Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening
Primaquine for radical cure of <i>Plasmodium vivax</i> malaria poses a potentially life-threatening risk of haemolysis in G6PD-deficient patients. Herein, we review five events of acute haemolytic anaemia following the administration of primaquine in four malaria trials from Indonesia, t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/12/9/1176 |
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| author | Ayleen Kosasih Robert James Nguyen Hoang Chau Michelle M. Karman Lydia Visita Panggalo Lyndes Wini Ngo Viet Thanh Thomas Obadia Ari Winasti Satyagraha Puji Budi Setia Asih Din Syafruddin Walter R. J. Taylor Ivo Mueller Inge Sutanto Harin Karunajeewa Ayodhia Pitaloka Pasaribu J. Kevin Baird |
| author_facet | Ayleen Kosasih Robert James Nguyen Hoang Chau Michelle M. Karman Lydia Visita Panggalo Lyndes Wini Ngo Viet Thanh Thomas Obadia Ari Winasti Satyagraha Puji Budi Setia Asih Din Syafruddin Walter R. J. Taylor Ivo Mueller Inge Sutanto Harin Karunajeewa Ayodhia Pitaloka Pasaribu J. Kevin Baird |
| author_sort | Ayleen Kosasih |
| collection | DOAJ |
| description | Primaquine for radical cure of <i>Plasmodium vivax</i> malaria poses a potentially life-threatening risk of haemolysis in G6PD-deficient patients. Herein, we review five events of acute haemolytic anaemia following the administration of primaquine in four malaria trials from Indonesia, the Solomon Islands, and Vietnam. Five males aged 9 to 48 years were improperly classified as G6PD-normal by various screening procedures and included as subjects in trials of anti-relapse therapy with daily primaquine. Routine safety monitoring by physical examination, urine inspection, and blood haemoglobin (Hb) assessment were performed in all those trials. Early signs of acute haemolysis, i.e., dark urine and haemoglobin drop >20%, occurred only after day 3 and as late as day 8 of primaquine dosing. All patients were hospitalized and fully recovered, all but one following blood transfusion rescue. Hb nadir was 4.7 to 7.9 g/dL. Hospitalization was for 1 to 7 days. Hb levels returned to baseline values 3 to 10 days after transfusion. Failed G6PD screening procedures in these trials led G6PD-deficient patients to suffer harmful exposures to primaquine. The safe application of primaquine anti-relapse therapy requires G6PD screening and anticipation of its failure with a means of prompt detection and rescue from the typically abrupt haemolytic crisis. |
| first_indexed | 2024-03-10T22:17:53Z |
| format | Article |
| id | doaj.art-db19cecdf3674fc392d49356c1636f68 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T22:17:53Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-db19cecdf3674fc392d49356c1636f682023-11-19T12:23:10ZengMDPI AGPathogens2076-08172023-09-01129117610.3390/pathogens12091176Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD ScreeningAyleen Kosasih0Robert James1Nguyen Hoang Chau2Michelle M. Karman3Lydia Visita Panggalo4Lyndes Wini5Ngo Viet Thanh6Thomas Obadia7Ari Winasti Satyagraha8Puji Budi Setia Asih9Din Syafruddin10Walter R. J. Taylor11Ivo Mueller12Inge Sutanto13Harin Karunajeewa14Ayodhia Pitaloka Pasaribu15J. Kevin Baird16Oxford University Clinical Research Unit Indonesia, Jakarta 10430, IndonesiaWalter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, AustraliaOxford University Clinical Research Unit, Hospital for Tropical Diseases, District 5, Ho Chi Minh City 749000, VietnamOxford University Clinical Research Unit Indonesia, Jakarta 10430, IndonesiaExeins Health Initiative, Jakarta 12870, IndonesiaVector-Borne Disease Control (VBDC) Division, Solomon Islands Ministry of Health and Medical Services, Honiara P.O. Box R113, Solomon IslandsOxford University Clinical Research Unit, Hospital for Tropical Diseases, District 5, Ho Chi Minh City 749000, VietnamInstitut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, F-75015 Paris, FranceExeins Health Initiative, Jakarta 12870, IndonesiaEijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong 16911, IndonesiaEijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong 16911, IndonesiaMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandWalter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, AustraliaDepartment of Parasitology, Faculty of Medicine, University of Indonesia, Jakarta 10430, IndonesiaDepartment of Medicine, Western Health, The University of Melbourne, Melbourne, VIC 3010, AustraliaDepartment of Pediatrics, Medical Faculty, Universitas Sumatera Utara, Medan 20155, IndonesiaOxford University Clinical Research Unit Indonesia, Jakarta 10430, IndonesiaPrimaquine for radical cure of <i>Plasmodium vivax</i> malaria poses a potentially life-threatening risk of haemolysis in G6PD-deficient patients. Herein, we review five events of acute haemolytic anaemia following the administration of primaquine in four malaria trials from Indonesia, the Solomon Islands, and Vietnam. Five males aged 9 to 48 years were improperly classified as G6PD-normal by various screening procedures and included as subjects in trials of anti-relapse therapy with daily primaquine. Routine safety monitoring by physical examination, urine inspection, and blood haemoglobin (Hb) assessment were performed in all those trials. Early signs of acute haemolysis, i.e., dark urine and haemoglobin drop >20%, occurred only after day 3 and as late as day 8 of primaquine dosing. All patients were hospitalized and fully recovered, all but one following blood transfusion rescue. Hb nadir was 4.7 to 7.9 g/dL. Hospitalization was for 1 to 7 days. Hb levels returned to baseline values 3 to 10 days after transfusion. Failed G6PD screening procedures in these trials led G6PD-deficient patients to suffer harmful exposures to primaquine. The safe application of primaquine anti-relapse therapy requires G6PD screening and anticipation of its failure with a means of prompt detection and rescue from the typically abrupt haemolytic crisis.https://www.mdpi.com/2076-0817/12/9/1176acute haemolytic anaemiaprimaquineG6PD deficiencyG6PD screeningrandomized controlled trials |
| spellingShingle | Ayleen Kosasih Robert James Nguyen Hoang Chau Michelle M. Karman Lydia Visita Panggalo Lyndes Wini Ngo Viet Thanh Thomas Obadia Ari Winasti Satyagraha Puji Budi Setia Asih Din Syafruddin Walter R. J. Taylor Ivo Mueller Inge Sutanto Harin Karunajeewa Ayodhia Pitaloka Pasaribu J. Kevin Baird Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening Pathogens acute haemolytic anaemia primaquine G6PD deficiency G6PD screening randomized controlled trials |
| title | Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening |
| title_full | Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening |
| title_fullStr | Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening |
| title_full_unstemmed | Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening |
| title_short | Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening |
| title_sort | case series of primaquine induced haemolytic events in controlled trials with g6pd screening |
| topic | acute haemolytic anaemia primaquine G6PD deficiency G6PD screening randomized controlled trials |
| url | https://www.mdpi.com/2076-0817/12/9/1176 |
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