Background: In a recent trial of intermittent preventive treatment in pregnancy (IPTp) in Uganda, dihydroartemisinin-piperaquine (DP) was superior to sulfadoxine-pyrimethamine (SP) in preventing maternal and placental malaria. Methods: We compared genotypes using sequencing, fluorescent microsphere, and quantitative polymerase chain reaction assays at loci associated with drug resistance in Plasmodium falciparum isolated from subjects receiving DP or SP. Results: Considering aminoquinoline resistance, DP was associated with increased prevalences of mutations at pfmdr1 N86Y, pfmdr1 Y184F, and pfcrt K76T compared to SP (64.6% vs 27.4%, P < .001; 93.9% vs 59.2%, P < .001; and 87.7% vs 75.4%, P = .03, respectively). Increasing plasma piperaquine concentration at the time of parasitemia was associated with increasing pfmdr1 86Y prevalence; no infections with the N86 genotype occurred with piperaquine >2.75 ng/mL. pfkelch13 propeller domain polymorphisms previously associated with artemisinin resistance were not identified. Recently identified markers of piperaquine resistance were uncommon and not associated with DP. Considering antifolate resistance, SP was associated with increased prevalence of a 5-mutation haplotype (pfdhfr 51I, 59R, and 108N; pfdhps 437G and 581G) compared to DP (90.8% vs 60.0%, P = .001). Conclusions: IPTp selected for genotypes associated with decreased sensitivity to treatment regimens, but genotypes associated with clinically relevant DP resistance in Asia have not emerged in Uganda.
Background: In a recent trial of intermittent preventive treatment in pregnancy (IPTp) in Uganda, dihydroartemisinin-piperaquine (DP) was superior to sulfadoxine-pyrimethamine (SP) in preventing maternal and placental malaria. Methods: We compared genotypes using sequencing, fluorescent microsphere, and quantitative polymerase chain reaction assays at loci associated with drug resistance in Plasmodium falciparum isolated from subjects receiving DP or SP. Results: Considering aminoquinoline resistance, DP was associated with increased prevalences of mutations at pfmdr1 N86Y, pfmdr1 Y184F, and pfcrt K76T compared to SP (64.6% vs 27.4%, P < .001; 93.9% vs 59.2%, P < .001; and 87.7% vs 75.4%, P = .03, respectively). Increasing plasma piperaquine concentration at the time of parasitemia was associated with increasing pfmdr1 86Y prevalence; no infections with the N86 genotype occurred with piperaquine >2.75 ng/mL. pfkelch13 propeller domain polymorphisms previously associated with artemisinin resistance were not identified. Recently identified markers of piperaquine resistance were uncommon and not associated with DP. Considering antifolate resistance, SP was associated with increased prevalence of a 5-mutation haplotype (pfdhfr 51I, 59R, and 108N; pfdhps 437G and 581G) compared to DP (90.8% vs 60.0%, P = .001). Conclusions: IPTp selected for genotypes associated with decreased sensitivity to treatment regimens, but genotypes associated with clinically relevant DP resistance in Asia have not emerged in Uganda.
Authors: Samuel L Nsobya; Christian Dokomajilar; Moses Joloba; Grant Dorsey; Philip J Rosenthal Journal: Antimicrob Agents Chemother Date: 2007-06-11 Impact factor: 5.191
Authors: Patrick Tumwebaze; Stephen Tukwasibwe; Aimee Taylor; Melissa Conrad; Emmanuel Ruhamyankaka; Victor Asua; Andrew Walakira; Joaniter Nankabirwa; Adoke Yeka; Sarah G Staedke; Bryan Greenhouse; Samuel L Nsobya; Moses R Kamya; Grant Dorsey; Philip J Rosenthal Journal: J Infect Dis Date: 2017-02-15 Impact factor: 5.226
Authors: Roland A Cooper; Melissa D Conrad; Quentin D Watson; Stephanie J Huezo; Harriet Ninsiima; Patrick Tumwebaze; Samuel L Nsobya; Philip J Rosenthal Journal: Antimicrob Agents Chemother Date: 2015-06-01 Impact factor: 5.191
Authors: Fredrick L Eyase; Hoseah M Akala; Luiser Ingasia; Agnes Cheruiyot; Angela Omondi; Charles Okudo; Dennis Juma; Redemptah Yeda; Ben Andagalu; Elizabeth Wanja; Edwin Kamau; David Schnabel; Wallace Bulimo; Norman C Waters; Douglas S Walsh; Jacob D Johnson Journal: PLoS One Date: 2013-05-13 Impact factor: 3.240
Authors: Erika Wallender; Nan Zhang; Melissa Conrad; Abel Kakuru; Mary Muhindo; Patrick Tumwebaze; Richard Kajubi; Daniel Mota; Jennifer Legac; Prasanna Jagannathan; Diane Havlir; Moses Kamya; Grant Dorsey; Francesca Aweeka; Philip J Rosenthal; Rada M Savic Journal: Antimicrob Agents Chemother Date: 2019-01-29 Impact factor: 5.191
Authors: Emma Hughes; Erika Wallender; Richard Kajubi; Prasanna Jagannathan; Teddy Ochieng; Abel Kakuru; Moses R Kamya; Tamara D Clark; Philip J Rosenthal; Grant Dorsey; Francesca Aweeka; Radojka M Savic Journal: Clin Infect Dis Date: 2022-08-31 Impact factor: 20.999
Authors: Michelle E Roh; Feiko O Ter Kuile; Francois Rerolle; M Maria Glymour; Stephen Shiboski; Roly Gosling; Julie Gutman; Abel Kakuru; Meghna Desai; Richard Kajubi; Anne L'Ianziva; Moses R Kamya; Grant Dorsey; R Matthew Chico Journal: Lancet Glob Health Date: 2020-07 Impact factor: 26.763
Authors: Mahamadou A Thera; Abdoulaye K Kone; Bourama Tangara; Elizabeth Diarra; Sirama Niare; Abdramane Dembele; Mahamadou S Sissoko; Ogobara K Doumbo Journal: Parasite Epidemiol Control Date: 2018-02-07
Authors: Patience Nayebare; Victor Asua; Melissa D Conrad; Richard Kajubi; Abel Kakuru; Joaniter I Nankabirwa; Dennis Muhanguzi; Grant Dorsey; Moses R Kamya; Sam Nsobya; Philip J Rosenthal Journal: Antimicrob Agents Chemother Date: 2020-11-17 Impact factor: 5.938