Unrevealing dry season Plasmodium falciparum replication biology

Descripción del proyecto

Cómo sobrevive la malaria a la estación seca

Un protozoo unicelular parásito de los humanos y que se multiplica rápidamente en la sangre es responsable de más de doscientos millones de casos de malaria en todo el mundo, y la mayor carga cae sobre los niños africanos. La mayoría de los casos se dan durante la estación de las lluvias, cuando hay abundancia de mosquitos. Durante la estación seca, el parásito se oculta y no suele causar síntomas a pesar de la disminución de niveles de anticuerpos específicos contra «Plasmodium falciparum». El proyecto NotToKill-NotToDie, financiado con fondos europeos, probará la hipótesis de que, durante la estación seca (sin mosquitos disponibles para transmitir la enfermedad), las series continuas de replicación del «P. falciparum» en estadio sanguíneo conducen a una expresión génica diferencial relacionada con la progresión del ciclo celular que permite el mantenimiento de niveles bajos de parasitemia.

Objetivo

Plasmodium falciparum is responsible for over 200 million yearly malaria cases and the major burden is upon African children. Public health strategies to control and ultimately eradicate malaria are very much needed. In Africa, seasonal transmission of this mosquito-borne parasite is very common. Infections in adults are clinically silent whilst in children it generally leads to clinical disease with nearly half a million deaths each year. The dry season represents a major challenge for the parasite’s survival due to the absence of the transmission vector; yet, P. falciparum seems to be capable of maintaining low parasitemias just enough not to kill but not to die. During the dry season, an important fraction of these children remains clinically silent for months despite the decrease in P. falciparum-specific antibody levels. This low parasitemia reservoir is indispensable to spread transmission in the following rainy season. How do parasites not increase to the point of causing clinical malaria in these children during the dry season? We hypothesize that during the dry season with no mosquitoes available to transmit, continuous rounds of P. falciparum blood stage replication lead to a differential gene expression related to cell cycle progression allowing the maintenance of low levels of parasitemia. The Center for Infectious Diseases, University Hospital Heidelberg has an interdisciplinary and translational orientation and is embedded in partnerships with groups in malaria endemic countries, representing a unique environment to execute the objectives of this project. I offer translational expertise in the malaria from my previous experience in malaria endemic areas of Brazil as well as in state-of-the-art laboratories in the US. This ambitious yet feasible project also offers the opportunity for me to broaden my expertise in malaria by acquiring knowledge in new area, which will allow me to build a solid background from which to become an independent researcher.