Therapeutic efficacy of dihydroartemisinin-piperaquine combination for the treatment of uncomplicated malaria in Ghana

In 2020, Dihydroartemisinin-Piperaquine (DHAP) was adopted as a second-line antimalarial for treatment of uncomplicated malaria in Ghana following a review of the country’s antimalarial medicines policy. Available data obtained in 2007 had shown PCR-uncorrected therapeutic efficacy of 93.3% using a 28-day follow-up schedule. In 2020, the standard 42-day follow-up schedule for DHAP was used to estimate efficacy levels among febrile children aged 6 months to 9 years in three malaria sentinel sites representing the three main ecological zones of the country- savannah, forest, and coastal. PCR genotyping distinguished between recrudescence and re-infection using merozoite surface protein 2 (MSP2)-specific primers for FC27 and 3D7 strains. Per protocol analyses showed day 28 efficacy of 100% in all three sentinel sites with day 42 PCR-corrected efficacy ranging between 90.3% (95% CI: 80.1 – 96.4%) in the savannah zone and 100% in the forest and coastal zones, yielding a national average of 97.0% (95% CI: 93.4 – 98.8). No day 3 parasitemia was observed in all three sites. Prevalence of measured fever (axillary temperature ≥ 37.5°C) declined from 50.0 - 98.8% on day 0 to 7.1-11.5% on day 1 whilst parasitemia declined from 100% on day 0 to 1.2 - 2.3% on day 1. Mean haemoglobin levels on days 28 and 42 were significantly higher than pre-treatment levels in all three sites. We conclude that DHAP is highly efficacious in the treatment of uncomplicated malaria in Ghana. This data will serve as baseline for subsequent DHAP efficacy studies in the country.

[1]  K. Otieno,et al.  Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria among Children in Western Kenya, 2016 to 2017 , 2022, Antimicrobial agents and chemotherapy.

[2]  Vito Baraka,et al.  Therapeutic efficacy of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in Sub-Saharan Africa: A systematic review and meta-analysis , 2022, PloS one.

[3]  A. Ghansah,et al.  Trends and predictive factors for treatment failure following artemisinin-based combination therapy among children with uncomplicated malaria in Ghana: 2005–2018 , 2021, BMC Infectious Diseases.

[4]  M. Kamya,et al.  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 , 2021, Malaria Journal.

[5]  E. Makonnen,et al.  Efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials , 2021, Malaria journal.

[6]  C. Karema,et al.  The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data , 2020, BMC Medicine.

[7]  N. Khim,et al.  High therapeutic efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated falciparum malaria in Somalia , 2019, Malaria Journal.

[8]  L. Quaye,et al.  Therapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine combinations for uncomplicated malaria in 10 sentinel sites across Ghana: 2015–2017 , 2019, Malaria Journal.

[9]  M. Nisingizwe,et al.  Efficacy of artemether-lumefantrine versus dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria among children in Rwanda: an open-label, randomized controlled trial. , 2019, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[10]  O. Doumbo,et al.  A randomized trial of dihydroartemisinin–piperaquine versus artemether–lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali , 2018, Malaria Journal.

[11]  D. Ménard,et al.  Efficacy of artemisinin-based combination therapies and prevalence of molecular markers associated with artemisinin, piperaquine and sulfadoxine-pyrimethamine resistance in Sierra Leone , 2018, Acta tropica.

[12]  D. Ménard,et al.  Efficacy of artesunate–amodiaquine in the treatment of falciparum uncomplicated malaria in Madagascar , 2018, Malaria Journal.

[13]  M. Lemnge,et al.  High efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated falciparum malaria in Muheza and Kigoma Districts, Tanzania , 2018, Malaria Journal.

[14]  C. Happi,et al.  Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria in Under-Five-Year-Old Nigerian Children Ten Years Following Adoption as First-Line Antimalarials. , 2018, The American journal of tropical medicine and hygiene.

[15]  P. Sawa,et al.  Pyronaridine–artesunate and artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a randomized controlled non-inferiority trial , 2018, Malaria Journal.

[16]  A. Ghansah,et al.  Efficacy of Artesunate/Amodiaquine in the Treatment of Uncomplicated Malaria among Children in Ghana. , 2017, The American journal of tropical medicine and hygiene.

[17]  P. Kofoed,et al.  Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau – An Open-Label Non-Inferiority Randomised Clinical Trial , 2016, PloS one.

[18]  N. Duah,et al.  Genetic diversity of Plasmodium falciparum isolates from uncomplicated malaria cases in Ghana over a decade , 2016, Parasites & Vectors.

[19]  L. Quaye,et al.  Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana , 2016, Malaria Journal.

[20]  N. Day,et al.  Randomized Comparison of the Efficacies and Tolerabilities of Three Artemisinin-Based Combination Treatments for Children with Acute Plasmodium falciparum Malaria in the Democratic Republic of the Congo , 2014, Antimicrobial Agents and Chemotherapy.

[21]  E. Purssell,et al.  Does the Use of Dihydroartemisinin-Piperaquine in Treating Patients with Uncomplicated falciparum Malaria Reduce the Risk for Recurrent New falciparum Infection More Than Artemether-Lumefantrine? , 2014, Malaria research and treatment.

[22]  S. Donegan,et al.  Dihydroartemisinin‐piperaquine for treating uncomplicated Plasmodium falciparum malaria , 2014, The Cochrane database of systematic reviews.

[23]  R. Price,et al.  Artemisinin combination therapy for malaria: beyond good efficacy. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[24]  L. Quaye,et al.  Efficacy of amodiaquine/artesunate combination therapy for uncomplicated malaria in children under five years in ghana. , 2008, Ghana medical journal.

[25]  H. Myint,et al.  Efficacy and safety of dihydroartemisinin-piperaquine. , 2007, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[26]  P. Rosenthal,et al.  Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial , 2007, PLoS clinical trials.

[27]  C. Karema,et al.  Safety and efficacy of dihydroartemisinin/piperaquine (Artekin) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan children. , 2006, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[28]  L. Quaye,et al.  Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana , 2012, Malaria Journal.

[29]  Organización Mundial de la Salud Guidelines for the treatment of malaria , 2010 .