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Meta-Analysis
. 2013 Oct 26;2013(10):CD004389.
doi: 10.1002/14651858.CD004389.pub3.

Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine

Gawrie N L Galappaththy  1 , Prathap Tharyan, Richard Kirubakaran
Affiliations
Meta-Analysis

Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine

Gawrie N L Galappaththy et al. Cochrane Database Syst Rev. .

Abstract

Background: Plasmodium vivax infections are an important contributor to the malaria burden worldwide. The World Health Organization recommends a 14-day course of primaquine (0.25 mg/kg/day, giving an adult dose of 15 mg/day) to eradicate the liver stage of the parasite and prevent relapse of the disease. Many people find a 14-day primaquine regimen difficult to complete, and there is a potential risk of haemolytic anaemia in people with glucose-6-phosphate-dehydrogenase enzyme (G6PD) deficiency. This review evaluates primaquine in P. vivax, particularly alternatives to the standard 14-day course.

Objectives: To compare alternative primaquine regimens to the recommended 14-day regimen for preventing relapses (radical cure) in people with P. vivax malaria treated for blood stage infection with chloroquine. We also summarize trials comparing primaquine to no primaquine that led to the recommendation for the 14-day regimen.

Search methods: We searched the Cochrane Infectious Diseases Group's Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE and LILACS up to 8 October 2013. We checked conference proceedings, trial registries and reference lists and contacted researchers and pharmaceutical companies for eligible studies.

Selection criteria: Randomized controlled trials (RCTs) and quasi-RCTs comparing various primaquine dosing regimens with the standard primaquine regimen (15 mg/day for 14 days), or with no primaquine, in people with vivax malaria treated for blood stage infection with chloroquine.

Data collection and analysis: We independently assessed trial eligibility, trial quality, and extracted data. We calculated risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model in meta-analyses if there was significant heterogeneity. We assessed the overall quality of the evidence using the GRADE approach.

Main results: We included 15 trials (two cluster-RCTs) of 4377 adult and child participants. Most trials excluded people with G6PD deficiency. Trials compared various regimens of primaquine with the standard primaquine regimen, or with placebo or no treatment. All trials treated blood stage infection with chloroquine. Alternative primaquine regimens compared to 14-day primaquineRelapse rates were higher over six months with the five-day primaquine regimen than the standard 14-day regimen (RR 10.05, 95% CI 2.82 to 35.86; two trials, 186 participants, moderate quality evidence). Similarly, relapse over six months was higher with three days of primaquine than the standard 14-day regimen (RR 3.18, 95% CI 2.1 to 4.81; two trials, 262 participants, moderate quality evidence; six months follow-up); and with primaquine for seven days followed up over two months, compared to 14-day primaquine (RR 2.24, 95% CI 1.24 to 4.03; one trial, 126 participants, low quality evidence).Relapse with once-weekly supervised primaquine for eight weeks was little different over nine months follow-up compared to 14-day self-administered primaquine in one small study (RR 2.97, 95% CI 0.34 to 25.87; one trial, 129 participants, very low quality evidence). Primaquine regimens compared to no primaquineThe number of people that relapsed was similar between people given five days of primaquine or given placebo or no primaquine (four trials, 2213 participants, high quality evidence; follow-up six to 15 months); but lower with 14 days of primaquine (RR 0.6; 95% CI 0.48 to 0.75; ten trials, 1740 participants, high quality evidence; follow-up seven weeks to 15 months).No serious adverse events were reported. Treatment-limiting adverse events were rare and non-serious adverse events were mild and transient. Trial authors reported that people tolerated the drugs.We did not find trials comparing higher dose primaquine regimens (0.5 mg/kg/day or more) for five days or more with the 14-day regimen.

Authors' conclusions: The analysis confirms the current World Health Organization recommendation for 14-day primaquine (15 mg/day) to prevent relapse of vivax malaria. Shorter primaquine regimens at the same daily dose are associated with higher relapse rates. The comparative effects with weekly primaquine are promising, but require further trials to establish equivalence or non-inferiority compared to the 14-day regimen in high malaria transmission settings.

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Conflict of interest statement

GG, PT and RK have no known conflicts of interest to declare.

Figures

1
1
Study flow diagram: 2013 review update
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Primaquine: 5 days versus 14 days, outcome: 1.1 P. vivax parasitaemia > 30 days after starting primaquine.
5
5
Primaquine (5 days) plus chloroquine versus chloroquine: P. vivax parasitaemia detected > 30 days after starting primaquine.
6
6
Forest plot of comparison: 6 Chloroquine plus primaquine (14 days) versus chloroquine, outcome: 6.1 P. vivax parasitaemia detected > 30 days after starting primaquine.
1.1
1.1. Analysis
Comparison 1 Primaquine: 5 days versus 14 days, Outcome 1 P. vivax parasitaemia > 30 days after starting primaquine.
2.1
2.1. Analysis
Comparison 2 Primaquine: 3 days versus 14 days, Outcome 1 P. vivax parasitaemia > 30 days after starting primaquine.
3.1
3.1. Analysis
Comparison 3 Primaquine: 7 days versus 14 days, Outcome 1 P. vivax parasitaemia > 30 days after starting primaquine.
4.1
4.1. Analysis
Comparison 4 Primaquine: weekly for 8 weeks versus daily for 14 days, Outcome 1 P. vivax parasitaemia > 30 days after starting primaquine.
5.1
5.1. Analysis
Comparison 5 Primaquine 5 days versus no primaquine, Outcome 1 P. vivax parasitaemia > 30 days after starting primaquine.
6.1
6.1. Analysis
Comparison 6 Primaquine 14 days versus no primaquine, Outcome 1 P. vivax parasitaemia detected > 30 days after starting primaquine.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Alvarez 2006 {published data only}
    1. Alvarez G, Pineros JG, Tobon A, Rios A, Maestre A, Blair S, et al. Efficacy of three chloroquine‐primaquine regimens for treatment of Plasmodium vivax malaria in Colombia. American Journal of Tropical Medicine and Hygiene 2006;75(4):605‐9. - PubMed
Carmona‐Fonseca 2009 {published data only}
    1. Carmona‐Fonseca J, Maestre A. Prevention of Plasmodium vivax malaria recurrence: efficacy of the standard total dose of primaquine administered over 3 days. Acta Tropica 2009;112(2):188‐92. - PubMed
Ganguly 2013 {published data only}
    1. Ganguly S. Studies on P. vivax malaria in urban population of Kolkata with special reference to chloroquine sensitivity and relapse pattern. Clinical Trials Registry India. [Registration Number: CTRI/2011/09/002031]
    1. Ganguly S, Saha P, Guha SK, Das S, Bera DK, Biswas A, et al. In vivo therapeutic efficacy of chloroquine alone or in combination with primaquine against vivax malaria in Kolkata, West Bengal, India, and polymorphism in pvmdr1 and pvcrt‐0 genes. Antimicrobial Agents and Chemotherapy 2013;57(3):1246‐51. - PMC - PubMed
Gogtay 1999 {published and unpublished data}
    1. Gogtay NJ, Deshai S, Kamtekar KD, Kadam VS, Dalvi SS, Kshirsagar NA. Efficacies of 5 and 14 day primaquine regimens in the prevention of relapses in Plasmodium vivax infections. Annals of Tropical Medicine and Parasitology 1999;93(8):809‐12. - PubMed
Kim 2012 {published data only (unpublished sought but not used)}
    1. ISRCTN14027467. Open label comparison of chloroquine (CQ) alone versus CQ plus 5 days unobserved primaquine or CQ plus 14 days unobserved primaquine. http://www.controlled‐trials.com/ISRCTN14027467/ Vol. (accessed 22 July 2013).
    1. Kim J‐R, Nandy A, Pukrittayakamee S, White NJ, Imwong M. A randomised trial to assess the effectiveness of different primaquine regimens for the radical treatment of vivax malaria in Kolkota. PLoS ONE 2012; Vol. 7, issue 7:S1.
    1. Kim JR, Nandy A, Maji AK, Addy M, Dondorp AM, Day NPJ, et al. Genotyping of Plasmodium vivax reveals both short and long latency relapse patterns in Kolkata. PLoS ONE 2012;7(7):e39645. - PMC - PubMed
Leslie 2004 {published data only}
    1. Leslie T, Rab MA, Ahmadzai H, Durrani N, Fayaz M, Kolaczinski J, et al. Compliance with 14‐day primaquine therapy for radical cure of vivax malaria ‐ a randomized placebo‐controlled trial comparing unsupervised with supervised treatment. Transactions of the Royal Society of Tropical Medicine and Hygiene 2004;98(3):168‐73. - PubMed
Leslie 2008 {published data only (unpublished sought but not used)}
    1. Leslie T, Mayan I, Mohammed N, Erasmus P, Kolaczinski J, Whitty CJ, et al. A randomised trial of an eight‐week, once weekly primaquine regimen to prevent relapse of Plasmodium vivax in Northwest Frontier Province, Pakistan. PLoS ONE 2008;3(8):e2861. - PMC - PubMed
    1. Leslie T, Mayan I, Mohammed N, Erasmus P, Kolaczinski J, Whitty CJ, et al. Abstract 337: A randomised trial of an eight‐week, once weekly primaquine regimen to prevent relapse of Plasmodium vivax in Pakistan. American Journal of Tropical Medicine and Hygiene 2008;79(Suppl 6):120. - PMC - PubMed
Pukrittayakamee 1994 {published data only}
    1. Pukrittayakamee S, Vanijanonta S, Chantra A, Clemens R, White NJ. Blood stage antimalarial efficacy of primaquine in Plasmodium vivax malaria. Journal of Infectious Diseases 1994;169(4):932‐5. - PubMed
Rajgor 2003 {published and unpublished data}
    1. Rajgor DD, Gogtay NJ, Kadam VS, Kamtekar KD, Dalvi SS, Chogle AR, et al. Efficacy of a 14‐day primaquine regimen in preventing relapses in patients with Plasmodium vivax malaria in Mumbai, India. Transactions of the Royal Society of Tropical Medicine and Hygiene 2003;97(4):438‐40. - PubMed
Rowland 1999a {published data only}
    1. Rowland M, Durrani N. Randomized controlled trials of 5‐ and 14‐days primaquine therapy against relapses of vivax malaria in an Afghan refugee settlement in Pakistan. Transactions of the Royal Society of Tropical Medicine and Hygiene 1999;93(6):641‐3. - PubMed
Rowland 1999b {published data only}
    1. Rowland M, Durrani N. Randomized controlled trials of 5‐ and 14‐days primaquine therapy against relapses of vivax malaria in an Afghan refugee settlement in Pakistan. Transactions of the Royal Society of Tropical Medicine and Hygiene 1999;93(6):641‐3. - PubMed
Villalobos 2000 {published data only}
    1. Villalobos‐Salcedo JM, Tada MS, Kimura E, Menezes MJ, Pereira da Silva LH. In‐vivo sensitivity of Plasmodium vivax isolates from Rondonia (western Amazon region, Brazil) to regimens including chloroquine and primaquine. Annals of Tropical Medicine and Parasitology 2000;94(8):749‐58. - PubMed
Walsh 2004 {published data only}
    1. Walsh DS, Wilairatana P, Tang DB, Heppner DG Jr, Brewer TG, Krudsood S, et al. Randomized trial of 3‐dose regimens of tafenoquine (WR238605) versus low‐dose primaquine for preventing Plasmodium vivax malaria relapse. Clinical Infectious Diseases 2004;39(8):1095‐103. - PubMed
Yadav 2002 {published data only}
    1. Yadav RS, Ghosh SK. Radical curative efficacy of five‐day regimen of primaquine for treatment of Plasmodium vivax malaria in India. Journal of Parasitology 2002;88(5):1042‐4. - PubMed
Yeshiwondim 2010 {published data only}
    1. Yeshiwondim AK, Tekle A, Dengela DO, Yohannes AM, Teklehaimanot A. Therapuetic efficacy of chloroquine and chloroquine plus primaquine for the treatment of Plasmodium vivax in Ethiopia. Acta Tropica 2010;113(2):105‐13. - PubMed

References to studies excluded from this review

Abdon 2001 {published data only}
    1. Abdon NP, Pinto AY, das Silva Rdo S, Souza JM. Assessment of the response to reduced treatment schemes for vivax malaria. Revista da Sociedade Brasileira de Medicina Tropical 2001;34(4):343‐8. - PubMed
ACTRN1261000055406 {unpublished data only}
    1. Congpuong K. Efficacy and safety of chloroquine for the treatment of uncomplicated Plasmodium vivax malaria in Mae Hong Son and Kanchanaburi provinces in Thailand. http://www.anzctr.org.au/ACTRN12610000554066.aspx (accessed November 28, 2010).
ACTRN12613000003774 {unpublished data only}
    1. Sim K. Assessing the safety of weekly administered primaquine in vivax malaria infected Cambodians. http://www.anzctr.org.au/ACTRN12613000003774.aspx (accessed 8 October 2013).
Appavoo 1984 {published data only}
    1. Appavoo NC, Roy RG, Kapali V. Results of 3‐day radical treatment of Plasmodium vivax in North Arcot and South Arcot Districts of Tamil Nadu. Indian Journal of Malariology 1984;21(1):21‐4. - PubMed
Arango 2012 {published data only}
    1. Arango EM, Upegui YA, Carmona‐Fonseca J. Efficacy of different primaquine‐based antimalarial regimens against Plasmodium falciparum gametocytemia. Acta Tropica 2012;122(2):177‐82. - PubMed
Baird 1995 {published data only}
    1. Baird JK, Fryauff DJ, Basri H, Bangs MJ, Subianto B, Wiady I, et al. Primaquine for prophylaxis against malaria among nonimmune transmigrants in Irian Jaya, Indonesia. American Journal of Tropical Medicine and Hygiene 1995;52(6):479‐84. - PubMed
Baird 2001 {published data only}
    1. Baird JK, Lacy MD, Basri H, Barcus MJ, Maguire JD, Bangs MJ, et al. Randomized, parallel placebo‐controlled trial of primaquine for malaria prophylaxis in Papua, Indonesia. Clinical Infectious Diseases 2001;33(12):1990‐7. - PubMed
Baird 2003b {published data only}
    1. Baird JK, Fryauff DJ, Hoffman SL. Primaquine for prevention of malaria in travellers. Clinical Infectious Diseases 2003;37(12):1659‐67. - PubMed
Basavaraj 1960 {published data only}
    1. Basavaraj HR. Observations on the treatment of 678 malaria cases with primaquine in an area free from malaria transmission in Mysore State, India. Indian Journal of Malariology 1960;14:269‐81. - PubMed
Betuela 2012a {published data only}
    1. Betuela I, Bassat Q, Kiniboro B, Robinson LJ, Rosanas‐Urgell A, Stanisic D, et al. Tolerability and safety of primaquine in Papua New Guinean children 1 to 10 years of age. Antimicrobial Agents and Chemotherapy 2012;56(4):2146‐9. - PMC - PubMed
Betuela 2012b {published data only}
    1. Betuela I, Rosanas A, Kiniboro B, Stanisic D, Samol L, Lazzari E, et al. Relapses are contributing significantly to risk of P. vivax infection and disease in Papua New Guinean children 1‐5 years of age. Tropical Medicine and International Health. 7th European Congress on Tropical Medicine and International Health; 2011 October 03‐06; Barcelona. Barcelona: Tropical Medicine and International Health, 2011; Vol. 16:60‐61.
    1. Betuela I, Rosanas‐Urgell A, Kiniboro B, Stanisic DI, Samol L, Lazzari E, et al. Relapses contribute significantly to the risk of Plasmodium vivax infection and disease in Papua New Guinean children 1‐5 years of age. Journal of Infectious Diseases 2012;206(11):1771‐80. - PubMed
Buchachart 2001 {published data only}
    1. Buchachart K, Krudsood S, Singhasivanon P, Treeprasertsuk S, Phophak N, Srivilairit S, et al. Effect of primaquine standard dose (15 mg/day for 14 days) in the treatment of vivax malaria patients in Thailand. Southeast Asian Journal of Tropical Medicine and Public Health 2001;32(4):720‐6. - PubMed
Bunnag 1994 {published data only}
    1. Bunnag D, Karbwang J, Thanavibul A, Chittamas S, Ratanapongse Y, Chalermrut K, et al. High dose of primaquine in primaquine resistant vivax malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 1994;88(2):218‐9. - PubMed
Carmona‐Fonseca 2003 {published data only}
    1. Carmona‐Fonseca J, Alvarez G. Plasmodium vivax malaria: treatment of primary attacks with primaquine, in three different doses, and a fixed dose of chloroquine, Antioquia, Colombia, 2003‐2004. Biomedica 2006;26(3):353‐65. - PubMed
Carmona‐Fonseca 2006 {published data only}
    1. Carmona‐Fonseca J, Alvarez G. Plasmodium vivax malaria: treatment of primary attacks with primaquine, in three different doses, and a fixed dose of chloroquine, Antioquia, Colombia, 2003‐2004. Biomedica 2006;26(3):353‐65. - PubMed
Carmona‐Fonseca 2009a {published data only}
    1. Carmona‐Fonseca J, Álvarez G, Maestre A. Methemoglobinemia and adverse events in Plasmodium vivax malaria patients associated with high doses of primaquine treatment. American Journal of Tropical Medicine and Hygiene 2009;80(2):188‐93. - PubMed
Carmona‐Fonseca 2010 {published data only}
    1. Carmona‐Fonseca J. Vivax malaria in children: recurrences with standard total dose of primaquine administered in 3 versus 7 days [Malaria vivax en ninos: recurrencias con dosis total estandar de primaquina administrada durante 3 frente a 7 dias]. Iatreia 2010;23(1):10‐20.
Cedillos 1978 {published data only}
    1. Cedillos RA, Warren M, Jeffery GM. Field evaluation of primaquine in the control of Plasmodium vivax. American Journal of Tropical Medicine and Hygiene 1978;27(3):466‐72. - PubMed
Clyde 1977 {published data only}
    1. Clyde DF, McCarthy VC. Radical cure of Chesson strain vivax malaria in man by 7, not 14, days of treatment with primaquine. American Journal of Tropical Medicine and Hygiene 1977;26(3):562‐3. - PubMed
Contacos 1974 {published data only}
    1. Contacos PG, Collins WE, Chin W, Jeter MH, Briesch PE. Combined chloroquine‐primaquine therapy against vivax malaria. American Journal of Tropical Medicine and Hygiene 1974;23(2):310‐2. - PubMed
CTRI/2011/09/002031 {unpublished data only}
    1. Maji A. A study to determine the effectiveness of two drugs chloroquine and primaquine in P. vivax malaria in Kolkata. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=3592 (accessed April 10, 2012). [CTRI/2011/09/002031]
CTRI/2012/03/002511 {unpublished data only}
    1. Joglekar S, Jalal, J. TAF112582‐ A multi‐centre, double‐blind, randomised, parallel‐group, active‐controlled study to evaluate the efficacy, safety and tolerability of tafenoquine (SB‐252263,WR238605) in subjects with Plasmodium vivax malaria. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=4295 (accessed 13 April 2012).
Dao 2007 {published data only}
    1. Dao NV, Cuong BT, Ngoa ND, Thuy le TT, The ND, Duy DN, et al. Vivax malaria: preliminary observations following a shorter course of treatment with artesunate plus primaquine. Transactions of the Royal Society of Tropical Medicine and Hygiene 2007;101(6):534‐9. - PubMed
da Silva 2003 {published data only}
    1. Silva Rdo S, Pinto AY, Calvosa VS, Souza JM. Short course schemes for vivax malaria treatment [Esquemas terapeuticos encurtados para o tratamento de malaria por Plasmodium vivax]. Revista da Sociedade Brasileira de Medicina Tropical 2003;36(2):235‐9. - PubMed
Dua 2001 {published data only}
    1. Dua VK, Sharma VP. Plasmodium vivax relapses after 5 days of primaquine treatment, in some industrial complexes of India. Annals of Tropical Medicine and Parasitology 2001;95(7):655‐9. - PubMed
Elmes 2008 {published data only}
    1. Elmes NJ, Nasveld PE, Kitchener SJ, Kocisko D A, Edstein MD. The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post‐exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2008;102(11):1095‐101. - PubMed
Fryauff 1997 {published data only}
    1. Fryauff DJ, Baird JK, Purnomo, Awalludin M, Jones T, Subianto B, et al. Malaria in a nonimmune population after extended chloroquine or primaquine prophylaxis. American Journal of Tropical Medicine and Hygiene 1997;56(2):137‐40. - PubMed
Gogtay 1998 {published data only}
    1. Gogtay N, Garg M, Kadam V, Kamtekar K, Kshirsagar NA. A 5 days primaquine regimen as anti‐relapse therapy for Plasmodium vivax. Transactions of the Royal Society of Tropical Medicine and Hygiene 1998;92(3):341. - PubMed
Hamedi 2004 {published data only}
    1. Hamedi Y, Safa O, Zare S, Tan‐ariya P, Kojima S, Looareesuwan S. Therapeutic efficacy of artesunate in Plasmodium vivax malaria in Thailand. Southeast Asian Journal of Tropical Medicine and Public Health 2004;35(3):570‐4. - PubMed
Herrera 2011 {published data only}
    1. Herrera S, Solarte Y, Jordán‐Villegas A, Echavarría JF, Rocha L, Palacios R, et al. Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria‐naive human volunteers. American Journal of Tropical Medicine and Hygiene 2011;2 Suppl:4‐11. - PMC - PubMed
ISRCTN82366390 {unpublished data only}
    1. Nelwn EJ. Randomized, open‐label trial of the safety, tolerability and efficacy of primaquine against relapse when combined with pyronaridine tetraphosphate‐artesunate or dihydroartemisinin‐piperquine phosphate for radical cure of acute Plasmodium vivax malaria in soldiers. http://isrctn.org/ISRCTN82366390 (accessed 8 October 2013).
Kolaczinski 2012 {published data only}
    1. Kolaczinski K, Leslie T, Ali I, Durrani N, Lee S, Barends M, et al. Defining Plasmodium falciparum treatment in South West Asia: a randomized trial comparing artesunate or primaquine combined with chloroquine or SP. PLoS One 2012;7(1):e28957. - PMC - PubMed
Looareesuwan 1999 {published data only}
    1. Looareesuwan S, Wilairatana P, Krudsood S, Treeprasertsuk S, Singhasivanon P, Bussaratid V, et al. Chloroquine sensitivity of Plasmodium vivax in Thailand. Annals of Tropical Medicine and Parasitology 1999;93(3):225‐30. - PubMed
Luxemburger 1999 {published data only}
    1. Luxemburger C, Vugt M, Jonathan S, McGready R, Looareesuwan S, White NJ, et al. Treatment of vivax malaria on the western border of Thailand. Transactions of the Royal Society of Tropical Medicine and Hygiene 1999;93(4):433‐8. - PubMed
Manneeboonyang 2011 {published data only}
    1. Maneeboonyang W, Lawpoolsri S, Puangsa‐Art S, Yimsamran S, Thanyavanich N, Wuthisen P, et al. Directly observed therapy with primaquine to reduce the recurrence rate of Plasmodium vivax infection along the Thai‐Myanmar border. Southeast Asian Journal of Tropical Medicine and Public Health 2011;42(1):9‐18. - PubMed
Nasveld 2010 {published data only}
    1. Nasveld PE, Edstein MD, Reid M, Brennan L, Harris IE, Kitchener SJ, et al. Randomized, double‐blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrobial Agents and Chemotherapy 2010;54(2):792‐8. - PMC - PubMed
NCT01074905 {unpublished data only}
    1. Chu C, Chia PY. A randomised open label study comparing the efficacy of chloroquine/primaquine, chloroquine and artesunate in the treatment of vivax malaria along the Thai‐Burmese border. http://clinicaltrials.gov/show/NCT01074905 (accessed 13 April 2012). [SMRU0908 ]
    1. Nosten F, Cheah PY. Study on the treatment of vivax malaria (VHX). http://clinicaltrials.gov/ct2/show/record/NCT01074905 (accessed November 28, 2010). [CTG: NCT01074905; Secondary ID: SMRU0908]
NCT01288820 {unpublished data only}
    1. Pasaribu AP. Comparison of the efficacy and safety of two ACTs plus primaquine for uncomplicated Plasmodium vivax malaria in North Sumatera, Indonesia: 1 year follow up. http://clinicaltrials.gov/show/NCT01288820 (accessed 13 April 2012).
NCT01290601 {unpublished data only}
    1. Looareesuwan S, Miller RE. Study to evaluate the efficacy and safety of tafenoquine for the treatment of Plasmodium vivax in adults. http://clinicaltrials.gov/show/NCT01290601 (accessed 13 April 2012).
NCT01716260 {unpublished data only}
    1. Dorjey Y. Parasitic clearance and recurrence rates among patients with vivax malaria on chloroquine and primaquine therapy. http://clinicaltrials.gov/show/NCT01716260 (accessed 8 October 2013).
NCT01780753 {unpublished data only}
    1. McGready R. A study of the pharmacokinetics of primaquine in lactating women and breastfed infants for the radical treatment of uncomplicated maternal P. vivax. http://clinicaltrials.gov/show/NCT01780753 (accessed 8 October 2013).
NCT01814683 {unpublished data only}
    1. Price R. Improving the radical cure of vivax malaria: A multicentre randomised comparison of short and long course primaquine regimens. http://clinicaltrials.gov/show/NCT01814683 (accessed 8 October 2013).
NCT01837992 {unpublished data only}
    1. Mueller I. Evaluation of Safety and Efficacy of Two Primaquine Dosing Regimens for the Radical Treatment of Plasmodium Vivax Malaria in Vanuatu and Solomon Islands. http://clinicaltrials.gov/show/NCT01837992 (accessed 8 October 2013).
Pasaribu 2013 {published data only}
    1. Pasaribu AP, Chokejindachai W, Sirivichayakul C, Tanomsing N, Chavez I, Tjitra E, et al. A randomized comparison of dihydroartemisinin‐piperaquine and artesunate‐amodiaquine combined With primaquine for radical treatment of vivax malaria in Sumatera, Indonesia. Journal of Infectious Diseases 2013;Aug 28:[Epub ahead of print]. - PMC - PubMed
Pinto 1998 {published data only}
    1. Pinto AY, Ventura AM, Calvosa VS, Silva Filho MG, Santos MA, Silva RS, et al. Clinical efficacy of four schemes for vivax malaria treatment in children. Jornal de Pediatria 1998;74(3):222‐7. - PubMed
Prasad 1991 {published data only}
    1. Prasad RN, Virk KJ, Sharma VP. Relapse/reinfection patterns of Plasmodium vivax infection: a four year study. Southeast Asian Journal of Tropical Medicine and Public Health 1991;22(4):499‐503. - PubMed
Pukrittayakamee 2010 {published data only}
    1. Pukrittayakamee S, Imwong M, Chotivanich K, Singhasivanon P, Day NP, White NJ. A comparison of two short‐course primaquine regimens for the treatment and radical cure of Plasmodium vivax malaria in Thailand. American Journal of Tropical Medicine and Hygiene 2010;82(4):542‐7. - PMC - PubMed
RBR‐77q7t3 {unpublished data only}
    1. Pereira D. Study of efficacy and safety of a new co‐blister packs of chloroquine and primaquine for malaria treatment of uncomplicated Plasmodium vivax in Brasil. http://www.ensaiosclinicos.gov.br/rg/RBR‐77q7t3/v1/ (accessed 13 April 2012).
Roy 1977 {published data only}
    1. Roy RG, Chakrapani KP, Dhinagaran D, Sitaraman NL, Ghosh RB. Efficacy of 5‐day radical treatment of P. vivax infection in Tamil Nadu. Indian Journal of Medical Research 1977;65(5):652‐6. - PubMed
Saint‐Yves 1977 {published data only}
    1. Saint‐Yves IF. Comparison of treatment schedules for Plasmodium vivax infections in the Solomon Islands. Papua New Guinea Medical Journal 1977;20(2):62‐5. - PubMed
Schwartz 2000 {published data only}
    1. Schwartz E, Regev‐Yochay G, Kurnik D. Short report: a consideration of primaquine dose adjustment for radical cure of Plasmodium vivax malaria. American Journal of Tropical Medicine and Hygiene 2000;62(3):393‐5. - PubMed
Sharma 1973 {published data only}
    1. Sharma MID, Sehgal PN, Vaid BK, Dubey RC, Nagendra S, Paithne PK, et al. Effectiveness of drug schedule being followed under the National Malaria Eradication Programme, India, for radical cure of vivax malaria cases. Journal of Communicable Diseases 1973;5:167‐74.
Shekalaghe 2010 {published data only}
    1. Shekalaghe SA, ter Braak R, Daou M, Kavishe R, Bijllaardt W, Bosch S, et al. In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose‐6‐phosphate dehydrogenase‐deficient (G6PD A‐) individuals. Antimicrobial Agents and Chemotherapy 2010;54(5):1762‐8. - PMC - PubMed
Shekalaghe 2011 {published data only}
    1. Shekalaghe SA, Drakeley C, Bosch S, Ter Braak R, Bijllaardt W, Mwanziva C, et al. A cluster‐randomized trial of mass drug administration with a gametocytocidal drug combination to interrupt malaria transmission in a low endemic area in Tanzania. Malaria Journal 2011;10:247. - PMC - PubMed
Shin 2011 {published data only}
    1. Shin CS, Kwak YG, Lee KD, Borghini‐Fuhrer I, Miller RM, Duparc S. Treatment of Korean vivax malaria patients with the fixed‐dose combination of pyronaridine/artesunate. Tropical Medicine and International Health. 7th European Congress on Tropical Medicine and International Health; January 3 to 6, 2011; Barcelona. Barcelona: Tropical Medicine and International Health, 2011; Vol. 16, issue 1:149.
Singh 1990 {published data only}
    1. Singh N, Mishra AK, Sharma VP. Radical treatment of vivax malaria in Madhya Pradesh, India. Indian Journal of Malariology 1990;27(1):55‐6. - PubMed
Sinha 1989 {published data only}
    1. Sinha S, Dua VK, Sharma VP. Efficacy of 5 day radical treatment of primaquine in Plasmodium vivax cases at the BHEL industrial complex, Hardwar (U.P.). Indian Journal of Malariology 1989;26(2):83‐6. - PubMed
Smithuis 2010 {published data only}
    1. Smithuis F, Kyaw MK, Phe O, Win T, Aung PP, Oo AP, et al. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open‐label randomised trial. Lancet Infectious Diseases 2010;10(10):673‐81. - PMC - PubMed
Soto 1998 {published data only}
    1. Soto J, Toledo J, Rodriquez M, Sanchez J, Herrera R, Padilla J, et al. Primaquine prophylaxis against malaria in nonimmune Colombian soldiers: efficacy and toxicity. A randomized, double‐blind, placebo‐controlled trial. Annals of Internal Medicine 1998;129(3):241‐4. - PubMed
Soto 1999 {published data only}
    1. Soto J, Toledo J, Rodriquez M, Sanchez J, Herrera R, Padilla J, et al. Double‐blind, randomized, placebo‐controlled assessment of chloroquine/primaquine prophylaxis for malaria in nonimmune Colombian soldiers. Clinical Infectious Diseases 1999;29(1):199‐201. - PubMed
Sutanto 2012 {published data only}
    1. Sutanto I, Tjahjono B, Basri H, Taylor WR, Putri FA, Meilia RA, et al. Randomized, open label trial of primaquine against vivax malaria relapse in Indonesia. Antimicrobial Agents and Chemotherapy 2012;57(3):1128‐35. - PMC - PubMed
Takeuchi 2010 {published data only}
    1. Takeuchi R, Lawpoolsri S, Imwong M, Kobayashi J, Kaewkungwal J, Pukrittayakamee S, et al. Directly‐observed therapy (DOT) for the radical 14‐day primaquine treatment of Plasmodium vivax malaria on the Thai‐Myanmar border. Malaria Journal 2010;9:308. - PMC - PubMed
Valibayov 2003 {published data only}
    1. Valibayov A, Abdullayev F, Mammadov S, Gasimov E, Sabatinelli G, Kondrachine AV, et al. Clinical efficacy of chloroquine followed by primaquine for Plasmodium vivax treatment in Azerbaijan. Acta Tropica 2003;88(1):99‐102. - PubMed
Vásquez 2009 {published data only}
    1. Vásquez AM, Sanín F, Álvarez LG, Tobón A, Ríos A, Blair S. Therapeutic efficacy of a regimen of artesunate‐mefloquine‐primaquine treatment for Plasmodium falciparum malaria and treatment effects on gametocytic development [Estudio piloto de la eficacia y de los efectos sobre los gametocitos del esquema artesunato‐mefloquina‐primaquina para la malaria por Plasmodium falciparum]. Biomédica 2009;29(2):307‐19. - PubMed
Wilairatana 1999 {published data only}
    1. Wilairatana P, Silachamroon U, Krudsood S, Singhasivanon P, Treeprasertsuk S, Bussaratid V, et al. Efficacy of primaquine regimens for primaquine‐resistant Plasmodium vivax malaria in Thailand. American Journal of Tropical Medical Hygiene 1999;61(6):973‐7. - PubMed

References to ongoing studies

NCT01178021 {unpublished data only}
    1. Awab GR, Cheah YP, Woodrow C. Estimating the risk of Plasmodium vivax relapses in Afghanistan (VRA). http://clinicaltrials.gov/ct2/show/study/NCT01178021 (accessed November 28, 2010). [CTG: NCT01178021 ; Secondary ID: BAKMAL0903]
NCT01376167 {unpublished data only}
    1. Hudson C. Ph 2B/3 tafenoquine (TFQ) study in prevention of vivax relapse. http://clinicaltrials.gov/show/NCT01376167 (accessed 13 April 2012).
NCT01640574 {unpublished data only}
    1. Chu C. Randomised parallel open label comparison between 7 and 14 day primaquine combined with 3‐day dihydroartemisinin‐piperaquine or 3‐day chloroquine regimens for radical cure of plasmodium vivax. http://clinicaltrials.gov/show/NCT01640574 (accessed 8 October 2013).
NCT01680406 {unpublished data only}
    1. Centers for Disease Control and Prevention. Ethiopia antimalarial in vivo efficacy study 2012: Evaluating the efficacy of artemether‐lumefantrine alone compared to artemether‐lumefantrine plus primaquine and chloroquine alone compared to chloroquine plus primaquine for Plasmodium vivax infection. http://clinicaltrials.gov/ct2/show/record/NCT01680406 (accessed 21 July 2013).

Additional references

Adak 2001
    1. Adak T, Valecha N, Sharma VP. Plasmodium vivax polymorphism in a clinical drug trial. Clinical and Diagnostic Laboratory Immunology 2001;8(5):891‐4. - PMC - PubMed
Alves 2002
    1. Alves FP, Durlacher RR, Menezes MJ, Krieger H, Silva LH, Camargo EP. High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations. American Journal of Tropical Medicine and Hygiene 2002;66(6):641‐8. - PubMed
Alving 1955
    1. Alving AS, Arnold J, Hockwald RS, Clayman CB, Dern RJ, Beutler E, et al. Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine. Journal of Laboratory and Clinical Medicine 1955;46(2):301‐6. - PubMed
Alving 1960
    1. Alving AS, Johnson CF, Tarlov AR, Brewer GJ, Kellermeyer RW, Carson PE. Mitigation of the haemolytic effect of primaquine and enhancement of its action against exoerythrocytic forms of the Chesson strain of Plasmodium vivax by intermittent regimens of drug administration: a preliminary report. Bulletin of the World Health Organization 1960;22:621‐31. - PMC - PubMed
Anstey 2007
    1. Anstey NM, Handojo T, Pain MC, Kenangalem E, Tjitra E, Price RN, et al. Lung injury in vivax malaria: pathophysiological evidence for pulmonary vascular sequestration and posttreatment alveolar‐capillary inflammation. Journal of Infectious Diseases 2007;195(4):589‐96. - PMC - PubMed
Baird 1997
    1. Baird JK, Leksana B, Masbar S, Fryauff DJ, Sutanihardja MA, Suradi, et al. Diagnosis of resistance to chloroquine by Plasmodium vivax: Timing of recurrence and whole blood chloroquine levels. American Journal of Tropical Medicine and Hygiene 1997;56(6):621‐6. - PubMed
Baird 2003a
    1. Baird JK, Rieckmann KH. Can primaquine therapy for vivax malaria be improved?. Trends in Parasitology 2003;19(3):115‐20. - PubMed
Baird 2004
    1. Baird JK, Hoffman SL. Primaquine therapy for malaria. Clinical Infectious Diseases 2004;39(9):1336‐45. - PubMed
Baird 2009
    1. Baird JK. Resistance to therapies for infection by Plasmodium vivax. Clinical Microbiology Reviews 2009;22(3):508‐34. - PMC - PubMed
Barcus 2007
    1. Barcus MJ, Basri H, Picarima H, Manyakori C, Sekartuti, Elyazar I, et al. Demographic risk factors for severe and fatal vivax and falciparum malaria among hospital admissions in northeastern Indonesian Papua. American Journal of Tropical Medicine and Hygiene. 2007;77(5):984‐91. - PubMed
Beg 2008
    1. Beg MA, Sani N, Mehraj V, Jafri W, Khan MA, Malik A, et al. Comparative features and outcomes of malaria at a tertiary care hospital in Karachi, Pakistan. International Journal of Infectious Diseases 2008;12(1):37‐42. - PubMed
Beutler 1994
    1. Beutler E. G6PD deficiency. Blood 1994;84(11):3613‐36. - PubMed
Beutler 2007
    1. Beutler E, Duparc S, G6PD Deficiency Working Group. Glucose‐6‐phosphate dehydrogenase deficiency and antimalarial drug development. American Journal of Tropical Medicine and Hygiene 2007;77(4):779‐89. - PubMed
Bouma 1995
    1. Bouma MJ, Goris M, Akhtar T, Khan N, Khan N, Kita E. Prevalence and clinical presentation of glucose‐6‐phosphate dehydrogenase deficiency in Pakistani Pathan and Afghan refugee communities in Pakistan; implications for the use of primaquine in regional malaria control programmes. Transactions of the Royal Society of Tropical Medicine and Hygiene 1995;89(1):62‐4. - PubMed
Breman 2001
    1. Breman JG. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. American Journal of Medicine and Hygiene 2001;64(Suppl 1‐2):1‐11. - PubMed
Campbell 2004
    1. Campbell MK, Elbourne DR, Altman DG, CONSORT group. CONSORT statement: extension to cluster randomised trials. BMJ 2004;328(7441):702‐8. - PMC - PubMed
Cappellini 2008
    1. Cappellini MD, Fiorelli G. Glucose‐6‐phosphate dehydrogenase deficiency. Lancet 2008;371(9606):64‐74. - PubMed
CDC 2005
    1. Centers for Disease Control and Prevention, Kozarsky PE, Arguin PM, Navin AW. Health information for international travel 2005–2006. Philadelphia: Elsevier, 2005.
CDC 2011
    1. Centres for Disease Control and Prevention. Treatment of malaria (guidelines for clinicians). Available at: www.cdc.gov/malaria/pdf/treatmenttable.pdf, 2011.
Charoenlarp 1973
    1. Charoenlarp P, Harinasuta T. Relapses of vivax malaria after a conventional course of primaquine and chloroquine: report of 2 cases. Southeast Asian Journal of Tropical Medicine and Public Health 1973;4(1):135‐7. - PubMed
Chen 2007
    1. Chen N, Auliff A, Rieckmann K, Gatton M, Cheng Q. Relapses of Plasmodium vivax infection result from clonal hypnozoites activated at predetermined intervals. Journal of Infectious Diseases 2007;195(7):934‐41. - PubMed
Cogswell 1992
    1. Cogswell FB. The hypnozoite and relapse in primate malaria. Clinical Microbiology Review 1992;5(1):26‐35. - PMC - PubMed
Collins 1996
    1. Collins WE, Jeffery GM. Primaquine resistance in P. vivax. American Journal of Tropical Medicine and Hygiene 1996;55(3):243‐9. - PubMed
Craig 1996
    1. Craig AA, Kain KC. Molecular analysis of strains of Plasmodium vivax from paired primary and relapse infections. Journal of Infectious Diseases 1996;174(2):373‐9. - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. Available from www.cochrane‐handbook.org. Chichester: John Wiley & Sons.
Divine 1992
    1. Divine GW, Brown JT, Frazier LM. The unit of analysis error in studies about physicians' patient care behavior. Journal of General Internal Medicine 1992;7(6):623‐9. - PubMed
Doolan 2009
    1. Doolan DL, Dobano C, Baird JK. Acquired immunity to malaria. Clinical Microbiology Reviews 2009;22(1):13‐36. - PMC - PubMed
Douglas 2010
    1. Douglas NM, Anstey NM, Angus BJ, Nosten F, Price RN. Artemisinin combination therapy for vivax malaria. Lancet Infectious Diseases 2010;10(6):405‐16. - PMC - PubMed
Duarte 2001
    1. Duarte EC, Pang LW, Ribeiro LC, Fontes CJ. Association of subtherapeutic dosages of a standard drug regimen with failures in preventing relapses of vivax malaria. American Journal of Tropical Medicine and Hygiene 2001;65(5):417‐6. - PubMed
Ebringer 2011
    1. Ebringer A, Heathcote G, Baker J, Waller M, Shanks GD, Edstein MD. Evaluation of the safety and tolerability of a short higher‐dose primaquine regimen for presumptive anti‐relapse therapy in healthy subjects. Transactions of the Royal Society of Tropical Medicine and Hygiene 2011;105(10):568‐73. - PubMed
Fonseka 1987
    1. Fonseka J, Mendis KN. A metropolitan hospital in a non‐endemic area provides a sampling pool for epidemiological studies on vivax malaria in Sri Lanka. Transactions of the Royal Society of Tropical Medicine and Hygiene 1987;81(3):360‐4. - PubMed
Gamble 2006
    1. Gamble CL, Ekwaru JP, ter Kuile FO. Insecticide‐treated nets for preventing malaria in pregnancy. Cochrane Database of Systematic Reviews 2006, Issue 2. [DOI: 10.1002/14651858.CD003755] - DOI - PMC - PubMed
Genton 2008
    1. Genton B, D’Acremont V, Rare L, Baea K, Reeder JC, Alpers MP, et al. Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea. PLoS Med 2008;5(6):e127. - PMC - PubMed
Gogtay 2000
    1. Gogtay NJ, Desai S, Kadam VS, Kamtekar KD, Dalvi SS, Kshirsagar NA. Relapse pattern of Plasmodium vivax in Mumbai: a study of 283 cases of vivax malaria. Journal of the Association of Physicians of India 2000;48(11):1085‐6. - PubMed
Goller 2007
    1. Goller JL, Jolley D, Ringwald P, Biggs BA. Rerional differences in the response of Plasmodium vivax malaria to primaquine as anti‐relapse therapy. American Jourrnal of Tropical Medicine and Hygiene 2007;76(2):203‐7. - PubMed
GRADE 2004 [Computer program]
    1. Brozek J, Oxman A, Schunemann H. GRADEpro. Version 3.6 for Windows. 2012.
Grietens 2010
    1. Grietens KP, Soto V, Erhart A, Ribera JM, Toomer E, Tenorio A, et al. Adherence to 7‐day primaquine treatment for the radical cure of P. vivax in the Peruvian Amazon. American Journal of Tropical Medicine and Hygiene 2010;82(6):1017‐23. - PMC - PubMed
Guerra 2010
    1. Guerra CA, Howes RE, Patil AP, Gething PW, Boeckel TP, Temperley WH, et al. The International limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Neglected Tropical Diseases 2010;4(8):e774. - PMC - PubMed
Gunawardena 2010
    1. Gunawardena S, Karunaweera ND, Ferreira MU, Phone‐Kyaw M, Pollack RJ, Alifrangis M, et al. Geographic structure of Plasmodium vivax: microsatellite analysis of parasite populations from Sri Lanka, Myanmar, and Ethiopia. American Journal of Tropical Medicine and Hygiene 2010;82(2):235‐42. - PMC - PubMed
Havryliuk 2009
    1. Havryliuk T, Ferreira MU. A closer look at multiple‐clone Plasmodium vivax infections: detection methods, prevalence and consequences. Memórias do Instituto Oswaldo Cruz 2009;104(1):67‐73. - PubMed
Hay 2004
    1. Hay SI, Guerra CA, Tatem AJ, Noor AM, Snow RW. The global distribution and population at risk of malaria: past, present, and future. Lancet Infectious Diseases 2004;4(6):327‐36. - PMC - PubMed
Haynes 2008
    1. Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD000011] - DOI - PubMed
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2005
    1. Higgins JPT, Green S, editors. Highly sensitive search strategies for identifying reports of randomized controlled trials in MEDLINE. Cochrane Handbook for Systematic Reviews of Interventions [4.2.5] updated [May 2005]; Appendix 5b. Available from www.cochrane‐handbook.org.
Higgins 2011a
    1. Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Higgins 2011b
    1. Higgins JPT, Deeks JJ, Altman DG (editors). Chapter 16: Special topics in statistics. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hill 2006
    1. Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ. Primaquine: Report from CDC expert meeting on malaria chemoprophylaxis I. American Journal of Tropical Medicine and Hygiene 2006;75(3):402‐15. - PubMed
Imwong 2007a
    1. Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JR, Nandy A. Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. Journal of Infectious Diseases 2007;195(7):927‐33. - PubMed
Imwong 2007b
    1. Imwong M, Nair S, Pukrittayakamee S, Sudimack D, Williams JT, Mayxay M, et al. Contrasting genetic structure in Plasmodium vivax populations from Asia and South America. International Journal of Parasitology 2007;37(8‐9):1013‐22. - PubMed
Imwong 2012
    1. Imwong M, Boel ME, Pagornrat W, Pimanpanarak M, McGready R, Day NP, et al. The first Plasmodium vivax relapses of life are usually genetically homologous. Journal of Infectious Diseases 2012;205(4):680‐3. - PMC - PubMed
John 2012
    1. John GK, Douglas NM, Seidlein L, Nosten F, Baird JK, White NJ, et al. Primaquine radical cure of Plasmodium vivax: a critical review of the literature. Malaria Journal 2012;11:280. - PMC - PubMed
Karunaweera 2008
    1. Karunaweera ND, Ferreira MU, Munasinghe A, Barnwell JW, Collins WE, King CL, et al. Extensive microsatellite diversity in the human malaria parasite Plasmodium vivax. Gene 2008;410(1):105‐12. - PubMed
Kitchner 2007
    1. Kitchener S, Nasveld P, Edstein MD. Tafenoquine for the treatment of recurrent Plasmodium vivax malaria. American Journal of Tropical Medicine and Hygiene 2007;76(3):494‐6. - PubMed
Kochar 2010
    1. Kochar DK, Tanwar GS, Khatri PC, Kochar SK, Sengar GS, Gupta A, et al. Clinical features of children hospitalized with Malaria ‐ a study from Bikaner, northwest India. American Journal of Tropical Medicine and Hygiene 2010;83(5):981‐9. - PMC - PubMed
Krotoski 1985
    1. Krotoski WA. Discovery of the hypnozoite and a new theory of malarial relapse. Transactions of the Royal Society of Medicine 1985;79(1):1‐11. - PubMed
Krudsood 2006
    1. Krudsood S, Wilairatana P, Tangpukdee N, Chalermrut K, Srivilairit S, Thanachartwet V, et al. Safety and tolerability of elubaquine (bulaquine, CDRI 80/53) for treatment of Plasmodium vivax malaria in Thailand. Korean Journal of Parasitology 2006;44(3):221‐8. - PMC - PubMed
Krudsood 2008
    1. Krudsood S, Tangpukdee N, Wilairatana P, Phophak N, Baird JK, Brittenham GM, et al. High‐dose primaquine regimens against relapse of Plasmodium vivax malaria. American Journal of Tropical Medicine and Hygiene 2008;78(5):736‐40. - PMC - PubMed
Kshirsagar 2006
    1. Kshirsagar NA. Malaria: anti malarial resistance and policy ramifications and challenges. Journal of Postgraduate Medicine 2006;52(4):291‐3. - PubMed
Kumar 2007
    1. Kumar A, Valecha N, Jain T, Dash AP. Burden of malaria in India: retrospective and prospective view. American Journal of Tropical. Medicine and Hygiene 2007;77(Suppl 6):69‐78. - PubMed
Lalloo 2007
    1. Lalloo DG, Shingadia D, Pasvol G, Chiodini PL, Whitty CJ, Beeching NJ, et al. UK malaria treatment guidelines. Journal of Infection 2007;54(2):111‐21. - PubMed
Lengeler 2004
    1. Lengeler C. Insecticide‐treated bed nets and curtains for preventing malaria. Cochrane Database of Systematic Reviews 2004, Issue 2. [DOI: 10.1002/14651858.CD000363] - DOI - PubMed
Leslie 2010
    1. Leslie T, Briceño M, Mayan I, Mohammed N, Klinkenberg E, Sibley CH, et al. The impact of phenotypic and genotypic G6PD deficiency on risk of Plasmodium vivax infection: a case‐control study amongst Afghan refugees in Pakistan. PLoS Med 2010;7(5):e1000283. - PMC - PubMed
Lin 2010
    1. Lin E, Kiniboro B, Gray L, Dobbie S, Robinson L, Laumaea A, et al. Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children. PLoS ONE 2010;5(2):e9047. - PMC - PubMed
Looareesuwan 1997
    1. Looareesuwan S, Buchachart K, Wilairatana P, Chalermrut K, Rattanapong Y, Amradee S, et al. Primaquine‐tolerant vivax malaria in Thailand. Annals of Tropical Medicine and Hygiene 1997;91(8):939‐43. - PubMed
Louicharoen 2009
    1. Louicharoen C, Patin E, Paul R, Nuchprayoon I, Witoonpanich B, Peerapittayamongkol C, et al. Positively selected G6PD‐Mahidol mutation reduces Plasmodium vivax density in Southeast Asians. Science 2009;326(5959):1546‐9. - PubMed
Maguire 2010
    1. Maguire JD, Baird JK. The 'non‐falciparum' malarias: the roles of epidemiology, parasite biology, clinical syndromes, complications and diagnostic rigour in guiding therapeutic strategies. Annals of Tropical Medicine and Parasitology 2010;104(4):283‐301. - PubMed
Mendis 2001
    1. Mendis K, Sina JB, Marchesini P, Carter R. The neglected burden of P. vivax malaria. American Journal of Medicine and Hygiene 2001;64(Suppl 1‐2):97‐106. - PubMed
Michon 2007
    1. Michon P, Cole‐Tobian JL, Dabod E, Schoepflin S, Igu J, Susapu M, et al. The risk of malarial infections and disease in Papua New Guinean children. American Journal of Tropical Medicine and Hygiene 2007;76(6):997‐1008. - PMC - PubMed
Moher 2010
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Journal of Clinical Epidemiology 2010;63(8):e‐1‐37. - PubMed
Mueller 2009
    1. Mueller I, Galinski MR, Baird JK, Carlton JM, Kochar DK, Alonso PL, et al. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infectious Diseases 2009;9(9):555‐66. - PubMed
Naing 2010
    1. Naing C, Aung K, Win DK, Wah MJ. Efficacy and safety of chloroquine for treatment in patients with uncomplicated Plasmodium vivax infections in endemic countries. Transactions of the Royal Society of Tropical Medicine and Hygiene 2010;104(11):695‐705. - PubMed
NIMR 2011
    1. National Institute of Malaria Research, Indian Council of Medical Research. Diagnosis and treatment of Malaria in India. 2nd Edition. New Delhi: National Insitute of Malaria Research, 2011.
Orjuela‐Sanchez 2009
    1. Orjuela‐Sanchez P, Silva NS, Silva‐Nunes M, Ferreira MU. Recurrent parasitemias and population dynamics of Plasmodium vivax polymorphisms in rural Amazonia. American Journal of Topical Medicine and Hygiene 2009;81(6):961‐8. - PubMed
Orton 2005
    1. Orton L, Barnish G. Unit‐dose packaged drugs for treating malaria. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD004614.pub2] - DOI - PMC - PubMed
Parfitt 1999
    1. Parfitt K, editor. Martindale: the complete drug reference. 2nd Edition. London: Pharmaceutical Press, 1999.
Piaggio 2006
    1. Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ, CONSORT group. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA 2006;295(10):1152‐60. - PubMed
Poespoprodjo 2008
    1. Poespoprodjo JR, Fobia W, Kenangalem E, Lampah DA, Warikar N, Seal A, et al. Adverse pregnancy outcomes in an area where multidrug‐resistant Plasmodium vivax and Plasmodium falciparum infections are endemic. Clinical Infectious Diseases 2008;46(9):1374‐81. - PMC - PubMed
Poespoprodjo 2009
    1. Poespoprodjo JR, Fobia W, Kenangalem E, Lampah DA, Hasanuddin A, Warikar N, et al. Vivax malaria: a major cause of morbidity in early infancy. Clinical Infectious Diseases 2009;48(12):1704‐12. - PMC - PubMed
Price 2007
    1. Price RN, Tjitra E, Guerra CA, Yeung S, White N, Anstey NM. Vivax malaria: neglected and not benign. American Journal of Tropical Medicine and Hygiene 2007;77(Suppl 6):79‐87. - PMC - PubMed
Price 2009
    1. Price RN, Douglas NM, Anstey NM. New developments in Plasmodium vivax malaria: severe disease and the rise of chloroquine resistance. Current Opinion in Infectious Diseases 2009;22(5):430‐35. - PubMed
Price 2011
    1. Price RN, Douglas NM, Anstey NM, Seidlein L. Plasmodium vivax treatments: what are we looking for?. Current Opinion in Infectious Diseases 2011;24(6):578‐85. - PMC - PubMed
Pukrittayakamee 2004
    1. Pukrittayakamee S, Chantra A, Simpson JA, Vanijanonta S, Clemens R, Looareesuwan S, et al. Therapeutic responses to different antimalarial drugs in vivax malaria. Antimicrobial Agents and Chemotherapy 2000;44(6):1680‐5. - PMC - PubMed
Pukrittayakamee 2008
    1. Pukrittayakamee S, Imwong M, Singhasivanon P, Stepniewska K, Day NJ, White NJ. Effects of different antimalarial drugs on gametocyte carriage in P. vivax malaria. American Journal of Tropical Medicine and Hygiene 2008;79(3):378‐84. - PubMed
Qingjun 1998
    1. Qingjun L, Jihui D, Laiyi T, Xiangjun Z, Jun L, Hay A, et al. The effect of drug packaging on patients' compliance with treatment for Plasmodium vivax malaria in China. Bulletin of the World Health Organization 1998;76(Suppl 1):21‐7. - PMC - PubMed
Review Manager 5.2 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Rowland 2001
    1. Rowland M, Nosten F. Malaria epidemiology and control in refugee camps and complex emergencies. Annals of Tropical Medicine and Parasitology 2001;95(8):741‐54. - PubMed
Saravu 2011
    1. Saravu K, Docherla M, Vasudev A, Shastry BA. Thrombocytopenia in vivax and falciparum malaria: an observational study of 131 patients in Karnataka, India. Annals of Tropical Medicine and Parasitology 2011;105(8):593‐8. - PMC - PubMed
Schmidt 1977
    1. Schmidt LH, Fradkin R, Vaughan D, Rasco J. Radical cure of infections with Plasmodium cynomolgi: a function of total 8‐aminoquinoline dose. American Journal of Tropical Medicine and Hygiene 1977;26(6 Pt 1):1116‐28. - PubMed
Schunemann 2008
    1. Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, Guyatt GH. Chapter 12: Interpreting results drawing conclusions. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Review of Intervention Version 5.0.1 [updated September 2008]. The Cochrane Collaboration, 2008. Available from www.cochrane‐handbook.org.
Sinclair 2011
    1. Sinclair D, Gogtay N, Brand F, Olliaro PL. Artemisinin‐based combination therapy for treating uncomplicated Plasmodium vivax malaria. Cochrane Database of Systematic Reviews 2011, Issue 7. [DOI: 10.1002/14651858.CD008492] - DOI - PubMed
Singh 2011
    1. Singh H, Parakh A, Basu S, Rath B. Plasmodium vivax malaria: is it actually benign?. Journal of Infection and Public Health. 2011;4(2):91‐5. - PubMed
Srivastava 2011
    1. Srivastava S, Ahmad S, Shirazi N, Kumar Verma S, Puri P. Retrospective analysis of vivax malaria patients presenting to tertiary referral centre of Uttarakhand. Acta Tropica 2011;117(2):82‐5. - PubMed
Tanwar 2011
    1. Tanwar GS, Khatri PC, Sengar GS, Kochar A, Kochar SK, Middha S, et al. Clinical profiles of 13 children with Plasmodium vivax cerebral malaria. Annals of Tropical Paediatrics 2011;31(4):351‐6. - PubMed
ter Kuile 2008
    1. ter Kuile FO, Rogerson SJ. Plasmodium vivax infection during pregnancy: an important problem in need of new solutions. Clinical Infectious Diseases 2008;46(9):1382‐84. - PubMed
Tjitra 2008
    1. Tjitra E, Anstey NM, Sugiarto P, Warikar N, Kenangalem E, Karyana M, et al. Multidrug‐resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia. PLoS Med 2008;5(6):e128. - PMC - PubMed
Tripathy 2007
    1. Tripathy V, Reddy BM. Present status of understanding on the G6PD deficiency and natural selection. Journal of Postgraduate Medicine 2007;53(3):193‐202. - PubMed
Tusting 2013
    1. Tusting LS, Thwing J, Sinclair D, Fillinger U, Gimnig J, Bonner KE, Bottomley C, Lindsay SW. Mosquito larval source management for controlling malaria. Cochrane Database of Systematic Reviews 2013, Issue 8. [DOI: 10.1002/14651858.CD008923.pub2] - DOI - PMC - PubMed
Vale 2008
    1. Vale N, Moreira R, Gomes P. Primaquine revisited six decades after its discovery. European Journal of Medicinal Chemistry 2008;44(3):937‐53. - PubMed
Valecha 2006
    1. Valecha N, Joshi H, Eapen A, Ravinderan J, Kumar A, Prajapati SK, et al. Therapeutic efficacy of chloroquine in Plasmodium vivax from areas with different epidemiological patterns in India and their Pvdhfr gene mutation pattern. Transactions of the Royal Society of Tropical Medicine and Hygiene 2006;100(9):831‐7. - PubMed
Valecha 2009
    1. Valecha N, Pinto RG, Turner GD, Kumar A, Rodrigues S, Dubhashi NG, et al. Histopathology of fatal respiratory distress caused by Plasmodium vivax malaria. American Journal of Tropical Medicine and Hygiene 2009;81(5):758‐62. - PubMed
Van den Eede 2010a
    1. Eede P, Auwera G, Delgado C, Huyse T, Soto‐Calle VE, Gamboa D, et al. Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon. Malaria Journal 2010;9:151. - PMC - PubMed
Van den Eede 2011
    1. Eede P, Soto‐Calle VE, Delgado C, Gamboa D, Grande T, Rodriguez H, et al. Plasmodium vivax sub‐patent infections after radical treatment are common in Peruvian patients: results of a 1‐year prospective cohort study. PLoS ONE 2011;6(1):e16257. - PMC - PubMed
White 2011
    1. White NJ. Determinants of relapse periodicity in Plasmodium vivax malaria. Malaria Journal 2011;10:297. - PMC - PubMed
WHO 2000
    1. World Health Organization. Severe falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 2000;94(Suppl 1):1‐90. - PubMed
WHO 2006
    1. World Health Organization. Guidelines for the treatment of malaria. Geneva: World Health Organization, 2006.
WHO 2009
    1. World Health Organization. Methods for surveillance of antimalarial drug efficacy. Geneva: World Health Organization, 2009.
WHO 2010a
    1. World Health Organization. Guidelines for the treatment of malaria ‐‐ 2nd edition. Geneva: World Health Organization, 2010.
WHO 2010b
    1. World Health Organization. Global report on antimalarial drug efficacy and drug resistance: 2000‐2010. Geneva: World Health Organization, 2010.
WHO 2011
    1. World Health Organization. World Malaria Report 2011. Geneva: World Health Organization, 2011.

References to other published versions of this review

Galappaththy 2007
    1. Galappaththy GN, Omari AA, Tharyan P. Primaquine for preventing relapses in people with Plasmodium vivax malaria. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD004389] - DOI - PubMed

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