Confirmation of Plasmodium falciparum in vitro resistance to monodesethylamodiaquine and chloroquine in Dakar, Senegal, in 2015

Abstract

BackgroundIn response to increasing resistance to anti-malarial drugs, Senegal adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria in 2006. However, resistance of Plasmodium falciparum parasites to artemisinin derivatives, characterized by delayed parasite clearance after treatment with ACT or artesunate monotherapy, has recently emerged and rapidly spread in Southeast Asia. After 10 years of stability with rates ranging from 5.6 to 11.8%, the prevalence of parasites with reduced susceptibility in vitro to monodesethylamodiaquine, the active metabolite of an ACT partner drug, increased to 30.6% in 2014 in Dakar. Additionally, after a decrease of the in vitro chloroquine resistance in Dakar in 2009–2011, the prevalence of parasites that showed in vitro chloroquine resistance increased again to approximately 50% in Dakar since 2013. The aim of this study was to follow the evolution of the susceptibility to ACT partners and other anti-malarial drugs in 2015 in Dakar. An in vitro test is the only method currently available to provide an early indication of resistance to ACT partners.ResultsThirty-two P. falciparum isolates collected in 2015 in Dakar were analysed using a standard ex vivo assay based on an HRP2 ELISA. The prevalence of P. falciparum parasites with reduced susceptibility in vitro to monodesethylamodiaquine, chloroquine, mefloquine, doxycycline and quinine was 28.1, 46.9, 45.2, 31.2 and 9.7%, respectively. None of the parasites were resistant to lumefantrine, piperaquine, pyronaridine, dihydroartemisinin and artesunate. These results confirm an increase in the reduced susceptibility to monodesethylamodiaquine observed in 2014 in Dakar and the chloroquine resistance observed in 2013. The in vitro resistance seems to be established in Dakar. Additionally, the prevalence of parasites with reduced susceptibility to doxycycline has increased two-fold compared to 2014.ConclusionsThe establishment of a reduced susceptibility to monodesethylamodiaquine as well as chloroquine resistance, and the emergence of a reduced susceptibility to doxycycline are disturbing. The in vitro and in vivo surveillance of anti-malarial drugs must be implemented in Senegal.

Susceptibility of Plasmodium falciparum isolates to antimalarial drugs in a highly seasonal malaria endemic village in Mali

“…Also, the proportion of QN-resistant P. falciparum isolates defined as having an IC 50 <611 nM reached up to 40.5% in our study. This proportion was much higher than 19.4% (6/31) [19] in Ghana in 2011 and 9.7% (3/31) [20] in Senegal in 2017. Sharma, S. et al reported reduced sensiblity in 4% of P. falciparum isolates in vitro to QN in 2017 in India [21].…”

“…In terms of sensitivity, 6.8 % (5/73) of isolates had reduced sensitivity to AQ (CI 50 > 61 nM). Diawara, S. et al observed an increased in vitro resistance to AQ with 28.1% (9/32) in 2017 in Dakar, Sénégal [20]. Sharma, S. et al in 2017 in Inde found 8% reducted sensitivity to AQ [21].…”

School-aged children based seasonal malaria chemoprevention using artesunate-amodiaquine in Mali

“…Contrary to chloroquine, a structural related drug abandoned due to high frequency of resistance, AQ is still effective in most West African countries ( Olliaro and Mussano, 2003 ). A recent report of an increase in prevalence of parasites resistant in vitro to AQ, is a source of concern ( Diawara et al, 2017 ). However, AQ is a synergistic companion drug to AS ( Holmgren et al, 2007 ) and ASAQ has demonstrated sustained efficacy in the treatment of uncomplicated malaria ( Fröberg et al, 2012 ).…”

Ex-vivo Sensitivity of Plasmodium falciparum to Common Anti-malarial Drugs: The Case of Kéniéroba, a Malaria Endemic Village in Mali

“…This was interesting because AQ is one of the most commonly associated molecules with artemisinin in the ACT used in Mali. Higher prevalence of AQ-resistant parasites have been reported in 2017 in Senegal (28.1%) [ 29 ] and in India (8%) [ 37 ]. A strict adhesion to the NMCP’s malaria treatment guideline in conjunction with the World Health Organization guidelines [ 38 ] may considerably reduce the spread of the AQ resistance in Africa.…”