Abstract
BackgroundThere are increasing reports of severe clinical cases exclusively associated with Plasmodium vivax infections. Notably, this severity has been recently suggested to be associated with chloroquine resistance.PatientsTwo different patients presented at the Hospital Clinic in Barcelona with P. vivax malaria episodes. One patient had severe symptoms and the other mild symptoms. Both patients traveled through the Brazilian Amazon (Manaus) in 2007. For both patients the current diagnosis of malaria was the first. Two other patients with mild symptoms presented to the "Centro de Pesquisa em Medicina Tropical", also in the Brazilian Amazon (Rondônia) in 2000.MethodsTo exclude the possibility that the patient's severe symptoms were due to Plasmodium falciparum, a nested PCR was performed. A magnetic method was used to purify P. vivax free of human leukocytes. Quantitative real-time PCR was performed to compare the transcript levels of two main transporters likely to be involved in chloroquine resistance in P. vivax, namely the P. vivax chloroquine resistance transporter, pvcrt-o, and the P. vivax multidrug resistance transporter, pvmdr 1.ResultsResults demonstrated that the severe clinical symptoms were exclusively due to P. vivax. The patient presented acute respiratory conditions requiring admission to the intensive care unit. The magnetic method showed highly purified infected-reticulocytes with mature stages. In addition, it was found that parasites obtained from the severe patient had up to 2.9-fold increase in pvmdr1 levels and up to 21.9-fold increase in pvcrt-o levels compared to expression levels of parasites from the other patients with mild symptoms.ConclusionThis is the first clinical case of severe disease exclusively associated with vivax malaria in Spain. Moreover, these findings suggest that clinical severity could be associated with increased expression levels of parasite genes likely involved in chloroquine resistance. It is necessary to further explore the potential of pvmdr1 and particularly pvcrt-o expression levels as molecular markers of severe disease in P. vivax.
Highlights
There are increasing reports of severe clinical cases exclusively associated with Plasmodium vivax infections
It was found that parasites obtained from the severe patient had up to 2.9-fold increase in pvmdr1 levels and up to 21.9-fold increase in pvcrt-o levels compared to expression levels of parasites from the other patients with mild symptoms
These findings suggest that clinical severity could be associated with increased expression levels of parasite genes likely involved in chloroquine resistance
Summary
There are increasing reports of severe clinical cases exclusively associated with Plasmodium vivax infections. This severity has been recently suggested to be associated with chloroquine resistance. One patient had severe symptoms and the other mild symptoms Both patients traveled through the Brazilian Amazon (Manaus) in 2007. Amino acid polymorphisms have not been associated with chloroquine resistance in pvcrt-o whereas pvmdr polymorphisms have been recently suggested to be associated with CQR in Southeast Asia [8]. This data indicates the involvement of other mechanisms in CQR in P. vivax. Candidates are gene amplifications and differential expression levels [9,10]
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