CE17 - Recherche translationnelle en santé

Development of tools to eliminate onchocerciasis in Loa loa-coendemic areas – EOLoa

Submission summary

Onchocerciasis is a parasitic vector-borne disease caused by the filaria Onchocerca volvulus (Ov) prevalent mainly in Africa. Due to its ocular and cutaneous complications, individual and public health burden are high where infection prevalence exceeds 40%. Since 1989, populations in such “meso-hyperendemic” areas receive “community-directed” mass treatment with ivermectin (IVM) (CDTI). CDTI is repeated annually because IVM kills the parasite's larval stage (microfilariae, mf, causing the symptoms and transmitted by the vector), but not the adult worms. CDTI has significantly reduced morbidity and even interrupted Ov transmission in some areas, leading the WHO to change its objective from disease control to infection elimination by 2025. This requires that interventions are expanded into hypoendemic areas. In Central Africa, CDTI is complicated by co-endemicity of another filariasis, loiasis (due to Loa loa), because individuals with high Loa microfilarial densities (MFD) in the blood can develop serious adverse events (SAE) after IVM treatment. CDTI's risk/benefits ratio is deemed acceptable in onchocerciasis meso-hyperendemic, but not in hypoendemic areas, where alternative treatment strategies (ATS) are needed. Among various ATS, two Test and Treat strategies (TNT) are possible. Loa-first TNT consists of identifying those at risk of post-IVM SAEs, to exclude them from IVM treatment, and to treat the rest (˜95%) of the population safely with IVM. Oncho-first TNT' consists of identifying those with active Ov-infection, testing only these for Loa loa MFD putting them at risk of post-IVM SAEs for exclusion from IVM treatment, and to safety treat the remaining Ov-infected individuals. This project will evaluate three tools for effective and cost-effective TNT. (1) A non-invasive diagnostic (LTS-2 patch) for patent Ov-infection. Its safety and performance (sensitivity and specificity using examination of skin snips as the reference method) will be evaluated in 1400 persons in Cameroon. This test could be applied within an Oncho-first TNT strategy in onchocerciasis hypoendemic areas (with or without Loa co-endemicity). (2) The drug levamisole (LEV), never evaluated for Loa loa but shown to induce a transient, relatively slow MFD reduction in Ov, Wuchereria bancrofti or Brugia malayi (which cause lymphatic filariasis) infected individuals. A trial involving 720 subjects in the Republic of Congo (6 cohorts with ascending Loa MFD), will assess whether a low dose of LEV (1-1.5 mg/kg) safely reduces Loa MFD. Should that be the case, mass LEV treatment could lower Loa MFD below the risk threshold of post-IVM SAE in the population so that CDTI could be safely implemented thereafter. (3) The drug moxidectin (MOX) reducing Ov MFD for longer than IVM, but never tested in Loa-infected subjects. We will compare the safety and effect on Loa MFD of IVM and a low MOX dose (2 mg) in a trial conducted in Cameroon in 3 cohorts with ascending Loa MFD (480 participants total). If the SAE incidence after IVM and MOX is comparable, further trials could establish the MOX-specific risk-threshold so that MOX could replace IVM in loiasis endemic areas as part of mass treatment in onchocerciasis meso-hyperendemic areas part of Loa-first TNT campaigns in onchocerciasis hypoendemic areas. This would allow to decrease Ov MFD in the population faster, and to accelerate Ov elimination. Furthermore, should Loa MFD be lower one year after MOX than IVM treatment, the risk of MOX-treated individuals having a Loa MFD above the risk threshold at that time would be very low and they would not require re-testing for Loa in the subsequent TNT campaign. The results of this translational research project would help develop innovative and cost-effective strategies to expand onchocerciasis control activities in central Africa and reach the WHO objective of Ov elimination.

Project coordination

Cédric Chesnais (Recherche translationnelle appliquée au VIH et aux Maladies Infectieuses)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

TransVIHMI Recherche translationnelle appliquée au VIH et aux Maladies Infectieuses

Help of the ANR 358,181 euros
Beginning and duration of the scientific project: - 24 Months

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