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
<strong>Background</strong> Malaria 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 pri...
| Κύριοι συγγραφείς: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Μορφή: | Journal article |
| Γλώσσα: | English |
| Έκδοση: |
BioMed Central
2019
|
| _version_ | 1826289586269061120 |
|---|---|
| author | Commons, RJ Simpson, JA Thriemer, K Chu, CS Douglas, NM Abreha, T Alemu, SG Añez, A Anstey, NM Aseffa, A Assefa, A Awab, GR Baird, JK Barber, BE Borghini-Fuhrer, I D’Alessandro, U Dahal, P Daher, A De Vries, PJ Erhart, A Gomes, MSM Grigg, MJ Hwang, J Kager, PA Ketema, T Khan, WA Lacerda, MVG Leslie, T Ley, B Lidia, K Monteiro, WM Pereira, DB Phan, GT Phyo, AP Rowland, M Saravu, K Sibley, CH Siqueira, AM Stepniewska, K Taylor, WRJ Thwaites, G Tran, BQ Hien, TT Vieira, JLF Wangchuk, S Watson, J William, T Woodrow, CJ Nosten, F Guerin, PJ White, NJ Price, RN |
| author_facet | Commons, RJ Simpson, JA Thriemer, K Chu, CS Douglas, NM Abreha, T Alemu, SG Añez, A Anstey, NM Aseffa, A Assefa, A Awab, GR Baird, JK Barber, BE Borghini-Fuhrer, I D’Alessandro, U Dahal, P Daher, A De Vries, PJ Erhart, A Gomes, MSM Grigg, MJ Hwang, J Kager, PA Ketema, T Khan, WA Lacerda, MVG Leslie, T Ley, B Lidia, K Monteiro, WM Pereira, DB Phan, GT Phyo, AP Rowland, M Saravu, K Sibley, CH Siqueira, AM Stepniewska, K Taylor, WRJ Thwaites, G Tran, BQ Hien, TT Vieira, JLF Wangchuk, S Watson, J William, T Woodrow, CJ Nosten, F Guerin, PJ White, NJ Price, RN |
| author_sort | Commons, RJ |
| collection | OXFORD |
| description | <strong>Background</strong> Malaria 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. <br/><br/> <strong>Methods</strong> A 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. <br/><br/> <strong>Results</strong> In 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 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/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 − 0.13 g/dL [− 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration − 0.72 g/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 < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL. <br/><br/> <strong>Conclusions</strong> Primaquine 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. <br/><br/> <strong>Trial registration</strong> This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016. |
| first_indexed | 2024-03-07T02:31:17Z |
| format | Journal article |
| id | oxford-uuid:a746ba1c-bd4e-485e-8ca2-7f77be2be852 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:31:17Z |
| publishDate | 2019 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:a746ba1c-bd4e-485e-8ca2-7f77be2be8522022-03-27T02:53:53ZThe 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-analysisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a746ba1c-bd4e-485e-8ca2-7f77be2be852EnglishSymplectic Elements at OxfordBioMed Central2019Commons, RJSimpson, JAThriemer, KChu, CSDouglas, NMAbreha, TAlemu, SGAñez, AAnstey, NMAseffa, AAssefa, AAwab, GRBaird, JKBarber, BEBorghini-Fuhrer, ID’Alessandro, UDahal, PDaher, ADe Vries, PJErhart, AGomes, MSMGrigg, MJHwang, JKager, PAKetema, TKhan, WALacerda, MVGLeslie, TLey, BLidia, KMonteiro, WMPereira, DBPhan, GTPhyo, APRowland, MSaravu, KSibley, CHSiqueira, AMStepniewska, KTaylor, WRJThwaites, GTran, BQHien, TTVieira, JLFWangchuk, SWatson, JWilliam, TWoodrow, CJNosten, FGuerin, PJWhite, NJPrice, RN<strong>Background</strong> Malaria 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. <br/><br/> <strong>Methods</strong> A 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. <br/><br/> <strong>Results</strong> In 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 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/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 − 0.13 g/dL [− 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration − 0.72 g/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 < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL. <br/><br/> <strong>Conclusions</strong> Primaquine 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. <br/><br/> <strong>Trial registration</strong> This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016. |
| spellingShingle | Commons, RJ Simpson, JA Thriemer, K Chu, CS Douglas, NM Abreha, T Alemu, SG Añez, A Anstey, NM Aseffa, A Assefa, A Awab, GR Baird, JK Barber, BE Borghini-Fuhrer, I D’Alessandro, U Dahal, P Daher, A De Vries, PJ Erhart, A Gomes, MSM Grigg, MJ Hwang, J Kager, PA Ketema, T Khan, WA Lacerda, MVG Leslie, T Ley, B Lidia, K Monteiro, WM Pereira, DB Phan, GT Phyo, AP Rowland, M Saravu, K Sibley, CH Siqueira, AM Stepniewska, K Taylor, WRJ Thwaites, G Tran, BQ Hien, TT Vieira, JLF Wangchuk, S Watson, J William, T Woodrow, CJ Nosten, F Guerin, PJ White, NJ Price, RN 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| work_keys_str_mv | AT commonsrj thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT simpsonja thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT thriemerk thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT chucs thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT douglasnm thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT abrehat thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT alemusg thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT aneza thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT ansteynm thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT aseffaa thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT assefaa thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT awabgr thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT bairdjk thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT barberbe thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT borghinifuhreri thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT dalessandrou thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT dahalp thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT dahera thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT devriespj thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT erharta thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT gomesmsm thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT griggmj thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT hwangj thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT kagerpa thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT ketemat thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT khanwa thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT lacerdamvg thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT lesliet thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT leyb thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT lidiak thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT monteirowm thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT pereiradb thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT phangt thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT phyoap thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT rowlandm thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT saravuk thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT sibleych thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT siqueiraam thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT stepniewskak thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT taylorwrj thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT thwaitesg thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT tranbq thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT hientt thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT vieirajlf thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT wangchuks thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT watsonj thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT williamt thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT woodrowcj thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT nostenf thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT guerinpj thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT whitenj thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT pricern thehaematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT commonsrj haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT simpsonja haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT thriemerk haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT chucs haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT douglasnm haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT abrehat haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT alemusg haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT aneza haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT ansteynm haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT aseffaa haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT assefaa haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT awabgr haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT bairdjk haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT barberbe haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT borghinifuhreri haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT dalessandrou haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT dahalp haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT dahera haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT devriespj haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT erharta haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT gomesmsm haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT griggmj haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT hwangj haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT kagerpa haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT ketemat haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT khanwa haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT lacerdamvg haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT lesliet haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT leyb haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT lidiak haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT monteirowm haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT pereiradb haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT phangt haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT phyoap haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT rowlandm haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT saravuk haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT sibleych haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT siqueiraam haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT stepniewskak haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT taylorwrj haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT thwaitesg haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT tranbq haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT hientt haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT vieirajlf haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT wangchuks haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT watsonj haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT williamt haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT woodrowcj haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT nostenf haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT guerinpj haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT whitenj haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis AT pricern haematologicalconsequencesofplasmodiumvivaxmalariaafterchloroquinetreatmentwithandwithoutprimaquineaworldwideantimalarialresistancenetworksystematicreviewandindividualpatientdatametaanalysis |