Mechanism of malaria parasite adhesion

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The greatest impact of Plasmodium falciparum malaria infection in Africa is on children and pregnant women. Malaria infected red blood cells stick to receptor molecules on cells lining blood vessels. The parasite produces a family of proteins called PfEMP1, expressed on the cell surface. These PfEMP1 proteins are responsible for the sticking, and are major targets of the host immune response to malaria. We have found two particular receptor molecules, sugars called chondroitin sulphate A (CSA) and hyaluronic acid (HA), to be particularly important in sticking in the placenta, and have identified a PfEMP1 molecule which sticks to these. We will study the role of antibodies against the parasite, and against the CSA and HA molecules, in protection against malaria. We believe that African women develop these antibodies with increasing pregnancies, protecting themselves and their babies from malaria in later pregnancies, and that men will not have these antibodies. Pregnant women who have HIV-AIDS have greater susceptiblity to malaria. We will compare antibody responses in HIV+ and HIV- women to see if this is because they produce less protective antibodies. The PfEMP1 proteins are the product of var genes. We can compare parasites using the var genes they express to fingerprint them. We will examine the var gene expression by parasites from different patients, and by the parasites circulating in the blood or stuck in the placenta (in pregnant women) or in the brain, lung, gut and other organs (of children who have died of malaria) to see if the fingerprints of var gene expression differ between these different patients, or between different places in the same patient.