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The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya

BACKGROUND: Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relation...

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Autores principales: Salgado, Christina, Ayodo, George, Macklin, Michael D., Gould, Meetha P., Nallandhighal, Srinivas, Odhiambo, Eliud O., Obala, Andrew, O’Meara, Wendy Prudhomme, John, Chandy C., Tran, Tuan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447531/
https://www.ncbi.nlm.nih.gov/pubmed/34535134
http://dx.doi.org/10.1186/s12936-021-03905-w
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author Salgado, Christina
Ayodo, George
Macklin, Michael D.
Gould, Meetha P.
Nallandhighal, Srinivas
Odhiambo, Eliud O.
Obala, Andrew
O’Meara, Wendy Prudhomme
John, Chandy C.
Tran, Tuan M.
author_facet Salgado, Christina
Ayodo, George
Macklin, Michael D.
Gould, Meetha P.
Nallandhighal, Srinivas
Odhiambo, Eliud O.
Obala, Andrew
O’Meara, Wendy Prudhomme
John, Chandy C.
Tran, Tuan M.
author_sort Salgado, Christina
collection PubMed
description BACKGROUND: Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission. METHODS: In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa–Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals. RESULTS: The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11–15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR. CONCLUSIONS: This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-021-03905-w.
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spelling pubmed-84475312021-09-17 The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya Salgado, Christina Ayodo, George Macklin, Michael D. Gould, Meetha P. Nallandhighal, Srinivas Odhiambo, Eliud O. Obala, Andrew O’Meara, Wendy Prudhomme John, Chandy C. Tran, Tuan M. Malar J Research BACKGROUND: Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission. METHODS: In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa–Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals. RESULTS: The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11–15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR. CONCLUSIONS: This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-021-03905-w. BioMed Central 2021-09-17 /pmc/articles/PMC8447531/ /pubmed/34535134 http://dx.doi.org/10.1186/s12936-021-03905-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Salgado, Christina
Ayodo, George
Macklin, Michael D.
Gould, Meetha P.
Nallandhighal, Srinivas
Odhiambo, Eliud O.
Obala, Andrew
O’Meara, Wendy Prudhomme
John, Chandy C.
Tran, Tuan M.
The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya
title The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya
title_full The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya
title_fullStr The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya
title_full_unstemmed The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya
title_short The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya
title_sort prevalence and density of asymptomatic plasmodium falciparum infections among children and adults in three communities of western kenya
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447531/
https://www.ncbi.nlm.nih.gov/pubmed/34535134
http://dx.doi.org/10.1186/s12936-021-03905-w
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