stages of Onchocerca volvulus: A revisited means to facilitate the elimination goals for onchocerciasis. PLoS Negl Trop Dis 15(2): e0009064. https://doi.org/10.1371/journal. pntd.0009064 Funding: Partial funding was provided to SL and JS by the Bill & Melinda Gates Foundation Grant OPP1017584, and by intramural funding from the New York Blood Center to SL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist.
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