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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

Molecular monitoring of plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Sandie Menard, Isabelle Morlais, Rachida Tahar, Collins Sayang, Pembe Issamou Mayengue, Xavier Iriart, Françoise Benoit-Vical, Brigitte Lemen, Jean-François Magnaval, Parfait Awono-Ambene, Leonardo K Basco, Antoine Berry
Wichtige Hinweise

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

SM, PIM, carried out the molecular genetic studies. SM, AB, XI conceived and designed the study protocol and analysed the results. SM, AB, FBV, LKB drafted the manuscript. JFM, FBV, XI participated in its design and helped to draft the manuscript. RT, CS, LKB and BL participated in study design, supervised clinical and laboratory diagnosis in the health care centres, and collected blood samples in Nlongkak, Olembe, and Nkolndongo, IM and PAA had the same role for the blood samples collected in Mfou. All authors read and approved the final manuscript.

Abstract

Background

Regular monitoring of the levels of anti-malarial resistance of Plasmodium falciparum is an essential policy to adapt therapy and improve malaria control. This monitoring can be facilitated by using molecular tools, which are easier to implement than the classical determination of the resistance phenotype. In Cameroon, chloroquine (CQ), previously the first-line therapy for uncomplicated malaria was officially withdrawn in 2002 and replaced initially by amodiaquine (AQ) monotherapy. Then, artemisinin-based combination therapy (ACT), notably artesunate-amodiaquine (AS-AQ) or artemether-lumefantrine (AL), was gradually introduced in 2004. This situation raised the question of the evolution of P. falciparum resistance molecular markers in Yaoundé, a highly urbanized Cameroonian city.

Methods

The genotype of pfcrt 72 and 76 and pfmdr1 86 alleles and pfmdr1 copy number were determined using real-time PCR in 447 P. falciparum samples collected between 2005 and 2009.

Results

This study showed a high prevalence of parasites with mutant pfcrt 76 (83%) and pfmdr1 86 (93%) codons. On the contrary, no mutations in the pfcrt 72 codon and no samples with duplication of the pfmdr1 gene were observed.

Conclusion

The high prevalence of mutant pfcrt 76T and pfmdr1 86Y alleles might be due to the choice of alternative drugs (AQ and AS-AQ) known to select such genotypes. Mutant pfcrt 72 codon was not detected despite the prolonged use of AQ either as monotherapy or combined with artesunate. The absence of pfmdr1 multicopies suggests that AL would still remain efficient. The limited use of mefloquine or the predominance of mutant pfmdr1 86Y codon could explain the lack of pfmdr1 amplification. Indeed, this mutant codon is rarely associated with duplication of pfmdr1 gene. In Cameroon, the changes of therapeutic strategies and the simultaneous use of several formulations of ACT or other anti-malarials that are not officially recommended result in a complex selective pressure, rendering the prediction of the evolution of P. falciparum resistance difficult. This public health problem should lead to increased vigilance and regular monitoring.
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