Browsing by Author "Djimde, A.A."
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Item K13-propeller polymorphisms in plasmodium falciparum parasites from sub-saharan Africa(Journal of Infectious Diseases, 2015-01) Kamau, E.; Campino, S.; Amenga-Etego, L.; Drury, E.; Ishengoma, D.; Johnson, K.; Mumba, D.; Kekre, M.; Yavo, W.; Mead, D.; Bouyou-Akotet, M.; Apinjoh, T.; Golassa, L.; Randrianarivelojosia, M.; Andagalu B, B.; Maiga-Ascofare, O.; Amambua-Ngwa, A.; Tindana, P.; Ghansah, A.; Macinnis, B.; Kwiatkowski, D.; Djimde, A.A.Mutations in the Plasmodium falciparum K13-propeller domain have recently been shown to be important determinants of artemisinin resistance in Southeast Asia. This study investigated the prevalence of K13-propeller polymorphisms across sub-Saharan Africa. A total of 1212 P. falciparum samples collected from 12 countries were sequenced. None of the K13-propeller mutations previously reported in Southeast Asia were found, but 22 unique mutations were detected, of which 7 were nonsynonymous. Allele frequencies ranged between 1% and 3%. Three mutations were observed in >1 country, and the A578S was present in parasites from 5 countries. This study provides the baseline prevalence of K13-propeller mutations in sub-Saharan Africa. © 2015 The Author. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.Item Major subpopulations of Plasmodium falciparum in sub-Saharan Africa(Science, 2019-08-23) Amenga-Etego, L.; Amambua-Ngwa, A.; Kamau, E.; Amato, R.; Ghansah, A.; Golassa, L.; Randrianarivelojosia, M.; Ishengoma, D.; Apinjoh, T.; Maïga-Ascofaré, O.; Andagalu, B.; Yavo, W.; Bouyou-Akotet, M.; Kolapo, O.; Mane, K.; Worwui, A.; Jeffries, D.; Simpson, V.; D’Alessandro, U.; Kwiatkowski, D.; Djimde, A.A.Understanding genomic variation and population structure of Plasmodium falciparum across Africa is necessary to sustain progress toward malaria elimination. Genome clustering of 2263 P. falciparum isolates from 24 malaria-endemic settings in 15 African countries identified major western, central, and eastern ancestries, plus a highly divergent Ethiopian population. Ancestry aligned to these regional blocs, overlapping with both the parasite’s origin and with historical human migration. The parasite populations are interbred and shared genomic haplotypes, especially across drug resistance loci, which showed the strongest recent identity-by-descent between populations. A recent signature of selection on chromosome 12 with candidate resistance loci against artemisinin derivatives was evident in Ghana and Malawi. Such selection and the emerging substructure may affect treatment-based intervention strategies against P. falciparum malaria.Item Monitoring parasite diversity for malaria elimination in sub-Saharan Africa(Science, 2014-09) Ghansah, A.; Amenga-Etego, L.; Amambua-Ngwa, A.; Andagalu, B.; Apinjoh, T.; Bouyou-Akotet, M.; Cornelius, V.; Golassa, L.; Andrianaranjaka, V.H.; Ishengoma, D.; Johnson, K.; Kamau, E.; Maïga-Ascofaré, O.; Mumba, D.; Tindana, P.; Tshefu-Kitoto, A.; Randrianarivelojosia, M.; William, Y.; Kwiatkowski, D.P.; Djimde, A.A.The African continent continues to bear the greatest burden of malaria and the greatest diversity of parasites, mosquito vectors, and human victims. The evolutionary plasticity of malaria parasites and their vectors is a major obstacle to eliminating the disease. Of current concern is the recently reported emergence of resistance to the front-line drug, artemisinin, in South-East Asia in Plasmodium falciparum, which calls for preemptive surveillance of the African parasite population for genetic markers of emerging drug resistance. Here we describe the Plasmodium Diversity Network Africa (PDNA), which has been established across 11 countries in sub-Saharan Africa to ensure that African scientists are enabled to work together and to play a key role in the global effort for tracking and responding to this public health threat.Item Plasmodium malariae and Plasmodium falciparum comparative susceptibility to antimalarial drugs in Mali(Journal of Antimicrobial Chemotherapy, 2021) Dembele, L.; Aniweh, Y.; Diallo, N.; Sogore, F.; Sangare, C.P.O; Haidara, A.S.; Traore, A.; Diakite´, S.A.S.; Diakite, M.; Campo, B.; Awandare, G.A.; Djimde, A.A.Objectives: To evaluate Plasmodium malariae susceptibility to current and lead candidate antimalarial drugs. Methods: We conducted cross-sectional screening and detection of all Plasmodium species malaria cases, which were nested within a longitudinal prospective study, and an ex vivo assessment of efficacy of a panel of antimalarials against P. malariae and Plasmodium falciparum, both PCR-confirmed mono-infections. Reference compounds tested included chloroquine, lumefantrine, artemether and piperaquine, while candidate antimalarials included the imidazolopiperazine GNF179, a close analogue of KAF156, and the Plasmodium phosphatidylinositol- 4-OH kinase (PI4K)-specific inhibitor KDU691. Results: We report a high frequency (3%–15%) of P. malariae infections with a significant reduction in ex vivo susceptibility to chloroquine, lumefantrine and artemether, which are the current frontline drugs against P. malariae infections. Unlike these compounds, potent inhibition of P. malariae and P. falciparum was observed with piperaquine exposure. Furthermore, we evaluated advanced lead antimalarial compounds. In this regard, we identified strong inhibition of P. malariae using GNF179, a close analogue of KAF156 imidazolopiperazines, which is a novel class of antimalarial drug currently in clinical Phase IIb testing. Finally, in addition to GNF179, we demonstrated that the Plasmodium PI4K-specific inhibitor KDU691 is highly inhibitory against P. malariae and P. falciparum. Conclusions: Our data indicated that chloroquine, lumefantrine and artemether may not be suitable for the treatment of P. malariae infections and the potential of piperaquine, as well as new antimalarials imidazolopiperazines and PI4K-specific inhibitor, for P. malariae cure.Item A shared Asian origin of the triple-mutant DHFR allele in plasmodium falciparum from sites across Africa.(2007-07-01) Maiga, O.; Djimde, A.A.; Hubert, V.; Renard, E.; Aubouy, A.; Kironde, F.; Nsimba, B.; Koram, K.A.; Doumbo, O.K.; Le Bras, J.; Clain, J.Background. Usefulness of sulfadoxine-pyrimethamine as first-line therapy for uncomplicated Plasmodium falciparum malaria and intermittent preventive treatment in pregnancy throughout sub-Saharan Africa is compromised by the spread of dhfr alleles associated with pyrimethamine resistance. A predominant haplotype associated with the N51I+C59R+S108N triple-mutant dhfr allele has been reported recently in 4 African countries. A more comprehensive picture of the evolution of this mutant allele in Africa is lacking. Methods. Seventy-five P. falciparum isolates carrying the wild-type dhfr allele and 204 carrying the triple-mutant dhfr allele from 11 African countries were selected. The genetic diversity of the chromosomes bearing these alleles was analyzed with 4 microsatellite markers closely linked to the dhfr gene. Results. Seventy-three different 4-locus haplotypes carrying the wild-type dhfr allele were found. By contrast, 175 (85%) of 204 isolates carrying the triple-mutant dhfr allele shared a unique haplotype, identical to the one identified in Thailand. For the remaining triple-mutant isolates and one isolate with the quadruple-mutant dhfr allele (N51I+C59R+S108N+I164L), haplotypes were closely related to the predominant haplotype by mutation or recombination. Conclusions. Migration of parasites carrying an ancestral triple-mutant dhfr allele drives the spread of dhfr alleles associated with pyrimethamine resistance throughout West and Central Africa. © 2007 by the Infectious Diseases Society of America. All rights reserved.