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The reduction in malaria transmission achieved through ivermectin would mostly derive from mosquito mortality [ 22 ], hence ivermectin should be seen as a new paradigm of vector control, as opposed to a transmission-blocking drug that would treat malaria and also decrease transmission [ 15 ]. Moreover, as currently envisioned, ivermectin is not a stand-alone tool, but rather a complementary vector control strategy to be added to the emerging elimination strategy. Finally, the use of ivermectin will provide personal benefit in terms of NTDs and ectoparasites. The caveat is animal studies that indicate a direct of effect of ivermectin on Plasmodium liver stages [ 6 , 7 ]. This is preliminary, intriguing and needs to be better understood, in terms of mechanism and possible effect in humans.
Ivermectin is the drug of choice for the treatment of onchocerciasis. It is also the only drug used in campaigns aimed at eliminating onchocerciasis. In Africa alone, the overlap between onchocerciasis [40] and malaria endemicity [41] is practically 100% as shown in Fig. . An increase frequency in the administration of ivermectin (as could be expected if used for malaria) could shorten the time to interrupt transmission of onchocerciasis in certain settings [42] and has been previously advocated as a necessary measure in areas where interruption of transmission has not been achieved after 10 years of annual treatment [43]. If there is potential to shorten the time during which ivermectin donation is needed, this could have profound implications for the business model used today. Moreover, ivermectin has also been demonstrated, in a triple combination, to have remarkable potential impact on elimination lymphatic filariasis [44].
While the single dose used for each of these diseases is not sufficient for impact on malaria, distribution for malaria indication should suffice as a dose for either disease, so careful coordination between malaria and NTD communities would result in most efficient use of supply. Additionally, ivermectin has at least partial activity against several soil-transmitted helminths and ectoparasites, it is reasonable to expect benefit in this context in communities where an ivermectin-based tool for malaria is implemented [45].
This potential tool will optimally require collaboration between the malaria and NTD programmes, including joint research efforts. Two examples or effective collaboration could be:
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Data sharing at programme level to optimize timing of ivermectin distribution for malaria and increase impact (dry vs rainy season) and avoid unnecessary duplication of NTD programmes.
Ivermectin distribution for malaria with the co-administrations [ 46 47 ] needed as an NTD intervention.
There have been concerns about increasing selective pressure on soil-transmitted helminths and filariae with a wider use of ivermectin. There is limited data on this possibility. Previous reports of ivermectin-resistant Onchocerca [48] have been the subject of debate [49–52]. The drug has in fact been used for decades with excellent results in reducing NTD transmission. Additionally, if used in malaria elimination efforts the number of MDA rounds will be limited. There is previous positive experience on the impact of malaria interventions on NTD transmission such as the possibility to halt LF transmission by scaling up LLINs in Nigeria [53].
There is increasing interest in the potential use of Moxidectin for onchocerciasis [54], having a second drug available for onchocerciasis might help manage resistance concerns. However, given the similarities in molecular structure and mode of action [55] there is potential for co-resistance [56]. The lethal concentration 50 of moxidectin for Anopheles mosquitoes [34] is one order of magnitude above the Cmax reached using maximum moxidectin doses in humans [57]. In the meantime, ivermectin remains the sole drug for the control and elimination of onchocerciasis and an important pillar for the treatment of lymphatic filariasis.
An additional potential risk is diverting the drug supply away from NTD programmes. Yet this is also an opportunity. A novel indication for malaria would increase market and demand, which should serve as incentive for manufacturers to go through the WHO-PQ process.
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