Hemolytic Dynamics of Weekly Primaquine Antirelapse Therapy Among Cambodians With Acute Plasmodium vivax Malaria With or Without Glucose-6-Phosphate Dehydrogenase Deficiency.
Adolescent
Adult
Antimalarials
/ administration & dosage
Asian People
Chemoprevention
/ adverse effects
Child
Child, Preschool
Female
Glucosephosphate Dehydrogenase
Glucosephosphate Dehydrogenase Deficiency
Hemoglobins
/ analysis
Hemolysis
Humans
Malaria, Vivax
/ drug therapy
Male
Middle Aged
Primaquine
/ administration & dosage
Reticulocyte Count
Secondary Prevention
/ methods
Young Adult
Cambodia
Primaquine
glucose-6-phosphate dehydrogenase deficiency
hemoglobin E
malaria
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
22 10 2019
22 10 2019
Historique:
received:
14
05
2019
accepted:
18
06
2019
pubmed:
25
9
2019
medline:
20
5
2020
entrez:
25
9
2019
Statut:
ppublish
Résumé
Hemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (G6PD) deficient (G6PD-) patients treated weekly with the World Health Organization-recommended primaquine regimen (ie, 0.75 mg/kg/week for 8 weeks [PQ 0.75]). We treated Cambodians who had acute Plasmodium vivax infection with PQ0.75 and a 3-day course of dihydroartemisinin/piperaquine and determined the Hb level, reticulocyte count, G6PD genotype, and Hb type. Seventy-five patients (male sex, 63) aged 5-63 years (median, 24 years) were enrolled. Eighteen were G6PD deficient (including 17 with G6PD Viangchan) and 57 were not G6PD deficient; 26 had HbE (of whom 25 were heterozygous), and 6 had α-/β-thalassemia. Mean Hb concentrations at baseline (ie, day 0) were similar between G6PD deficient and G6PD normal patients (12.9 g/dL [range, 9‒16.3 g/dL] and 13.26 g/dL [range, 9.6‒16 g/dL], respectively; P = .46). G6PD deficiency (P = <.001), higher Hb concentration at baseline (P = <.001), higher parasitemia level at baseline (P = .02), and thalassemia (P = .027) influenced the initial decrease in Hb level, calculated as the nadir level minus the baseline level (range, -5.8-0 g/dL; mean, -1.88 g/dL). By day 14, the mean difference from the day 7 level (calculated as the day 14 level minus the day 7 level) was 0.03 g/dL (range, -0.25‒0.32 g/dL). Reticulocyte counts decreased from days 1 to 3, peaking on day 7 (in the G6PD normal group) and day 14 (in the G6PD deficient group); reticulocytemia at baseline (P = .001), G6PD deficiency (P = <.001), and female sex (P = .034) correlated with higher counts. One symptomatic, G6PD-deficient, anemic male patient was transfused on day 4. The first PQ0.75 exposure was associated with the greatest decrease in Hb level and 1 blood transfusion, followed by clinically insignificant decreases in Hb levels. PQ0.75 requires monitoring during the week after treatment. Safer antirelapse regimens are needed in Southeast Asia. ACTRN12613000003774.
Sections du résumé
BACKGROUND
Hemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (G6PD) deficient (G6PD-) patients treated weekly with the World Health Organization-recommended primaquine regimen (ie, 0.75 mg/kg/week for 8 weeks [PQ 0.75]).
METHODS
We treated Cambodians who had acute Plasmodium vivax infection with PQ0.75 and a 3-day course of dihydroartemisinin/piperaquine and determined the Hb level, reticulocyte count, G6PD genotype, and Hb type.
RESULTS
Seventy-five patients (male sex, 63) aged 5-63 years (median, 24 years) were enrolled. Eighteen were G6PD deficient (including 17 with G6PD Viangchan) and 57 were not G6PD deficient; 26 had HbE (of whom 25 were heterozygous), and 6 had α-/β-thalassemia. Mean Hb concentrations at baseline (ie, day 0) were similar between G6PD deficient and G6PD normal patients (12.9 g/dL [range, 9‒16.3 g/dL] and 13.26 g/dL [range, 9.6‒16 g/dL], respectively; P = .46). G6PD deficiency (P = <.001), higher Hb concentration at baseline (P = <.001), higher parasitemia level at baseline (P = .02), and thalassemia (P = .027) influenced the initial decrease in Hb level, calculated as the nadir level minus the baseline level (range, -5.8-0 g/dL; mean, -1.88 g/dL). By day 14, the mean difference from the day 7 level (calculated as the day 14 level minus the day 7 level) was 0.03 g/dL (range, -0.25‒0.32 g/dL). Reticulocyte counts decreased from days 1 to 3, peaking on day 7 (in the G6PD normal group) and day 14 (in the G6PD deficient group); reticulocytemia at baseline (P = .001), G6PD deficiency (P = <.001), and female sex (P = .034) correlated with higher counts. One symptomatic, G6PD-deficient, anemic male patient was transfused on day 4.
CONCLUSIONS
The first PQ0.75 exposure was associated with the greatest decrease in Hb level and 1 blood transfusion, followed by clinically insignificant decreases in Hb levels. PQ0.75 requires monitoring during the week after treatment. Safer antirelapse regimens are needed in Southeast Asia.
CLINICAL TRIALS REGISTRATION
ACTRN12613000003774.
Identifiants
pubmed: 31549159
pii: 5573052
doi: 10.1093/infdis/jiz313
pmc: PMC6804333
doi:
Substances chimiques
Antimalarials
0
Hemoglobins
0
G6PD protein, human
EC 1.1.1.49
Glucosephosphate Dehydrogenase
EC 1.1.1.49
Primaquine
MVR3634GX1
Banques de données
ANZCTR
['ACTRN12613000003774']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1750-1760Subventions
Organisme : World Health Organization
ID : 001
Pays : International
Organisme : Wellcome Trust
ID : B9RJIXO
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Malar J. 2019 Jan 30;18(1):30
pubmed: 30700282
Br J Haematol. 1997 Apr;97(1):169-74
pubmed: 9136961
J Lab Clin Med. 1975 Apr;85(4):531-9
pubmed: 1120926
Lancet. 2007 Mar 3;369(9563):757-765
pubmed: 17336652
West J Med. 1982 Sep;137(3):186-90
pubmed: 7147932
Bull World Health Organ. 1981;59(3):391-5
pubmed: 6976846
Malar J. 2011 Oct 11;10:297
pubmed: 21989376
PLoS One. 2018 Jan 11;13(1):e0190272
pubmed: 29324864
Malar J. 2010 Dec 27;9:376
pubmed: 21184691
J Lab Clin Med. 1954 Sep;44(3):439-42
pubmed: 13201853
Elife. 2017 Feb 04;6:
pubmed: 28155819
J Lab Clin Med. 1967 Jul;70(1):80-93
pubmed: 6027097
Br J Haematol. 1988 Sep;70(1):99-103
pubmed: 3179231
Southeast Asian J Trop Med Public Health. 2010 Sep;41(5):1035-41
pubmed: 21073022
Mediterr J Hematol Infect Dis. 2016 Aug 20;8(1):e2016038
pubmed: 27648201
Malar J. 2013 May 28;12:171
pubmed: 23714236
Bull World Health Organ. 1960;22:621-31
pubmed: 13793053
Transfus Med Hemother. 2012 Oct;39(5):328-34
pubmed: 23801924
Am J Trop Med Hyg. 1996 Sep;55(3):243-9
pubmed: 8842108
PLoS One. 2011;6(12):e28357
pubmed: 22164279
Eur J Pediatr. 2009 Jul;168(7):779-82
pubmed: 19263080
Nephron Clin Pract. 2012;120(4):c179-84
pubmed: 22890468
Ann Trop Paediatr. 1993;13(4):391-4
pubmed: 7506889
Malar J. 2012 Apr 27;11:135
pubmed: 22540175
BMC Med. 2014 Nov 18;12:217
pubmed: 25406857
Hemoglobin. 2004 Aug;28(3):197-204
pubmed: 15481886
Clin Nephrol. 2014 Mar;81(3):203-9
pubmed: 23006341
J Pharmacol Exp Ther. 2004 Apr;309(1):79-85
pubmed: 14724225
Am J Trop Med Hyg. 2001 Nov;65(5):614-22
pubmed: 11716124
PLoS Pathog. 2015 Jan 08;11(1):e1004558
pubmed: 25569250
Malar J. 2013 Jun 19;12:209
pubmed: 23777546
J Infect Dis. 2012 Dec 1;206(11):1771-80
pubmed: 22966124
N Engl J Med. 2004 Feb 5;350(6):552-9
pubmed: 14762182
Ann Intern Med. 1946 Jul;25:103-12
pubmed: 20991220
BMC Med. 2015 Aug 25;13:203
pubmed: 26303162
J Infect Dis. 2016 Nov 15;214(10):1557-1564
pubmed: 27630198
PLoS Med. 2008 Jun 17;5(6):e127
pubmed: 18563961
Blood. 2006 Oct 15;108(8):2569-77
pubmed: 16804108
Antimicrob Agents Chemother. 2013 Mar;57(3):1128-35
pubmed: 23254437
PLoS Negl Trop Dis. 2015 Mar 17;9(3):e0003595
pubmed: 25780913
Blood. 1989 Nov 1;74(6):2194-202
pubmed: 2804358
Clin Infect Dis. 2001 Dec 15;33(12):1968-74
pubmed: 11700577
Am J Trop Med Hyg. 2003 Apr;68(4):410-2
pubmed: 12875288