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Demba, M. A.

Publications and source records attributed to Demba, M. A..

2 recordsLinked to original sources

Characterising recent antimalarial resistance in West Africa: Insights from amplicon sequencing of 17,384 Plasmodium falciparum infection samples

Plasmodium falciparum (P. falciparum) infection remains a significant public health threat in West Africa, where chemoprevention and first-line therapies are key interventions against malaria. However, the development and spread of resistance to commonly used antimalarials poses a growing threat to the efficacy of these strategies. This study characterises the recent landscape of antimalarial resistance in West Africa by analysing targeted amplicon sequences from 17,384 P. falciparum infection samples. Across countries, the prevalence of the pyrimethamine resistance-associated dhfr triple mutant allele (51I/59R/108N) exceeded 80%, while its combination with the sulphadoxine resistance-associated dhps 437G exceeded 60% of infections. Unlike the parasite genotypes in East Africa, the prevalence of the dhps 540E mutant was low (1.5%), whereas dhps 436A was common (43.8%). The chloroquine resistance marker crt 76T showed greatest geographic heterogeneity, ranging from low prevalence in Ghana (1.3%) to very common in The Gambia (64.9%). Non-synonymous mutants of kelch13 were uncommon, most with unknown relevance to artemisinin resistance and observed for the first time in Africa. However, mutants that are artemisinin resistance-associated elsewhere were detected in three infection samples from Ghana (574L, 561H, 469Y), and one in Cameroon (538V). This large-scale genomic surveillance of P. falciparum infections highlights the need for ongoing monitoring of drug resistance and for data integration throughout the region.

genomics↗

Regional Plasmodium falciparum subpopulations and malaria transmission connectivity in Africa were detected with an enlarged panel of genome-wide microsatellite loci

Unravelling the genetic diversity of Plasmodium falciparum malaria parasite provides critical information on how populations are affected by interventions and the environment, especially the evolution of molecular markers associated with parasite fitness and adaptation to drugs and vaccines. This study expands previous studies based on small sets of microsatellite loci, which often showed limited substructure in African populations of P. falciparum. Combining several short tandem repeat detection algorithms, we genotyped and analysed 2329 polymorphic microsatellite loci from next-generation sequences of 992 low-complexity P. falciparum isolates from 15 sub-Saharan African countries. Based on pairwise relatedness, we identified seven subpopulations and gene flow between the Central and Eastern African populations. The most divergent subpopulation was from Ethiopia, while unexpected unique subpopulations from Gabon and Malawi were resolved. Isolates from the Democratic Republic of Congo shared ancestry with multiple regional populations, suggesting a possible founder population of P. falciparum from the Congo basin, where there was stronger geneflow eastwards to Tanzania, and Kenya. and Malawi. The most differentiated microsatellite loci were those around the P. falciparum dihydropteroate synthase (Pfdhps) gene associated with sulphadoxine resistance. Haplotypes around the Pfdhps gene separated the West, Central, and East Africa parasite populations into distinct clusters, suggesting independent local evolution of Pfdhps-associated sulphadoxine resistance alleles in each African region. Overall, this study presents genome-wide microsatellites as markers for resolving P. falciparum population diversity, structure, and evolution in populations like Africa, where there is high gene flow.

genomics↗