<it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>allele frequency and diversity in sub-Saharan Africa

<p>Abstract</p> <p>Background</p> <p>The efficacy of anti-malarial drugs is assessed over a period of 28-63 days (depending on the drugs' residence time) following initiation of treatment in order to capture late failures. However, prolonged follow-up increases the...

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Main Authors: Snounou Georges, Sumari Deborah, Beck Hans-Peter, Schoepflin Sonja, Nkwengulila Gamba, Mwingira Felista, Felger Ingrid, Olliaro Piero, Mugittu Kefas
Format: Article
Language:English
Published: BMC 2011-04-01
Series:Malaria Journal
Online Access:http://www.malariajournal.com/content/10/1/79
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author Snounou Georges
Sumari Deborah
Beck Hans-Peter
Schoepflin Sonja
Nkwengulila Gamba
Mwingira Felista
Felger Ingrid
Olliaro Piero
Mugittu Kefas
author_facet Snounou Georges
Sumari Deborah
Beck Hans-Peter
Schoepflin Sonja
Nkwengulila Gamba
Mwingira Felista
Felger Ingrid
Olliaro Piero
Mugittu Kefas
author_sort Snounou Georges
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The efficacy of anti-malarial drugs is assessed over a period of 28-63 days (depending on the drugs' residence time) following initiation of treatment in order to capture late failures. However, prolonged follow-up increases the likelihood of new infections depending on transmission intensity. Therefore, molecular genotyping of highly polymorphic regions of <it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>loci is usually carried out to distinguish recrudescence (true failures) from new infections. This tool has now been adopted as an integral part of anti-malarial efficacy studies and clinical trials. However, there are concerns over its utility and reliability because conclusions drawn from molecular typing depend on the genetic profile of the respective parasite populations, but this profile is not systematically documented in most endemic areas. This study presents the genetic diversity of <it>P. falciparum msp1, msp2 </it>and <it>glurp </it>markers in selected sub-Saharan Africa countries with varying levels of endemicity namely Malawi, Tanzania, Uganda, Burkina Faso and São Tomé.</p> <p>Methods</p> <p>A total 780 baseline (Day 0) blood samples from children less than seven years, recruited in a randomized controlled clinical trials done between 1996 and 2000 were genotyped. DNA was extracted; allelic frequency and diversity were investigated by PCR followed by capillary electrophoresis for <it>msp2 </it>and fragment sizing by a digitalized gel imager for <it>msp1 </it>and <it>glurp</it>.</p> <p>Results and Conclusion</p> <p><it>Plasmodium falciparum msp1, msp2 </it>and <it>glurp </it>markers were highly polymorphic with low allele frequencies. A total of 17 <it>msp1 </it>genotypes [eight MAD20-, one RO33- and eight K1-types]; 116 <it>msp2 </it>genotypes [83 3D7 and 33 FC27- types] and 14 <it>glurp </it>genotypes were recorded. All five sites recorded very high expected heterozygosity (H<sub>E</sub>) values (0.68 - 0.99). H<sub>E </sub>was highest in <it>msp2 </it>locus (H<sub>E </sub>= 0.99), and lowest for <it>msp1 </it>(H<sub>E </sub>= 0.68) (P < 0.0001). The genetic diversity and allelic frequency recorded were independent of transmission intensity (P = 0.84, P = 0.25 respectively. A few genotypes had particularly high frequencies; however the most abundant showed only a 4% probability that a new infection would share the same genotype as the baseline infection. This is unlikely to confound the distinction of recrudescence from new infection, particularly if more than one marker is used for genotyping. Hence, this study supports the use of <it>msp1, msp2 </it>and <it>glurp </it>in malaria clinical trials in sub-Saharan Africa to discriminate new from recrudescent infections.</p>
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spelling doaj.art-f829f4b085c049acbb459aaf2990b19c2022-12-21T20:28:19ZengBMCMalaria Journal1475-28752011-04-011017910.1186/1475-2875-10-79<it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>allele frequency and diversity in sub-Saharan AfricaSnounou GeorgesSumari DeborahBeck Hans-PeterSchoepflin SonjaNkwengulila GambaMwingira FelistaFelger IngridOlliaro PieroMugittu Kefas<p>Abstract</p> <p>Background</p> <p>The efficacy of anti-malarial drugs is assessed over a period of 28-63 days (depending on the drugs' residence time) following initiation of treatment in order to capture late failures. However, prolonged follow-up increases the likelihood of new infections depending on transmission intensity. Therefore, molecular genotyping of highly polymorphic regions of <it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>loci is usually carried out to distinguish recrudescence (true failures) from new infections. This tool has now been adopted as an integral part of anti-malarial efficacy studies and clinical trials. However, there are concerns over its utility and reliability because conclusions drawn from molecular typing depend on the genetic profile of the respective parasite populations, but this profile is not systematically documented in most endemic areas. This study presents the genetic diversity of <it>P. falciparum msp1, msp2 </it>and <it>glurp </it>markers in selected sub-Saharan Africa countries with varying levels of endemicity namely Malawi, Tanzania, Uganda, Burkina Faso and São Tomé.</p> <p>Methods</p> <p>A total 780 baseline (Day 0) blood samples from children less than seven years, recruited in a randomized controlled clinical trials done between 1996 and 2000 were genotyped. DNA was extracted; allelic frequency and diversity were investigated by PCR followed by capillary electrophoresis for <it>msp2 </it>and fragment sizing by a digitalized gel imager for <it>msp1 </it>and <it>glurp</it>.</p> <p>Results and Conclusion</p> <p><it>Plasmodium falciparum msp1, msp2 </it>and <it>glurp </it>markers were highly polymorphic with low allele frequencies. A total of 17 <it>msp1 </it>genotypes [eight MAD20-, one RO33- and eight K1-types]; 116 <it>msp2 </it>genotypes [83 3D7 and 33 FC27- types] and 14 <it>glurp </it>genotypes were recorded. All five sites recorded very high expected heterozygosity (H<sub>E</sub>) values (0.68 - 0.99). H<sub>E </sub>was highest in <it>msp2 </it>locus (H<sub>E </sub>= 0.99), and lowest for <it>msp1 </it>(H<sub>E </sub>= 0.68) (P < 0.0001). The genetic diversity and allelic frequency recorded were independent of transmission intensity (P = 0.84, P = 0.25 respectively. A few genotypes had particularly high frequencies; however the most abundant showed only a 4% probability that a new infection would share the same genotype as the baseline infection. This is unlikely to confound the distinction of recrudescence from new infection, particularly if more than one marker is used for genotyping. Hence, this study supports the use of <it>msp1, msp2 </it>and <it>glurp </it>in malaria clinical trials in sub-Saharan Africa to discriminate new from recrudescent infections.</p>http://www.malariajournal.com/content/10/1/79
spellingShingle Snounou Georges
Sumari Deborah
Beck Hans-Peter
Schoepflin Sonja
Nkwengulila Gamba
Mwingira Felista
Felger Ingrid
Olliaro Piero
Mugittu Kefas
<it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>allele frequency and diversity in sub-Saharan Africa
Malaria Journal
title <it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>allele frequency and diversity in sub-Saharan Africa
title_full <it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>allele frequency and diversity in sub-Saharan Africa
title_fullStr <it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>allele frequency and diversity in sub-Saharan Africa
title_full_unstemmed <it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>allele frequency and diversity in sub-Saharan Africa
title_short <it>Plasmodium falciparum msp1</it>, <it>msp2 </it>and <it>glurp </it>allele frequency and diversity in sub-Saharan Africa
title_sort it plasmodium falciparum msp1 it it msp2 it and it glurp it allele frequency and diversity in sub saharan africa
url http://www.malariajournal.com/content/10/1/79
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