<i>Plasmodium falciparum</i>In Vitro Resistance to Monodesethylamodiaquine, Dakar, Senegal, 2014

Fall, B.; Madamet, Marylin; Camara, Cheikhou; Amalvict, Rémy; Fall, Mansour; Nakoulima, Aminata; Diatta, Bakary; Diémé, Yaya; Wade, B.; Pradines, Bruno

doi:10.3201/eid2205.151321

Cited by 16 publications

(29 citation statements)

References 24 publications

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“…This prevalence is slightly above that observed in Senegal for 15 years (2.8 to 6%) [4–7, 9, 30]. The two patients treated with quinine were successfully cured.…”

Section: Discussionmentioning

confidence: 62%

“…In 2015, no isolate with reduced in vitro susceptibility to pyronaridine was detected in Dakar. The geometric mean in 2015 in Dakar (8.72 nM) was intermediate between those observed in 2013 in Dakar (5.8 nM) or in Dielmo, in southeastern Senegal, in 1996 and 1997 (3.8 and 4.5 nM) and in 2014 in Dakar (10.5 nM) [6, 7, 24, 25]. However, a decrease in pyronaridine susceptibility is feared in the future due to the association of in vitro reduced pyronaridine susceptibility with the pfcrt K76T mutation [26].…”

Section: Discussionmentioning

confidence: 92%

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

Diawara

Madamet

Kounta

et al. 2017

Malar J

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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.

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“…This prevalence is slightly above that observed in Senegal for 15 years (2.8 to 6%) [4–7, 9, 30]. The two patients treated with quinine were successfully cured.…”

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 92%

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

Diawara

Madamet

Kounta

et al. 2017

Malar J

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“…The susceptibility of the isolates was assessed without culture adaptation. The parasitized red blood cells (final maximum parasitemia, 0.5%; final hematocrit, 1.5%) were incubated in 96-well plates predosed with antimalarial drugs (piperaquine [ (19,20). PPQ was first dissolved in methanol and then diluted in water to final concentrations that ranged from 1.9 to 998 nM.…”

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confidence: 99%

“…PPQ was first dissolved in methanol and then diluted in water to final concentrations that ranged from 1.9 to 998 nM. An ex vivo histidine-rich protein 2 (HRP2)-based enzyme-linked immunosorbent assay (ELISA) was then performed using a commercial Malaria Ag competitive enzyme-linked immunosorbent assay (CELISA) kit (reference no., KM2159; Cellabs PTY Ltd., Brookvale, Australia), as previously described (19,20). Each batch of 96-well plates predosed with antimalarial drugs was validated on the CQ-resistant W2 strain (isolated in Indochina; obtained from MR4, VA, USA) in four independent experiments using the same conditions described below.…”

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confidence: 99%

Baseline Ex Vivo and Molecular Responses of Plasmodium falciparum Isolates to Piperaquine before Implementation of Dihydroartemisinin-Piperaquine in Senegal

Robert

Tsombeng

Gendrot

et al. 2019

Antimicrob Agents Chemother

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Dihydroartemisinin-piperaquine, which was registered in 2017 in Senegal, is not currently used as the first-line treatment against uncomplicated malaria. A total of 6.6% to 17.1% of P. falciparum isolates collected in Dakar in 2013 to 2015 showed ex vivo-reduced susceptibility to piperaquine. Neither the exonuclease E415G mutation nor the copy number variation of the plasmepsin II gene (Pfpm2), associated with piperaquine resistance in Cambodia, was detected in Senegalese parasites.

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“…The drug susceptibility assay was revealed by the HRP2 enzyme-linked immunosorbent assay (ELISA)-based assay implemented in the Malaria Ag complement-enzyme linked immuno sorbent assay (CELISA) kit (reference KM2159; Cellabs Pty. Ltd., Brookvale, Australia) as previously described (14). The 50% inhibitory concentrations (IC 50 s) were validated only if the optical density (OD) ratio (OD at zero concentration/OD at maximum concentration of drug) was above 1.6 and the 95% confidence interval of the IC 50 estimation was below 2.0.…”

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confidence: 99%

Absence of a High Level of Duplication of the Plasmepsin II Gene in Africa

Robert

Tsombeng

Gendrot

et al. 2018

Antimicrob Agents Chemother

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Resistance to piperaquine has been associated with the amplification of the plasmepsin II gene in Cambodia. None of the 175 African isolates that we analyzed had plasmepsin II gene amplification (piperaquine 50% inhibitory concentration ranged from 0.94 to 137.5 nM), suggesting there is a low prevalence of piperaquine reduced susceptibility in Africa. Additionally, the few isolates with reduced susceptibility to piperaquine did not harbor amplification of the plasmepsin II gene.

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Plasmodium falciparumIn Vitro Resistance to Monodesethylamodiaquine, Dakar, Senegal, 2014

Abstract: In vitro and in vivo surveillance of all artemisinin-based combination therapy partners is warranted.

Cited by 16 publications

References 24 publications

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

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

Baseline Ex Vivo and Molecular Responses of Plasmodium falciparum Isolates to Piperaquine before Implementation of Dihydroartemisinin-Piperaquine in Senegal

Absence of a High Level of Duplication of the Plasmepsin II Gene in Africa

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