PMID- 26599634 OWN - NLM STAT- MEDLINE DCOM- 20160623 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 11 DP - 2015 TI - Risks of Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficient Infants Exposed to Chlorproguanil-Dapsone, Mefloquine and Sulfadoxine-Pyrimethamine as Part of Intermittent Presumptive Treatment of Malaria in Infants. PG - e0142414 LID - 10.1371/journal.pone.0142414 [doi] LID - e0142414 AB - BACKGROUND: Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi) antimalarial regimens. We sought to examine the joint effects of G6PD status and IPTi antimalarial treatment on incidence of hemolysis in asymptomatic children treated with CD, sulfadoxine-pyrimethamine (SP), and mefloquine (MQ). METHODS: A secondary analysis of data from a double-blind, placebo-controlled trial of IPTi was conducted. Hemoglobin (Hb) measurements were made at IPTi doses, regular follow-up and emergency visits. G6PD genotype was determined at 9 months looking for SNPs for the A- genotype at coding position 202. Multivariable linear and logistic regression models were used to examine hemolysis among children with valid G6PD genotyping results. Hemolysis was defined as the absolute change in Hb or as any post-dose Hb <8 g/dL. These outcomes were assessed using either a single follow-up Hb on day 7 after an IPTi dose or Hb obtained 1 to 14 or 28 days after each IPTi dose. FINDINGS: Relative to placebo, CD reduced Hb by approximately 0.5 g/dL at day 7 and within 14 days of an IPTi dose, and by 0.2 g/dL within 28 days. Adjusted declines in the CD group were larger than in the MQ and SP groups. At day 7, homo-/hemizygous genotype was associated with higher odds of Hb <8 g/dL (adjusted odds ratio = 6.7, 95% CI 1.7 to 27.0) and greater absolute reductions in Hb (-0.6 g/dL, 95% CI -1.1 to 0.003). There was no evidence to suggest increased reductions in Hb among homo-/hemizygous children treated with CD compared to placebo, SP or MQ. CONCLUSIONS: While treatment with CD demonstrated greater reductions in Hb at 7 and 14 days after an IPTi dose compared to both SP and MQ, there was no evidence that G6PD deficiency exacerbated the adverse effects of CD, despite evidence for higher hemolysis risk among G6PDd infants. FAU - Poirot, Eugenie AU - Poirot E AD - Global Health Group, University of California San Francisco, San Francisco, California, United States of America. AD - Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America. FAU - Vittinghoff, Eric AU - Vittinghoff E AD - Global Health Group, University of California San Francisco, San Francisco, California, United States of America. FAU - Ishengoma, Deus AU - Ishengoma D AD - Tanga Medical Research Centre, National Institute for Medical Research, Tanga, United Republic of Tanzania. FAU - Alifrangis, Michael AU - Alifrangis M AD - Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. AD - Department of Infectious Diseases, National University Hospital (Rigshospitalet), Copenhagen, Denmark. FAU - Carneiro, Ilona AU - Carneiro I AD - Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. FAU - Hashim, Ramadhan AU - Hashim R AD - Mwanza Interventions Trial Unit, National Institute for Medical Research, Mwanza, United Republic of Tanzania. FAU - Baraka, Vito AU - Baraka V AD - Tanga Medical Research Centre, National Institute for Medical Research, Tanga, United Republic of Tanzania. AD - International Health Unit, Department of Epidemiology, University of Antwerp, Antwerp, Belgium. FAU - Mosha, Jacklin AU - Mosha J AD - Mwanza Interventions Trial Unit, National Institute for Medical Research, Mwanza, United Republic of Tanzania. FAU - Gesase, Samwel AU - Gesase S AD - Tanga Medical Research Centre, National Institute for Medical Research, Tanga, United Republic of Tanzania. FAU - Chandramohan, Daniel AU - Chandramohan D AD - Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. FAU - Gosling, Roland AU - Gosling R AD - Global Health Group, University of California San Francisco, San Francisco, California, United States of America. AD - Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20151123 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antimalarials) RN - 0 (Drug Combinations) RN - 0 (Hemoglobins) RN - 0 (chloroguanil, dapsone drug combination) RN - 37338-39-9 (fanasil, pyrimethamine drug combination) RN - 88463U4SM5 (Sulfadoxine) RN - 8W5C518302 (Dapsone) RN - EC 1.1.1.49 (Glucosephosphate Dehydrogenase) RN - S61K3P7B2V (Proguanil) RN - TML814419R (Mefloquine) RN - Z3614QOX8W (Pyrimethamine) SB - IM MH - Antimalarials/administration & dosage/therapeutic use MH - Cohort Studies MH - Dapsone/*administration & dosage/adverse effects/therapeutic use MH - Double-Blind Method MH - Drug Combinations MH - Female MH - Genotype MH - Glucosephosphate Dehydrogenase/genetics MH - Glucosephosphate Dehydrogenase Deficiency/*genetics/metabolism MH - Hemoglobins/analysis MH - Hemolysis/*drug effects MH - Humans MH - Infant MH - Logistic Models MH - Malaria/*drug therapy/prevention & control MH - Male MH - Mefloquine/*administration & dosage/therapeutic use MH - Multivariate Analysis MH - Odds Ratio MH - Poisson Distribution MH - Polymorphism, Single Nucleotide MH - Proguanil/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use MH - Pyrimethamine/*administration & dosage/therapeutic use MH - Sulfadoxine/*administration & dosage/therapeutic use MH - Tanzania PMC - PMC4658078 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/11/26 06:00 MHDA- 2016/06/24 06:00 PMCR- 2015/11/23 CRDT- 2015/11/25 06:00 PHST- 2015/06/18 00:00 [received] PHST- 2015/10/20 00:00 [accepted] PHST- 2015/11/25 06:00 [entrez] PHST- 2015/11/26 06:00 [pubmed] PHST- 2016/06/24 06:00 [medline] PHST- 2015/11/23 00:00 [pmc-release] AID - PONE-D-15-26775 [pii] AID - 10.1371/journal.pone.0142414 [doi] PST - epublish SO - PLoS One. 2015 Nov 23;10(11):e0142414. doi: 10.1371/journal.pone.0142414. eCollection 2015.