Plasmodium Falciparum Msp1, Msp2 And Glurp Allele Frequency and Diversity in Sub-Saharan Africa
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Date
2011
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
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 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.
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 msp2 and fragment
sizing by a digitalized gel imager for msp1 and glurp.
Plasmodium 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.
Description
Keywords
Anti-malarial drugs, Sub-Saharan Africa, Malaria
Citation
Mwingira, F., Nkwengulila, G., Schoepflin, S., Sumari, D., Beck, H.P., Snounou, G., Felger, I., Olliaro, P. and Mugittu, K., 2011. Plasmodium falciparum msp1, msp2 and glurp allele frequency and diversity in sub-Saharan Africa. Malar J, 10(1), pp.79-88.