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845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers
BACKGROUND: Falciparum malaria transmission has failed to decline in proportion to control efforts in certain regions such as Bungoma county, western Kenya. One proposed strategy to eradicate malaria is ring testing and treatment; however, it remains unknown whether infections spread locally or if a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6809055/ http://dx.doi.org/10.1093/ofid/ofz359.030 |
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author | Nelson, Cody S Sumner, Kelsey Freedman, Betsy Obala, Andrew Mangeni, Jane Taylor, Steve O’Meara, Wendy |
author_facet | Nelson, Cody S Sumner, Kelsey Freedman, Betsy Obala, Andrew Mangeni, Jane Taylor, Steve O’Meara, Wendy |
author_sort | Nelson, Cody S |
collection | PubMed |
description | BACKGROUND: Falciparum malaria transmission has failed to decline in proportion to control efforts in certain regions such as Bungoma county, western Kenya. One proposed strategy to eradicate malaria is ring testing and treatment; however, it remains unknown whether infections spread locally or if asymptomatically infected household members are a risk factor for clinical disease. METHODS: From April 2013 to June 2014, we enrolled 442 cases (RDT+ children hospitalized with malaria) and 442 matched controls; all household members of cases and controls were also enrolled and tested, of which 13.6% (n = 608/4449) were RDT+. From each RDT+ participant, parasite gDNA was PCR-amplified at both Pf circumsporozoite protein (csp) and apical membrane antigen 1 (ama1) loci, amplicons sequenced on an Illumina Miseq, and haplotypes inferred using dada2. RESULTS: We identified 120 csp and 180 ama1 unique haplotypes (Figure 1). We evaluated the genetic distance between infected individuals using three novel indices: sharing of parasite haplotypes on binary and proportional scales and the L1 norm. Case children median [IQR] binary/proportional sharing of both csp and ama1 haplotypes was significantly increased with members of their origin household (e.g., csp binary sharing: origin = 50.3 [0–87.5] vs. similar household = 0 [0–50.3]; P = 0.01; Wilcoxon sign-rank test), indicating that cases are more likely to share haplotype-identical parasites with members of their own household (Figure 2). We also computed population-level haplotype sharing indices for all pairs of case children and observed no association between genetic relatedness and geographic distance. In contrast, we identified a strong inverse relationship between haplotype sharing and temporal distance, which we exploited to identify the molecular signature of an outbreak (Figure 3). CONCLUSION: Overall, these findings suggest that, although haplotype sharing is more common within households, temporal rather than geographic proximity predicts parasite genetic similarity. The observation that identical haplotype combinations are found nearly simultaneously across the study area implies that ring testing approaches may not effectively reduce transmission. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All Authors: No reported Disclosures. |
format | Online Article Text |
id | pubmed-6809055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68090552019-10-28 845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers Nelson, Cody S Sumner, Kelsey Freedman, Betsy Obala, Andrew Mangeni, Jane Taylor, Steve O’Meara, Wendy Open Forum Infect Dis Abstracts BACKGROUND: Falciparum malaria transmission has failed to decline in proportion to control efforts in certain regions such as Bungoma county, western Kenya. One proposed strategy to eradicate malaria is ring testing and treatment; however, it remains unknown whether infections spread locally or if asymptomatically infected household members are a risk factor for clinical disease. METHODS: From April 2013 to June 2014, we enrolled 442 cases (RDT+ children hospitalized with malaria) and 442 matched controls; all household members of cases and controls were also enrolled and tested, of which 13.6% (n = 608/4449) were RDT+. From each RDT+ participant, parasite gDNA was PCR-amplified at both Pf circumsporozoite protein (csp) and apical membrane antigen 1 (ama1) loci, amplicons sequenced on an Illumina Miseq, and haplotypes inferred using dada2. RESULTS: We identified 120 csp and 180 ama1 unique haplotypes (Figure 1). We evaluated the genetic distance between infected individuals using three novel indices: sharing of parasite haplotypes on binary and proportional scales and the L1 norm. Case children median [IQR] binary/proportional sharing of both csp and ama1 haplotypes was significantly increased with members of their origin household (e.g., csp binary sharing: origin = 50.3 [0–87.5] vs. similar household = 0 [0–50.3]; P = 0.01; Wilcoxon sign-rank test), indicating that cases are more likely to share haplotype-identical parasites with members of their own household (Figure 2). We also computed population-level haplotype sharing indices for all pairs of case children and observed no association between genetic relatedness and geographic distance. In contrast, we identified a strong inverse relationship between haplotype sharing and temporal distance, which we exploited to identify the molecular signature of an outbreak (Figure 3). CONCLUSION: Overall, these findings suggest that, although haplotype sharing is more common within households, temporal rather than geographic proximity predicts parasite genetic similarity. The observation that identical haplotype combinations are found nearly simultaneously across the study area implies that ring testing approaches may not effectively reduce transmission. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All Authors: No reported Disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6809055/ http://dx.doi.org/10.1093/ofid/ofz359.030 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Abstracts Nelson, Cody S Sumner, Kelsey Freedman, Betsy Obala, Andrew Mangeni, Jane Taylor, Steve O’Meara, Wendy 845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers |
title | 845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers |
title_full | 845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers |
title_fullStr | 845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers |
title_full_unstemmed | 845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers |
title_short | 845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers |
title_sort | 845. children with clinical plasmodium falciparum infection have increased sharing of haplotypes with household members as well as temporally proximal, symptomatic peers |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6809055/ http://dx.doi.org/10.1093/ofid/ofz359.030 |
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