Gametocyte Carriage, Antimalarial Use, and Drug Resistance in Cambodia, 2008–2014

Jessica T. Lin Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina;

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Jaymin C. Patel Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina;

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Lauren Levitz Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina;

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Mariusz Wojnarski Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Suwanna Chaorattanakawee Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, Thailand;

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Panita Gosi Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Nillawan Buathong Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Soklyda Chann Armed Forces Research Institute of Medical Sciences, Phnom Penh, Cambodia;

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Rekol Huy National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia;

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Khengheng Thay National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia;

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Darapiseth Sea Armed Forces Research Institute of Medical Sciences, Phnom Penh, Cambodia;

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Nou Samon Armed Forces Research Institute of Medical Sciences, Phnom Penh, Cambodia;

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Shannon Takala-Harrison Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Mark Fukuda Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Philip Smith Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Michele Spring Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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David Saunders U.S. Army Medical Materiel Development Activity, Fort Detrick, Maryland

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Chanthap Lon Armed Forces Research Institute of Medical Sciences, Phnom Penh, Cambodia;

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Gametocytes are the malaria parasite stages responsible for transmission from humans to mosquitoes. Gametocytemia often follows drug treatment, especially as therapies start to fail. We examined Plasmodium falciparum gametocyte carriage and drug resistance profiles among 824 persons with uncomplicated malaria in Cambodia to determine whether prevalent drug resistance and antimalarial use has led to a concentration of drug-resistant parasites among gametocyte carriers. Although report of prior antimalarial use increased from 2008 to 2014, the prevalence of study participants presenting with microscopic gametocyte carriage declined. Gametocytemia was more common in those reporting antimalarial use within the past year, and prior antimalarial use was correlated with higher IC50s to piperaquine and mefloquine, as well as to increased pfmdr1 copy number. However, there was no association between microscopic gametocyte carriage and parasite drug resistance. Thus, we found no evidence that the infectious reservoir, marked by those carrying gametocytes, is enriched with drug-resistant parasites.

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Author Notes

Address correspondence to Jessica T. Lin, Division of Infectious Diseases, University of North Carolina School of Medicine, 130 Mason Farm Rd., CB 7030, Chapel Hill, NC 27599. E-mail: jessica_lin@med.unc.edu

Financial support: Funding was provided by the Global Emerging Infections Surveillance (GEIS) Program, the Armed Forces Health Surveillance Center, the U.S. Department of Defense, and the National Institute of Allergy and Infectious Diseases (K08 AI110651 to J. T. L.).

Authors’ addresses: Jessica T. Lin, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, E-mail: jessica_lin@med.unc.edu. Jaymin C. Patel and Lauren Levitz, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, E-mails: jaymin86@gmail.com and lauren.levitz@gmail.com. Mariusz Wojnarski, Panita Gosi, Nillawan Buathong, Mark Fukuda, Philip Smith, and Michele Spring, Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mails: mariusz.wojnarski.mil@afrims.org, panitag.fsn@afrims.org, nillawanb.fsn@afrims.org, mark.fukuda.mil@afrims.org, philip.smith.mil@afrims.org, and michele.spring.ctr@afrims.org. Suwanna Chaorattanakawee, Department of Parasitology and Public Health, Mahidol University, Bangkok, Thailand, E-mail: suwann67@yahoo.com. Soklyda Chann, Chanthap Lon, Sea Darapiseth, and Samon Nou, Armed Forces Research Institute of Medical Sciences, AFRIMS Cambodia, Phnom Penh, Cambodia, E-mails: channs.ctr@afrims.org, darapiseths.ca@afrims.org, chanthapl.ca@afrims.org, and samon.nu.ctr@afrims.org. Huy Rekol and Khengheng Thay, National Malaria Center, Malaria Phnom Penh, Ministry of Health, Phnom Penh, Cambodia, E-mails: kolhuy@gmail.com and thaykhengheng@yahoo.com. Shannon Takala-Harrison, Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD, E-mail: stakala@som.umaryland.edu. David Saunders, Immunology, Armed Forces Research Institute of Medical Sciences, Fort Detrick, MD, E-mail: david.l.saunders.mil@mail.mil.

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