Project Title

Pre-treatment of hypermicrofilaremic loiasis for eligibility to Community Directed Ivermectin Intervention for Onchocerciasis control in co-endemic settings of Gabon

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

Main Objective The objective of this study is to determine an albendazole optimal and safe regimen for the treatment of Loa loa hypermicrofilaraemia in patients living in a loiasis-onchocerchiasis coendemic for their eligibility to the CDTI. Secondary objectives: • To evaluate the clinical and parasiticidal activity of 400 and 800 mg albendazole regimens on the Day (D) 30 and the adequate clinical and parasitological response (ACPR) of hypermicrofilaraemic loiasis treatment; • To evaluate the dose-response of albendazole on selected secondary endpoints [time to microfilariae clearance, observed microfilaraemia rate reduction (MRR) below 8,000 mf/mL at different estimated time points, microfilaraemia clearance rate and microfilaraemia recrudescence at 6 months, D180; • To evaluate the safety and tolerability of the different dosages of albendazole for the treatment of patients with Loa loa hypermicrofilaraemia; • To characterize the pharmacokinetics (PK) of albendazole and its metabolite in plasma of patients with different levels of L. loa microfilareamia according to the treatment regimens; • To evaluate the relationship between ACPR and concentration of albendazole and its metabolites Tertiary objectives • To compare the frequency of STH infection between the pre-treated individuals and those who will directly benefit from IVM MDA after the interventions. • To determine the dose regimen suitable for recommendation of an albendazole curative treatment regimen of loiasis.

Study Design

Clinical trial of phase IIb

Project Summary

In areas where onchocerciasis and loiasis are co-endemic, Community-Directed Treatment with Ivermectin (CDTI) strategy for onchocerciasis control is hampered by the presence of hypermicrofilaremic individuals who have Loa loa microfilaraemia exceeding 8,000 microfilariae per milliliter of blood (mf/mL). They are at risk of developing post-treatment severe and/or serious adverse reactions (SARs) after ivermectin (IVM) administration. These SARs are frequent in almost 10.0% of exposed population of loiasis hyperendemic settings such as in Gabon where both filariasis are endemic, Loa iinfection prevalence exceeding 40.0% in some villages with O. volvulus-infected individuals. A treatment that can safely reduce high L. loa microfilaremia (HLMF) below the risk threshold for SARs for a time sufficiently long to implement IVM MDA, would be a major contribution to efforts to control and eliminate onchocerciasis. Albendazole is considered as an alternative to DEC or IVM for the treatment of loiasis, it can reduce the hypermicrofilaraemia by at least 50% or even below 8,000 mf/mL for at least 4 months. Moreover this drug is equally effective on Soil-Transmitted helminthiases (STH) which are also prevalent in loiasisonchocerchiasis co-endemic settings. We hypothesize that a 30 days treatment of HMLF patients with albendazole will be sufficient to reduce the microfilaraemia below the threshold of 8,000 mf/ml and will allow this neglected population to be eligible for the CDTI for onchocerciasis control in co-endemic areas. The objective of this Phase IIb controlled randomized trial is to assess and to compare the safety and efficacy of two different regimens (daily 400mg or 800mg albendazole during 30 days) for the treatment of hypermicroflaremic loiasis in Moudouma; a village of Gabon with Loa loa-Onchocerca volvulus and STH co-endemicity. A total of 105 hypermicrofilaraemic individuals will be randomized and allocated in one of the treatment arms and the Adequate Clinical and Parasitological Response (ACPR) defined as a the reduction of microfilaraemia below 8,000mf/ml will be determined at day 30. The comparator arm will be composed by 35 low microfilaraemic patients treated with 400mg albendazole. For the first time albendazole pharmacokinetic and metabolites will be determined in filarialinfected individuals using High Performance Liquid Chromatography and analysed according to the microfilaraemia. The follow-up will last 180 days and the parasite clearance as well as impact on STH prevalence will be evaluated. This will be the first study in Gabon evaluating a pretreatment test and treat strategy for onchocerchiasis control including loiasis and STH.

Host Organisation

Sites

Current Organisation

Department of Fundamental Sciences of the Faculty of Medicine of the Université des Sciences de la Santé

Current Job Title

Lecturer-Researcher

Biography

Publications