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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

Sandie Menard1, Isabelle Morlais23, Rachida Tahar34, Collins Sayang35, Pembe Issamou Mayengue6, Xavier Iriart1, Françoise Benoit-Vical6, Brigitte Lemen7, Jean-François Magnaval8, Parfait Awono-Ambene3, Leonardo K Basco39 and Antoine Berry1*

Author Affiliations

1 Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Toulouse et UMR152 UPS-IRD, Université de Toulouse, Toulouse, France

2 Institut de Recherche pour le Développement, UMR MIVEGEC, Montpellier, France

3 Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Yaoundé, Cameroon

4 Unité Mixte de Recherche 216, Institut de Recherche pour le Développement (IRD), Université Paris Descartes, Laboratoire de Parasitologie, Faculté de Pharmacie, Paris, France

5 Centre de Formation et de Recherche en Médecine et Santé Tropicale, Faculté de Médecine Nord, Université de la Méditerranée, Marseille, France

6 CNRS, LCC (Laboratoire de Chimie de Coordination), et Université de Toulouse Paul Sabatier, UPS, INPT, LCC, Toulouse, France

7 Centre d'Animation Sociale et Sanitaire (CASS), Yaoundé, Cameroon

8 CNRS UMR 5288 Anthropobiology, Université de Toulouse, Toulouse, France

9 Unité Mixte de Recherche 198, Institut de Recherche pour le Développement (IRD), Faculté de Médecine La Timone, Université de la Méditerranée, Marseille, France

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Malaria Journal 2012, 11:113  doi:10.1186/1475-2875-11-113

Published: 12 April 2012

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 In Cameroon, chloroquine (CQ), previously the first-line therapy for uncomplicated malaria was officially withdrawn in 2002 and replaced initially by amodiaquine (AQ) monotherapy.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.

Keywords:
Malaria; Cameroon; pfcrt; pfmdr1; pfmdr1 copy number; Resistance; LNA probes