The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis

English version

Autoři: Robert J. Commons ^aff001; Julie A. Simpson ^aff003; Kamala Thriemer ^aff001; Tesfay Abreha ^aff004; Ishag Adam ^aff005; Nicholas M. Anstey ^aff001; Ashenafi Assefa ^aff006; Ghulam R. Awab ^aff007; J. Kevin Baird ^aff009; Bridget E. Barber ^aff001; Cindy S. Chu ^aff010; Prabin Dahal ^aff010; André Daher ^aff014; Timothy M. E. Davis ^aff017; Arjen M. Dondorp ^aff007; Matthew J. Grigg ^aff001; Georgina S. Humphreys ^aff013; Jimee Hwang ^aff018; Harin Karunajeewa ^aff020; Moses Laman ^aff017; Kartini Lidia ^aff023; Brioni R. Moore ^aff017; Ivo Mueller ^aff020; Francois Nosten ^aff010; Ayodhia P. Pasaribu ^aff007; Dhelio B. Pereira ^aff028; Aung P. Phyo ^aff012; Jeanne R. Poespoprodjo ^aff030; Carol H. Sibley ^aff013; Kasia Stepniewska ^aff010; Inge Sutanto ^aff034; Guy Thwaites ^aff010; Tran T. Hien ^aff010; Nicholas J. White ^aff007; Timothy William ^aff011; Charles J. Woodrow ^aff007; Philippe J. Guerin ^aff010; Ric N. Price ^aff001
Působiště autorů: Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia ^aff001; WorldWide Antimalarial Resistance Network (WWARN), Clinical module, Darwin, Northern Territory, Australia ^aff002; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia ^aff003; ICAP, Columbia University Mailman School of Public Health, Addis Ababa, Ethiopia ^aff004; Faculty of Medicine, University of Khartoum, Khartoum, Sudan ^aff005; Malaria and Neglected Tropical Diseases Research Team, Bacterial, Parasitic, Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, Addis Ababa, Ethiopia ^aff006; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand ^aff007; Nangarhar Medical Faculty, Nangarhar University, Jalalabad, Afghanistan ^aff008; Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia ^aff009; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom ^aff010; Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia ^aff011; Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand ^aff012; WorldWide Antimalarial Resistance Network (WWARN), Oxford, United Kingdom ^aff013; Institute of Drug Technology (Farmanguinhos), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil ^aff014; Vice‑presidency of Research and Reference Laboratories, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil ^aff015; Liverpool School of Tropical Medicine, Liverpool, United Kingdom ^aff016; Medical School, The University of Western Australia, Fremantle Hospital Unit, Fremantle, Western Australia, Australia ^aff017; U.S. President's Malaria Initiative, Malaria Branch, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America ^aff018; Global Health Group, University of California San Francisco, San Francisco, California, United States of America ^aff019; Division of Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, Victoria, Australia ^aff020; Western Centre for Health Research and Education, Western Health, Melbourne, Victoria, Australia ^aff021; Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea ^aff022; The Department of Pharmacology and Therapy, Faculty of Medicine, Nusa Cendana University, Kupang, Indonesia ^aff023; School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Western Australia, Australia ^aff024; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia ^aff025; Parasites and Insect Vectors Department, Institut Pasteur, Paris, France ^aff026; Medical Faculty, Universitas Sumatera Utara, Medan, North Sumatera, Indonesia ^aff027; Centro de Pesquisa em Medicina Tropical de Rondônia (CEPEM), Porto Velho, Rondônia, Brazil ^aff028; Universidade Federal de Rondônia (UNIR), Porto Velho, Rondônia, Brazil ^aff029; Mimika District Hospital, Timika, Indonesia ^aff030; Timika Malaria Research Programme, Papuan Health and Community Development Foundation, Timika, Indonesia ^aff031; Paediatric Research Office, Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, Indonesia ^aff032; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America ^aff033; Department of Parasitology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia ^aff034; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam ^aff035; Gleneagles Hospital, Kota Kinabalu, Sabah, Malaysia ^aff036
Vyšlo v časopise: The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis. PLoS Med 16(10): e32767. doi:10.1371/journal.pmed.1002928
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1002928

Souhrn

Background

Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax.

Methods and findings

Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7–49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1–12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40–24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48–0.84), p = 0.0013 and 0.83 (0.73–0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99–1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01–0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10–0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01–0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups.

Conclusions

In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis.

Klíčová slova:

Antimalarials – Dose prediction methods – Malaria – Plasmodium – Primaquine – Systematic reviews – Chloroquine

Zdroje

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