Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort.

Autor:	Ataide R; Disease Elimination, Burnet Institute, Melbourne, VIC 3004, Australia., Ashley EA; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research, University of Oxford, Oxford OX3 7FZ, United Kingdom., Powell R; Disease Elimination, Burnet Institute, Melbourne, VIC 3004, Australia., Chan JA; Disease Elimination, Burnet Institute, Melbourne, VIC 3004, Australia., Malloy MJ; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia.; Victorian Cytology Service Ltd., Melbourne, VIC 3002, Australia., O'Flaherty K; Disease Elimination, Burnet Institute, Melbourne, VIC 3004, Australia., Takashima E; Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan., Langer C; Disease Elimination, Burnet Institute, Melbourne, VIC 3004, Australia., Tsuboi T; Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan., Dondorp AM; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research, University of Oxford, Oxford OX3 7FZ, United Kingdom., Day NP; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research, University of Oxford, Oxford OX3 7FZ, United Kingdom., Dhorda M; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research, University of Oxford, Oxford OX3 7FZ, United Kingdom.; Worldwide Antimalarial Resistance Network, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford OX3 7FZ, United Kingdom.; Howard Hughes Medical Institute, Malaria Group, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201-1559., Fairhurst RM; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852., Lim P; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.; National Center for Parasitology, Entomology and Malaria Control, Phnom Penh 12101, Cambodia., Amaratunga C; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852., Pukrittayakamee S; Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand., Hien TT; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research, University of Oxford, Oxford OX3 7FZ, United Kingdom.; Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Quan 5, Ho Chi Minh City, Vietnam., Htut Y; Department of Medical Research, Lower Myanmar, Yangon 11191, Myanmar., Mayxay M; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research, University of Oxford, Oxford OX3 7FZ, United Kingdom.; Lao-Oxford-Mahosot Hospital-Wellcome Trust-Research Unit, Mahosot Hospital, Vientiane, Lao PDR.; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Lao PDR., Faiz MA; Malaria Research Group & Dev Care Foundation, Chittagong, Bangladesh., Beeson JG; Disease Elimination, Burnet Institute, Melbourne, VIC 3004, Australia., Nosten F; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research, University of Oxford, Oxford OX3 7FZ, United Kingdom.; Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Tak 63110, Thailand., Simpson JA; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia., White NJ; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research, University of Oxford, Oxford OX3 7FZ, United Kingdom., Fowkes FJ; Disease Elimination, Burnet Institute, Melbourne, VIC 3004, Australia; fowkes@burnet.edu.au.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia.; Department of Epidemiology and Preventive Medicine, Department of Infectious Diseases, Monash University, Melbourne, VIC 3004, Australia.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Mar 28; Vol. 114 (13), pp. 3515-3520. Date of Electronic Publication: 2017 Mar 13.
DOI:	10.1073/pnas.1615875114
Abstrakt:	Artemisinin-resistant falciparum malaria, defined by a slow-clearance phenotype and the presence of kelch13 mutants, has emerged in the Greater Mekong Subregion. Naturally acquired immunity to malaria clears parasites independent of antimalarial drugs. We hypothesized that between- and within-population variations in host immunity influence parasite clearance after artemisinin treatment and the interpretation of emerging artemisinin resistance. Antibodies specific to 12 Plasmodium falciparum sporozoite and blood-stage antigens were determined in 959 patients (from 11 sites in Southeast Asia) participating in a multinational cohort study assessing parasite clearance half-life (PCt 1/2 ) after artesunate treatment and kelch13 mutations. Linear mixed-effects modeling of pooled individual patient data assessed the association between antibody responses and PCt 1/2. P. falciparum antibodies were lowest in areas where the prevalence of kelch13 mutations and slow PCt 1/2 were highest [Spearman ρ = -0.90 (95% confidence interval, -0.97, -0.65), and Spearman ρ = -0.94 (95% confidence interval, -0.98, -0.77), respectively]. P. falciparum antibodies were associated with faster PCt 1/2 (mean difference in PCt 1/2 according to seropositivity, -0.16 to -0.65 h, depending on antigen); antibodies have a greater effect on the clearance of kelch13 mutant compared with wild-type parasites (mean difference in PCt 1/2 according to seropositivity, -0.22 to -0.61 h faster in kelch13 mutants compared with wild-type parasites). Naturally acquired immunity accelerates the clearance of artemisinin-resistant parasites in patients with falciparum malaria and may confound the current working definition of artemisinin resistance. Immunity may also play an important role in the emergence and transmission potential of artemisinin-resistant parasites.
Databáze:	MEDLINE
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