Browsing by Author "Ishengoma, D.S."
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Item The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC(Nature Communications, 2020-04-30) Ghansah, A.; Verity, R.; Aydemir, O.; Brazeau, N.F.; Watson, O.J.; Hathaway, N.J.; Mwandagalirwa, M.K.; Marsh, P.W.; Thwai, K.; Fulton, T.; Denton, M.; Morgan, A.P.; Parr, J.B.; Tumwebaze, P.K.; Conrad, M.; Rosenthal, P.J.; Ishengoma, D.S.; Ngondi, J.; Gutman, J.; Mulenga, M.; Norris, D.E.; Moss, W.J.; Mensah, B.A.; Myers-Hansen, J.L.; Tshefu, A.K.; Ghani, A.C.; Meshnick, S.R.; Bailey, J.A.; Juliano, J.J.The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.Item An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples(2021) MalariaGEN; Ahouidi, A.; Ali, M.; Almagro-Garcia, J.; Amambua-Ngwa, A.; Amaratunga, C.; Amato, R.; Amenga-Etego, L.; Andagalu, B.; Anderson, T.J.C.; Andrianaranjaka, V.; Apinjoh, T.; Ariani, C.; Ashley, E.A.; Auburn, S.; Awandare, G.A.; Ba, H.; Baraka, V.; Barry, A.E.; Bejon, P.; Bertin, G.I.; Boni, M.F.; Borrmann, S.; Bousema, T.; Branch, O.; Bull, P.C.; Busby, G.B.J.; Chookajorn, T.; Chotivanich, K.; Claessens, A.; Conway, D.; Craig, A.; D'Alessandro, U.; Dama, S.; Day, N.P.J.; Denis, B.; Diakite, M.; Djimdé, A.; Dolecek, C.; Dondorp, A.M.; Drakeley, C.; Drury, E.; Duffy, P.; Echeverry, D.F.; Egwang, T.G.; Erko, B.; Fairhurst, R.M.; Faiz, A.; Fanello, C.A.; Fukuda, M.M.; Gamboa, D.; Ghansah, A.; Golassa, L.; Goncalves, S.; Hamilton, W.L.; Harrison, G.L.A.; Hart, L.; Henrichs, C.; Hien, T.T.; Hill, C.A.; Hodgson, A.; Hubbart, C.; Imwong, M.; Ishengoma, D.S.; Jackson, S.A.; Jacob, C.G.; Jeffery, B.; Jeffreys, A.E.; Johnson, K.J.; Jyothi, D.; Kamaliddin, C.; Kamau, E.; Kekre, M.; Kluczynski, K.; Kochakarn, T.; Konaté, A.; Kwiatkowski, D.P.; Kyaw, M.P.; Lim, P.; Lon, C.; Loua, K.M.; Maïga-Ascofaré, O.; Malangone, C.; Manske, M.; Marfurt, J.; Marsh, K.; Mayxay, M.; Miles, A.; Miotto, O.; Mobegi, V.; Mokuolu, O.A.; Montgomery, J.; Mueller, I.; Newton, P.N.; Nguyen, T.; Nguyen, T.; Noedl, H.; Nosten, F.; Noviyanti, R.; Nzila, A.; Ochola-Oyier, L.I.; Ocholla, H.; Oduro, A.; Omedo, I.; Onyamboko, M.A.; Ouedraogo, J.; Oyebola, K.; Pearson, R.D.; Peshu, N.; Phyo, A.P.; Plowe, C.V.; Price, R.N.; Pukrittayakamee, S.; Randrianarivelojosia, M.; Rayner, J.C.; Ringwald, P.; Rockett, K.A.; Rowlands, K.; Ruiz, L.; Saunders, D.; Shayo, A.; Siba, P.; Simpson, V.J.; Stalker, J.; Su, X.; Sutherland, C.; Takala-Harrison, S.; Tavul, L.; Thathy, V.; Tshefu, A.; Verra, F.; Vinetz, J.; Wellems, T.E.; Wendler, J.; White, N.J.; Wright, I.; Yavo, W.; Ye, H.MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.Item Plasmodium malariae structure and genetic diversity in sub‑Saharan Africa determined from microsatellite variants and linked SNPs in orthologues of antimalarial resistance genes(Scientific reports, 2022) Oriero, E.C.; Demba, M.A.; Diop, M.F.; Ishengoma, D.S.; Amenga‑Etego, L.N.; Ghansah, A.; Apinjoh, T.; Issiaka, S.Plasmodium malariae, a neglected human malaria parasite, contributes up to 10% of malaria infections in sub-Saharan Africa (sSA). Though P. malariae infection is considered clinically benign, it presents mostly as coinfections with the dominant P. falciparum. Completion of its reference genome has paved the way to further understand its biology and interactions with the human host, including responses to antimalarial interventions. We characterized 75 P. malariae isolates from seven endemic countries in sSA using highly divergent microsatellites. The P. malariae infections were highly diverse and five subpopulations from three ancestries (independent of origin of isolates) were determined. Sequences of 11 orthologous antimalarial resistance genes, identifed low frequency single nucleotide polymorphisms (SNPs), strong linkage disequilibrium between loci that may be due to antimalarial drug selection. At least three sub-populations were detectable from a subset of denoised SNP data from mostly the mitochondrial cytochrome b coding region. This evidence of diversity and selection calls for including P. malariae in malaria genomic surveillance towards improved tools andItem Plasmodium malariae, current knowledge and future research opportunities on a neglected malaria parasite species(Taylor & Francis Group, 2021) Oriero, E.C.; Amenga-Etego, L.; Ishengoma, D.S.; Amambua-Ngwa, A.Plasmodium malariae is often reported as a benign malaria parasite. There are limited data on its biology and disease burden in sub-Saharan Africa (sSA) possibly due to the unavailability of specific and affordable tools for routine diagnosis and large epidemiology studies. In addition, P. malariae occurs at low parasite densities and in co-infections with other species, predominately P. falciparum. The paucity of data on P. malariae infections limits the capacity to accurately deter mine its contribution to malaria and the effect of control interventions against P. falciparum on its prevalence. Here, we summarise the current knowledge on P. malariae epidemiology in sSA - overall prevalence ranging from 0-32%, as detected by different diagnostic methods; seroprevalence ranging from 0–56% in three countries (Mozambique, Benin and Zimbabwe), and explore the future application of next-generation sequencing technologies as a tool for enriching P. malariae genomic epidemiology. This will provide insights into important adaptive mechanisms of this neglected non-falciparum species, including antimalarial drug resistance, local and regional parasite transmission patterns and genomic signatures of selection. Improved diagnosis and genomic surveillance of non-falciparum malaria parasites in Africa would be helpful in evaluating progress towards elimination of all human Plasmodium species.Item Targeted Next Generation Sequencing for malaria research in Africa: current status and outlook(Malaria Journal, 2019-09-23) Ghansah, A.; Kamau, E.; Amambua‑Ngwa, A.; Ishengoma, D.S.; Maiga‑Ascofare, O.; Amenga‑Etego, L.; Deme, A.; Yavo, W.; Randrianarivelojosia, M.; Ochola‑Oyier, L.I.; Helegbe, G.K.; Bailey, J.; Alifrangis, M.; Djimde, A.Targeted Next Generation Sequencing (TNGS) is an efficient and economical Next Generation Sequencing (NGS) platform and the preferred choice when specific genomic regions are of interest. So far, only institutions located in middle and high-income countries have developed and implemented the technology, however, the efficiency and cost savings, as opposed to more traditional sequencing methodologies (e.g. Sanger sequencing) make the approach potentially well suited for resource-constrained regions as well. In April 2018, scientists from the Plasmodium Diversity Network Africa (PDNA) and collaborators met during the 7th Pan African Multilateral Initiative of Malaria (MIM) conference held in Dakar, Senegal to explore the feasibility of applying TNGS to genetic studies and malaria surveillance in Africa. The group of scientists reviewed the current experience with TNGS platforms in sub-Saharan Africa (SSA) and identified potential roles the technology might play to accelerate malaria research, scientific discoveries and improved public health in SSA. Research funding, infrastructure and human resources were highlighted as challenges that will have to be mitigated to enable African scientists to drive the implementation of TNGS in SSA. Current roles of important stakeholders and strategies to strengthen existing networks to effectively harness this powerful technology for malaria research of public health importance were discussed