Development of tools to eliminate onchocerciasis in Loa loa co-endemic areas
Onchocerciasis is a mainly African parasitosis caused by the filaria Onchocerca volvulus. Due to its ocular and cutaneous complications, it constitutes a significant burden for communities when its prevalence is >40%. Since 1989, community-directed ivermectin treatments have been organized in these "meso-hyperendemic" areas. Annual treatments have been successful in reducing morbidity and interrupting O. volvulus transmission in some households. This has led World Health Organization to shift its focus from disease control to elimination of infection, but this requires intervention in hypoendemic areas as well. In Central Africa, ivermectin treatments are complicated by the presence of another filariasis, loasis (caused by Loa loa). Indeed, subjects with high Loa microfilarial density in the blood are at risk of post-ivermectin severe side effects. The benefit/risk ratio of mass drug administration of ivermectin, acceptable when onchocerciasis is meso-hyperendemic, is not acceptable in hypoendemic areas, where alternative treatment strategies must be applied.
Evaluate, through a clinical trial conducted in Congo if levamisole is well tolerated and progressively reduces Loa microfilarial densities. If this were the case, mass treatment with levamisole could reduce microfilarial densities below the risk threshold for post-ivermectin adverse reaction in the population, and they could then benefit from safe mass drug administration with ivermectin.
Evaluate the effect of moxidectin on O. volvulus microfilarial densities, compared to ivermectin and evaluate its safety in Loa infected subjects. We will compare the tolerance and effect on Loa of a dose of ivermectin and a low dose of moxidectin in Cameroon.
Evaluate a non-invasive test (LTS-2 patch) to identify Onchocerca volvulus infected subjects. Its tolerance and performance will be evaluated in Cameroon.
We expect to have new tools allowing the improved strategies to accelerate the elimination of onchocerciasis.
These new tools could be implemented as ATSs and will be dedicated to the loiasis coendemic areas.
Single dose of levamisole (2.5 mg/kg) is safe in Loa loa-infected subjects and reduces microfilaremia temporarily. Higher doses or longer regimens should be tested to evaluate whether levamisole can be used as a pre-treatment to prevent post-ivermectin Loa-related encephalopathy.
Given the low dose of DEC contained in the LTS-2 patch, we expect that it will not induce SAEs and that the presence of a coinfection with Loa will not influence its result. We expect that the specificity and the sensitivity of the LTS-2 patch will be such that it could replace the examination of skin snip as a gold standard to diagnose an active infection with Ov, and that this tool will be deployed widely for various purposes: identification of infected individuals as part of an Oncho-first TNT strategy in Loa- coendemic or non-coendemic areas, but also for the evaluation of the impact of long-lasting CTDI programmes or for mapping untreated onchocerciasis hypoendemic areas where control activities have to be implemented.
Last, we expect that a low dose of MOX will induce a decrease in the Loa MFD but that this decrease will not be more rapid, and induce more AEs, than after IVM treatment