Abstract
BackgroundOver the last years, significant progress has been made in the comprehension of the molecular mechanism of malaria resistance to drugs. Together with in vivo tests, the molecular monitoring is now part of the survey strategy of the Plasmodium sensitivity. Currently, DNA-microarray analysis allows the simultaneous study of many single nucleotide polymorphisms (SNP) of Plasmodium isolates. In December 2005, the International Federation of the Red Cross distributed two million three hundred thousand long-lasting insecticide nets to pregnant women and mothers of under five years children in the whole Niger. Then, Niger adopted artemisinin-based combination therapy as first-line treatment.MethodsThirty four SNPs of pfcrt, pfdhfr, pfdhps, pfmdr and pfATPase were analysed by DNA-microarray and PCR/RFLP in two villages – Zindarou and Banizoumbou – with different durations of malaria transmission. The main objective of the study was to measure the dynamics of Plasmodium falciparum resistant strains and associated factors.ResultsThis study shows a global and clear increase of the drug-resistance associated molecular markers frequencies during a relatively short-time period of four years. Markers associated with resistance to chloroquine and sulphonamids were more frequently found in the short transmission zone than in the long transmission one. The pfcrt76T mutation is significantly more present at Banizoumbou than Zindarou (38.3% vs 25.2%, p = 0.013).This work allowed the screening of several field strains for five SNPs of PfATPase6 gene. The pfATPase6S769N, candidate mutation of resistance to artemisinin was not found. However the pfATPsaeA623E mutation was found in 4.7% of samples.ConclusionA significant increase of several SNPs frequencies was highlighted over a four-year period. The polymorphism of five PfATPase6 gene SNPs was described. The global, large and fast increase of the molecular resistance is discussed in the context of current changes of health policy and malaria control in Niger.
Highlights
IntroductionSignificant progress has been made in the comprehension of the molecular mechanism of malaria resistance to drugs
Over the last years, significant progress has been made in the comprehension of the molecular mechanism of malaria resistance to drugs
If regularly monitoring the pattern of drug resistance is of prime importance, questioning the processes involved in the emergence of resistance and selection helps to define the treatment policy
Summary
Significant progress has been made in the comprehension of the molecular mechanism of malaria resistance to drugs. Together with in vivo tests, the molecular monitoring is part of the survey strategy of the Plasmodium sensitivity. If regularly monitoring the pattern of drug resistance is of prime importance, questioning the processes involved in the emergence of resistance and selection helps to define the treatment policy. Plasmodium falciparum has been shown to use several mechanisms for drug resistance. These last decades, the knowledge about molecular mechanisms of malaria drug resistance has significantly increased. Molecular surveys are included in the P. falciparum sensitivity surveillance strategy promoted by the WHO, in association with in vivo tests. The resistance to chloroquine is linked to the pfcrtK76T mutation, a gene located on chromosome 7 [2], and clinical assays have confirmed this association [3,4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
