Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether–lumefantrine treatment in Mali

Dama, Souleymane; Niangaly, Hamidou; Ouattara, Amed; Sagara, Issaka; Sissoko, Sekou; Traoré, Oumou; Bamadio, Amadou; Dara, Niawanlou; Djimdé, Moussa; Alhousseini, Mohamed Lamine; Goïta, Siaka; Maiga, Hamma; Dara, Antoine; Doumbo, Ogobara K.; Djimdé, Abdoulaye

doi:10.1186/s12936-017-1700-8

Cited by 30 publications

(24 citation statements)

References 44 publications

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“…This result was similar to that reported by Diawara,S. et al,,in Sénégal [20] and Dama et al, in Mali, both in 2017 [25]. Interestingly, Fall, B.et al,, in order to predict the different combinations possible in case of resistance to AL.…”

Section: Resultssupporting

confidence: 90%

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

Traoré

Diakité

Bah³

et al. 2019

Preprint

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Background: In 2006, the National Malaria Control Program (NMCP) in Mali recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. Since the introduction of ACT, few reports are available on the level of resistance of Plasmodium falciparum (P. falciparum) to antimalarial drugs in Mali. Dihydroartermisinin is the active metabolite of artemisinin derivatives. Here, we conducted an ex-vivo drug sensitivity testing in a rural area of southern Mali, namely the Kéniéroba village from 2016 to 2017. Methods: Seventy-five (75) isolates of P. falciparum were successfully evaluated for ex-vivo sensitivity to key anti-malarial drugs, namely chloroquine (CQ), quinine (QN), amodiaquine (AQ), mefloquine (MQ), lumefantrine (LUM), dihydroartermisinin (DHA) , and piperaquine (PPQ). P. falciparum sensitivity to these drugs was assessed using the World Wide Antimalarial Resistance Network (WWARN) SYBR-GREEN method of inhibitory concentration of 50% (IC50) determination. Reduced sensitivity to antimalarial drugs was defined as IC50 less than the WWARN standard IC50. Results: The proportion of resistant P. falciparum isolates was 20.2% for CQ, 40.5% for QN, 6.8% for AQ, and 1.3% for MQ. All tested P. falciparum isolates were sensitive to LUM, DHA, and PPQ. A statistically significant correlation was found between QN and AQ IC50 values (r = 0.80; r2 = 0.64, P<0.0001). Conclusions: P. falciparum isolates were sensitive to all ACT derivates tested in Kenieroba in Mali. In contrast, P. falciparum isolates were resistant to, CQ, QN, and AQ as evidenced by high IC50 to these drugs.

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Section: Resultssupporting

confidence: 90%

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

Traoré

Diakité

Bah³

et al. 2019

Preprint

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“… 3 , 5 Analysis of P falciparum isolates obtained in this study from patients in Mali showed decreased susceptibility to both artemether and lumefantrine. 31 Although there was no effect on clinical efficacy, these findings highlight the potential risks of using a single ACT. Further investigations are ongoing, including plasmepsin 2 and plasmepsin 3 copy number and exonuclease polymorphisms as molecular markers of piperaquine resistance.…”

Section: Discussionmentioning

confidence: 86%

Pyronaridine–artesunate or dihydroartemisinin–piperaquine versus current first-line therapies for repeated treatment of uncomplicated malaria: a randomised, multicentre, open-label, longitudinal, controlled, phase 3b/4 trial

Sagara¹,

Béavogui²,

Zongo³

et al. 2018

The Lancet

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SummaryBackgroundArtemether–lumefantrine and artesunate–amodiaquine are used as first-line artemisinin-based combination therapies (ACTs) in west Africa. Pyronaridine–artesunate and dihydroartemisinin–piperaquine are potentially useful for diversification of ACTs in this region, but further safety and efficacy data are required on malaria retreatment.MethodsWe did a randomised, multicentre, open-label, longitudinal, controlled phase 3b/4 clinical trial at seven tertiary centres in Burkina Faso, Guinea, and Mali. Eligible participants for first malaria episode and all retreatment episodes were adults and children aged 6 months and older with microscopically confirmed Plasmodium spp malaria (>0 to <200 000 parasites per μL of blood) and fever or history of fever in the previous 24 h. Individuals with severe or complicated malaria, an alanine aminotransferase concentration of more than twice the upper limit of normal, or a QTc greater than 450 ms were excluded. Using a randomisation list for each site, masked using sealed envelopes, participants were assigned to either pyronaridine–artesunate or dihydroartemisinin–piperaquine versus either artesunate–amodiaquine or artemether–lumefantrine. Block sizes were two or four if two treatments were allocated, and three or six if three treatments were allocated. Microscopists doing the parasitological assessments were masked to treatment allocation. All treatments were once-daily or twice-daily tablets or granules given orally and dosed by bodyweight over 3 days at the study centre. Patients were followed up as outpatients up to day 42, receiving clinical assessments on days 0, 1, 2, 3, 7, 14, 21, 28, 35, and 42. Two primary outcomes were compared for non-inferiority: the 2-year incidence rate of all microscopically confirmed, complicated and uncomplicated malaria episodes in patients in the intention-to-treat population (ITT; non-inferiority margin 20%); and adequate clinical and parasitological response (ACPR) in uncomplicated malaria across all episodes (unadjusted and PCR-adjusted for Plasmodium falciparum and unadjusted for other Plasmodium spp) in the per-protocol population on days 28 and 42 (non-inferiority margin 5%). Safety was assessed in all participants who received one dose of study drug. This study is registered at the Pan African Clinical Trials Registry (PACTR201105000286876).FindingsBetween Oct 24, 2011, and Feb 1, 2016, we assigned 4710 eligible participants to the different treatment strategies: 1342 to pyronaridine–artesunate, 967 to artemether–lumefantrine, 1061 to artesunate–amodiaquine, and 1340 to dihydroartemisinin–piperaquine. The 2-year malaria incidence rate in the ITT population was non-inferior for pyronaridine–artesunate versus artemether–lumefantrine (1·77, 95% CI 1·63–1·93 vs 1·87, 1·72–2·03; rate ratio [RR] 1·05, 95% CI 0·94–1·17); and versus artesunate–amodiaquine (1·39, 95% CI 1·22–1·59 vs 1·35, 1·18–1·54; RR 0·97, 0·87–1·07). Similarly, this endpoint was non-inferior for dihydroartemisinin–piperaquine versus artemether–lumefantrine (1·16...

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“…This might be accounted for the shorter half-life of lumefantrine [ 32 ] compared to amodiaquine [ 33 ] and piperaquine [ 34 ], that provided a shorter prophylactic effect as noted in other studies [ 35 ]. Nevertheless it might be an initial indication of the parasites reduce susceptibility to AM–LM, as suggested by Dama and colleagues [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of artesunate–amodiaquine, dihydroartemisinin–piperaquine and artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Maradi, Niger

Grandesso¹,

Guindo

Messe

et al. 2018

Malar J

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BackgroundMalaria endemic countries need to assess efficacy of anti-malarial treatments on a regular basis. Moreover, resistance to artemisinin that is established across mainland South-East Asia represents today a major threat to global health. Monitoring the efficacy of artemisinin-based combination therapies is of paramount importance to detect as early as possible the emergence of resistance in African countries that toll the highest burden of malaria morbidity and mortality.MethodsA WHO standard protocol was used to assess efficacy of the combinations artesunate–amodiaquine (AS–AQ Winthrop®), dihydroartemisinin–piperaquine (DHA–PPQ, Eurartesim®) and artemether–lumefantrine (AM–LM, Coartem®) taken under supervision and respecting pharmaceutical recommendations. The study enrolled for each treatment arm 212 children aged 6–59 months living in Maradi (Niger) and suffering with uncomplicated falciparum malaria. The Kaplan–Meier 42-day PCR-adjusted cure rate was the primary outcome. A standardized parasite clearance estimator was used to assess delayed parasite clearance as surrogate maker of suspected artemisinin resistance.ResultsNo early treatment failures were found in any of the study treatment arms. The day-42 PCR-adjusted cure rate estimates were 99.5, 98.4 and 99.0% in the AS–AQ, DHA–PPQ and AM–LM arms, respectively. The reinfection rate (expressed also as Kaplan–Meier estimates) was higher in the AM–LM arm (32.4%) than in the AS–AQ (13.8%) and the DHA–PPQ arm (24.9%). The parasite clearance rate constant was 0.27, 0.26 and 0.25 per hour for AS–AQ, DHA–PPQ and AM–LM, respectively.ConclusionsAll the three treatments evaluated largely meet WHO criteria (at least 95% efficacy). AS–AQ and AL–LM may continue to be used and DHA–PPQ may be also recommended as first-line treatment for uncomplicated falciparum malaria in Maradi. The parasite clearance rate were consistent with reference values indicating no suspected artemisinin resistance. Nevertheless, the monitoring of anti-malarial drug efficacy should continue.Trial registration details Registry number at ClinicalTrial.gov: NCT01755559

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Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether–lumefantrine treatment in Mali

Cited by 30 publications

References 44 publications

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

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

Pyronaridine–artesunate or dihydroartemisinin–piperaquine versus current first-line therapies for repeated treatment of uncomplicated malaria: a randomised, multicentre, open-label, longitudinal, controlled, phase 3b/4 trial

Efficacy of artesunate–amodiaquine, dihydroartemisinin–piperaquine and artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Maradi, Niger

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