BACKGROUND: In Uganda, artemether-lumefantrine is recommended for malaria treatment and sulfadoxine-pyrimethamine for chemoprevention during pregnancy, but drug resistance may limit efficacies. METHODS: Genetic polymorphisms associated with sensitivities to key drugs were characterized in samples collected from 16 sites across Uganda in 2018 and 2019 by ligase detection reaction fluorescent microsphere, molecular inversion probe, dideoxy sequencing, and quantitative polymerase chain reaction assays. RESULTS: Considering transporter polymorphisms associated with resistance to aminoquinolines, the prevalence of Plasmodium falciparum chloroquine resistance transporter (PfCRT) 76T decreased, but varied markedly between sites (0-46% in 2018; 0-23% in 2019); additional PfCRT polymorphisms and plasmepsin-2/3 amplifications associated elsewhere with resistance to piperaquine were not seen. For P. falciparum multidrug resistance protein 1, in 2019 the 86Y mutation was absent at all sites, the 1246Y mutation had prevalence ≤20% at 14 of 16 sites, and gene amplification was not seen. Considering mutations associated with high-level sulfadoxine-pyrimethamine resistance, prevalences of P. falciparum dihydrofolate reductase 164L (up to 80%) and dihydropteroate synthase 581G (up to 67%) were high at multiple sites. Considering P. falciparum kelch protein propeller domain mutations associated with artemisinin delayed clearance, prevalence of the 469Y and 675V mutations has increased at multiple sites in northern Uganda (up to 23% and 41%, respectively). CONCLUSIONS: We demonstrate concerning spread of mutations that may limit efficacies of key antimalarial drugs.
BACKGROUND: In Uganda, artemether-lumefantrine is recommended for malaria treatment and sulfadoxine-pyrimethamine for chemoprevention during pregnancy, but drug resistance may limit efficacies. METHODS: Genetic polymorphisms associated with sensitivities to key drugs were characterized in samples collected from 16 sites across Uganda in 2018 and 2019 by ligase detection reaction fluorescent microsphere, molecular inversion probe, dideoxy sequencing, and quantitative polymerase chain reaction assays. RESULTS: Considering transporter polymorphisms associated with resistance to aminoquinolines, the prevalence of Plasmodium falciparum chloroquine resistance transporter (PfCRT) 76T decreased, but varied markedly between sites (0-46% in 2018; 0-23% in 2019); additional PfCRT polymorphisms and plasmepsin-2/3 amplifications associated elsewhere with resistance to piperaquine were not seen. For P. falciparum multidrug resistance protein 1, in 2019 the 86Y mutation was absent at all sites, the 1246Y mutation had prevalence ≤20% at 14 of 16 sites, and gene amplification was not seen. Considering mutations associated with high-level sulfadoxine-pyrimethamine resistance, prevalences of P. falciparum dihydrofolate reductase 164L (up to 80%) and dihydropteroate synthase 581G (up to 67%) were high at multiple sites. Considering P. falciparum kelch protein propeller domain mutations associated with artemisinin delayed clearance, prevalence of the 469Y and 675V mutations has increased at multiple sites in northern Uganda (up to 23% and 41%, respectively). CONCLUSIONS: We demonstrate concerning spread of mutations that may limit efficacies of key antimalarial drugs.
Authors: Stephanie A Rasmussen; Frida G Ceja; Melissa D Conrad; Patrick K Tumwebaze; Oswald Byaruhanga; Thomas Katairo; Samuel L Nsobya; Philip J Rosenthal; Roland A Cooper Journal: Antimicrob Agents Chemother Date: 2017-11-22 Impact factor: 5.191
Authors: Steve M Taylor; Christian M Parobek; Derrick K DeConti; Kassoum Kayentao; Sheick Oumar Coulibaly; Brian M Greenwood; Harry Tagbor; John Williams; Kalifa Bojang; Fanta Njie; Meghna Desai; Simon Kariuki; Julie Gutman; Don P Mathanga; Andreas Mårtensson; Billy Ngasala; Melissa D Conrad; Philip J Rosenthal; Antoinette K Tshefu; Ann M Moormann; John M Vulule; Ogobara K Doumbo; Feiko O Ter Kuile; Steven R Meshnick; Jeffrey A Bailey; Jonathan J Juliano Journal: J Infect Dis Date: 2014-09-01 Impact factor: 5.226
Authors: Ozkan Aydemir; Mark Janko; Nick J Hathaway; Robert Verity; Melchior Kashamuka Mwandagalirwa; Antoinette K Tshefu; Sofonias K Tessema; Patrick W Marsh; Alice Tran; Thomas Reimonn; Azra C Ghani; Anita Ghansah; Jonathan J Juliano; Bryan R Greenhouse; Michael Emch; Steven R Meshnick; Jeffrey A Bailey Journal: J Infect Dis Date: 2018-08-14 Impact factor: 5.226
Authors: Oriana Kreutzfeld; Patrick K Tumwebaze; Oswald Byaruhanga; Thomas Katairo; Martin Okitwi; Stephen Orena; Stephanie A Rasmussen; Jennifer Legac; Melissa D Conrad; Sam L Nsobya; Ozkan Aydemir; Jeffrey A Bailey; Maelle Duffey; Roland A Cooper; Philip J Rosenthal Journal: J Infect Dis Date: 2022-02-15 Impact factor: 7.759
Authors: Douglas G Paton; Alexandra S Probst; Erica Ma; Kelsey L Adams; W Robert Shaw; Naresh Singh; Selina Bopp; Sarah K Volkman; Domombele F S Hien; Prislaure S L Paré; Rakiswendé S Yerbanga; Abdoullaye Diabaté; Roch K Dabiré; Thierry Lefèvre; Dyann F Wirth; Flaminia Catteruccia Journal: PLoS Pathog Date: 2022-06-10 Impact factor: 7.464
Authors: Victor Osoti; Mercy Akinyi; Kevin Wamae; Kelvin M Kimenyi; Zaydah de Laurent; Leonard Ndwiga; Paul Gichuki; Collins Okoyo; Stella Kepha; Charles Mwandawiro; Regina Kandie; Philip Bejon; Robert W Snow; Lynette Isabella Ochola-Oyier Journal: Antimicrob Agents Chemother Date: 2022-03-10 Impact factor: 5.938
Authors: Victor S Koko; Marian Warsame; Benjamin Vonhm; Moses K Jeuronlon; Didier Menard; Laurence Ma; Fahn Taweh; Lekilay Tehmeh; Paye Nyansaiye; Oliver J Pratt; Sei Parwon; Patrick Kamara; Magnus Asinya; Aaron Kollie; Pascal Ringwald Journal: Malar J Date: 2022-04-27 Impact factor: 3.469
Authors: Oriana Kreutzfeld; Stephanie A Rasmussen; Aarti A Ramanathan; Patrick K Tumwebaze; Oswald Byaruhanga; Thomas Katairo; Victor Asua; Martin Okitwi; Stephen Orena; Jennifer Legac; Melissa D Conrad; Samuel L Nsobya; Ozkan Aydemir; Jeffrey Bailey; Maelle Duffey; Brett R Bayles; Akhil B Vaidya; Roland A Cooper; Philip J Rosenthal Journal: Antimicrob Agents Chemother Date: 2021-08-02 Impact factor: 5.938
Authors: Barbara H Stokes; Satish K Dhingra; Kelly Rubiano; Sachel Mok; Judith Straimer; Nina F Gnädig; Ioanna Deni; Kyra A Schindler; Jade R Bath; Kurt E Ward; Josefine Striepen; Tomas Yeo; Leila S Ross; Eric Legrand; Frédéric Ariey; Clark H Cunningham; Issa M Souleymane; Adama Gansané; Romaric Nzoumbou-Boko; Claudette Ndayikunda; Abdunoor M Kabanywanyi; Aline Uwimana; Samuel J Smith; Olimatou Kolley; Mathieu Ndounga; Marian Warsame; Rithea Leang; François Nosten; Timothy Jc Anderson; Philip J Rosenthal; Didier Ménard; David A Fidock Journal: Elife Date: 2021-07-19 Impact factor: 8.140