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.
Highlights
Malaria is a potentially severe disease widely distributed in tropical and subtropical regions worldwide
Poor quality primaquine was considered a potential cause of relapse, after more than three relapses occurred in a short period of time
Overall median time to relapse obtained by the Kaplan-Meier method was 108.0 days [95% CI 69 – not achieved], i.e., 50% of relapses occurred less than 108 days after start of treatment (Figure 1)
Summary
Malaria is a potentially severe disease widely distributed in tropical and subtropical regions worldwide. The radical cure of Plasmodium vivax infection can be achieved, 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. A common feature of this type of malaria, is defined as the reappearance of the disease and parasitaemia after initial eradication of blood forms. It is caused by the survival of hypnozoites (dormant forms of P. vivax or Plasmodium ovale latent in the liver) [4]. Other factors – such as individual pharmacokinetic variations (poor absorption, rapid elimination or low biotransformation of drugs), adherence to the treatment, drug interactions, adverse drug events, dose adjustment to body weight, and treatment duration – are directly related to the infection’s response to antimalarial treatment, primaquine tolerance is a very important issue that few studies have addressed [9,10]
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