A molecular epidemiological study of var gene diversity to characterize the reservoir of Plasmodium falciparum in humans in Africa
BACKGROUND: The reservoir of Plasmodium infection in humans has traditionally been defined by blood slide positivity. This study was designed to characterize the local reservoir of infection in relation to the diverse var genes that encode the major surface antigen of Plasmodium falciparum blood sta...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
Public Library of Science
2011
|
_version_ | 1826301851640791040 |
---|---|
author | Chen, D Barry, A Leliwa-Sytek, A Smith, T Peterson, I Brown, S Migot-Nabias, F Deloron, P Kortok, M Marsh, K Daily, J Ndiaye, D Sarr, O Mboup, S Day, K |
author_facet | Chen, D Barry, A Leliwa-Sytek, A Smith, T Peterson, I Brown, S Migot-Nabias, F Deloron, P Kortok, M Marsh, K Daily, J Ndiaye, D Sarr, O Mboup, S Day, K |
author_sort | Chen, D |
collection | OXFORD |
description | BACKGROUND: The reservoir of Plasmodium infection in humans has traditionally been defined by blood slide positivity. This study was designed to characterize the local reservoir of infection in relation to the diverse var genes that encode the major surface antigen of Plasmodium falciparum blood stages and underlie the parasite's ability to establish chronic infection and transmit from human to mosquito. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the molecular epidemiology of the var multigene family at local sites in Gabon, Senegal and Kenya which differ in parasite prevalence and transmission intensity. 1839 distinct var gene types were defined by sequencing DBLα domains in the three sites. Only 76 (4.1%) var types were found in more than one population indicating spatial heterogeneity in var types across the African continent. The majority of var types appeared only once in the population sample. Non-parametric statistical estimators predict in each population at minimum five to seven thousand distinct var types. Similar diversity of var types was seen in sites with different parasite prevalences. CONCLUSIONS/SIGNIFICANCE: Var population genomics provides new insights into the epidemiology of P. falciparum in Africa where malaria has never been conquered. In particular, we have described the extensive reservoir of infection in local African sites and discovered a unique var population structure that can facilitate superinfection through minimal overlap in var repertoires among parasite genomes. Our findings show that var typing as a molecular surveillance system defines the extent of genetic complexity in the reservoir of infection to complement measures of malaria prevalence. The observed small scale spatial diversity of var genes suggests that var genetics could greatly inform current malaria mapping approaches and predict complex malaria population dynamics due to the import of var types to areas where no widespread pre-existing immunity in the population exists. |
first_indexed | 2024-03-07T05:38:38Z |
format | Journal article |
id | oxford-uuid:e4cb7815-e2d1-47dc-9fec-fa54e32cf295 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T05:38:38Z |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | dspace |
spelling | oxford-uuid:e4cb7815-e2d1-47dc-9fec-fa54e32cf2952022-03-27T10:19:12ZA molecular epidemiological study of var gene diversity to characterize the reservoir of Plasmodium falciparum in humans in AfricaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e4cb7815-e2d1-47dc-9fec-fa54e32cf295EnglishSymplectic Elements at OxfordPublic Library of Science2011Chen, DBarry, ALeliwa-Sytek, ASmith, TPeterson, IBrown, SMigot-Nabias, FDeloron, PKortok, MMarsh, KDaily, JNdiaye, DSarr, OMboup, SDay, KBACKGROUND: The reservoir of Plasmodium infection in humans has traditionally been defined by blood slide positivity. This study was designed to characterize the local reservoir of infection in relation to the diverse var genes that encode the major surface antigen of Plasmodium falciparum blood stages and underlie the parasite's ability to establish chronic infection and transmit from human to mosquito. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the molecular epidemiology of the var multigene family at local sites in Gabon, Senegal and Kenya which differ in parasite prevalence and transmission intensity. 1839 distinct var gene types were defined by sequencing DBLα domains in the three sites. Only 76 (4.1%) var types were found in more than one population indicating spatial heterogeneity in var types across the African continent. The majority of var types appeared only once in the population sample. Non-parametric statistical estimators predict in each population at minimum five to seven thousand distinct var types. Similar diversity of var types was seen in sites with different parasite prevalences. CONCLUSIONS/SIGNIFICANCE: Var population genomics provides new insights into the epidemiology of P. falciparum in Africa where malaria has never been conquered. In particular, we have described the extensive reservoir of infection in local African sites and discovered a unique var population structure that can facilitate superinfection through minimal overlap in var repertoires among parasite genomes. Our findings show that var typing as a molecular surveillance system defines the extent of genetic complexity in the reservoir of infection to complement measures of malaria prevalence. The observed small scale spatial diversity of var genes suggests that var genetics could greatly inform current malaria mapping approaches and predict complex malaria population dynamics due to the import of var types to areas where no widespread pre-existing immunity in the population exists. |
spellingShingle | Chen, D Barry, A Leliwa-Sytek, A Smith, T Peterson, I Brown, S Migot-Nabias, F Deloron, P Kortok, M Marsh, K Daily, J Ndiaye, D Sarr, O Mboup, S Day, K A molecular epidemiological study of var gene diversity to characterize the reservoir of Plasmodium falciparum in humans in Africa |
title | A molecular epidemiological study of var gene diversity to characterize the reservoir of Plasmodium falciparum in humans in Africa |
title_full | A molecular epidemiological study of var gene diversity to characterize the reservoir of Plasmodium falciparum in humans in Africa |
title_fullStr | A molecular epidemiological study of var gene diversity to characterize the reservoir of Plasmodium falciparum in humans in Africa |
title_full_unstemmed | A molecular epidemiological study of var gene diversity to characterize the reservoir of Plasmodium falciparum in humans in Africa |
title_short | A molecular epidemiological study of var gene diversity to characterize the reservoir of Plasmodium falciparum in humans in Africa |
title_sort | molecular epidemiological study of var gene diversity to characterize the reservoir of plasmodium falciparum in humans in africa |
work_keys_str_mv | AT chend amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT barrya amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT leliwasyteka amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT smitht amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT petersoni amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT browns amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT migotnabiasf amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT deloronp amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT kortokm amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT marshk amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT dailyj amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT ndiayed amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT sarro amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT mboups amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT dayk amolecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT chend molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT barrya molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT leliwasyteka molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT smitht molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT petersoni molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT browns molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT migotnabiasf molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT deloronp molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT kortokm molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT marshk molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT dailyj molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT ndiayed molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT sarro molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT mboups molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica AT dayk molecularepidemiologicalstudyofvargenediversitytocharacterizethereservoirofplasmodiumfalciparuminhumansinafrica |