Malaria evolution in South Asia: knowledge for control and elimination

Abstract

The study of malaria parasites on the Indian subcontinent should help us understand unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and Plasmodium vivax infections. The Malaria Evolution in South Asia (MESA) research program is one of ten International Centers of Excellence for Malaria Research (ICEMR) sponsored by the US National Institutes of Health. In this second of two reviews, we describe why population structures of Plasmodia in India will be characterized and how we will determine their consequences on disease presentation, outcome and patterns. Specific projects will determine if genetic diversity, possibly driven by parasites with higher genetic plasticity, plays a role in changing epidemiology, pathogenesis, vector competence of parasite populations and whether innate human genetic traits protect Indians from malaria today. Deep local clinical knowledge of malaria in India will be supplemented by basic scientists who bring new research tools. Such tools will include whole genome sequencing and analysis methods; in vitro assays to measure genome plasticity, RBC cytoadhesion, invasion, and deformability; mosquito infectivity assays to evaluate changing parasite-vector compatibilities; and host genetics to understand protective traits in Indian populations. The MESA-ICEMR study sites span diagonally across India and include a mixture of very urban and rural hospitals, each with very different disease patterns and patient populations. Research partnerships include government-associated research institutes, private medical schools, city and state government hospitals, and hospitals with industry ties. Between 2012 and 2017, in addition to developing clinical research and basic science infrastructure at new clinical sites, our training workshops will engage new scientists and clinicians throughout South Asia in the malaria research field.

Fig. 1

Annual Parasite Incidence (malaria cases/1000 population) in India for the year 2008 (Left, National Vector Borne Disease Control Programme, New Delhi). State map of India (right, http://blog.lookindia.in)

Fig. 2

Fig. 2A. Annual Parasite Incidence (malaria cases/1000 population) in India for the year 2008 (Left, National Vector Borne Disease Control Programme, New Delhi). Fig. 2B. Distribution of MESA- ICEMR study sites across India. (right)

Fig. 3

A generic scheme to illustrate how genetic plasticity is measured by selection of resistant parasites from a minimum number of freshly expanded P. falciparum cells required to reproducibly select for resistance to a new test antimalarial.

Fig. 4

Illustration of two different microfluidic platforms to characterize physical properties of P. falciparum-infected RBCs from individual patients. (A) Cytoadhesion of surface attached mammalian endothelial cells to parasitized erythrocytes under flow. Unattached, uninfected RBCs are flowing too fast to be seen. (B) Entrapment of infected erythrocytes (upper set) compared to uninfected RBCs (Lower set). The penetration of individual cells into the wedges captures information on surface area and volume, which in turn is related to the deformability of RBCs.