Molecular monitoring of <it>plasmodium falciparum </it>drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future
<p>Abstract</p> <p>Background</p> <p>Regular monitoring of the levels of anti-malarial resistance of <it>Plasmodium falciparum </it>is an essential policy to adapt therapy and improve malaria control. This monitoring can be facilitated by using molecular too...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-04-01
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| Series: | Malaria Journal |
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| Online Access: | http://www.malariajournal.com/content/11/1/113 |
| _version_ | 1818208048399777792 |
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| author | Menard Sandie Morlais Isabelle Tahar Rachida Sayang Collins Mayengue Pembe Iriart Xavier Benoit-Vical Françoise Lemen Brigitte Magnaval Jean-François Awono-Ambene Parfait Basco Leonardo K Berry Antoine |
| author_facet | Menard Sandie Morlais Isabelle Tahar Rachida Sayang Collins Mayengue Pembe Iriart Xavier Benoit-Vical Françoise Lemen Brigitte Magnaval Jean-François Awono-Ambene Parfait Basco Leonardo K Berry Antoine |
| author_sort | Menard Sandie |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Regular monitoring of the levels of anti-malarial resistance of <it>Plasmodium falciparum </it>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 In Cameroon, chloroquine (CQ), previously the first-line therapy for uncomplicated malaria was officially withdrawn in 2002 and replaced initially by amodiaquine (AQ) monotherapy.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 <it>P. falciparum </it>resistance molecular markers in Yaoundé, a highly urbanized Cameroonian city.</p> <p>Methods</p> <p>The genotype of <it>pfcrt </it>72 and 76 and <it>pfmdr1 </it>86 alleles and <it>pfmdr1 </it>copy number were determined using real-time PCR in 447 <it>P. falciparum </it>samples collected between 2005 and 2009.</p> <p>Results</p> <p>This study showed a high prevalence of parasites with mutant <it>pfcrt </it>76 (83%) and <it>pfmdr1 </it>86 (93%) codons. On the contrary, no mutations in the <it>pfcrt </it>72 codon and no samples with duplication of the <it>pfmdr1 </it>gene were observed.</p> <p>Conclusion</p> <p>The high prevalence of mutant <it>pfcrt </it>76T and <it>pfmdr1 </it>86Y alleles might be due to the choice of alternative drugs (AQ and AS-AQ) known to select such genotypes. Mutant <it>pfcrt </it>72 codon was not detected despite the prolonged use of AQ either as monotherapy or combined with artesunate. The absence of <it>pfmdr1 </it>multicopies suggests that AL would still remain efficient. The limited use of mefloquine or the predominance of mutant <it>pfmdr1 </it>86Y codon could explain the lack of <it>pfmdr1 </it>amplification. Indeed, this mutant codon is rarely associated with duplication of <it>pfmdr1 </it>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 <it>P. falciparum </it>resistance difficult. This public health problem should lead to increased vigilance and regular monitoring.</p> |
| first_indexed | 2024-12-12T04:38:37Z |
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| id | doaj.art-36c8a49ebe7f47b09af8f22b28c5d189 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-12T04:38:37Z |
| publishDate | 2012-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-36c8a49ebe7f47b09af8f22b28c5d1892022-12-22T00:37:52ZengBMCMalaria Journal1475-28752012-04-0111111310.1186/1475-2875-11-113Molecular monitoring of <it>plasmodium falciparum </it>drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the futureMenard SandieMorlais IsabelleTahar RachidaSayang CollinsMayengue PembeIriart XavierBenoit-Vical FrançoiseLemen BrigitteMagnaval Jean-FrançoisAwono-Ambene ParfaitBasco Leonardo KBerry Antoine<p>Abstract</p> <p>Background</p> <p>Regular monitoring of the levels of anti-malarial resistance of <it>Plasmodium falciparum </it>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 <it>P. falciparum </it>resistance molecular markers in Yaoundé, a highly urbanized Cameroonian city.</p> <p>Methods</p> <p>The genotype of <it>pfcrt </it>72 and 76 and <it>pfmdr1 </it>86 alleles and <it>pfmdr1 </it>copy number were determined using real-time PCR in 447 <it>P. falciparum </it>samples collected between 2005 and 2009.</p> <p>Results</p> <p>This study showed a high prevalence of parasites with mutant <it>pfcrt </it>76 (83%) and <it>pfmdr1 </it>86 (93%) codons. On the contrary, no mutations in the <it>pfcrt </it>72 codon and no samples with duplication of the <it>pfmdr1 </it>gene were observed.</p> <p>Conclusion</p> <p>The high prevalence of mutant <it>pfcrt </it>76T and <it>pfmdr1 </it>86Y alleles might be due to the choice of alternative drugs (AQ and AS-AQ) known to select such genotypes. Mutant <it>pfcrt </it>72 codon was not detected despite the prolonged use of AQ either as monotherapy or combined with artesunate. The absence of <it>pfmdr1 </it>multicopies suggests that AL would still remain efficient. The limited use of mefloquine or the predominance of mutant <it>pfmdr1 </it>86Y codon could explain the lack of <it>pfmdr1 </it>amplification. Indeed, this mutant codon is rarely associated with duplication of <it>pfmdr1 </it>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 <it>P. falciparum </it>resistance difficult. This public health problem should lead to increased vigilance and regular monitoring.</p>http://www.malariajournal.com/content/11/1/113MalariaCameroon<it>pfcrt</it><it>pfmdr1</it><it>pfmdr1 </it>copy numberResistanceLNA probes |
| spellingShingle | Menard Sandie Morlais Isabelle Tahar Rachida Sayang Collins Mayengue Pembe Iriart Xavier Benoit-Vical Françoise Lemen Brigitte Magnaval Jean-François Awono-Ambene Parfait Basco Leonardo K Berry Antoine Molecular monitoring of <it>plasmodium falciparum </it>drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future Malaria Journal Malaria Cameroon <it>pfcrt</it> <it>pfmdr1</it> <it>pfmdr1 </it>copy number Resistance LNA probes |
| title | Molecular monitoring of <it>plasmodium falciparum </it>drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future |
| title_full | Molecular monitoring of <it>plasmodium falciparum </it>drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future |
| title_fullStr | Molecular monitoring of <it>plasmodium falciparum </it>drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future |
| title_full_unstemmed | Molecular monitoring of <it>plasmodium falciparum </it>drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future |
| title_short | Molecular monitoring of <it>plasmodium falciparum </it>drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future |
| title_sort | molecular monitoring of it plasmodium falciparum it drug susceptibility at the time of the introduction of artemisinin based combination therapy in yaounde cameroon implications for the future |
| topic | Malaria Cameroon <it>pfcrt</it> <it>pfmdr1</it> <it>pfmdr1 </it>copy number Resistance LNA probes |
| url | http://www.malariajournal.com/content/11/1/113 |
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