Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutant genotype frequencies in African Plasmodium falciparum parasite populations
Abstract Background Mutations in the dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) genes of Plasmodium falciparum are associated with resistance to anti-folate drugs, most notably sulphadoxine-pyrimethamine (SP). Molecular studies document the prevalence of these mutations i...
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ftdoajarticles:oai:doaj.org/article:50416b722be145aa87b39ae3a626a16f 2023-05-15T15:14:29+02:00 Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutant genotype frequencies in African Plasmodium falciparum parasite populations Sridaran Sankar McClintock Shannon K Syphard Luke M Herman Karen M Barnwell John W Udhayakumar Venkatachalam 2010-08-01T00:00:00Z https://doi.org/10.1186/1475-2875-9-247 https://doaj.org/article/50416b722be145aa87b39ae3a626a16f EN eng BMC http://www.malariajournal.com/content/9/1/247 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-247 1475-2875 https://doaj.org/article/50416b722be145aa87b39ae3a626a16f Malaria Journal, Vol 9, Iss 1, p 247 (2010) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2010 ftdoajarticles https://doi.org/10.1186/1475-2875-9-247 2022-12-31T04:34:07Z Abstract Background Mutations in the dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) genes of Plasmodium falciparum are associated with resistance to anti-folate drugs, most notably sulphadoxine-pyrimethamine (SP). Molecular studies document the prevalence of these mutations in parasite populations across the African continent. However, there is no systematic review examining the collective epidemiological significance of these studies. This meta-analysis attempts to: 1) summarize genotype frequency data that are critical for molecular surveillance of anti-folate resistance and 2) identify the specific challenges facing the development of future molecular databases. Methods This review consists of 220 studies published prior to 2009 that report the frequency of select dhfr and dhps mutations in 31 African countries. Maps were created to summarize the location and prevalence of the highly resistant dhfr triple mutant (N51I, C59R, S108N) genotype and dhps double mutant (A437G and K540E) genotype in Africa. A hierarchical mixed effects logistic regression was used to examine the influence of various factors on reported mutant genotype frequency. These factors include: year and location of study, age and clinical status of sampled population, and reporting conventions for mixed genotype data. Results A database consisting of dhfr and dhps mutant genotype frequencies from all African studies that met selection criteria was created for this analysis. The map illustrates particularly high prevalence of both the dhfr triple and dhps double mutant genotypes along the Kenya-Tanzania border and Malawi. The regression model shows a statistically significant increase in the prevalence of both the dhfr triple and dhps double mutant genotypes in Africa. Conclusion Increasing prevalence of the dhfr triple mutant and dhps double mutant genotypes in Africa are consistent with the loss of efficacy of SP for treatment of clinical malaria in most parts of this continent. Continued assessment of the ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 9 1 247 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Sridaran Sankar McClintock Shannon K Syphard Luke M Herman Karen M Barnwell John W Udhayakumar Venkatachalam Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutant genotype frequencies in African Plasmodium falciparum parasite populations |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Mutations in the dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) genes of Plasmodium falciparum are associated with resistance to anti-folate drugs, most notably sulphadoxine-pyrimethamine (SP). Molecular studies document the prevalence of these mutations in parasite populations across the African continent. However, there is no systematic review examining the collective epidemiological significance of these studies. This meta-analysis attempts to: 1) summarize genotype frequency data that are critical for molecular surveillance of anti-folate resistance and 2) identify the specific challenges facing the development of future molecular databases. Methods This review consists of 220 studies published prior to 2009 that report the frequency of select dhfr and dhps mutations in 31 African countries. Maps were created to summarize the location and prevalence of the highly resistant dhfr triple mutant (N51I, C59R, S108N) genotype and dhps double mutant (A437G and K540E) genotype in Africa. A hierarchical mixed effects logistic regression was used to examine the influence of various factors on reported mutant genotype frequency. These factors include: year and location of study, age and clinical status of sampled population, and reporting conventions for mixed genotype data. Results A database consisting of dhfr and dhps mutant genotype frequencies from all African studies that met selection criteria was created for this analysis. The map illustrates particularly high prevalence of both the dhfr triple and dhps double mutant genotypes along the Kenya-Tanzania border and Malawi. The regression model shows a statistically significant increase in the prevalence of both the dhfr triple and dhps double mutant genotypes in Africa. Conclusion Increasing prevalence of the dhfr triple mutant and dhps double mutant genotypes in Africa are consistent with the loss of efficacy of SP for treatment of clinical malaria in most parts of this continent. Continued assessment of the ... |
format |
Article in Journal/Newspaper |
author |
Sridaran Sankar McClintock Shannon K Syphard Luke M Herman Karen M Barnwell John W Udhayakumar Venkatachalam |
author_facet |
Sridaran Sankar McClintock Shannon K Syphard Luke M Herman Karen M Barnwell John W Udhayakumar Venkatachalam |
author_sort |
Sridaran Sankar |
title |
Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutant genotype frequencies in African Plasmodium falciparum parasite populations |
title_short |
Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutant genotype frequencies in African Plasmodium falciparum parasite populations |
title_full |
Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutant genotype frequencies in African Plasmodium falciparum parasite populations |
title_fullStr |
Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutant genotype frequencies in African Plasmodium falciparum parasite populations |
title_full_unstemmed |
Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutant genotype frequencies in African Plasmodium falciparum parasite populations |
title_sort |
anti-folate drug resistance in africa: meta-analysis of reported dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutant genotype frequencies in african plasmodium falciparum parasite populations |
publisher |
BMC |
publishDate |
2010 |
url |
https://doi.org/10.1186/1475-2875-9-247 https://doaj.org/article/50416b722be145aa87b39ae3a626a16f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 9, Iss 1, p 247 (2010) |
op_relation |
http://www.malariajournal.com/content/9/1/247 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-247 1475-2875 https://doaj.org/article/50416b722be145aa87b39ae3a626a16f |
op_doi |
https://doi.org/10.1186/1475-2875-9-247 |
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Malaria Journal |
container_volume |
9 |
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1 |
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247 |
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1766344936138997760 |