PMID- 27287612 OWN - NLM STAT- MEDLINE DCOM- 20170608 LR - 20231111 IS - 1475-2875 (Electronic) IS - 1475-2875 (Linking) VI - 15 DP - 2016 Jun 10 TI - Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. PG - 316 LID - 10.1186/s12936-016-1341-3 [doi] LID - 316 AB - BACKGROUND: This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. METHODS: Men and non-pregnant, non-lactating women aged >/=1 year with uncomplicated P. falciparum malaria were enrolled and randomized to either standard artemether-lumefantrine (AL) regimen alone or with a 0.25 mg/kg single-dose of PQ. PQ was administered concomitantly with the first AL dose. All drug doses were supervised. Safety was evaluated between days 0 and 28. G6PD status was assessed using rapid test (CareStart) and molecular genotyping. The primary endpoint was mean percentage relative reduction in haemoglobin (Hb) concentration (g/dL) between days 0 and 7 by genotypic G6PD status and treatment arm. RESULTS: Overall, 220 patients, 110 per treatment arm, were enrolled, of whom 33/217 (15.2 %) were phenotypically G6PD deficient, whereas 15/110 (13.6 %) were genotypically hemizygous males, 5/110 (4.5 %) homozygous females and 22/110 (20 %) heterozygous females. Compared to genotypically G6PD wild-type/normal [6.8, 95 % confidence interval (CI) 4.67-8.96], only heterozygous patients in AL arm had significant reduction in day-7 mean relative Hb concentration (14.3, 95 % CI 7.02-21.55, p=0.045), however, none fulfilled the pre-defined haemolytic threshold value of >/=25 % Hb reduction. After adjustment for baseline parasitaemia, Hb, age and sex the mean relative Hb reduction was not statistically significant in both heterozygous and hemizygous/homozygous patients in both arms. A majority of the adverse events (AEs) were mild and unrelated to the study drugs. However, six (4.4 %) episodes, three per treatment arm, of acute haemolytic anaemia occurred between days 0 and 7. Three occurred in phenotypically G6PD deficient patients, two in AL and one in AL + PQ arm, but none in genotypically hemizygous/homozygous patients. All patients with acute haemolytic anaemia recovered without medical intervention. CONCLUSION: The findings support that the WHO recommendation of adding a single low-dose of PQ to standard AL regimen is safe for the treatment of acute uncomplicated P. falciparum malaria regardless of G6PD status in Tanzania. Trial registration number NCT02090036. FAU - Mwaiswelo, Richard AU - Mwaiswelo R AD - Department of Parasitology and Medical Entomology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. FAU - Ngasala, Billy E AU - Ngasala BE AD - Department of Parasitology and Medical Entomology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. bngasala@muhas.ac.tz. FAU - Jovel, Irina AU - Jovel I AD - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. FAU - Gosling, Roland AU - Gosling R AD - Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA. AD - Global Health Group, University of California San Francisco, San Francisco, CA, USA. FAU - Premji, Zul AU - Premji Z AD - Aga Khan University Hospital, Nairobi, Kenya. FAU - Poirot, Eugenie AU - Poirot E AD - Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA. AD - Global Health Group, University of California San Francisco, San Francisco, CA, USA. FAU - Mmbando, Bruno P AU - Mmbando BP AD - National Institute for Medical Research, Tanga Centre, Tanga, Tanzania. FAU - Bjorkman, Anders AU - Bjorkman A AD - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. FAU - Martensson, Andreas AU - Martensson A AD - Department of Women's and Children's Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden. LA - eng SI - ClinicalTrials.gov/NCT02090036 PT - Journal Article PT - Randomized Controlled Trial DEP - 20160610 PL - England TA - Malar J JT - Malaria journal JID - 101139802 RN - 0 (Antimalarials) RN - 0 (Artemether, Lumefantrine Drug Combination) RN - 0 (Artemisinins) RN - 0 (Drug Combinations) RN - 0 (Ethanolamines) RN - 0 (Fluorenes) RN - 0 (Hemoglobins) RN - EC 1.1.1.49 (Glucosephosphate Dehydrogenase) RN - MVR3634GX1 (Primaquine) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Antimalarials/administration & dosage/*adverse effects MH - Artemether, Lumefantrine Drug Combination MH - Artemisinins/administration & dosage/*adverse effects MH - Child MH - Child, Preschool MH - Drug Combinations MH - Drug-Related Side Effects and Adverse Reactions/*epidemiology/pathology MH - Ethanolamines/administration & dosage/*adverse effects MH - Female MH - Fluorenes/administration & dosage/*adverse effects MH - Genotyping Techniques MH - Glucosephosphate Dehydrogenase/genetics MH - Hemoglobins/*analysis MH - Humans MH - Infant MH - Malaria, Falciparum/*drug therapy MH - Male MH - Middle Aged MH - Primaquine/administration & dosage/*adverse effects MH - Single-Blind Method MH - Tanzania MH - Young Adult PMC - PMC4901409 OTO - NOTNLM OT - Anaemia OT - Glucose-6-phosphate dehydrogenase OT - Plasmodium falciparum malaria OT - Primaquine EDAT- 2016/06/12 06:00 MHDA- 2017/06/09 06:00 PMCR- 2016/06/10 CRDT- 2016/06/12 06:00 PHST- 2016/04/27 00:00 [received] PHST- 2016/05/11 00:00 [accepted] PHST- 2016/06/12 06:00 [entrez] PHST- 2016/06/12 06:00 [pubmed] PHST- 2017/06/09 06:00 [medline] PHST- 2016/06/10 00:00 [pmc-release] AID - 10.1186/s12936-016-1341-3 [pii] AID - 1341 [pii] AID - 10.1186/s12936-016-1341-3 [doi] PST - epublish SO - Malar J. 2016 Jun 10;15:316. doi: 10.1186/s12936-016-1341-3.