About 3 billion individuals around the world are at risk for malaria, there are about 250 million cases per year, with about 1 million deaths. While deployment of insecticide impregnated bed nets, new drug combinations, and possibly new vaccines may help control malaria, we hypothesize that shrinking parasite population sizes would place greater burdens on the pathogens to change at faster rates, possibly contributing to higher virulence. Initially, such evolution could be to overcome drugs and cause resistance. However, once the capacity for faster genetic change is in place, the traits may favor acquisition of new niches, within vectors (to favor propagation ofthe disease) and within himian hosts (possibly presenting new disease presentations). This multicenter Program Project application will study the evolution of malaria parasites in South Asia. Malaria is not imiform across South Asia. One sees large variation in species-dominance from NE to Southem states, one sees frequent epidemics of severe malaria, sometimes for unexplained reasons. We hypothesize that South Asia harbors virulent forms of P. falciparum from SE Asia that display the Accelerated Resistance to Multiple Drugs (ARMD) phenotype. This may help ARMD P. falciparum over run traditional P. vivax. In addition to drug resistance, the transmission and virulence properties of sites harboring ARMD parasites, are expected to be different. The Program Director proposes a 5 project Center that touches on epidemiology, parasite plasticity, pathogenesis, transmission, and human genetics in South Asia. Research will be facilitated by scientific partnerships between physicians and academic researchers in India and the US, and by Administration, Data Management, and Statistical support from partners in Delhi and Kolkota. Parasites and their interactions with hximans, and mosquitoes, will be studied in Assam and Tripura (near Myanmar), in Ranchi (proximal forested sites with highly endemic malaria), in Wardha in Central India, and finally in the Westem cities of Mumbai and Goa (with urban malaria, low endemicity, and high human genetic diversity). The results will teach us about propagation of malaria across subcontinents, and about the possible barriers and breakdown of barriers against the spread of virulent malaria parasites.
Understanding the genetic plasticity of malaria parasites in South Asia, and their relationship to Drug resistance, virulence, transmission, and human immunity, should greatly assist assesment of malaria threat levels in South Asia. Such information may also have predictive value in understanding new, unexpected outbreaks of severe malaria.
|Rangel, Gabriel W; Clark, Martha A; Kanjee, Usheer et al. (2018) Enhanced Ex Vivo Plasmodium vivax Intraerythrocytic Enrichment and Maturation for Rapid and Sensitive Parasite Growth Assays. Antimicrob Agents Chemother 62:|
|Patankar, Swati; Sharma, Shobhona; Rathod, Pradipsinh K et al. (2018) Malaria in India: The Need for New Targets for Diagnosis and Detection of Plasmodium vivax. Proteomics Clin Appl 12:e1700024|
|Mohanty, Ajeet Kumar; Nina, Praveen Balabaskaran; Ballav, Shuvankar et al. (2018) Susceptibility of wild and colonized Anopheles stephensi to Plasmodium vivax infection. Malar J 17:225|
|White, John; Rathod, Pradipsinh K (2018) Indispensable malaria genes. Science 360:490-491|
|Narayan, Aishwarya; Mastud, Pragati; Thakur, Vandana et al. (2018) Heterologous expression in Toxoplasma gondii reveals a topogenic signal anchor in a Plasmodium apicoplast protein. FEBS Open Bio 8:1746-1762|
|Balabaskaran Nina, Praveen; Mohanty, Ajeet Kumar; Ballav, Shuvankar et al. (2017) Dynamics of Plasmodium vivax sporogony in wild Anopheles stephensi in a malaria-endemic region of Western India. Malar J 16:284|
|Shaw-Saliba, Kathryn; Clarke, David; Santos, Jorge M et al. (2016) Infection of laboratory colonies of Anopheles mosquitoes with Plasmodium vivax from cryopreserved clinical isolates. Int J Parasitol 46:679-83|
|White 3rd, John; Mascarenhas, Anjali; Pereira, Ligia et al. (2016) In vitro adaptation of Plasmodium falciparum reveal variations in cultivability. Malar J 15:33|
|Hostetler, Jessica B; Lo, Eugenia; Kanjee, Usheer et al. (2016) Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications. PLoS Negl Trop Dis 10:e0005091|
|Lim, Caeul; Pereira, Ligia; Saliba, Kathryn Shaw et al. (2016) Reticulocyte Preference and Stage Development of Plasmodium vivax Isolates. J Infect Dis 214:1081-4|
Showing the most recent 10 out of 43 publications