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Seeking Therapeutic Options to Prevent Filarial infections and post-Ivermectin Loa-related Adverse Reactions

​This project has received funding from the Agence Nationale de la Recherche (ANR) - Young researchers

STOP-FiLAR: Service


Onchocerciasis and loiasis are vector-borne parasitic diseases caused by Onchocerca volvulus (Ov) and Loa loa (Loa), respectively. Onchocerciasis is transmitted by the bites of black flies (Simulium spp.), and loiasis by the bites of tabanids (Chrysops spp.).

Onchocerciasis is endemic in 31 African countries, as well as in a large focus spanning the Venezuela/Brazil border and in Yemen, while loiasis is present only in Central Africa. An estimated 37 million people are infected with Ov and 15 million people are infected with Loa.

From the early 1990s, African endemic countries implemented onchocerciasis control programmes based on annual mass drug administration (MDA) of ivermectin (IVM). In hyper- and mesoendemic areas, where the disease constitutes a public health problem, all individuals aged ≥5 years are offered the drug without prior diagnosis. IVM has a strong microfilaricidal effect, i.e. it kills most parasite’s larval stage (microfilariae, mf) present in the skin. However, it has little effect on the adult worms (macrofilariae) viability, which live up to 15 years. Consequently, MDA have to be repeated annually for at least 15 years to interrupt onchocerciasis transmission in a defined focus. In 2010, the African Programme for Onchocerciasis Control (WHO-APOC) shifted its objective from control of the disease to the elimination of infection, meaning that interventions have to be expanded to hypoendemic areas.

Loiasis is not currently targeted by a dedicated control programme, but it impedes onchocerciasis elimination activities in areas where both diseases coexist because IVM can induce an encephalopathy with coma in individuals with Loa microfilarial densities (MFD) exceeding 30,000 mf/mL of blood. In co-endemic areas where onchocerciasis is hypoendemic, the risk of post-IVM SAE outweighs the individual benefits of treatment. To date, there is no short-term perspective of a treatment that can be used widely and that is both effective against onchocerciasis and safe in subjects with high Loa MFD. Besides this programmatic issue, individual treatment of subjects with very high Loa MFD remains challenging. Treatment strategies for these subjects include the use of apheresis or a 3-week daily course of albendazole (ALB) followed by IVM and/or diethylcarbamazine. These protocols are difficult to apply both in Central Africa and in Europe for the management of imported cases, because of SAEs that may occur.

Solutions have been proposed to treat areas where onchocerciasis is hypoendemic and loiasis is co-endemic. These so-called “alternative treatment strategies” (ATS) include the pre-treatment of the whole population with a drug reducing progressively (thus safely) the Loa MFD under the threshold above which a post-IVM SAE can occur, and apply IVM MDA subsequently. Elimination of onchocerciasis could be accelerated by treating all subjects (either infected or not) living in endemic areas with a “chemo-prophylactic” drug preventing the parasite development from the first larval stages in humans to fecund adult worms. This strategy would reduce new active infections and lead to a progressive attrition of the parasite reservoir in the exposed population. It could also be applied at individual level to uninfected subjects visiting endemic areas.



The objectives of the present project are to evaluate alternative treatment strategies to accelerate onchocerciasis elimination and/or to prevent filarial infections in loiasis-coendemic areas:
1.     Levamisole (LEV), which has already demonstrated a light to moderate microfilaricidal activity when used as a single dose (2018-JCJC-ANR project “EOLoa”) and could be distributed as a “pre-treatment” to the whole population to decrease progressively (thus safely) the Loa MFD before distributing (again safely) IVM.
2.     ALB, which has already been evaluated in individuals infected with Loa, but with very few data for subjects with high Loa MFD, making it impossible to conclude on its use as a suitable treatment.
Both these drugs can also be useful in individual treatment of subjects with very high Loa MFD.
3.     IVM, moxidectin (MOX) and ALB as potential prophylactic treatments for Ov and Loa infections.



We expect to find new applications for already available drugs that will accelerate the elimination of onchocerciasis. Moreover, we expect to find a safe and efficient way to treat individuals with high Loa MFD. Given the promising results of the trial which evaluated a single 2.5 mg/kg dose of LEV on individuals with Loa MFD, we expect to demonstrate a similar safety profile and a higher efficacy with LEV 2.5 mg administered over 3 and/or 5 days. Should it be the case, LEV could be used to treat individuals with high Loa MFD, and be administered as a mass pre-treatment to the entire population living in loiasis-coendemic areas, before the latter receives safe IVM MDA. WP2 will allow us to assess to which extent a long ALB regimen reduces high Loa MFD. Like WP1 on LEV, should 3-weeks ALB treatment result in a progressive reduction in Loa MFD, it could be integrated into onchocerciasis elimination programmes as an ATS, and also be a therapeutic option for individual treatment of subjects with high MFDs. Finally, through WP3, we hope to demonstrate a significant prophylactic effect of at least one of the three molecules tested on onchocerciasis and loiasis when administered at 3-month intervals: ALB, MOX or IVM. If such an effect is demonstrated, it may accelerate elimination of onchocerciasis by acting on the first stages of parasite development in the human host and thus reducing the incidence of infection. Furthermore, if this effect exists and is being shared with populations, it could increase population compliance with MDAs. At the same time, it could make it possible to offer pre-exposure prophylaxis to the temporary visitors, including expatriates, who have to travel to onchocerciasis and/or loiasis endemic areas.


Scientific consortium

This ANR project is a collaborative research project including the French Institut de Recherche pour le Développement, TransVIHMI, the Centre for Research on Filariasis and other Tropical Diseases (CRFilMT) – based in Yaoundé, Cameroon and the Programme National de Lutte contre l’Onchocercose (PNLO) – based in Brazzaville, Republic of the Congo.

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