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RELATIVE CONTRIBUTION OF LOW-DENSITY AND ASYMPTOMATIC INFECTIONS TO PLASMODIUM VIVAX TRANSMISSION IN THE AMAZON: POOLED ANALYSIS OF INDIVIDUAL PARTICIPANT DATA FROM POPULATION-BASED CROSS-SECTIONAL SURVEYS
Plasmodium vivax
Infecções assintomáticas
Infecções de sub-patente
Limiar de febre
Amazonas
Plasmodium vivax
Asymptomatic infections
Sub-patent infections
fever threshold
Amazon
Author
Affilliation
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. São Paulo, SP, Brasil / Nova University of Lisbon. Institute of Hygiene and Tropical Medicine. Global Health and Tropical Medicine. Lisbon, Portugal.
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. São Paulo, SP, Brasil.
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. São Paulo, SP, Brasil.
Institute of Tropical Medicine. Department of Biomedical Sciences. Antwerp, Belgium.
London School of Hygiene and Tropical Medicine. Department of Infection Biology. London, UK.
Université Catholique de Louvain. Institute of Health and Society. Brussels, Belgium.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.
State University of New York. University at Albany. School of Public Health. Department of Biomedical Sciences. Albany, NY, USA / New York State Department of Health. Wadsworth Center. Albany, NY, USA.
Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical “Alexander von Humboldt”. Lima, Peru.
Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical “Alexander von Humboldt”. Lima, Peru / Universidad Peruana Cayetano Heredia. Facultad de Ciencias y Filosofia. Departamento de Ciencias Celulares y Moleculares. Laboratorios de Investigación y Desarrollo. Laboratorio ICEMR-Amazonia. Lima, Peru.
Institute of Tropical Medicine. Department of Biomedical Sciences. Antwerp, Belgium.
Universidad Peruana Cayetano Heredia. Facultad de Ciencias y Filosofia. Departamento de Ciencias Celulares y Moleculares. Laboratorios de Investigación y Desarrollo. Laboratorio ICEMR-Amazonia. Lima, Peru / Yale School of Medicine. Department of Internal Medicine. Section of Infectious Diseases. New Haven, CT, USA.
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. São Paulo, SP, Brasil.
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Parasitologia. São Paulo, SP, Brasil.
Institute of Tropical Medicine. Department of Biomedical Sciences. Antwerp, Belgium.
London School of Hygiene and Tropical Medicine. Department of Infection Biology. London, UK.
Université Catholique de Louvain. Institute of Health and Society. Brussels, Belgium.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.
State University of New York. University at Albany. School of Public Health. Department of Biomedical Sciences. Albany, NY, USA / New York State Department of Health. Wadsworth Center. Albany, NY, USA.
Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical “Alexander von Humboldt”. Lima, Peru.
Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical “Alexander von Humboldt”. Lima, Peru / Universidad Peruana Cayetano Heredia. Facultad de Ciencias y Filosofia. Departamento de Ciencias Celulares y Moleculares. Laboratorios de Investigación y Desarrollo. Laboratorio ICEMR-Amazonia. Lima, Peru.
Institute of Tropical Medicine. Department of Biomedical Sciences. Antwerp, Belgium.
Universidad Peruana Cayetano Heredia. Facultad de Ciencias y Filosofia. Departamento de Ciencias Celulares y Moleculares. Laboratorios de Investigación y Desarrollo. Laboratorio ICEMR-Amazonia. Lima, Peru / Yale School of Medicine. Department of Internal Medicine. Section of Infectious Diseases. New Haven, CT, USA.
Abstract
Background—Low-density and asymptomatic Plasmodium vivax infections remain largely undetected and untreated and may contribute significantly to malaria transmission in the Amazon.
Methods—We analysed individual participant data from population-based surveys that measured P vivax prevalence by microscopy and polymerase chain reaction (PCR) between 2002 and 2015 and modelled the relationship between parasite density and infectiousness to vectors using membrane feeding assay data. We estimated the proportion of sub-patent (i.e., missed by microscopy) and asymptomatic P vivax infections and examined how parasite density relates to clinical manifestations and mosquito infection in Amazonian settings.
Findings—We pooled 24,986 observations from six sites in Brazil and Peru. P vivax was detected in 6·8% and 2·1% of them by PCR and microscopy, respectively. 58·5% to 92·6% of P vivax infections were asymptomatic and 61·2% to 96·3% were sub-patent across study sites. P vivax density thresholds associated with clinical symptoms were one order of magnitude higher in children than in adults. We estimate that sub-patent parasite carriers are minimally infectious and contribute 12·7% to 24·9% of the community-wide P vivax transmission, while asymptomatic carriers are the source of 28·2% to 79·2% of mosquito infections.
Interpretation—Asymptomatic P vivax carriers constitute a vast infectious reservoir that, if targeted by malaria elimination strategies, could substantially reduce malaria transmission in the Amazon. Infected children may remain asymptomatic despite high parasite densities that elicit clinical manifestations in adults.
Funding—US National Institutes of Health, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Belgium Development Cooperation.
Keywords in Portuguese
MaláriaPlasmodium vivax
Infecções assintomáticas
Infecções de sub-patente
Limiar de febre
Amazonas
Keywords
MalariaPlasmodium vivax
Asymptomatic infections
Sub-patent infections
fever threshold
Amazon
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