Microgeographical Differences of Plasmodium vivax Relapse and Re-Infection in the Peruvian Amazon

Raul Chuquiyauri Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California; Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of Cellular and Molecular Sciences, Faculty of Sciences and the Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Asociación Benéfica PRISMA, Lima, Perú; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California

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Pablo Peñataro Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California; Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of Cellular and Molecular Sciences, Faculty of Sciences and the Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Asociación Benéfica PRISMA, Lima, Perú; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California

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Kimberly C. Brouwer Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California; Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of Cellular and Molecular Sciences, Faculty of Sciences and the Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Asociación Benéfica PRISMA, Lima, Perú; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California

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Manuel Fasabi Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California; Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of Cellular and Molecular Sciences, Faculty of Sciences and the Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Asociación Benéfica PRISMA, Lima, Perú; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California

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Maritza Calderon Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California; Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of Cellular and Molecular Sciences, Faculty of Sciences and the Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Asociación Benéfica PRISMA, Lima, Perú; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California

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Sonia Torres Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California; Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of Cellular and Molecular Sciences, Faculty of Sciences and the Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Asociación Benéfica PRISMA, Lima, Perú; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California

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Robert H. Gilman Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California; Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of Cellular and Molecular Sciences, Faculty of Sciences and the Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Asociación Benéfica PRISMA, Lima, Perú; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California

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Margaret Kosek Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California; Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of Cellular and Molecular Sciences, Faculty of Sciences and the Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Asociación Benéfica PRISMA, Lima, Perú; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California

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Joseph M. Vinetz Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California; Alexander von Humboldt Institute of Tropical Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of Cellular and Molecular Sciences, Faculty of Sciences and the Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Asociación Benéfica PRISMA, Lima, Perú; Department of Medicine, Division of Global Public Health, University of California San Diego, La Jolla, California

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To determine the magnitude of Plasmodium vivax relapsing malaria in rural Amazonia, we carried out a study in four sites in northeastern Peru. Polymerase chain reaction-restriction fragment length polymorphism of PvMSP-3α and tandem repeat (TR) markers were compared for their ability to distinguish relapse versus reinfection. Of 1,507 subjects with P. vivax malaria, 354 developed > 1 episode during the study; 97 of 354 (27.5%) were defined as relapse using Pvmsp-3α alone. The addition of TR polymorphism analysis significantly reduced the number of definitively defined relapses to 26 of 354 (7.4%) (P < 0.05). Multivariate logistic regression modeling showed that the probability of having > 1 infection was associated with the following: subjects in Mazan (odds ratio [OR] = 2.56; 95% confidence interval [CI] 1.87, 3.51), 15–44 years of age (OR = 1.49; 95% CI 1.03, 2.15), traveling for job purposes (OR = 1.45; 95%CI 1.03, 2.06), and travel within past month (OR = 1.46; 95% CI 1.0, 2.14). The high discriminatory capacity of the molecular tools shown here is useful for understanding the micro-geography of malaria transmission.

Author Notes

* Address correspondence to Joseph M. Vinetz, University of California at San Diego, Division of Infectious Diseases, Department of Medicine, 9500 Gilman Drive Mail Code 0741, Cellular and Molecular Medicine, George Palade Building, Room 125, La Jolla, CA 92093-0741. E-mail: jvinetz@ucsd.edu

Financial support: This work was supported by the following grants from the United States Public Health Service, National Institutes of Health/National Institute of Allergy and Infectious Diseases: D43TW007120, K24AI068903, R01AI067727, U19AI089681. In addition, we are grateful for guidance and inspiration from Stephanie Brodine, John Weeks, and Richard Garfein, members of Dr. Chuquiyauri's thesis committee in the San Diego State University-University of California San Diego Doctoral Program in Global Health (supported by NIH grant R25TW007500).

Authors' addresses: Raul Chuquiyauri, ‘Alexander von Humboldt’ Tropical Medicine Institute, Cayetano Heredia Peruvian University, Lima, Peru, E-mail: rachuqui@ucsd.edu. Pablo Peñataro, Margaret Kosek, and Robert H. Gilman, Johns Hopkins Bloomberg School of Public Health, Department of International Health, Division of Global Disease Epidemiology and Control, Baltimore, MD, E-mails: pyori@jhsph.edu, mkosek@jhsph.edu, and rgilman@jhsph.edu. Manuel Fasabi, Maritza Calderon, and Sonia Torres, AB Prisma, Lima, Peru, E-mails: manuelmani1@gmail.com, mmcalderons@yahoo.es, and soniatadimi@yahoo.com. Kimberly C. Brouwer, Division of Global Public Health, School of Medicine, University of California San Diego, La Jolla, CA, E-mail: kbrouwer@ucsd.edu. Joseph M. Vinetz, Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA, E-mail: jvinetz@ucsd.edu.

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