Plasmodium vivax malaria relapses at a travel medicine centre in Rio de Janeiro, a non-endemic area in Brazil

Abstract

BackgroundMalaria is a potentially severe disease widely distributed in tropical and subtropical regions worldwide. Clinically, the progression of the disease can be life-threatening if it is not promptly diagnosed and properly treated. Through treatment, the radical cure of Plasmodium vivax infection can be achieved, thus preventing potential relapses and the emergence of new cases outside the Amazon region in Brazil. Surveillance for therapeutic failure in non-endemic areas is advantageous, as it is unlikely that recurrence of the disease can be attributed to a new malaria infection in these regions.MethodsAn observational study of 53 cases of P. vivax and mixed (P. vivax and Plasmodium falciparum) malaria was conducted at a travel medicine centre between 2005 and 2011 in Rio de Janeiro and a descriptive analysis of the potential factors related to recurrence of P. vivax malaria was performed. Groups with different therapeutic responses were compared using survival analysis based on the length of time to recurrence and a set of independent variables thought to be associated with recurrence.ResultsTwenty-one relapses (39.6%) of P. vivax malaria were observed. The overall median time to relapse, obtained by the Kaplan-Meier method, was 108 days, and the survival analysis demonstrated an association between non-weight-adjusted primaquine dosing and the occurrence of relapse (p < 0.03). Primaquine total dose at 3.6 mg/kg gave improved results in preventing relapses.ConclusionsA known challenge to individual cure and environmental control of malaria is the possibility of an inappropriate, non-weight-based primaquine dosing, which should be considered a potential cause of P. vivax malaria relapse. Indeed, the total dose of primaquine associated with non-occurrence of relapses was higher than recommended by Brazilian guidelines.

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

“…Although the difference in cumulative incidences of recurrence is seemingly little between these two studies, recurrences in the previous study are more likely to have been cases of reinfection, rather than relapses, since the API in that study was much higher than that in the present one (30 versus 3) (15,44). In addition, a maximum PQ dose of 210 mg was used in the previous study, so participants weighing more than 60 kg received a lower dose than recommended; in the present study, all participants were dosed by body weight to avoid relapse due to underdosing, as previously reported in other studies (26,45,46). P. vivax recurrences may have an impact on patient well-being via clinical symptoms and the risk of complicated malaria.…”

Efficacy of Three Different Regimens of Primaquine for the Prevention of Relapses of Plasmodium vivax Malaria in the Amazon Basin of Peru

“…Relapses are common in the Amazon Basin (up to 40% in returning nonendemic travelers without reinfection risk). 32 Relapses with different genotypes at one or more loci may be caused by (1) initial polyclonal infections with one or more clones undetected because of low density or (2) latent hypnozoites from previous infections. 20,33 Both these factors can be common in our study area.…”

Plasmodium vivax Landscape in Brazil: Scenario and Challenges

“…In a study undertaken in Sao Paulo, one-third of P. vivax –infected patients treated with chloroquine and primaquine (15 mg/day for 14 days) presented relapses between 1 to more than 6 months after the initial episode 31. A recent series of patients followed up in a reference center in Rio de Janeiro described 39.6% of patients presenting relapse, where receiving a total primaquine dose below 3.5 mg/kg (administered during 14 days) was the most important factor associated with recurrence 32. Six individuals who acquired P. vivax in the Brazilian Amazon region presented incubation periods longer than 3 months,33 with important implications for control of this parasite in an elimination context.…”

“…Primaquine treatment failure has been reported in settings with expected high compliance31 even from individuals in transmission-free areas receiving adequate doses 32. In a recent multicenter tafenoquine trial, although only six patients from Brazil received primaquine for 14 days the efficacy of this regimen was considerably high, at 83% 58.…”