Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis
Background The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse.Methods A systematic review identified P. vivax efficacy studies from South As...
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BMJ Publishing Group
2023-12-01
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| Series: | BMJ Global Health |
| Online Access: | https://gh.bmj.com/content/8/12/e012675.full |
| _version_ | 1827394842334855168 |
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| author | Philippe J Guérin Kavitha Saravu Julie A Simpson Komal Raj Rijal Prakash Ghimire Mark Rowland Sasithon Pukrittayakamee Amit Sharma Manju Rahi Praveen K Bharti Ric N Price Megha Rajasekhar Toby Leslie Reena Verma Rishikesh Kumar Sauman Singh-Phulgenda Robert J Commons Apoorv Gupta Nitika Kamala Thriemer Mohammad Shafiul Alam Wasif A Khan Benedikt Ley Alejandro Llanos-Cuentas |
| author_facet | Philippe J Guérin Kavitha Saravu Julie A Simpson Komal Raj Rijal Prakash Ghimire Mark Rowland Sasithon Pukrittayakamee Amit Sharma Manju Rahi Praveen K Bharti Ric N Price Megha Rajasekhar Toby Leslie Reena Verma Rishikesh Kumar Sauman Singh-Phulgenda Robert J Commons Apoorv Gupta Nitika Kamala Thriemer Mohammad Shafiul Alam Wasif A Khan Benedikt Ley Alejandro Llanos-Cuentas |
| author_sort | Philippe J Guérin |
| collection | DOAJ |
| description | Background The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse.Methods A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to <70 g/L, or an absolute drop of >50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose.Results In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to <5 mg/kg) and 0% (96 patients; 0 recurrences) following high total dose primaquine (≥5 mg/kg). In the subsequent two-stage meta-analysis of nine studies (3529 patients), the pooled proportions of P. vivax recurrences by day 180 were 12.1% (95% CI 7.7% to 17.2%), 2.3% (95% CI 0.3% to 5.4%) and 0.7% (95% CI 0% to 6.1%), respectively. No patients had a >25% drop in haemoglobin to <70 g/L.Conclusions Primaquine treatment led to a marked decrease in P. vivax recurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events.PROSPERO registration number CRD42022313730. |
| first_indexed | 2024-03-08T18:20:03Z |
| format | Article |
| id | doaj.art-d5a65b6646194773abb3815858e8dc2b |
| institution | Directory Open Access Journal |
| issn | 2059-7908 |
| language | English |
| last_indexed | 2024-03-08T18:20:03Z |
| publishDate | 2023-12-01 |
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| record_format | Article |
| series | BMJ Global Health |
| spelling | doaj.art-d5a65b6646194773abb3815858e8dc2b2023-12-31T01:45:10ZengBMJ Publishing GroupBMJ Global Health2059-79082023-12-0181210.1136/bmjgh-2023-012675Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysisPhilippe J Guérin0Kavitha Saravu1Julie A Simpson2Komal Raj Rijal3Prakash Ghimire4Mark Rowland5Sasithon Pukrittayakamee6Amit Sharma7Manju Rahi8Praveen K Bharti9Ric N Price10Megha Rajasekhar11Toby Leslie12Reena Verma13Rishikesh Kumar14Sauman Singh-Phulgenda15Robert J Commons16Apoorv Gupta17 Nitika18Kamala Thriemer19Mohammad Shafiul Alam20Wasif A Khan21Benedikt Ley22Alejandro Llanos-Cuentas233 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UKManipal Centre for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, IndiaBiostatisticianCentral Department of Microbiology, Tribhuvan University, Kirtipur, NepalDepartment of Microbiology, Tribhuvan University, Kirtipur, Kathmandu, NepalDisease Control, London School of Hygiene & Tropical Medicine, London, UKMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandDepartment of Internal Medicine, SUNY Upstate Medical University, Syracuse, New York, USA4 Epidemiology and Communicable Diseases, Indian Council of Medical Research (ICMR), New Delhi, Delhi, IndiaICMR-National Institute of Malaria Research, New Delhi, IndiaCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UKMelbourne School Of Population And Global Health, The University of Melbourne, Melbourne, Victoria, Australiatechnical directorICMR-National Institute of Malaria Research, New Delhi, India1 Indian Council of Medical Research (ICMR)–Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Patna, IndiaCentre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UKGlobal Health Division, Menzies School of Health Research, Charles Darwin University, Tiwi, Northern Territory, AustraliaICMR-National Institute of Malaria Research, New Delhi, IndiaICMR-National Institute of Malaria Research, New Delhi, IndiaGlobal Health Division, Menzies School of Health Research, Charles Darwin University, Tiwi, Northern Territory, AustraliaInternational Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, BangladeshInternational Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, BangladeshGlobal Health Division, Menzies School of Health Research, Charles Darwin University, Tiwi, Northern Territory, AustraliaUnit of Leishmaniasis and Malaria, Instituto de Medicina Tropical “Alexander von Humboldt”, Universidad Peruana Cayetano Heredia, Lima, PeruBackground The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse.Methods A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to <70 g/L, or an absolute drop of >50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose.Results In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to <5 mg/kg) and 0% (96 patients; 0 recurrences) following high total dose primaquine (≥5 mg/kg). In the subsequent two-stage meta-analysis of nine studies (3529 patients), the pooled proportions of P. vivax recurrences by day 180 were 12.1% (95% CI 7.7% to 17.2%), 2.3% (95% CI 0.3% to 5.4%) and 0.7% (95% CI 0% to 6.1%), respectively. No patients had a >25% drop in haemoglobin to <70 g/L.Conclusions Primaquine treatment led to a marked decrease in P. vivax recurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events.PROSPERO registration number CRD42022313730.https://gh.bmj.com/content/8/12/e012675.full |
| spellingShingle | Philippe J Guérin Kavitha Saravu Julie A Simpson Komal Raj Rijal Prakash Ghimire Mark Rowland Sasithon Pukrittayakamee Amit Sharma Manju Rahi Praveen K Bharti Ric N Price Megha Rajasekhar Toby Leslie Reena Verma Rishikesh Kumar Sauman Singh-Phulgenda Robert J Commons Apoorv Gupta Nitika Kamala Thriemer Mohammad Shafiul Alam Wasif A Khan Benedikt Ley Alejandro Llanos-Cuentas Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis BMJ Global Health |
| title | Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis |
| title_full | Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis |
| title_fullStr | Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis |
| title_full_unstemmed | Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis |
| title_short | Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis |
| title_sort | safety and efficacy of primaquine in patients with plasmodium vivax malaria from south asia a systematic review and individual patient data meta analysis |
| url | https://gh.bmj.com/content/8/12/e012675.full |
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