Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia

Abstract

Plasmodium vivax recurrences help maintain malaria transmission. They are caused by recrudescence, reinfection, or relapse, which are not easily differentiated. A longitudinal observational study took place in Turbo municipality, Colombia. Participants with uncomplicated P. vivax infection received supervised treatment concomitantly with 25 mg/kg chloroquine and 0.25 mg/kg/ day primaquine for 14 days. Incidence of recurrence was assessed over 180 days. Samples were genotyped, and origins of recurrences were established. A total of 134 participants were enrolled between February 2012 and July 2013, and 87 were followed for 180 days, during which 29 recurrences were detected. The cumulative incidence of first recurrence was 24.1% (21/87) (95% confidence interval [CI], 14.6 to 33.7%), and 86% (18/21) of these events occurred between days 51 and 110. High genetic diversity of P. vivax strains was found, and 12.5% (16/128) of the infections were polyclonal. Among detected recurrences, 93.1% (27/29) of strains were genotyped as genetically identical to the strain from the previous infection episode, and 65.5% (19/29) of infections were classified as relapses. Our results indicate that there is a high incidence of P. vivax malaria recurrence after treatment in Turbo municipality, Colombia, and that a large majority of these episodes are likely relapses from the previous infection. We attribute this to the primaquine regimen currently used in Colombia, which may be insufficient to eliminate hypnozoites.

The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis

“…232 published P vivax clinical trials were identified, 134 of which included patients treated with chloroquine and were published between Jan 1, 2000, and March 22, 2017 ( figure 1 ). Individual patient data were available from 33 published studies 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 including 6491 patients (21·2%) of the target sample size of 30 656. Additionally, patient data from four unpublished studies including 1780 patients and an additional 117 patients related to patient cohorts from the published studies, but not described in the manuscripts, were available ( figure 1 ; appendix pp 7–9, 13–15 ).…”

Prevalence of malarial recurrence and hematological alteration following the initial drug regimen: a retrospective study in Western Thailand

“…This indicated very well the surveillance and control of malaria through the strategies of the Thailand National Malaria Elimination Plan [10]. A previous study reported that 24.1% of patients with P. vivax infection had at least one recurrence within 180 days of full treatment, and this was caused by therapeutic failure [25]. Other studies reported that the incidence of recurrence was 0 to 13.5% after treatment with standard malarial regimen [26–28].…”

Epidemiological profiles of recurrent malaria episodes in an endemic area along the Thailand-Myanmar border: a prospective cohort study

“…A study conducted in Brazil showed that relapse episodes mostly occurred between the day 28 and 90 after initiating treatment [9]. Similarly in Colombia, 86% of the first P. vivax recurrent events occurred between day 51 and 110, and 65.5% of these subsequent episodes were genetically classified as relapses [7]. Identification of relapse is challenging as the relapse episodes could be caused by the activation of the parasites that have different genotypes from that of the initial infection [35, 36].…”