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Professor
John P. A. Lusingu

Tanzania, United Republic of

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Profile EDCTP Fellowship 1

Project Title

Malaria Research Capacity building for Field Trials in Tanzania (MaReCa)

Project Objectives

1. To document burden of malaria in the study area over years 2. To develop and characterize efficacious malaria vaccine for children and pregnant women. 3. To build malaria research capacity at Masters and PhD levels. 4. To establish and maintain mentorship programme. 5. To sustain clinical research and clinical trials in Korogwe Research Station.

Results & Outcomes

MaReCa Project is based on the continuation of (1) Passive case detection (PCD) of febrile episodes by community owned resource persons (CORPs) which started in January 2003, (2) Paediatric study with the intention to treat for malaria since January 2005, (3) Cross-sectional community malaria surveys during peak transmission season which started in 2003. Henceforth, the trend of the burden of malaria at community and health facility levels has been documented. Samples and data analyses are progressing well. Staff areundergoing Masters and PhD training as well as mentorship programme. The ethical approval of theprotocol has been extended and a refresher training of the team has been conducted. Appropriate management of malaria cases at community and health facility levels that has relieved participants and relatives from the undesired effects and let them get involved in social and income generating activities. The local Tanzanian team are working very closely with their counterparts from Denmark, and Belgium as part of capacity building and strengthening for the site. As part of the MaReCa study, the first PhD student, Geofrey Makenga, who is supported by the grant has already published three papers. as indicated above. Interestingly, the findings from the Clinical Trial by Makenga et al., calls upon the need to introduce intermittent preventive treatment of malaria in schoolchildren as an important tool to control malaria. The first MSc student, Paul Martine, has graduated and his article has been published in Malaria Journal as shown in the link provided above. The findings highlight the need for targeted interventions focusing on asymptomatic infections which is an important risk factor for anaemia in the community and act as a source of continued transmission of malaria in the study area. It is our expectation that through the ongoing analyses several other manuscripts will be developed and published in peer reviewed journals by the second Masters and the second

Host Organisation

Department Institution Country
Tanga Centre National Institute for Medical research (NIMR) TZ

EDCTP Project

TMA2015SF998

EDCTP Program

EDCTP2

EDCTP Project Call

Senior Fellowship (SF)

Study Design

Longitudinal cohort study

Project Summary

The most deadly form of malaria is caused by Plasmodium falciparum, that expresses antigens on the surface of the infected erythrocyte that enable the parasite to sequester to the vascular endothelium. The binding is mediated by a family of antigens called Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) encoded by about 60 var genes in each genome. Protective antibodies block the binding between the infected red blood cells and receptors on vascular endothelium. Due to the extensive variation within the PfEMP1 family a large repertoire of antibodies is needed before the individual is completely protected. Protection against severe forms of malaria is acquired after a few infections such as pregnancy-associated malaria. Here disease is caused by parasites expressing the variant of PfEMP1 called VAR2CSA, and anti-VAR2CSA antibodies mediate immunity against the syndrome. Recently we identified Endothelial Protein C Receptor (EPCR) as the most pathogenic PfEMP1 in severe malaria in children, and we need to characterize it by using well defined malaria patients. Interestingly vaccines based on PfEMP1 are attractive because they mimic natural occurring protective immune responses and could avert syndromes responsible for the vast proportion of malaria deaths. The theoretical background for our approach is that antibodies that prevent the interaction between PfEMP1 and its receptors are the main targets for acquired immunity, and that such antibodies can be induced by vaccination. To pursue the goal of making malaria vaccines, we will use bioinformatics, molecular biology, gene technologies, protein chemistry, structural chemistry, immunology, parasitology, vaccinology and clinical sciences. The vaccines that we are aiming to develop will be subject to administration to young children and women. The mosquirix (RTS,S/AS01) malaria vaccine protective efficacy is moderate and requires four doses. A more efficacious vaccine would be ideal and that is why we believe a PfEMP1 based malaria vaccine would meet such demands. The venture towards placental malaria vaccine and more efficacious malaria vaccine for children requires the availability of qualified scientists to conduct field trials in malaria endemic communities and apply molecular, immunology, parasitology and genomics to evaluate malaria vaccines at different stages of clinical development. We believe that through a Senior Fellowship whereby a field team will be established in Korogwe and sustained through the fellowship as well as capacity development at Masters and PhD level for junior research scientist, the site will be readily prepared to test vaccine for placental malaria and a more potent malaria vaccine for children.

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