EXPERIMENTAL INFECTION OF THE NEOTROPICAL MALARIA VECTOR ANOPHELES DARLINGI BY HUMAN PATIENT-DERIVED PLASMODIUM VIVAX IN THE PERUVIAN AMAZON

AJAY R. BHARTI University of California San Diego School of Medicine, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Naval Medical Research Center Detachment, Iquitos, Peru

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RAUL CHUQUIYAURI University of California San Diego School of Medicine, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Naval Medical Research Center Detachment, Iquitos, Peru

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KIMBERLY C. BROUWER University of California San Diego School of Medicine, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Naval Medical Research Center Detachment, Iquitos, Peru

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JEFFREY STANCIL University of California San Diego School of Medicine, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Naval Medical Research Center Detachment, Iquitos, Peru

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JESSICA LIN University of California San Diego School of Medicine, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Naval Medical Research Center Detachment, Iquitos, Peru

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ALEJANDRO LLANOS-CUENTAS University of California San Diego School of Medicine, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Naval Medical Research Center Detachment, Iquitos, Peru

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JOSEPH M. VINETZ University of California San Diego School of Medicine, La Jolla, California; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Naval Medical Research Center Detachment, Iquitos, Peru

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Malaria transmission from humans to mosquitoes is modulated by human host immune factors. Understanding mechanisms by which the human host response may impair parasite infectivity for mosquitoes has direct implications for the development of transmission-blocking vaccines. We hypothesized that despite a low transmission intensity of malaria in the Peruvian Amazon region of Iquitos, transmission-blocking immunity against Plasmodium vivax might be common, given an unexpectedly high proportion of asymptomatic parasitemic individuals in this region. To test this hypothesis, the ability of symptomatic P. vivax malaria patients to experimentally infect wild-caught outbred Anopheles darlingi mosquitoes was tested using the indirect membrane feeding technique. Only half (52/102) of P. vivax parasitemic patients successfully infected mosquitoes. Transmitters were more likely to have gametocytes (OR 6.35, P = 0.003), high parasitemia (OR 3.79, P = 0.024), and, in terms of basic clinical parameters, a slower pulse rate (mean ± SD: 82.3 ± 12.3 versus 88.7 ± 13.5, P = 0.016) than non-transmitters. Log10 gametocytemia and log10 real-time reverse transcriptase Pvs25 PCR quantifying gametocytes were significantly and positively correlated with oocyst counts (correlation coefficient 0.505, R2 = 0.26, P = 0.001). These experiments are the first to establish a system of determining transmission patterns in experimental infection of outbred natural neotropical malaria vectors in the Amazon region. Patients with P. vivax inefficiently infect outbred An. darlingi mosquitoes, raising the possibility that some degree of naturally occurring transmission-blocking immunity is present on a population basis in the Peruvian Amazon, an area of low intensity of malaria transmission.

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