The malaria parasite can cause unusually severe cases of the eponymous disease in patients, leading to higher mortality and poorer health outcomes among survivors. But scientists have long struggled to understand why some patients develop severe malaria.
The University of Washington’s International Center of Excellence for Malaria Research in South Asia — along with partners at the Center for Infectious Disease Research (CIDR) andGoa Medical College (GMC) of India — have discovered that specific types of parasite proteins, when combined with high parasite biomass, strongly predict severe malaria disease in adults. The discovery, published May 16 in the journal Proceedings of the National Academy of Sciences, is a significant advancement in understanding the causes of severe malaria. Quantitative characterization of disease presentations and biotechnology capabilities at the ICEMR lab at Goa Medical College combined with specialized assays for molecular host-parasite interactions and machine learning tools at the CIDR helped unlock the mysteries of what leads to the development of severe malaria disease.
In India, malaria kills 50,000 to 100,000 people each year, accounting for approximately 20 percent of malaria deaths globally. In south and southeast Asia, severe malaria primarily occurs in adults. The molecular basis for severe manifestations of the disease in adults is not well-understood. This study, led by Joseph Smith and colleagues at Seattle-based CIDR and the University of Washington, shows that in patients with severe malaria, red blood cells infected with the malaria parasite bind to a key regulatory protein on blood vessels, endothelial protein C receptor. Adhesion proteins from the malaria parasite facilitate this interaction. The researchers found that expression of these parasite proteins, accompanied by high parasite load, predicts severe manifestations in adults with malaria. These findings may help develop future treatments for severe malaria.
This multi-institutional collaboration is part of MESA-ICEMR, the Malaria Evolution in South Asia (MESA) initiative based at the UW International Center of Excellence for Malaria Research (ICEMR) and funded by the U.S. National Institute of Allergy and Infectious Diseases, part of the U.S. National Institutes of Health. With the approval and support of the Indian Council of Medical Research, this program has established new malaria research sites across India, including one at Goa Medical College.
“Such complex interactions between physicians, scientists, and patients are possible due to the local leadership of Dr. Edwin Gomes, the Head of the Department of Medicine at Goa Medical College,” said Laura Chery, associate director of the MESA-ICEMR.
The MESA-ICEMR has enrolled more than 1,000 malaria patients at GMC since April 2012.
“This study, involving CIDR, GMC and UW, is a model for how US-India partnerships can contribute to our understanding of a potentially lethal disease,” said co-author Pradipsinh Rathod, UW professor of chemistry and MESA-ICEMR Program Director.