The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

被引：35

作者：

Commons, Robert J. ^{[1
,2
,3
]}

Simpson, Julie A. ^{[4
]}

Thriemer, Kamala ^{[1
,2
]}

Chu, Cindy S. ^{[5
,6
]}

Douglas, Nicholas M. ^{[1
,2
,4
]}

Abreha, Tesfay ^{[7
]}

Alemu, Sisay G. ^{[8
,9
]}

Anez, Arletta ^{[10
,11
]}

Anstey, Nicholas M. ^{[1
,2
]}

Aseffa, Abraham ^{[9
]}

Assefa, Ashenafi ^{[12
]}

Awab, Ghulam R. ^{[13
,14
]}

Baird, J. Kevin ^{[5
,15
]}

Barber, Bridget E. ^{[1
,2
,16
]}

Borghini-Fuhrer, Isabelle ^{[17
]}

D'Alessandro, Umberto ^{[18
]}

Dahal, Prabin ^{[5
,19
]}

Daher, Andre ^{[20
,21
,22
]}

de Vries, Peter J. ^{[23
]}

Erhart, Annette ^{[18
]}

Gomes, Margarete S. M. ^{[24
,25
]}

Grigg, Matthew J. ^{[1
,2
,16
]}

Hwang, Jimee ^{[26
,27
]}

Kager, Piet A. ^{[28
]}

Ketema, Tsige ^{[29
,30
]}

Khan, Wasif A. ^{[31
]}

Lacerda, Marcus V. G. ^{[32
,34
]}

Leslie, Toby ^{[35
,36
]}

Ley, Benedikt ^{[1
,2
]}

Lidia, Kartini ^{[37
]}

Monteiro, Wuelton M. ^{[32
,33
]}

Pereira, Dhelio B. ^{[38
,39
]}

Phan, Giao T. ^{[40
,41
]}

Phyo, Aung P. ^{[6
]}

Rowland, Mark ^{[35
]}

Saravu, Kavitha ^{[42
,43
]}

Sibley, Carol H. ^{[19
,44
]}

Siqueira, Andre M. ^{[32
,45
,46
]}

Stepniewska, Kasia ^{[5
,19
]}

Taylor, Walter R. J. ^{[5
,13
]}

Thwaites, Guy ^{[5
,47
]}

Tran, Binh Q. ^{[41
]}

Hien, Tran T. ^{[5
,47
]}

Vieira, Jose Luiz F. ^{[48
]}

Wangchuk, Sonam ^{[49
]}

Watson, James ^{[5
,13
]}

William, Timothy ^{[16
,50
]}

Woodrow, Charles J. ^{[13
]}

Nosten, Francois ^{[5
,6
]}

Guerin, Philippe J. ^{[5
,19
]}

机构：

[1] Menzies Sch Hlth Res, Global Hlth Div, Darwin, NT, Australia

[2] Charles Darwin Univ, Darwin, NT, Australia

[3] WorldWide Antimalarial Resistance Network WWARN, Clin Module, Darwin, NT, Australia

[4] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia

[5] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England

[6] Mahidol Univ, Fac Trop Med, Shoklo Malaria Res Unit, Mahidol Oxford Trop Med Res Unit, Mae Sot, Thailand

[7] Columbia Univ, ICAP, Mailman Sch Publ Hlth, Addis Ababa, Ethiopia

[8] Addis Ababa Univ, Addis Ababa, Ethiopia

[9] Armauer Hansen Res Inst, Addis Ababa, Ethiopia

[10] Univ Barcelona, Dept Salud Publ, Barcelona, Spain

[11] Org Panamer Salud, Oficina Pais Bolivia, La Paz, Bolivia

[12] Ethiopian Publ Hlth Inst, Malaria & Neglected Trop Dis Res Team, Bacterial, Parasit,Zoonot Dis Res Directorate, Addis Ababa, Ethiopia

[13] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit MORU, Bangkok, Thailand

[14] Nangarhar Univ, Nangarhar Med Fac, Jalalabad, Afghanistan

[15] Eijkman Oxford Clin Res Unit, Jakarta, Indonesia

[16] Menzies Sch Hlth Res, Infect Dis Soc Sabah, Clin Res Unit, Kota Kinabalu, Sabah, Malaysia

[17] Med Malaria Venture, Geneva, Switzerland

[18] MRC, Unit Gambia LSTMH, Fajara, Gambia

[19] WorldWide Antimalarial Resistance Network WWARN, Oxford, England

[20] Oswaldo Cruz Fdn FIOCRUZ, Inst Drug Technol Farmanguinhos, Rio De Janeiro, Brazil

[21] Oswaldo Cruz Fdn FIOCRUZ, Vice Presidency Res & Reference Labs, Rio De Janeiro, Brazil

[22] Univ Liverpool Liverpool Sch Trop Med, Liverpool, Merseyside, England

[23] Tergooi Hosp, Dept Internal Med, Hilversum, Netherlands

[24] Superintendencia Vigilancia Saude Estado Amapa SV, Macapa, Amapa, Brazil

[25] Univ Fed Amapa UNIFAP, Macapa, Amapa, Brazil

[26] US Ctr Dis Control & Prevent, US Presidents Malaria Initiat, Malaria Branch, Atlanta, GA USA

[27] Univ Calif San Francisco, Global Hlth Grp, San Francisco, CA 94143 USA

[28] Acad Med Ctr, Ctr Infect & Immun Amsterdam CINEMA, Div Infect Dis Trop Med & AIDS, Amsterdam, Netherlands

[29] Addis Ababa Univ, Dept Biol, Addis Ababa, Ethiopia

[30] Jimma Univ, Dept Biol, Jimma, Ethiopia

[31] Int Ctr Diarrheal Dis & Res, Dhaka, Bangladesh

[32] Fundacao Med Trop Dr Heitor Vieira Dourado, Manaus, Amazonas, Brazil

[33] Univ Estado Amazonas, Manaus, Amazonas, Brazil

[34] Fundacao Oswaldo Cruz, Inst Leonidas & Maria Deane FIOCRUZ Amazonas, Manaus, Amazonas, Brazil

[35] London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London, England

[36] HealthNet TPO, Kabul, Afghanistan

[37] Nusa Cendana Univ, Dept Pharmacol & Therapy, Fac Med, Kupang, Indonesia

[38] Ctr Pesquisa Med Trop Rondonia CEPEM, Porto Velho, Rondonia, Brazil

[39] Univ Fed Rondonia UNIR, Porto Velho, Rondonia, Brazil

[40] Acad Med Ctr, Divis Infect Dis Trop Med & AIDS, Amsterdam, Netherlands

[41] Cho Ray Hosp, Trop Dis Clin Res Ctr, Ho Chi Minh City, Vietnam

[42] Manipal Acad Higher Educ, Kasturba Med Coll, Dept Med, Manipal, Karnataka, India

[43] Manipal Acad Higher Educ, Manipal McGill Ctr Infect Dis, Manipal, Karnataka, India

[44] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[45] Univ Estado Amazonas, Programa Posgrad Med Trop, Manaus, Amazonas, Brazil

[46] Fundacao Oswaldo Cruz, Inst Nacl Infectol Evandro Chagas, Rio De Janeiro, Brazil

[47] Oxford Univ Clin Res Unit, Ho Chi Minh City, Vietnam

[48] Univ Fed Para UFPA, Fed Univ Para, Belem, Para, Brazil

[49] Minist Hlth, Dept Publ Hlth, Publ Hlth Lab, Thimphu, Bhutan

[50] Gleneagles Hosp, Kota Kinabalu, Saga, Malaysia

来源：

BMC MEDICINE | 2019年 / 17卷 / 1期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

Plasmodium vivax; Chloroquine; Primaquine; Haemoglobin; Pooled analysis; Haemolysis; DIHYDROARTEMISININ-PIPERAQUINE; SULFADOXINE-PYRIMETHAMINE; OPEN-LABEL; P.-VIVAX; FALCIPARUM; COMBINATION; INFECTION; EFFICACY; MALAYSIA;

D O I：

10.1186/s12916-019-1386-6

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundMalaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax.MethodsA systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model.ResultsIn total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64g/dL [11.36, 11.93] on day 2, before rising to 12.88g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was -0.13g/dL [-0.27, 0.01] lower at day of nadir (p=0.072), but 0.49g/dL [0.28, 0.69] higher by day 42 (p<0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration -0.72g/dL [-0.90, -0.54] lower than patients without recurrence (p<0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin >25% to <7g/dL) and a 1% (4/389) risk of a fall in haemoglobin >5g/dL.ConclusionsPrimaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals.Trial registrationThis trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.

引用

页数：13

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