Tracing the origins and signatures of selection of antifolate resistance in island populations of <it>Plasmodium falciparum</it>
<p>Abstract</p> <p>Background</p> <p>Resistance of the malaria parasite <it>Plasmodium falciparum </it>to sulfadoxine-pyrimethamine (SP) has evolved worldwide. In the archipelago of São Tomé and Principe (STP), West Africa, although SP resistance is highly p...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-06-01
|
| Series: | BMC Infectious Diseases |
| Online Access: | http://www.biomedcentral.com/1471-2334/10/163 |
| _version_ | 1811280899581411328 |
|---|---|
| author | Pinto João Cravo Pedro do Rosário Virgílio E Galvão André Teófilo Vânia Ferreira Conceição Vicente José L Salgueiro Patrícia |
| author_facet | Pinto João Cravo Pedro do Rosário Virgílio E Galvão André Teófilo Vânia Ferreira Conceição Vicente José L Salgueiro Patrícia |
| author_sort | Pinto João |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Resistance of the malaria parasite <it>Plasmodium falciparum </it>to sulfadoxine-pyrimethamine (SP) has evolved worldwide. In the archipelago of São Tomé and Principe (STP), West Africa, although SP resistance is highly prevalent the drug is still in use in particular circumstances. To address the evolutionary origins of SP resistance in these islands, we genotyped point mutations at <it>P. falciparum dhfr </it>and <it>dhps </it>genes and analysed microsatellites flanking those genes.</p> <p>Methods</p> <p>Blood samples were collected in July and December 2004 in three localities of São Tomé Island and one in Principe Island. Species-specific nested-PCR was used to identify <it>P. falciparum </it>infected samples. Subsequently, SNPs at the <it>dhfr </it>and <it>dhps </it>genes were identified through PCR-RFLP. Isolates were also analysed for three microsatellite loci flanking the <it>dhfr </it>gene, three loci flanking <it>dhps </it>and four loci located at putative neutral genomic regions.</p> <p>Results</p> <p>An increase of resistance-associated mutations at <it>dhfr </it>and <it>dhps </it>was observed, in particular for the <it>dhfr</it>/<it>dhps </it>quintuple mutant, associated with clinical SP failure. Analysis of flanking microsatellites suggests multiple independent introductions for <it>dhfr </it>and <it>dhps </it>mutant haplotypes, possibly from West Africa. A reduced genetic diversity and increased differentiation at flanking microsatellites when compared to neutral loci is consistent with a selective sweep for resistant alleles at both loci.</p> <p>Conclusions</p> <p>This study provides additional evidence for the crucial role of gene flow and drug selective pressures in the rapid spread of SP resistance in <it>P. falciparum </it>populations, from only a few mutation events giving rise to resistance-associated mutants. It also highlights the importance of human migration in the spread of drug resistant malaria parasites, as the distance between the islands and mainland is not consistent with mosquito-mediated parasite dispersal.</p> |
| first_indexed | 2024-04-13T01:24:08Z |
| format | Article |
| id | doaj.art-3aaec66f6aee44748ddbbdbdb945080c |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-04-13T01:24:08Z |
| publishDate | 2010-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-3aaec66f6aee44748ddbbdbdb945080c2022-12-22T03:08:41ZengBMCBMC Infectious Diseases1471-23342010-06-0110116310.1186/1471-2334-10-163Tracing the origins and signatures of selection of antifolate resistance in island populations of <it>Plasmodium falciparum</it>Pinto JoãoCravo Pedrodo Rosário Virgílio EGalvão AndréTeófilo VâniaFerreira ConceiçãoVicente José LSalgueiro Patrícia<p>Abstract</p> <p>Background</p> <p>Resistance of the malaria parasite <it>Plasmodium falciparum </it>to sulfadoxine-pyrimethamine (SP) has evolved worldwide. In the archipelago of São Tomé and Principe (STP), West Africa, although SP resistance is highly prevalent the drug is still in use in particular circumstances. To address the evolutionary origins of SP resistance in these islands, we genotyped point mutations at <it>P. falciparum dhfr </it>and <it>dhps </it>genes and analysed microsatellites flanking those genes.</p> <p>Methods</p> <p>Blood samples were collected in July and December 2004 in three localities of São Tomé Island and one in Principe Island. Species-specific nested-PCR was used to identify <it>P. falciparum </it>infected samples. Subsequently, SNPs at the <it>dhfr </it>and <it>dhps </it>genes were identified through PCR-RFLP. Isolates were also analysed for three microsatellite loci flanking the <it>dhfr </it>gene, three loci flanking <it>dhps </it>and four loci located at putative neutral genomic regions.</p> <p>Results</p> <p>An increase of resistance-associated mutations at <it>dhfr </it>and <it>dhps </it>was observed, in particular for the <it>dhfr</it>/<it>dhps </it>quintuple mutant, associated with clinical SP failure. Analysis of flanking microsatellites suggests multiple independent introductions for <it>dhfr </it>and <it>dhps </it>mutant haplotypes, possibly from West Africa. A reduced genetic diversity and increased differentiation at flanking microsatellites when compared to neutral loci is consistent with a selective sweep for resistant alleles at both loci.</p> <p>Conclusions</p> <p>This study provides additional evidence for the crucial role of gene flow and drug selective pressures in the rapid spread of SP resistance in <it>P. falciparum </it>populations, from only a few mutation events giving rise to resistance-associated mutants. It also highlights the importance of human migration in the spread of drug resistant malaria parasites, as the distance between the islands and mainland is not consistent with mosquito-mediated parasite dispersal.</p>http://www.biomedcentral.com/1471-2334/10/163 |
| spellingShingle | Pinto João Cravo Pedro do Rosário Virgílio E Galvão André Teófilo Vânia Ferreira Conceição Vicente José L Salgueiro Patrícia Tracing the origins and signatures of selection of antifolate resistance in island populations of <it>Plasmodium falciparum</it> BMC Infectious Diseases |
| title | Tracing the origins and signatures of selection of antifolate resistance in island populations of <it>Plasmodium falciparum</it> |
| title_full | Tracing the origins and signatures of selection of antifolate resistance in island populations of <it>Plasmodium falciparum</it> |
| title_fullStr | Tracing the origins and signatures of selection of antifolate resistance in island populations of <it>Plasmodium falciparum</it> |
| title_full_unstemmed | Tracing the origins and signatures of selection of antifolate resistance in island populations of <it>Plasmodium falciparum</it> |
| title_short | Tracing the origins and signatures of selection of antifolate resistance in island populations of <it>Plasmodium falciparum</it> |
| title_sort | tracing the origins and signatures of selection of antifolate resistance in island populations of it plasmodium falciparum it |
| url | http://www.biomedcentral.com/1471-2334/10/163 |
| work_keys_str_mv | AT pintojoao tracingtheoriginsandsignaturesofselectionofantifolateresistanceinislandpopulationsofitplasmodiumfalciparumit AT cravopedro tracingtheoriginsandsignaturesofselectionofantifolateresistanceinislandpopulationsofitplasmodiumfalciparumit AT dorosariovirgilioe tracingtheoriginsandsignaturesofselectionofantifolateresistanceinislandpopulationsofitplasmodiumfalciparumit AT galvaoandre tracingtheoriginsandsignaturesofselectionofantifolateresistanceinislandpopulationsofitplasmodiumfalciparumit AT teofilovania tracingtheoriginsandsignaturesofselectionofantifolateresistanceinislandpopulationsofitplasmodiumfalciparumit AT ferreiraconceicao tracingtheoriginsandsignaturesofselectionofantifolateresistanceinislandpopulationsofitplasmodiumfalciparumit AT vicentejosel tracingtheoriginsandsignaturesofselectionofantifolateresistanceinislandpopulationsofitplasmodiumfalciparumit AT salgueiropatricia tracingtheoriginsandsignaturesofselectionofantifolateresistanceinislandpopulationsofitplasmodiumfalciparumit |