Main Article Content

Authors

Objective:

To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax.

Methods:

A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg / kg / day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated.

Results:

For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found.

Conclusion:

Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax.

Lina Marcela Zuluaga-Idarraga, Malaria Group, School of Medicine. University of Antioquia. Medellin, Colombia Epidemiology and Biostatistics Group, CES University. Medellin, Colombia

Teacher-Researcher, Division of Public Health, Faculty University CES

Maria-Eulalia Tamayo Perez, Grupo Académico de Epidemiología Clínica, Facultad de Medicina. Universidad de Antioquia. Medellín, Colombia

Docente-Investigadora, Facultad de Medicina

Daniel Camilo Aguirre-Acevedo, Academic Group for Clinical Epidemiology, Faculty of Medicine. University of Antioquia. Medellin, Colombia

Teacher-Researcher, School of Medicine
Zuluaga-Idarraga, L. M., Tamayo Perez, M.-E., & Aguirre-Acevedo, D. C. (2015). Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax: A systematic review and meta-analysis. Colombia Medica, 46(4), 183–191. https://doi.org/10.25100/cm.v46i4.2098

Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, Temperley WH, et al. The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl Trop Dis. 2010;4(8):774–774.

World Health Organization . World Malaria Report 2013. 2014. http://www.who.int/malaria/publications/world_malaria_report_2013/report/en/

White NJ. Determinants of relapse periodicity in Plasmodium vivax malaria. Malar J. 2011;10:297–297.

Garnham PC, Bray RS, Bruce-Chwatt LJ, Draper CC, Killick-Kendrick R, Sergiev PG, et al. A strain of Plasmodium vivax characterized by prolonged incubation: morphological and biological characteristics. Bull World Health Organ. 1975;52(1):21–32.

Krotoski WA, Garnham PC, Cogswell FB, Collins WE, Bray RS, Gwasz RW, et al. Observations on early and late post-sporozoite tissue stages in primate malaria. IV. Pre-erythrocytic schizonts and/or hypnozoites of Chesson and North Korean strains of Plasmodium vivax in the chimpanzee. Am J Trop Med Hyg. 1986;35(2):263–274.

Baird JK. Malaria caused by Plasmodium vivax: recurrent, difficult to treat, disabling, and threatening to life--the infectious bite preempts these hazards. Pathog Glob Health. 2013;107(8):475–479.

World Health Organization . Guidelines for the treatment of malaria. 2015. http://apps.who.int/iris/bitstream/10665/162441/1/9789241549127_eng.pdf.

World Health Organization . Methods for surveillance of antimalarial drug efficacy. 2009. http://www.who.int/malaria/publications/atoz/9789241597531/en/

Baird JK. Resistance to therapies for infection by Plasmodium vivax. Clin Microbiol Rev. 2009;22(3):508–534.

Galappaththy GN, Tharyan P, Kirubakaran R. Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine. Cochrane Database Syst Rev. 2013;10:CD004389–CD004389.

John GK, Douglas NM, von Seidlein L, Nosten F, Baird JK, White NJ, et al. Primaquine radical cure of Plasmodium vivax: a critical review of the literature. Malar J. 2012;11:280–280.

Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg. 2006;75(3):402–415.

Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–269.

Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso-Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias) J Clin Epidemiol. 2011;64(4):407–415.

Abdon NP, Pinto AY, das Silva Rdo S , de Souza JM. Assessment of the response to reduced treatment schemes for vivax malaria. Rev Soc Bras Med Trop. 2001;34(4):343–348.

da Silva Rdo S , Pinto AY, Calvosa VS , de Souza JM . Short course schemes for vivax malaria treatment. Rev Soc Bras Med Trop. 2003;36(2):235–239.

Durand S, Cabezas C, Lescano AG, Galvez M, Gutierrez S, Arrospide N, et al. Efficacy of three different regimens of primaquine for the prevention of relapses of Plasmodium vivax malaria in the Amazon Basin of Peru. Am J Trop Med Hyg. 2014;91(1):18–26.

Pinto AY, Ventura AM, Calvosa VS, Silva MG, Filho, Santos MA, Silva RS, et al. Clinical efficacy of four schemes for vivax malaria treatment in children. J Pediatr (Rio J) 1998;74(3):222–227.

Rajgor DD, Gogtay NJ, Kadam VS, Kocharekar MM, Parulekar MS, Dalvi SS, et al. Antirelapse Efficacy of Various Primaquine Regimens for Plasmodium vivax. Malar Res Treat. 2014;2014:347018–347018.

Ensayo clínico del tratamiento de la malaria vivax con esquema acortado de primaquina comparado con el esquema tradicional. Rev Soc Peru Med Intern. 2002;15(4):197–199.

Carmona-Fonseca J. Malaria vivax en niños: recurrencias con dosis total estándar de primaquina administrada durante 3 frente a 7 días. Iatreia. 2010;23:10–20.

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):2861–2861.

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. Antimicrob Agents Chemother. 2013;57(3):1128–1135.

Diagana TT. Supporting malaria elimination with 21st century antimalarial agent drug discovery. Drug Discov Today. 2015;20(10):1265–1270.

Carmona-Fonseca J. Primaquine and relapses of Plasmodium vivax. Meta analysis of controlled clinical trials. Rev Bras Epidemiol. 2015;18(1):174–193.

World Health Organization . Methods and techniques for assessing exposure to antimalarial drugs in clinical field studies. 2010. http://apps.who.int/iris/bitstream/10665/44653/1/9789241502061_eng.pdf

Kim JR, Nandy A, Maji AK, Addy M, Dondorp AM, Day NP, et al. Genotyping of Plasmodium vivax reveals both short and long latency relapse patterns in Kolkata. PloS One. 2012;7(7):39645–39645.

Delgado-Ratto C, Soto-Calle VE, Van den Eede P, Gamboa D, Rosas A, Abatih EN, et al. Population structure and spatio-temporal transmission dynamics of Plasmodium vivax after radical cure treatment in a rural village of the Peruvian Amazon. Malar J. 2014;13:8–8.

Looareesuwan S, Wilairatana P, Glanarongran R, Indravijit KA, Supeeranontha L, Chinnapha S, et al. Atovaquone and proguanil hydrochloride followed by primaquine for treatment of Plasmodium vivax malaria in Thailand. Trans R Soc Trop Med Hyg. 1999;93(6):637–640.

Orjuela-Sanchez P, da Silva NS, da Silva-Nunes M, Ferreira MU. Recurrent parasitemias and population dynamics of Plasmodium vivax polymorphisms in rural Amazonia. Am J Trop Med Hyg. 2009;81(6):961–968.

Van den Eede P, Soto-Calle VE, Delgado C, Gamboa D, Grande T, Rodriguez H. 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):16257–16257.

Harris I, Sharrock WW, Bain LM, Gray KA, Bobogare A, Boaz L, et al. A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting. Malar J. 2010;9:254–254.

Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun. 2012;3:1237–1237.

Downloads

Download data is not yet available.
Received 2015-09-17
Accepted 2015-12-01
Published 2015-12-30

Similar Articles

You may also start an advanced similarity search for this article.