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Malaria parasites developing inside red blood cells approximately 30 hours after they have invaded the cells
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Annually, 25 April is a day of unified commemoration of the global effort to provide effective control of malaria around the world. The day was previously commemorated as Africa Malaria Day but during the sixtieth World Health Assembly in May 2007, a call was made to change the name to World Malaria Day. It is an opportunity for research and academic institutions to flag their scientific advances to both experts and the general public, and for international partners, companies and foundations to showcase their efforts and reflect on how to scale up what has worked.
What causes malaria?
"Malaria is caused by protozoan parasites of the genus Plasmodium that are transmitted between human individuals by Anopheles vector mosquitoes. This combination of parasite and mosquito has caused devastation in much of the tropical and sub-tropical regions of the world for many generations. Sub-Saharan Africa is the hardest hit, with hundreds of millions of new cases annually. Although fatalities are mostly limited to infants below the age of five, the debilitating symptoms caused by malaria are thought to be a major contributor to the stifling of productivity and economic development in many endemic countries," says Dr Heinrich Hoppe of the CSIR pharmacology research group.
Hoppe further explains that malaria control strategies are supported by the following three basic pillars:
- The use of prophylactic (preventative) and therapeutic (curative) drugs;
- The development of malaria vaccines for widespread inoculation; and
- Public health and environmental interventions, e.g. mosquito vector control through insecticide-spraying initiatives, the distribution of mosquito-repellent bed-nets and the destruction of mosquito breeding sites through wetland drainage programmes.
CSIR's response to the burden of malaria
Five of the CSIR's research groups are currently involved in exploring research methods aimed at developing anti-malarial drugs. These are the discovery chemistry group, the pharmacology group, the structural biology group, the bioprospecting group and the systems biology group.
Discovery chemistry group
This group is currently involved in exploring the three-dimensional structure of the malaria enzyme dihydrofolate reductase (DHFR), the major target of anti-folates, aimed at developing an anti-malarial drug. The group has designed and synthesised a number of anti-folate derivatives that display potencies equal or better than existing anti-folate drugs against cultured parasites. Funding to expand the development of this class of compounds is currently being sought from the Innovation Fund.
Pharmacology group
The group evaluates the anti-malaria potential of new compounds, using assays based on cultured malaria parasites that are validated and standardised in-house. The group further explores the possibility of using the assays to screen compound and natural product libraries for novel anti-malaria entities.
Structural biology group
The structural biology group is involved in a project that uses integrated grid computer networks to perform high-throughput in silico screens of chemical structures that potentially inhibit malaria target proteins, using advanced computational docking methods based on the 3D structures of the proteins obtained from databases or by in silico modelling. The project is being conducted in collaboration with scientists at the University of Pretoria Bioinformatics Institute.
Bioprosprecting group
The bioprospecting group uses South African traditional herbal plants as a source to identify novel therapeutics in a number of disease applications, including malaria. The work is being pursued through collaborations with the University of Basel, MMV (Medicines for Malaria Venture) and DNDi (Drugs for Neglected Diseases Initiative).
Systems biology group
The group uses state-of-the-art transcriptomic and proteomic methods to identify novel malaria parasite drug targets. The group has already identified several parasite gene products that are consistently and significantly upregulated in response to drug stress, which likely represent critical metabolic pathways that the parasite endeavours to maintain when challenged. Efforts to characterise and validate these putative targets are currently underway and include advanced genetic manipulation experiments aimed at over-expressing and knocking out the relevant genes in the parasite.
Collaboration with other entities
CSIR scientists also play a leading role in the South African Malaria Initiative (SAMI), the Department of Science and Technology-funded national consortium of malaria researchers.
More information on malaria.
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