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
Year: 2019
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: 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.
Source: PLoS Medicine
Authors: Robert J. Commons, Julie A. Simpson, Kamala Thriemer, Tesfay Abreha, Ishag Adam, Nicholas M. Anstey, Ashenafi Assefa, Ghulam R. Awab, J. Kevin Baird, Bridget E. Barber, Cindy S. Chu, Prabin Dahal, André Daher, Timothy M. E. Davis, Arjen M. Dondorp, Matthew J. Grigg, Georgina S. Humphreys, Jimee Hwang, Harin Karunajeewa, Moses Laman, Kartini Lidia, Brioni R. Moore, Ivo Mueller, Francois Nosten, Ayodhia P. Pasaribu, Dhelio B. Pereira, Aung P. Phyo, Jeanne R. Poespoprodjo, Carol H. Sibley, Kasia Stepniewska, Inge Sutanto, Guy Thwaites, Tran T. Hien, Nicholas J. White, Timothy William, Charles J. Woodrow, Philippe J. Guerin, Ric N. Price
Institutions: Charles Darwin University, Menzies School of Health Research, The University of Melbourne, Columbia University, University of Khartoum, Ethiopian Public Health Institute, Mahidol University, Nangarhar University, Mahidol Oxford Tropical Medicine Research Unit, University of Oxford, Oxford University Clinical Research Unit Indonesia, Shoklo Malaria Research Unit, Liverpool School of Tropical Medicine, Instituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, The University of Western Australia, Fremantle Hospital, Centers for Disease Control and Prevention, University of California, San Francisco, U.S. President's Malaria Initiative, Walter and Eliza Hall Institute of Medical Research, Western Health, Papua New Guinea Institute of Medical Research, University of Nusa Cendana, Curtin University, Institut Pasteur, Universitas Sumatera Utara, Universidade Federal de Rondônia, Universitas Gadjah Mada, Rumah Sakit Umum Pusat Dr. Sardjito, Rumah Sakit Umum Daerah Kabupaten Mimika, University of Washington, University of Indonesia, Oxford University Clinical Research Unit
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,927
Awards: G1617459808, Pathophysiology and treatment of malaria in our region, G3253273863, G3350072673, Impact of malaria elimination on immunity and risk of malaria rebound in Myanmar, Integration of biostatistics and mathematical modelling to improve the control of infectious diseases, Comparative incidence and clinical spectrum of Plasmodium knowlesi malaria, a longitudinal study in Sabah, Malaysia, Improving the treatment of Plasmodium vivax, G730015249, Risk factors, mechanisms, and treatment of knowlesi malaria, G7597818247, Improving the treatment of Plasmodium vivax, G8654089671, Centre for Research Excellence in Malaria Elimination
OpenAlex ID: W2978009241