PMID- 30909922 OWN - NLM STAT- MEDLINE DCOM- 20190426 LR - 20231006 IS - 1475-2875 (Electronic) IS - 1475-2875 (Linking) VI - 18 IP - 1 DP - 2019 Mar 25 TI - High cure rates and tolerability of artesunate-amodiaquine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Kibaha and Kigoma, Tanzania. PG - 99 LID - 10.1186/s12936-019-2740-z [doi] LID - 99 AB - BACKGROUND: The Tanzanian National Malaria Control Programme (NMCP) and its partners have been implementing regular therapeutic efficacy studies (TES) to monitor the performance of different drugs used or with potential use in Tanzania. However, most of the recent TES focused on artemether-lumefantrine, which is the first-line anti-malarial for the treatment of uncomplicated falciparum malaria. Data on the performance of other artemisinin-based combinations is urgently needed to support timely review and changes of treatment guidelines in case of drug resistance to the current regimen. This study was conducted at two NMCP sentinel sites (Kibaha, Pwani and Ujiji, Kigoma) to assess the efficacy and safety of artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DP), which are the current alternative artemisinin-based combinations in Tanzania. METHODS: This was a single-arm prospective evaluation of the clinical and parasitological responses of ASAQ and DP for directly observed treatment of uncomplicated falciparum malaria. Children aged 6 months to 10 years and meeting the inclusion criteria were enrolled and treated with either ASAQ or DP. In each site, patients were enrolled sequentially; thus, enrolment of patients for the assessment of one artemisinin-based combination was completed before patients were recruited for assessment of the second drugs. Follow-up was done for 28 or 42 days for ASAQ and DP, respectively. The primary outcome was PCR corrected cure rates while the secondary outcome was occurrence of adverse events (AEs) or serious adverse events (SAEs). RESULTS: Of the 724 patients screened at both sites, 333 (46.0%) were enrolled and 326 (97.9%) either completed the 28/42 days of follow-up, or attained any of the treatment outcomes. PCR uncorrected adequate clinical and parasitological response (ACPR) for DP on day 42 was 98.8% and 75.9% at Kibaha and Ujiji, respectively. After PCR correction, DP's ACPR was 100% at both sites. For ASAQ, no parasite recurrence occurred giving 100% ACPR on day 28. Only one patient in the DP arm (1.1%) from Ujiji had parasites on day 3. Of the patients recruited (n = 333), 175 (52.6%) had AEs with 223 episodes (at both sites) in the two treatment groups. There was no SAE and the commonly reported AE episodes (with > 5%) included, cough, running nose, abdominal pain, diarrhoea and fever. CONCLUSION: Both artemisinin-based combinations had high cure rates with PCR corrected ACPR of 100%. The two drugs had adequate safety with no SAE and all AEs were mild, and not associated with the anti-malarials. Continued TES is critical to monitor the performance of nationally recommended artemisinin-based combination therapy and supporting evidence-based review of malaria treatment policies. Trial registration This study is registered at ClinicalTrials.gov, No. NCT03431714. FAU - Mandara, Celine I AU - Mandara CI AUID- ORCID: 0000-0003-4317-4425 AD - National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania. drceline2010@gmail.com. AD - Kilimanjaro Christian Medical University College, Moshi, Tanzania. drceline2010@gmail.com. FAU - Francis, Filbert AU - Francis F AD - National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania. FAU - Chiduo, Mercy G AU - Chiduo MG AD - National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania. FAU - Ngasala, Billy AU - Ngasala B AD - Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. FAU - Mandike, Renata AU - Mandike R AD - National Malaria Control Programme, Dar es Salaam, Tanzania. FAU - Mkude, Sigsbert AU - Mkude S AD - National Malaria Control Programme, Dar es Salaam, Tanzania. FAU - Chacky, Frank AU - Chacky F AD - National Malaria Control Programme, Dar es Salaam, Tanzania. FAU - Molteni, Fabrizio AU - Molteni F AD - National Malaria Control Programme, Dar es Salaam, Tanzania. AD - Swiss Tropical and Public Health Institute, Dar es Salaam, Tanzania. FAU - Njau, Ritha AU - Njau R AD - World Health Organization Country Office, Dar es Salaam, Tanzania. FAU - Mohamed, Ally AU - Mohamed A AD - National Malaria Control Programme, Dar es Salaam, Tanzania. FAU - Warsame, Marian AU - Warsame M AD - Global Malaria Programme, World Health Organization, 20 Avenue Appia, 1211, Geneva 27, Switzerland. AD - Gothenburg University, Gothenburg, Sweden. FAU - Ishengoma, Deus S AU - Ishengoma DS AD - National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania. LA - eng SI - ClinicalTrials.gov/NCT03431714 GR - 001/WHO_/World Health Organization/International PT - Journal Article DEP - 20190325 PL - England TA - Malar J JT - Malaria journal JID - 101139802 RN - 0 (Antimalarials) RN - 0 (Artemisinins) RN - 0 (Drug Combinations) RN - 0 (Quinolines) RN - 0 (amodiaquine, artesunate drug combination) RN - 220236ED28 (Amodiaquine) RN - 6A9O50735X (artenimol) RN - A0HV2Q956Y (piperaquine) SB - IM MH - Amodiaquine/*therapeutic use MH - Antimalarials/*therapeutic use MH - Artemisinins/*therapeutic use MH - Child MH - Child, Preschool MH - Drug Combinations MH - Female MH - Humans MH - Infant MH - Malaria, Falciparum/*drug therapy MH - Male MH - Quinolines/*therapeutic use MH - Tanzania PMC - PMC6434871 OTO - NOTNLM OT - Artesunate-amodiaquine OT - Dihydroartemisinin-piperaquine OT - Efficacy OT - Plasmodium falciparum OT - Safety OT - Tanzania COIS- The authors declare that they have no competing interests. EDAT- 2019/03/27 06:00 MHDA- 2019/04/27 06:00 PMCR- 2019/03/25 CRDT- 2019/03/27 06:00 PHST- 2018/12/04 00:00 [received] PHST- 2019/03/20 00:00 [accepted] PHST- 2019/03/27 06:00 [entrez] PHST- 2019/03/27 06:00 [pubmed] PHST- 2019/04/27 06:00 [medline] PHST- 2019/03/25 00:00 [pmc-release] AID - 10.1186/s12936-019-2740-z [pii] AID - 2740 [pii] AID - 10.1186/s12936-019-2740-z [doi] PST - epublish SO - Malar J. 2019 Mar 25;18(1):99. doi: 10.1186/s12936-019-2740-z.