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

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 In Cameroon, chloroquine (CQ), previously the first-line therapy for uncomplicated malaria was officially withdrawn in 2002 and replaced initially by amodiaquine (AQ) monotherapy.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

Therapy and Prevention for Human Toxocariasis

For the last four decades, knowledge about human toxocariasis with regard to its epidemiology, pathophysiology, clinical spectrum, and imaging or laboratory diagnosis has substantially progressed. Knowledge about specific therapy with anthelmintics has lagged behind. To date, only four drugs are registered for human use, and their efficacy has rarely been assessed in prospective controlled trials. It is likely that the repurposing of potent anthelmintics from veterinary medicine will improve this situation. Due to its wide availability and a lack of major side effects during short regimens, albendazole has become the drug of choice. However, its efficacy should be more precisely assessed. The role of anthelmintics in the treatment of neurological or ocular toxocariasis remains to be clarified. Prophylactic measures in humans or companion animals are efficient and represent first-line treatments for the control of this zoonosis. Unfortunately, their implementation in areas or countries where toxocariasis epidemiology is driven by poverty is quite difficult or unrealistic

Anguillulose et HTLV 1 en Guyane française

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocSudocFranceF

Nosographie de la trichinellose humaine (description de l'épidémie de septembre-octobre 1998 en région Midi-Pyrénées)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Application de la PCR au diagnostic de routine du paludisme d'importation

TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

La sarcocystose musculaire humaine (à propos de 7 cas probables)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Evaluation d'un antigène recombinant (TES-32) pour le diagnostic immunologique de la toxocarose humaine

La toxocarose est une zoonose parasitaire causée par l'errance, dans l'organisme humain, de larves de Toxocara. Deux syndromes majeurs sont décrits chez l'Homme : le syndrome de larva migrans viscérale et la toxocarose oculaire. Le diagnostic de la toxocarose s'effectue, par un test ELISA, en mesurant la réponse anticorps vis à vis d'antigènes d'excrétion-sécrétion de larves de Toxocara (TES). Les nombreuses réactions croisées observées avec d'autres helminthiases, ont incité à développer des antigènes recombinants afin d'augmenter la spécificité du test. Dans notre étude, nous avons évalué l'antigène recombinant TES-32. Ce dernier montre une meilleure spécificité mais une sensibilité médiocre pour les patients atteints de toxocarose active. D'autre part cet antigène recombinant n'apporte pas d'amélioration pour le diagnostic sérologique de la toxocarose oculaire et souffre des mêmes problèmes de réactions croisées observées avec les antigènes TES.TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocSudocFranceF

Diagnostic de la toxocarose par western-blot (évaluation d'une trousse LD-BIO, Le-WB24G)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocSudocFranceF