TY - JOUR
T1 - The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence
T2 - a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis
AU - Commons, Robert J.
AU - Simpson, Julie A.
AU - Thriemer, Kamala
AU - Humphreys, Georgina S.
AU - Abreha, Tesfay
AU - Alemu, Sisay G.
AU - Añez, Arletta
AU - Anstey, Nicholas M.
AU - Awab, Ghulam R.
AU - Baird, J. Kevin
AU - Barber, Bridget E.
AU - Borghini-Fuhrer, Isabelle
AU - Chu, Cindy S.
AU - D'Alessandro, Umberto
AU - Dahal, Prabin
AU - Daher, André
AU - de Vries, Peter J.
AU - Erhart, Annette
AU - Gomes, Margarete S.M.
AU - Gonzalez-Ceron, Lilia
AU - Grigg, Matthew J.
AU - Heidari, Aliehsan
AU - Hwang, Jimee
AU - Kager, Piet A.
AU - Ketema, Tsige
AU - Khan, Wasif A.
AU - Lacerda, Marcus V.G.
AU - Leslie, Toby
AU - Ley, Benedikt
AU - Lidia, Kartini
AU - Monteiro, Wuelton M.
AU - Nosten, Francois
AU - Pereira, Dhelio B.
AU - Phan, Giao T.
AU - Phyo, Aung P.
AU - Rowland, Mark
AU - Saravu, Kavitha
AU - Sibley, Carol H.
AU - Siqueira, André M.
AU - Stepniewska, Kasia
AU - Sutanto, Inge
AU - Taylor, Walter R.J.
AU - Thwaites, Guy
AU - Tran, Binh Q.
AU - Tran, Hien T.
AU - Valecha, Neena
AU - Vieira, José Luiz F.
AU - Wangchuk, Sonam
AU - William, Timothy
AU - Woodrow, Charles J.
AU - Zuluaga-Idarraga, Lina
AU - Guerin, Philippe J.
AU - White, Nicholas J.
AU - Price, Ric N.
N1 - Funding Information:
RJC is supported by a Postgraduate Australian National Health and Medical Research Council (NHMRC) Scholarship and a Royal Australasian College of Physicians NHMRC Kincaid-Smith Scholarship. JAS is funded by an Australian NHMRC Senior Research Fellowship 1104975. KT is funded by the Asia Pacific Malaria Elimination Network and optimising primaquine regimens for the radical cure of vivax malaria (OPRA) clinical trial funding, supported by the Bill & Melinda Gates Foundation (OPP1164105 and OPP1054404). NMA is funded by an Australian NHMRC Senior Principal Research Fellowship (1135820). PD is funded by Tropical Network Fund, Nuffield Department of Clinical Medicine, University of Oxford. MJG is supported by an Australian NHMRC Early Career Fellowship (1138860). NJW is a Wellcome Trust Principal Fellow. RNP is a Wellcome Trust Senior Fellow in Clinical Science (200909). WWARN is funded by the Bill & Melinda Gates Foundation and Exxon Mobil Foundation grants. We thank all patients and staff who participated in these clinical trials at all the sites, the WWARN team for technical and administrative support, and the Malaria Atlas Project for transmission estimates. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Funding Information:
AA reports grants from USAID Iniciativa Amazónica contra la Malaria/Red Amazónica de la Vigilancia de las Drogas Antimaláricas AMI/RAVREDA and personal fees from Pan American Health Organization PWR (BOL). AD is an employee of the Institute of Drug Technology (Farmanguinhos), Oswaldo Cruz Foundation (Fiocruz), a Brazilian governmental institution of the Ministry of Health. PJdV reports personal fees from ACE Pharma. DBP reports grants from GSK. All other authors declare no competing interests.
Publisher Copyright:
© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2018/9
Y1 - 2018/9
N2 - Background: Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings. Methods: A systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310. Findings: Of 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34·8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32·4% (95% CI 29·8–35·1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0·82, 95% CI 0·69–0·97; p=0·021) and in children younger than 5 years (0·59, 0·41–0·86; p=0·0058). Adding primaquine reduced the risk of recurrence to 4·9% (95% CI 3·1–7·7) by day 42, which is lower than with chloroquine alone (AHR 0·10, 0·05–0·17; p<0·0001). Interpretation: Chloroquine is commonly under-dosed in the treatment of vivax malaria. Increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given. Radical cure with primaquine was highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax. Funding: Wellcome Trust, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation.
AB - Background: Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings. Methods: A systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310. Findings: Of 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34·8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32·4% (95% CI 29·8–35·1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0·82, 95% CI 0·69–0·97; p=0·021) and in children younger than 5 years (0·59, 0·41–0·86; p=0·0058). Adding primaquine reduced the risk of recurrence to 4·9% (95% CI 3·1–7·7) by day 42, which is lower than with chloroquine alone (AHR 0·10, 0·05–0·17; p<0·0001). Interpretation: Chloroquine is commonly under-dosed in the treatment of vivax malaria. Increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given. Radical cure with primaquine was highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax. Funding: Wellcome Trust, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation.
UR - http://www.scopus.com/inward/record.url?scp=85053837530&partnerID=8YFLogxK
U2 - 10.1016/S1473-3099(18)30348-7
DO - 10.1016/S1473-3099(18)30348-7
M3 - Article
AN - SCOPUS:85053837530
VL - 18
SP - 1025
EP - 1034
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
SN - 1473-3099
IS - 9
ER -