Research - Malaria Unit
Our malaria research aims directly to improve the treatment of the disease globally. The focus of MORU is on the treatment of severe malaria, mechanisms and spread of anitmalarial drug resistance, and the pathophysiology of falciparum and vivax malaria. These are not isolated areas, i.e. studies on pathophysiology are used to formulate novel adjuvant therapies and studies on drug resistance translate into recommendations on the use of artemisinin based combination therapies.
Laboratory studies are conducted in our laboratories in Bangkok, though there is a network of collaborators (see appendix). The laboratories in Bangkok also support the clinical studies. Clinical studies on severe malaria are conducted in Rourkela, Orissa, India and Chittagong, Bangladesh. Moreover, the multicentre trials ‘SEAQUAMAT’ and 'AQUAMAT' used sites elsewhere in the tropics. Fewer severe malaria patients are recruited nowadays in Mae Sot, on the Thai-Myanmar border, where the focus has shifted to detailed studies in uncomplicated malaria. A clinical study on vivax malaria is currently conducted in Calcutta, India.
Background - Malaria Unit
Human malaria infection is caused by four species of mosquito-borne parasites of the genus Plasmodium. In Southeast Asia, P. vivax and P. falciparum both contribute about equally to the burden of disease, but P. falciparum is far more lethal. Malaria remains a massive health problem worldwide, causing over one million deaths annually. Malaria is estimated to be responsible for 20 percent of deaths in African children under five years old, but is also an important cause of death in all age groups in South and Southeast Asia.
A better understanding of how malaria infection causes disease and death is vital for the development of better treatments. Our group studies patients with malaria, looking to discover exactly how the mechanics of the disease operate, how malaria parasites develop drug resistance, how to manage patients who are gravely ill with severe malaria, and how to safeguard those who are most vulnerable to malaria - pregnant woman and young children. We evaluate new treatments for malaria and improve deployment of existing antimalarial drug treatments.
Boy with severe malaria, Tanzania
Malaria in adults
Pathophysiology of malaria
In our search for parasite virulence factors, we identified differences in selectivity of P. falciparum strains. Parasites more likely to cause severe disease are able to invade a larger population of red blood cells, or, in other words, are less selective.
We have also visualised parasite sequestration in the microcirculation in living patients with severe malaria, and were able to correlate this with severity. We identified a reduction in red blood cell deformability as an important risk factor for a fatal outcome in severe malaria, presumably though its contribution to further obstruction of the microcirculation by sequestered parasitised red cells. We developed a method to estimate the number of sequestered parasitised red cells by quantitating a protein (PfHRP2) released from the parasite. We identified additional acids, other than lactic acid, contributing to the metabolic acidosis in severe malaria, which have an additional prognostic value. This will give insight into additional pathways important in the pathophysiology of severe malaria.
