National Institute of Malaria Research, India
Severe clinical cases exclusively associated with Plasmodium vivax are increasingly being reported worldwide with complications like renal failure, jaundice, acute respiratory distress syndrome, cerebral malaria, seizures, anemia, thrombocytopenia, pulmonary edema, splenic rupture and death. Emergence of P. falciparum like severity in P. vivax and its pathogenesis has been speculated to be linked to increasing chloroquine resistance (CQR). Two main transporters studied with regard to CQR in P. vivax are P. vivax chloroquine resistance transporter, pvcrt-o; and the P. vivax multidrug resistance transporter, pvmdr1 which are orthologous to the pfcrt and pfmdr1 genes respectively. Even though these transporters are not established as molecular markers for CQR, they have a speculated role in CQR of P. vivax. Further, it has been demonstrated that the clinical severity in P. vivax could be associated with increased expression levels of parasite transporter genes likely to be involved in CQR i.e. pvcrt-o and pvmdr1. In this study, relative expression levels of pvcrt-o and pvmdr1 genes were analyzed in severe and non-severe P. vivax cases compared to a non-severe control group. P. vivax positive isolates were classified as severe and non-severe according to the WHO guidelines for severe malaria. Transcription analysis of drug resistance genes was carried out for severe and non-severe P. vivax isolates by real-time PCR normalized to β-tubulin; the endogenous gene. The severe P. vivax isolates were found to have higher expression levels of the drug resistance genes (pvcrt-o and pvmdr1) as compared to the non-severe P. vivax infections. Increased expression levels of CQR transporters in severe infections indicate their role in the changing pathogenesis of P. vivax that can no longer be considered benign. It brings to light how genes linked to the emerging CQR in P. vivax might impart virulence to vivax malaria making them excellent genetic markers for disease severity.