Background
The current therapeutic strategy of Onchocerciasis that relies on annual ivermectin mass drug administration (IVM-MDA) has not been very successful in rain forest of Central and West Africa, due to severe adverse events reported on individuals harboring high load of Loa loa microfilariae. Studies carried out in animal models recently demonstrated that elevated exposures to orally-administered rifampicin can lead to Wolbachia depletions from filariae more rapidly than those achieved by doxycycline. In a second study the combination of Rifampicin plus Albendazole given for only 7 days depleted Wolbachia in adult worms drastically, blocked embryogenesis, and stopped microfilariae production. This trial is designed to validate the above pre-clinical observations with a perspective of repurposing the existing drugs for the treatment of onchocerciasis in areas where Ivermectin does not give satisfactory results because of Loa loa. This project will also give opportunity for community and public engagement and training of scientists in clinical trials in the central African sub-region where there is a great need of clinical trial scientists.

Scientific Aims
The main objective is to show efficacy of the combination Rifampicin plus Albendazole, in adult worms using immunohistology and molecular techniques compared to Doxycycline plus Albendazole, Doxycycline alone or Ivermectin alone.
Developmental Aims:
The main developmental aim to be delivered will be the training through research scientists in research methodologies, laboratory skills, clinical trial skills, statistics, research governance and administration from Cameroon.

Study Design
A prospective randomized, Phase II, non-inferiority study of 10mg/kg/d Rifampicin plus 400mg Albendazole for 14 days, 35mg/kg/d Rifampicin plus 400mg Albendazole for 7 days and 14 days, compared to 200mg Doxycycline plus 400mg Albendazole for 14 days, or 200mg Doxycycline alone 28 days.

Primary Endpoint
The primary end point will be the proportions of living female worms with normal vs. interrupted embryogenesis assessed by immunohistology and the Wolbachia load assessed by molecular technique (PCR) after 18(±2) months.

Secondary Endpoints
Proportion of study participants with absence of microfilariae in the skin or blood, assessed 3.5, 6, 12 and 18 (±) months compared to pre-treatment.

Impact
If treatment proves successful, it will provide a new treatment for onchocerciasis which could help accelerating the elimination of the disease in areas of loiasis co-endemicity using a “test and treat approach”. This project will help to consolidate my ability to carry out complex clinical trial research. Through this senior fellowship, scientists from Cameroon and Chad will have opportunities to acquire new skills for field work, molecular biology techniques and participating to the development of drugs against infectious diseases of poverty.