Abstract

AKO A. Aristide Berenger*, Kouman KB Angelo, ASSI S-Brice, Ouattara Yacouba, Koui T. Stephane, Gbessi A.Eric, N’Guessan T. Landry, YAO S. Stephane, Trebissou N.D. Johnson, Beourou Sylvain, Toure A. Offianan

Introduction: In recent years, the therapeutic arsenal used to fight against malaria in Côte d'Ivoire has been enriched with several Artemisinin-Based Combinated Treatment (ATCs), all of which are well-tolerated. The sensitivity of P. falciparum to these molecules was even confirmed by molecular and phenotypic tests in force. However, these tests only evaluate the sensitivity of artemisinin derivatives and not that of the partner molecule. One of these ATCs, Dihydroartemisinin-Piperaquine (DHA-PPQ), was officially introduced in 2018 for the management of uncomplicated malaria and deployed throughout the country. This study aims to test the hypothesis that pfpm2 multiple copies carrying isolates, one of the molecular markers of resistance to PPQ, were circulating well before its official introduction.

Methodology: P. falciparum DNA was obtained from archived Dried Blood Spot (DBS) cards. These DBS correspond to isolates collected at five sentinel sites where clinical trials were conducted between 2013 and 2019. The number of copies of the pfpm2 gene was estimated by N=2^-ΔΔCt. The Cochran-Armitage trend test was used to compare annual proportions of isolates carrying more than one copy of pfpm2 per site and per year.

Results: During the study period, 850 DBS were examined. On average, more than 50% of isolates carried multiple copies of pfpm2 at each site studied. In Ayamé, the average proportion reached 78.6% (95% CI: 72.8-83.4%), while it was 94.6% (95% CI: 88.2-97.8%) in Bouaké and 74.9% (95% CI: 67.4-81.1%) in Man. This latter site experienced a significant decrease in this proportion (p=0.0033 and z?0), while it increased significantly in Yamoussoukro (p=2.6 e^-12 and z>0).

Conclusion: Overall, the study sites revealed proportions of isolates carrying multiple copies of the pfpm2 gene exceeding 50% during the period from 2013 to 2019, with a significant decrease in Man and a significant increase in Yamoussoukro. Prior evaluation would have been opportune before the deployment of the DHA-PPQ combination.