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The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia

The widespread use of primaquine (PQ) radical cure for P. vivax, is constrained by concerns over its safety. We used routinely collected patient data to compare the overall morbidity and mortality in patients treated with and without PQ without prior testing of Glucose-6-Phosphate-Dehydrogenase (G6P...

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Autores principales: Thriemer, Kamala, Poespoprodjo, Jeanne-Rini, Kenangalem, Enny, Douglas, Nicholas M., Sugiarto, Paulus, Anstey, Nicholas M., Simpson, Julie Anne, Price, Ric N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657498/
https://www.ncbi.nlm.nih.gov/pubmed/33175835
http://dx.doi.org/10.1371/journal.pntd.0008838
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author Thriemer, Kamala
Poespoprodjo, Jeanne-Rini
Kenangalem, Enny
Douglas, Nicholas M.
Sugiarto, Paulus
Anstey, Nicholas M.
Simpson, Julie Anne
Price, Ric N.
author_facet Thriemer, Kamala
Poespoprodjo, Jeanne-Rini
Kenangalem, Enny
Douglas, Nicholas M.
Sugiarto, Paulus
Anstey, Nicholas M.
Simpson, Julie Anne
Price, Ric N.
author_sort Thriemer, Kamala
collection PubMed
description The widespread use of primaquine (PQ) radical cure for P. vivax, is constrained by concerns over its safety. We used routinely collected patient data to compare the overall morbidity and mortality in patients treated with and without PQ without prior testing of Glucose-6-Phosphate-Dehydrogenase (G6PD) deficiency in Papua, Indonesia, where there is a low prevalence of G6PD deficiency. Records were collated from patients older than 1 year, with P. vivax infection, who were treated with an artemisinin combination therapy (ACT). The risks of re-presentation, hospitalization, major fall in haemoglobin and death within 30 days were quantified and compared between patients treated with and without PQ using a Cox regression model. In total 26,216 patients with P. vivax malaria presented to the hospital with malaria during the study period. Overall 27.56% (95% Confidence Interval (95%CI): 26.96–28.16) of 21,344 patients treated with PQ re-presented with any illness within 30 days and 1.69% (1.51–1.88) required admission to hospital. The corresponding risks were higher in the 4,872 patients not treated with PQ; Adjusted Hazard Ratio (AHR) = 0.84 (0.79–0.91; p<0.001) and 0.54 (0.41–0.70; p<0.001) respectively. By day 30, 14.15% (12.45–16.05) of patients who had received PQ had a fall in haemoglobin (Hb) below 7g/dl compared to 20.43% (16.67–24.89) of patients treated without PQ; AHR = 0.66 (0.45–0.97; p = 0.033). A total of 75 (0.3%) patients died within 30 days of treatment with a mortality risk of 0.27% (0.21–0.35) in patients treated with PQ, compared to 0.38% (0.24–0.60) without PQ; AHR = 0.79 (0.43–1.45; p = 0.448). In Papua, Indonesia routine administration of PQ radical cure without prior G6PD testing, was associated with lower risk of all cause hospitalization and other serious adverse clinical outcomes. In areas where G6PD testing is not available or cannot be delivered reliably, the risks of drug induced haemolysis should be balanced against the potential benefits of reducing recurrent P. vivax malaria and its associated morbidity and mortality.
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spelling pubmed-76574982020-11-18 The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia Thriemer, Kamala Poespoprodjo, Jeanne-Rini Kenangalem, Enny Douglas, Nicholas M. Sugiarto, Paulus Anstey, Nicholas M. Simpson, Julie Anne Price, Ric N. PLoS Negl Trop Dis Research Article The widespread use of primaquine (PQ) radical cure for P. vivax, is constrained by concerns over its safety. We used routinely collected patient data to compare the overall morbidity and mortality in patients treated with and without PQ without prior testing of Glucose-6-Phosphate-Dehydrogenase (G6PD) deficiency in Papua, Indonesia, where there is a low prevalence of G6PD deficiency. Records were collated from patients older than 1 year, with P. vivax infection, who were treated with an artemisinin combination therapy (ACT). The risks of re-presentation, hospitalization, major fall in haemoglobin and death within 30 days were quantified and compared between patients treated with and without PQ using a Cox regression model. In total 26,216 patients with P. vivax malaria presented to the hospital with malaria during the study period. Overall 27.56% (95% Confidence Interval (95%CI): 26.96–28.16) of 21,344 patients treated with PQ re-presented with any illness within 30 days and 1.69% (1.51–1.88) required admission to hospital. The corresponding risks were higher in the 4,872 patients not treated with PQ; Adjusted Hazard Ratio (AHR) = 0.84 (0.79–0.91; p<0.001) and 0.54 (0.41–0.70; p<0.001) respectively. By day 30, 14.15% (12.45–16.05) of patients who had received PQ had a fall in haemoglobin (Hb) below 7g/dl compared to 20.43% (16.67–24.89) of patients treated without PQ; AHR = 0.66 (0.45–0.97; p = 0.033). A total of 75 (0.3%) patients died within 30 days of treatment with a mortality risk of 0.27% (0.21–0.35) in patients treated with PQ, compared to 0.38% (0.24–0.60) without PQ; AHR = 0.79 (0.43–1.45; p = 0.448). In Papua, Indonesia routine administration of PQ radical cure without prior G6PD testing, was associated with lower risk of all cause hospitalization and other serious adverse clinical outcomes. In areas where G6PD testing is not available or cannot be delivered reliably, the risks of drug induced haemolysis should be balanced against the potential benefits of reducing recurrent P. vivax malaria and its associated morbidity and mortality. Public Library of Science 2020-11-11 /pmc/articles/PMC7657498/ /pubmed/33175835 http://dx.doi.org/10.1371/journal.pntd.0008838 Text en © 2020 Thriemer et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Thriemer, Kamala
Poespoprodjo, Jeanne-Rini
Kenangalem, Enny
Douglas, Nicholas M.
Sugiarto, Paulus
Anstey, Nicholas M.
Simpson, Julie Anne
Price, Ric N.
The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia
title The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia
title_full The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia
title_fullStr The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia
title_full_unstemmed The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia
title_short The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia
title_sort risk of adverse clinical outcomes following treatment of plasmodium vivax malaria with and without primaquine in papua, indonesia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657498/
https://www.ncbi.nlm.nih.gov/pubmed/33175835
http://dx.doi.org/10.1371/journal.pntd.0008838
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