Project Title

  “This project has received funding from the EDCTP2 programme, supported by the European Union and Novartis International AG”

Role of host immune responses in Plasmodium falciparum gametocytes carriage

GAMETO

Dr Hamtandi Magloire NATAMA

TMA2020CDF-3219

Malaria parasites in human blood need to undergo sexual differentiation and produce gametocytes in order to transmit the infection to mosquitoes during a blood meal. Understanding how and when this phenomenon occurs is essential to improve and/or develop control measures targeting transmission. Gametocyte production in P. falciparumcan vary depending on intrinsic parasite factors and multiple in-host environmental factors encountered during the course of an infection. That commitment to sexual development (also known as gametocytogenesis) is thought to be influenced by the environment in response to hostile and stressful growth conditions such as the host immune system. Immune responses to the malaria parasite are partially understood and most knowledge comes from the asexual blood stage of the parasites. However, little is known about the responses to sexual blood stages and how they affect transmission.

In this proposal, we aim to investigate the role of host immune responses in P. falciparum gametocytes carriage and the expression of molecular markers of sexual conversion during natural malaria infections. the proposal is embedded in an on-going 2-year longitudinal cohort study aiming to determine the contribution of In-Host factors (haemoglobin variants, proportion of reticulocytes, antimalarial treatment, occurrence of symptoms and immune responses) to P. falciparum gametocyte production and current burden of malaria infection/disease in Burkina Faso. In the present proposal we are proposing to thoroughly investigate the modulatory effect of antibodies responses against sexual and asexual stages of P. falciparum antigens (as determined by the luminex technology) on the occurrence of sexual conversion leading to gametocyte production in natural malaria infections. Prior to such investigation, will will characterize P. falciparum gametocyte carriage dynamics within the “In-Host” study using molecular tools. In addition, we will determine the transcript levels of the molecular markers of parasite sexual conversion in different conditions. These outcome variables (gametocyte carriage and transcript levels of molecular markers of sexual conversion) will be used to assess the association/correlation with antibodies levels (total IgG and IgG1-4 subclasses) against a panel of asexual and sexual stages antigens. We expect that by identifying relevant in-host factors directly linked to gametocyte production, results will shed light on the processes governing malaria transmission and inform new or adapted strategies for malaria control and elimination.