Plasmodium falciparum msp1, msp2 and glurp allele frequency and diversity in sub-Saharan Africa

Malaria Journal

Research

Felista Mwingira¹  Gamba Nkwengulila²  Deborah Sumari³  Kefas Mugittu³  Hans-Peter Beck⁴  Sonja Schoepflin⁴  Ingrid Felger⁴  Piero Olliaro⁵  Georges Snounou⁶ 

[1] Dares Salaam University College of Education, P.O.BOX 2329, Dar es Salaam, Tanzania;Department of Zoology and Wildlife Conservation, University of Dar es Salaam, PO Box 35064, Dar es Salaam, Tanzania;Department of Zoology and Wildlife Conservation, University of Dar es Salaam, PO Box 35064, Dar es Salaam, Tanzania;Ifakara Health Institute, P. O. Box 74, Bagamoyo, Tanzania;Swiss Tropical and Public Health Institute, Socinstrasse 57, CH 4002, Basel, Switzerland;University of Basel, Petersplatz 1, 4003, Basel, Switzerland;UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, World Health Organization, Room CA 1118, Centre Casai, 51-53 Avenue Louis Casai, 1216, Cointrin, Geneva, Switzerland;Centre for Tropical Medicine and Vaccinology, Nuffield Department of Medicine, University of Oxford, Churchill Hospital, OX37LJ, Oxford, UK;UPMC/INSERM UMR S 945, Faculté de Médecine Pitié-Salpêtrière Université Pierre & Marie Curie, 91 Boulevard de l'Hôpital, 75013, Paris, France;

关键词: Transmission Intensity;    Artesunate;    Artemisinin Combination Therapy;    Allelic Family;    High Expect;   

DOI  :  10.1186/1475-2875-10-79

 received in 2010-10-22, accepted in 2011-04-06,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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 Plasmodium falciparum msp1, msp2 and glurp 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 P. falciparum msp1, msp2 and glurp markers in selected sub-Saharan Africa countries with varying levels of endemicity namely Malawi, Tanzania, Uganda, Burkina Faso and São Tomé.MethodsA 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 msp2 and fragment sizing by a digitalized gel imager for msp1 and glurp.Results and ConclusionPlasmodium falciparum msp1, msp2 and glurp markers were highly polymorphic with low allele frequencies. A total of 17 msp1 genotypes [eight MAD20-, one RO33- and eight K1-types]; 116 msp2 genotypes [83 3D7 and 33 FC27- types] and 14 glurp genotypes were recorded. All five sites recorded very high expected heterozygosity (HE) values (0.68 - 0.99). HE was highest in msp2 locus (HE = 0.99), and lowest for msp1 (HE = 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 msp1, msp2 and glurp in malaria clinical trials in sub-Saharan Africa to discriminate new from recrudescent infections.

【 授权许可】

Unknown   
© Mwingira et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.