Immune diagnostic for latent tuberculosis
Tuberculosis remains a major global health challenge. Despite progress in reducing the number of deaths due to tuberculosis, the global burden of disease remains enormous, with an estimated 10.4 million new cases and 1.8 million deaths in 2015. The objective of our project funded by the RIIP was to evaluate the HBHA-IGRA (for Heparin-Binding Hemagglutinin-Interferon Gamma Release Assay) in the diagnosis of latent tuberculosis in Africa. This project (TB-LaTAS project) was developed in different African countries as Madagascar, Tunisia and Senegal through the International Network of Pasteur institutes. This project was coordinated by the Pasteur Institute of Lille. The cell-mediated response was evaluated in response to mycobacterial antigens including tuberculin, ESAT-6 and HBHA, the later having been characterized by the team of Camille Locht. In St. Louis, the study included three groups: i) patients with active tuberculosis; ii) patients with latent tuberculosis iii) healthy subjects. Preliminary analysis indicates that the immune profile as antigens is different in patients with active tuberculosis compared to those diagnosed with latent tuberculosis suggesting that the HBHA-IGRA test could be transposable to African populations
In Senegal, a dam has created an ideal habitat for intermediate host (molluscs) of the intestinal and urinary schistosomiasis. In addition, the dam has caused the disappearance of one of the main predators of vector snails, an African freshwater prawn: Macrobrachium vollenhovenii. His role in the fight against schistosomiasis is the object of our study funded by the Bill & Melinda Gates Foundation, the National Science Foundation, USA, and The Grand Challenges of Canada. All the actors of the project are grouped in the Up Stream Alliance (www.theupstreamalliance.org). A first phase of experimentation, the results of which were published (PNAS, 2015), showed the interest of an effort to reintroduce these prawns in the river. Researchers compared the parasitological and malacological situations of two Senegalese villages, one receiving prawns at the water points, the other one as control. After eighteen months, we found a 80% reduction in the number of snails infected with parasites and a decrease of 50% schistosomiasis prevalence in the “prawn village” compared to the control one.
An experiment on a wider scale (Phase 2) is being developed to strengthen the interests of the relocation of freshwater shrimp. This project tests three major points:
- A cohort of 1500 children living in 16 villages are studied for the influence of the native prawns implantation on the reduction of schistosomiasis transmission and on children’s health;
- We assess the ecological impact of a sustainable presence of the indigenous prawns, Macrobachium vollenhovenii, on the biodiversity of the site.
- As an economical point of view for local population, we test the feasibility of aquaculture of the local Macrobrachium in a controlled environment. This component is developed in collaboration with the National Agency of Aquaculture in Senegal.
Development of a candidate vaccine against schistosomiasis
The immunization against parasites is still a challenge, but it could help reducing the morbidity of the exposed population. In the context of an integrated approach to prevent schistosomiasis, vaccination can be an crucial asset in addition of chemotherapy by increasing or initiating at an earlier stage a protective immune response controlling the worm load. The recombinant fatty-binding Protein Sm14, identify in Schistosoma mansoni, in solution with the adjuvant product GLA-SE (IDRI, USA) is one of the major schistosomiasis vaccine candidates in clinical development in the world. It was developed in Brazil by the Oswaldo Cruz Foundation (FIOCRUZ), with the support of WHO. A phase I Clinical trial data has already been completed that demonstrated tolerability and immunogenicity in healthy adult male and female volunteers living in a Brazilian area non-endemic for schistosomiasis. The lack of significant adverse events and strong humoral and cellular immunogenicity of the vaccine has paved the way for Phases II clinical trials in endemic areas. We are in charge in coordinating and carrying out these Phase II trials that focuses on evaluating safety and immunogenicity in adults (phase IIa) and in school children (phase IIb) living in Schistosoma mansoni and S. haematobium endemic areas. This program is funded by WHO, FIOCRUZ, Orygen S.A. (Brazil).