Falciparum malaria in the north of Laos: the occurrence and implications of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene haplotype SVMNT

Trop Med Int Health. 2005 Dec;10(12):1267-70. doi: 10.1111/j.1365-3156.2005.01514.x.

Abstract

Objective: The Pfcrt-gene encodes a transmembrane protein located in the Plasmodium falciparum digestive vacuole. Chloroquine resistant (CQR) strains of African and Southeast Asian origin carry the Pfcrt-haplotype (c72-76) CVIET, whereas most South American and Papua New Guinean CQR stains carry the SVMNT haplotype.

Method: Eighty-eight samples from an area with reported in vivo Chloroquine and in vitro Amodiaquine-resistance were screened for the K76T mutation and their Pfcrt-haplotype (c72-76) using a new SSOP-ELISA.

Results: Hundred percent of the analysed samples showed the K76T mutation which is highly associated with in vivo drug failure. This very high rate of a CQR-marker is alarming in an area were CQ is still used as first line drug. The distribution of the three main Pfcrt-haplotypes was as follows: 68% CVIET, 31% SVMNT, 0% CVMNT.

Conclusions: These data show, for the first time, the South American/PNG -haplotype (SVMNT) on mainland Southeast Asia. SVMNT-haplotype and others might be associated with a decreased efficacy of Amodiaquine and could therefore be potential markers for of amodiaquine resistance (AQR). If there is a correlation between AQR and the SVMNT-haplotype as suggested, 31% prevalence of a potential resistance marker is cause for concern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Antimalarials / therapeutic use
  • Child
  • Child, Preschool
  • Chloroquine / therapeutic use
  • Cross-Sectional Studies
  • Drug Resistance / genetics
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Haplotypes / genetics
  • Humans
  • Laos / epidemiology
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Membrane Transport Proteins
  • Middle Aged
  • Mutation / genetics
  • Nucleic Acid Hybridization / methods
  • Plasmodium falciparum / genetics*
  • Protozoan Proteins
  • Treatment Failure

Substances

  • Antimalarials
  • Membrane Proteins
  • Membrane Transport Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • Chloroquine