Working together to combat malaria.
"...information at the molecular level is vital to gain insights
into the pathogenesis of malaria, and potentially offers
the opportunity to develop better drugs."
~ Subra Suresh
Research programmesDiagnosticsA variety of techniques are available to detect malaria infections. The oldest and most widely used technique is the microscopic detection of stained parasites in peripheral blood smears from infected patients. Microscopy requires a source of electricity, a trained technician, dyes, and a microscope. Although microscopy is used as the standard to evaluate all other methods, there are a growing number of examples where it has failed to pick up a positive result in infected patients. Most malaria cases occur in areas where a reliable source of electricity is not guaranteed, and/or where there are no or limited numbers of trained technicians. Consequently, alternative rapid, reliable and easy to use diagnostic methods are required. Other methods of detection include the polymerase chain reaction (PCR), a fluorescent stain (called QBC) and "dipstick" based rapid diagnostic tests (RDTs). The dipstick tests have become popular as they are easy to use and results are available within a few minutes. However, various reports have indicated that there are problems with the sensitivity and specificity of the tests, which are influenced by, among others, storage conditions. False positives have been attributed to spurious recognition of the human rheumatoid factor by the mouse-raised antibodies used in the production of the RDTs. The SAMI malaria diagnostics programme aims to develop and evaluate improved reagents for dipstick-based RDTs, resulting in reliable, cost-effective, sensitive and specific diagnostic tools for malaria. The second component of the programme aims to use proteomics methodologies to identify and evaluate other parasite proteins as targets for rapid diagnostic tests as alternatives to the current rapid diagnostic tests. The three protein targets currently used for malaria diagnosis (P. falciparum lactate dehydrogenase (Pf LDH), P. falciparum histidine-rich protein II (Pf HRP II), and P. falciparum aldolase) were chosen as they are well characterised and available as recombinant proteins. However, these proteins have disadvantages. Pf LDH and Pf aldolase are not secreted by the parasite and appear to be present in "low" copy number within the parasite cytoplasm. Pf HRP II is secreted by the parasite and reported to be present in higher concentration than the two enzymes, but has been reported to undergo antigenic variation within peptide regions detected by the Pf HRP II diagnostic antibody suggesting potential problems for the test should this be a common phenomenon.
Current SAMI Research projects:
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