Browsing by Author "Gonahasa, Samuel"
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Item Efficacy and safety of artemether‑lumefantrine and dihydroartemisinin‑piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of molecular markers associated with artemisinin and partner drug resistance in Uganda(Malaria Journal, 2022) Ebong, Chris; Sserwanga, Asadu; Frances Namuganga, Jane; Kapisi, James; Mpimbaza, Arthur; Gonahasa, Samuel; Asua, Victor; Gudoi, Sam; Kigozi, Ruth; Tibenderana, James; Bwanika, John Bosco; Bosco, Agaba; Rubahika, Denis; Kyabayinze, Daniel; Opigo, Jimmy; Rutazana, Damian; Sebikaari, Gloria; Belay, Kassahun; Niang, Mame; Halsey, Eric S.; Moriarty, Leah F.; Lucchi, Naomi W.; Svigel Souza, Samaly S.; Nsobya, Sam L.; Kamya, Moses R.; Yeka, AdokeIn Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP) second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers of resistance in three sentinel sites in Uganda from 2018 to 2019. Methods: This was a randomized, open-label, phase IV clinical trial. Children aged 6 months to 10 years with uncomplicated falciparum malaria were randomly assigned to treatment with AL or DP and followed for 28 and 42 days, respectively. Genotyping was used to distinguish recrudescence from new infection, and a Bayesian algorithm was used to assign each treatment failure a posterior probability of recrudescence. For monitoring resistance, Pfk13 and Pfmdr1 genes were Sanger sequenced and plasmepsin-2 copy number was assessed by qPCR. Results: There were no early treatment failures. The uncorrected 28-day cumulative efficacy of AL ranged from 41.2 to 71.2% and the PCR-corrected cumulative 28-day efficacy of AL ranged from 87.2 to 94.4%. The uncorrected 28-day cumulative efficacy of DP ranged from 95.8 to 97.9% and the PCR-corrected cumulative 28-day efficacy of DP ranged from 98.9 to 100%. The uncorrected 42-day efficacy of DP ranged from 73.5 to 87.4% and the PCR-corrected 42-day efficacy of DP ranged from 92.1 to 97.5%. There were no reported serious adverse events associated with any of the regimens. No resistance-associated mutations in the Pfk13 gene were found in the successfully sequenced samples. In the AL arm, the NFD haplotype (N86Y, Y184F, D1246Y) was the predominant Pfmdr1 haplotype, present in 78 of 127 (61%) and 76 of 110 (69%) of the day 0 and day of failure samples, respectively. All the day 0 samples in the DP arm had one copy of the plasmepsin-2 gene. Conclusions: DP remains highly effective and safe for the treatment of uncomplicated malaria in Uganda. Recurrent infections with AL were common. In Busia and Arua, the 95% confidence interval for PCR-corrected AL efficacy fell below 90%. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended. Trial registration The trial was also registered with the Pan African Clinical Trial Registry (https:// pactr. samrc. ac. za/) with study Trial No. PACTR201811640750761.Item The impact of stopping and starting indoor residual spraying on malaria burden in Uganda(Nature communications, 2021) Namuganga, Jane F.; Epstein, Adrienne; Nankabirwa, Joaniter I.; Mpimbaza, Arthur; Kiggundu, Moses; Sserwanga, Asadu; Kapisi, James; Arinaitwe, Emmanuel; Gonahasa, Samuel; Opigo, Jimmy; Ebong, Chris; Staedke, Sarah G.; Shililu, Josephat; Okia, Michael; Rutazaana, Damian; Maiteki-Sebuguzi, Catherine; Belay, Kassahun; Kamya, Moses R.; Dorsey, Grant; Rodriguez-Barraquer, IsabelThe scale-up of malaria control efforts has led to marked reductions in malaria burden over the past twenty years, but progress has slowed. Implementation of indoor residual spraying (IRS) of insecticide, a proven vector control intervention, has been limited and difficult to sustain partly because questions remain on its added impact over widely accepted interventions such as bed nets. Using data from 14 enhanced surveillance health facilities in Uganda, a country with high bed net coverage yet high malaria burden, we estimate the impact of starting and stopping IRS on changes in malaria incidence. We show that stopping IRS was associated with a 5-fold increase in malaria incidence within 10 months, but reinstating IRS was associated with an over 5-fold decrease within 8 months. In areas where IRS was initiated and sustained, malaria incidence dropped by 85% after year 4. IRS could play a critical role in achieving global malaria targets, particularly in areas where progress has stalled.