Variation in Glucose-6-Phosphate Dehydrogenase activity following acute malaria

Benedikt Ley; Mohammad Shafiul Alam; Ari Winasti Satyagraha; Ching Swe Phru; Kamala Thriemer; Dagimawie Tadesse; Tamiru Shibiru; Asrat Hailu; Mohammad Golam Kibria; Mohammad Sharif Hossain; Hisni Rahmat; Jeanne R. Poespoprodjo; Wasif Ali Khan; Julie A. Simpson; Ric N. Price

doi:10.1371/journal.pntd.0010406

Variation in Glucose-6-Phosphate Dehydrogenase activity following acute malaria

Benedikt Ley, Mohammad Shafiul Alam, Ari Winasti Satyagraha, Ching Swe Phru, Kamala Thriemer, Dagimawie Tadesse, Tamiru Shibiru, Asrat Hailu, Mohammad Golam Kibria, Mohammad Sharif Hossain, Hisni Rahmat, Jeanne R. Poespoprodjo, Wasif Ali Khan, Julie A. Simpson, Ric N. Price

Global and Tropical Health

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Abstract

Primaquine and tafenoquine are the only licensed drugs with activity against Plasmodium vivax hypnozoites but cause haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Malaria also causes haemolysis, leading to the replacement of older erythrocytes with low G6PD activity by reticulocytes and young erythrocytes with higher activity. Aim of this study was to assess the impact of acute malaria on G6PD activity. Selected patients with uncomplicated malaria were recruited in Bangladesh (n = 87), Indonesia (n = 75), and Ethiopia (n = 173); G6PD activity was measured at the initial presentation with malaria and a median of 176 days later (range 140 to 998) in the absence of malaria. Among selected participants (deficient participants preferentially enrolled in Bangladesh but not at other sites) G6PD activity fell between malaria and follow up by 79.1% (95%CI: 40.4 to 117.8) in 6 participants classified as deficient (<30% activity), 43.7% (95%CI: 34.2 to 53.1) in 39 individuals with intermediate activity (30% to <70%), and by 4.5% (95%CI: 1.4 to 7.6) in 290 G6PD normal (≥70%) participants. In Bangladesh and Indonesia G6PD activity was significantly higher during acute malaria than when the same individuals were retested during follow up (40.9% (95%CI: 33.4-48.1) and 7.4% (95%CI: 0.2 to 14.6) respectively), whereas in Ethiopia G6PD activity was 3.6% (95%CI: -1.0 to -6.1) lower during acute malaria. The change in G6PD activity was apparent in patients presenting with either P. vivax or P. falciparum infection. Overall, 66.7% (4/6) severely deficient participants and 87.2% (34/39) with intermediate deficiency had normal activities when presenting with malaria. These findings suggest that G6PD activity rises significantly and at clinically relevant levels during acute malaria. Prospective case-control studies are warranted to confirm the degree to which the predicted population attributable risks of drug induced haemolysis is lower than would be predicted from cross sectional surveys.

Original language	English
Article number	e0010406
Pages (from-to)	1-15
Number of pages	15
Journal	PLoS Neglected Tropical Diseases
Volume	16
Issue number	5
DOIs	https://doi.org/10.1371/journal.pntd.0010406
Publication status	Published - 11 May 2022

Bibliographical note

Funding Information:
This study was funded by the Bill & Melinda Gates Foundation (OPP1054404 and OPP1164105 awarded to RNP). KT is a CSL Centenary fellow, RNP is funded by the Wellcome Trust (Senior Fellowship in Clinical Science, 200909). icddr,b is also grateful to the Governments of Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2022 Ley et al.

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Ley, B., Alam, M. S., Satyagraha, A. W., Phru, C. S., Thriemer, K., Tadesse, D., Shibiru, T., Hailu, A., Kibria, M. G., Hossain, M. S., Rahmat, H., Poespoprodjo, J. R., Khan, W. A., Simpson, J. A., & Price, R. N. (2022). Variation in Glucose-6-Phosphate Dehydrogenase activity following acute malaria. PLoS Neglected Tropical Diseases, 16(5), 1-15. Article e0010406. https://doi.org/10.1371/journal.pntd.0010406

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title = "Variation in Glucose-6-Phosphate Dehydrogenase activity following acute malaria",

abstract = "Primaquine and tafenoquine are the only licensed drugs with activity against Plasmodium vivax hypnozoites but cause haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Malaria also causes haemolysis, leading to the replacement of older erythrocytes with low G6PD activity by reticulocytes and young erythrocytes with higher activity. Aim of this study was to assess the impact of acute malaria on G6PD activity. Selected patients with uncomplicated malaria were recruited in Bangladesh (n = 87), Indonesia (n = 75), and Ethiopia (n = 173); G6PD activity was measured at the initial presentation with malaria and a median of 176 days later (range 140 to 998) in the absence of malaria. Among selected participants (deficient participants preferentially enrolled in Bangladesh but not at other sites) G6PD activity fell between malaria and follow up by 79.1% (95%CI: 40.4 to 117.8) in 6 participants classified as deficient (<30% activity), 43.7% (95%CI: 34.2 to 53.1) in 39 individuals with intermediate activity (30% to <70%), and by 4.5% (95%CI: 1.4 to 7.6) in 290 G6PD normal (≥70%) participants. In Bangladesh and Indonesia G6PD activity was significantly higher during acute malaria than when the same individuals were retested during follow up (40.9% (95%CI: 33.4-48.1) and 7.4% (95%CI: 0.2 to 14.6) respectively), whereas in Ethiopia G6PD activity was 3.6% (95%CI: -1.0 to -6.1) lower during acute malaria. The change in G6PD activity was apparent in patients presenting with either P. vivax or P. falciparum infection. Overall, 66.7% (4/6) severely deficient participants and 87.2% (34/39) with intermediate deficiency had normal activities when presenting with malaria. These findings suggest that G6PD activity rises significantly and at clinically relevant levels during acute malaria. Prospective case-control studies are warranted to confirm the degree to which the predicted population attributable risks of drug induced haemolysis is lower than would be predicted from cross sectional surveys.",

author = "Benedikt Ley and Alam, {Mohammad Shafiul} and Satyagraha, {Ari Winasti} and Phru, {Ching Swe} and Kamala Thriemer and Dagimawie Tadesse and Tamiru Shibiru and Asrat Hailu and Kibria, {Mohammad Golam} and Hossain, {Mohammad Sharif} and Hisni Rahmat and Poespoprodjo, {Jeanne R.} and Khan, {Wasif Ali} and Simpson, {Julie A.} and Price, {Ric N.}",

note = "Funding Information: This study was funded by the Bill & Melinda Gates Foundation (OPP1054404 and OPP1164105 awarded to RNP). KT is a CSL Centenary fellow, RNP is funded by the Wellcome Trust (Senior Fellowship in Clinical Science, 200909). icddr,b is also grateful to the Governments of Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2022 Ley et al.",

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language = "English",

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Ley, B, Alam, MS, Satyagraha, AW, Phru, CS, Thriemer, K, Tadesse, D, Shibiru, T, Hailu, A, Kibria, MG, Hossain, MS, Rahmat, H, Poespoprodjo, JR, Khan, WA, Simpson, JA & Price, RN 2022, 'Variation in Glucose-6-Phosphate Dehydrogenase activity following acute malaria', PLoS Neglected Tropical Diseases, vol. 16, no. 5, e0010406, pp. 1-15. https://doi.org/10.1371/journal.pntd.0010406

TY - JOUR

T1 - Variation in Glucose-6-Phosphate Dehydrogenase activity following acute malaria

AU - Ley, Benedikt

AU - Alam, Mohammad Shafiul

AU - Satyagraha, Ari Winasti

AU - Phru, Ching Swe

AU - Thriemer, Kamala

AU - Tadesse, Dagimawie

AU - Shibiru, Tamiru

AU - Hailu, Asrat

AU - Kibria, Mohammad Golam

AU - Hossain, Mohammad Sharif

AU - Rahmat, Hisni

AU - Poespoprodjo, Jeanne R.

AU - Khan, Wasif Ali

AU - Simpson, Julie A.

AU - Price, Ric N.

N1 - Funding Information: This study was funded by the Bill & Melinda Gates Foundation (OPP1054404 and OPP1164105 awarded to RNP). KT is a CSL Centenary fellow, RNP is funded by the Wellcome Trust (Senior Fellowship in Clinical Science, 200909). icddr,b is also grateful to the Governments of Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022 Ley et al.

PY - 2022/5/11

Y1 - 2022/5/11

N2 - Primaquine and tafenoquine are the only licensed drugs with activity against Plasmodium vivax hypnozoites but cause haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Malaria also causes haemolysis, leading to the replacement of older erythrocytes with low G6PD activity by reticulocytes and young erythrocytes with higher activity. Aim of this study was to assess the impact of acute malaria on G6PD activity. Selected patients with uncomplicated malaria were recruited in Bangladesh (n = 87), Indonesia (n = 75), and Ethiopia (n = 173); G6PD activity was measured at the initial presentation with malaria and a median of 176 days later (range 140 to 998) in the absence of malaria. Among selected participants (deficient participants preferentially enrolled in Bangladesh but not at other sites) G6PD activity fell between malaria and follow up by 79.1% (95%CI: 40.4 to 117.8) in 6 participants classified as deficient (<30% activity), 43.7% (95%CI: 34.2 to 53.1) in 39 individuals with intermediate activity (30% to <70%), and by 4.5% (95%CI: 1.4 to 7.6) in 290 G6PD normal (≥70%) participants. In Bangladesh and Indonesia G6PD activity was significantly higher during acute malaria than when the same individuals were retested during follow up (40.9% (95%CI: 33.4-48.1) and 7.4% (95%CI: 0.2 to 14.6) respectively), whereas in Ethiopia G6PD activity was 3.6% (95%CI: -1.0 to -6.1) lower during acute malaria. The change in G6PD activity was apparent in patients presenting with either P. vivax or P. falciparum infection. Overall, 66.7% (4/6) severely deficient participants and 87.2% (34/39) with intermediate deficiency had normal activities when presenting with malaria. These findings suggest that G6PD activity rises significantly and at clinically relevant levels during acute malaria. Prospective case-control studies are warranted to confirm the degree to which the predicted population attributable risks of drug induced haemolysis is lower than would be predicted from cross sectional surveys.

AB - Primaquine and tafenoquine are the only licensed drugs with activity against Plasmodium vivax hypnozoites but cause haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Malaria also causes haemolysis, leading to the replacement of older erythrocytes with low G6PD activity by reticulocytes and young erythrocytes with higher activity. Aim of this study was to assess the impact of acute malaria on G6PD activity. Selected patients with uncomplicated malaria were recruited in Bangladesh (n = 87), Indonesia (n = 75), and Ethiopia (n = 173); G6PD activity was measured at the initial presentation with malaria and a median of 176 days later (range 140 to 998) in the absence of malaria. Among selected participants (deficient participants preferentially enrolled in Bangladesh but not at other sites) G6PD activity fell between malaria and follow up by 79.1% (95%CI: 40.4 to 117.8) in 6 participants classified as deficient (<30% activity), 43.7% (95%CI: 34.2 to 53.1) in 39 individuals with intermediate activity (30% to <70%), and by 4.5% (95%CI: 1.4 to 7.6) in 290 G6PD normal (≥70%) participants. In Bangladesh and Indonesia G6PD activity was significantly higher during acute malaria than when the same individuals were retested during follow up (40.9% (95%CI: 33.4-48.1) and 7.4% (95%CI: 0.2 to 14.6) respectively), whereas in Ethiopia G6PD activity was 3.6% (95%CI: -1.0 to -6.1) lower during acute malaria. The change in G6PD activity was apparent in patients presenting with either P. vivax or P. falciparum infection. Overall, 66.7% (4/6) severely deficient participants and 87.2% (34/39) with intermediate deficiency had normal activities when presenting with malaria. These findings suggest that G6PD activity rises significantly and at clinically relevant levels during acute malaria. Prospective case-control studies are warranted to confirm the degree to which the predicted population attributable risks of drug induced haemolysis is lower than would be predicted from cross sectional surveys.

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Variation in Glucose-6-Phosphate Dehydrogenase activity following acute malaria

Abstract

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