4988492
doi
10.5061/dryad.230ps
oai:zenodo.org:4988492
user-dryad
Tiono, Alfred B.
Okebe, Joseph
Medical Research Council
Pett, Helmi
Coulibaly, Sam A.
Gonçalves, Bronner P.
Affara, Muna
Medical Research Council
Ouédraogo, Alphonse
Bougouma, Edith C.
Sanou, Guillaume S.
Nébié, Issa
Bradley, John
London School of Hygiene & Tropical Medicine
Lanke, Kjerstin H. W.
Radboud University Nijmegen
Niemi, Mikko
University of Helsinki
Sirima, Sodiomon B.
d'Alessandro, Umberto
Bousema, Teun
Radboud University Nijmegen
Drakeley, Chris
Bastiaens, Guido J. H.
Radboud University Nijmegen
Pett, Helmi E.
University of Helsinki
d'Alessandro, Umberto
Medical Research Council
Data from: Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males: two open-label, randomized, safety trials
Bastiaens, Guido
doi:10.1371/journal.pone.0190272
info:eu-repo/semantics/openAccess
Creative Commons Zero v1.0 Universal
https://creativecommons.org/publicdomain/zero/1.0/legalcode
Plasmodium falciparum
haemoglobin
primaquine
haemolysis
safety
gametocyte
reticulocytes
malaria
Background: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. Methods and findings: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0.25 (n = 20) or 0.40 mg/kg (n = 20) dosage; G6PD-normal males received AL plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. In The Gambia, G6PDd adult males and boys received DP alone (n = 10) or with 0.25 mg/kg PQ (n = 20); G6PD-normal males received DP plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. The primary study endpoint was change in hemoglobin concentration during the 28-day follow-up. Cytochrome P-450 isoenzyme 2D6 (CYP2D6) metabolizer status, gametocyte carriage, haptoglobin, lactate dehydrogenase levels and reticulocyte counts were also determined. In Burkina Faso, the mean maximum absolute change in hemoglobin was -2.13 g/dL (95% confidence interval [CI], -2.78, -1.49) in G6PDd individuals randomized to 0.25 PQ mg/kg and -2.29 g/dL (95% CI, -2.79, -1.79) in those receiving 0.40 PQ mg/kg. In The Gambia, the mean maximum absolute change in hemoglobin concentration was -1.83 g/dL (95% CI, -2.19, -1.47) in G6PDd individuals receiving 0.25 PQ mg/kg. After adjustment for baseline concentrations, hemoglobin reductions in G6PDd individuals in Burkina Faso were more pronounced compared to those in G6PD-normal individuals receiving the same PQ doses (P = 0.062 and P = 0.022, respectively). Hemoglobin levels normalized during follow-up. Abnormal haptoglobin and lactate dehydrogenase levels provided additional evidence of mild transient hemolysis post-PQ. Conclusions: Single low-dose PQ in combination with AL and DP was associated with mild and transient reductions in hemoglobin. None of the study participants developed moderate or severe anemia; there were no severe adverse events. This indicates that single low-dose PQ is safe in G6PDd African males when used with artemisinin-based combination therapy.
<div class="o-metadata__file-usage-entry">SAFEPRIM Burkina Faso Adverse Events<div class="o-metadata__file-description">Adverse events SAFEPRIM trial Burkina Faso</div><div class="o-metadata__file-name">DRYAD_SAFEPRIM Burkina Faso Adverse Events.xlsx<br></div></div><div class="o-metadata__file-usage-entry">SAFEPRIM Gambia Adverse Events<div class="o-metadata__file-description">Adverse events SAFEPRIM trial The Gambia</div><div class="o-metadata__file-name">DRYAD_SAFEPRIM Gambia Adverse Events.xlsx<br></div></div><div class="o-metadata__file-usage-entry">DRYAD SAFEPRIM main dataset Burkina Faso<div class="o-metadata__file-description">Laboratory results from clinical trial in Burkina Faso. Data include haemoglobin concentration, reticulocyte counts, full haematology and biochemistry.</div><div class="o-metadata__file-name"></div></div><div class="o-metadata__file-usage-entry">DRYAD SAFEPRIM main dataset The Gambia<div class="o-metadata__file-description">Laboratory results from clinical trial in The Gambia. Data include haemoglobin concentration, reticulocyte counts, full haematology and biochemistry.</div><div class="o-metadata__file-name"></div></div><p>Funding provided by: National Science Foundation<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000001<br>Award Number: BMGF OPP1034789</p>
Zenodo
2018-12-18
info:eu-repo/semantics/other
4988491
user-dryad
1653787306.538682
16923
md5:990ff03860ec1f00e5abc687521a40e9
https://zenodo.org/records/4988492/files/DRYAD_SAFEPRIM Gambia Adverse Events.xlsx
21686
md5:6af382f66aeea4078dadea0717d46d7e
https://zenodo.org/records/4988492/files/DRYAD_SAFEPRIM Burkina Faso Adverse Events.xlsx
131044
md5:777d0ebadeaf172e44f7017c786026ee
https://zenodo.org/records/4988492/files/DRYAD SAFEPRIM main dataset Burkina Faso.xlsx
47726
md5:ffe860c804a2a0197ceec8004b2e6158
https://zenodo.org/records/4988492/files/DRYAD SAFEPRIM main dataset The Gambia.xlsx
public
10.1371/journal.pone.0190272
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