Project 1 has the overall theme of studying the immuno-genetic epidemiology of complex malaria in India as part of the Center for the Study of Complex Malaria in India. Single-species infections by a malaria parasite, 'successive'(one after another) infections, mixed-species (two or more concurrent) infections, and mixed genotype infections will be detected during a 5 year longitudinal study at three eco-epidemiologically different field stations in India, and used in four sub-Projects. Sub-Project 1 will investigate the development of natural immunity to malaria in individuals: its association with prior exposure to malaria, parasite species, and parasite genetic diversity. Sub-Project 1 will also study complex mixed-species infections, and the differing ratios of Plasmodium species in infections across geography and time. Sub-Project 2 will determine the genetic diversity of the highly variable "var" gene family in Indian malaria parasites, which is thought to help the parasite evade the human immune system, and assess how var diversity relates to development of natural resistance to malaria by hosts. Sub-Project 3 will analyze the inflammatory immune response to malaria in Indian subjects, particularly in relation to production by the parasite of uric acid (a recently proposed mediator of malaria-induced inflammation), and the severity of malaria as a function of diversity of dendridic cells which control the activation of human immune response. Sub-Project 4 will investigate whether naturally-immune individuals in India harbor specific antibodies to regions of a known malaria antigen, CSP. Research Project 1 overall thus advances the CSCMi goals of developing the data and evidence-based strategies needed to support the intervention and control programs of Indian government organizations, and building research capacity in India and help train the next generation of malaria and mosquito vector biologists.

Public Health Relevance

Malaria is a huge public health problem in India, the world's largest democracy and its second most populous nation. Project 1 investigates which parasite and host factors determine level of malaria severity in India, which ranges from asymptomatic (natural immunity) to deadly. Project 1 results will inform the Center for the Study of Complex Malaria in India's goal of enhancing Indian malaria intervention and control programs.

National Institute of Health (NIH)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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New York University
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Hupalo, Daniel N; Bradic, Martina; Carlton, Jane M (2015) The impact of genomics on population genetics of parasitic diseases. Curr Opin Microbiol 23:49-54
Cator, Lauren J; Lynch, Penelope A; Thomas, Matthew B et al. (2014) Alterations in mosquito behaviour by malaria parasites: potential impact on force of infection. Malar J 13:164
Kar, Narayani Prasad; Kumar, Ashwani; Singh, Om P et al. (2014) A review of malaria transmission dynamics in forest ecosystems. Parasit Vectors 7:265
Cator, Lauren J; Thomas, Shalu; Paaijmans, Krijn P et al. (2013) Characterizing microclimate in urban malaria transmission settings: a case study from Chennai, India. Malar J 12:84
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Paaijmans, Krijn P; Cator, Lauren J; Thomas, Matthew B (2013) Temperature-dependent pre-bloodmeal period and temperature-driven asynchrony between parasite development and mosquito biting rate reduce malaria transmission intensity. PLoS One 8:e55777
Cator, Lauren J; George, Justin; Blanford, Simon et al. (2013) 'Manipulation' without the parasite: altered feeding behaviour of mosquitoes is not dependent on infection with malaria parasites. Proc Biol Sci 280:20130711
Carlton, Jane M; Das, Aparup; Escalante, Ananias A (2013) Genomics, population genetics and evolutionary history of Plasmodium vivax. Adv Parasitol 81:203-22
Laishram, Dolie D; Sutton, Patrick L; Nanda, Nutan et al. (2012) The complexities of malaria disease manifestations with a focus on asymptomatic malaria. Malar J 11:29
Das, Aparup; Anvikar, Anupkumar R; Cator, Lauren J et al. (2012) Malaria in India: the center for the study of complex malaria in India. Acta Trop 121:267-73

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