Cytokine profiles and regulatory T cell levels in children reovering from uncomplicated malaria living in highly endemic malaria areas

Background

Although virtually every child living in Sub-Saharan African will get infected with P. falciparum parasite at one stage in their lives, only about two percent of these will develop severe malaria which if untreated will result in death. The reasons why some of these children develop severe malaria are not fully known. However, the host immunological response to the infection is suspected to contribute substantially to the severity of the disease.

It is also known that it is mainly children who have had several bouts of uncomplicated malaria (UCM) previously who will end up developing one of the life-threatening forms of severe malaria, either cerebral malaria (CM), severe malarial anaemia (SMA) or severe respiratory distress (SRD). With regulatory T cells being associated with enhancing disease severity in mice model, do high levels of regulatory T cells and anti-inflammatory cytokines IL-10 and TGF-b during the time children are recovering from uncomplicated malaria predispose them to developing the more severe form of malaria?

Project Progress

This project is investigating T cell regulatory responses in children with malaria. 63 children with uncomplicated malaria have been recruited from Blantyre and Chikwawa,followed for three months after their acute illness and their immunological responses compared with an equal number of control children. Children with malaria had lymphopenia. The percentage of  FoxP3⁺ T regulatory  CD4 cells  was  increased during the acute phase of the illness but not the overall number.

Status: A request for an additional $7,000 to allow more cytokine assays to be done was made and approved. An extension of the project until October 2012 was also approved and during this period the additional cytokine assays will be completed.