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

Grandesso, Francesco; Guindo, Ousmane; Messe, Lynda Woi; Makarimi, Rockyath; Traoré, Aliou; Dama, Souleymane; Laminou, Ibrahim Maman; Rigal, Jean-François; Smet, Martin De; Oukem‐Boyer, Odile Ouwe Missi; Doumbo, Ogobara K.; Djimdé, Abdoulaye; Etard, Jean‐François

doi:10.1186/s12936-018-2200-1

Cited by 26 publications

(23 citation statements)

References 27 publications

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“…Therefore, based on these data, the choice of the two artemisinin-based combinations as first-line treatment for uncomplicated P. falciparum malaria was appropriate in Burkina Faso. Efficacy of both treatment was evaluated in other sub-Saharan African countries and similar good efficacy were reported in west Africa [34][35][36][37][38], and in eastern Africa [11,39]. In the current study, both treatments were equally efficacious with however, most treatment failure observed in AL arm (8.9%).…”

Section: Discussionsupporting

confidence: 72%

“…By this measure, recurrent parasitaemia rates were high in both arms with however a remarkably higher rate in the AL arm (50.2%). Most studies in sub-Saharan Africa reported similar results with up to 40% of recurrent parasitaemia [35,40,42,49]. The duration of post treatment prophylaxis is however an important criterium in the choice of anti-malarial drugs, especially in areas with a high risk of re-infection.…”

Section: Discussionmentioning

confidence: 92%

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In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso

Lingani

Bonkian²,

Yerbanga³

et al. 2020

Malar J

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Background: Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso. Methods: In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42. Results: Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05). Conclusion: These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 92%

In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso

Lingani

Bonkian²,

Yerbanga³

et al. 2020

Malar J

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“…Even in the worst case scenario, where participants with missing PCR results by day 42 were considered as treatment failures, the PCR-adjusted malaria cure rate was still > 94%. Additionally, AL achieved parasite clearance rates, similar to that in HIV-uninfected individuals [31–33]. Although there was no evidence of malaria recrudescence, at least 16% of the study participants had malaria recurrence by day 42, with the majority of the re-infections occurring between days 35 and 42.…”

Section: Discussionmentioning

confidence: 62%

Efficacy and safety of artemether–lumefantrine as treatment for Plasmodium falciparum uncomplicated malaria in adult patients on efavirenz-based antiretroviral therapy in Zambia: an open label non-randomized interventional trial

Banda

Chaponda

Mukaka

et al. 2019

Malar J

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Background HIV-infected individuals on antiretroviral therapy (ART) require treatment with artemisinin-based combination therapy (ACT) when infected with malaria. Artemether–lumefantrine (AL) is the most commonly used ACT for treatment of falciparum malaria in Africa but there is limited evidence on the safety and efficacy of AL in HIV-infected individuals on ART, among whom drug–drug interactions are expected. Day-42 adequate clinical and parasitological response (ACPR) and incidence of adverse events was assessed in HIV-infected individuals on efavirenz-based ART with uncomplicated falciparum malaria treated with AL. Methods A prospective, open label, non-randomized, interventional clinical trial was conducted at St Paul’s Hospital in northern Zambia, involving 152 patients aged 15–65 years with uncomplicated falciparum malaria, who were on efavirenz-based ART. They received a 3-day directly observed standard treatment of AL and were followed up until day 63. Day-42 polymerase chain reaction (PCR)-corrected ACPRs (95% confidence interval [CI]) were calculated for the intention-to-treat population. Results Enrolled patients had a baseline geometric mean (95% CI) parasite density of 1108 (841–1463) parasites/µL; 16.4% (25/152) of the participants had a recurrent malaria episode by day 42. However, PCR data was available for 17 out of the 25 patients who had malaria recurrence. Among all the 17 patients, PCR findings demonstrated malaria re-infection, making the PCR-adjusted day-42 ACPR 100% in the 144 patients who could be evaluated. Even when eight patients with missing PCR data were considered very conservatively as failures, the day-42 ACPR was over 94%. None of the participants, disease or treatment characteristics, including day-7 lumefantrine concentrations, predicted the risk of malaria recurrence by day 42. AL was well tolerated following administration. There were only two cases of grade 3 neutropaenia and one serious adverse event of lobar pneumonia, none of which was judged as probably related to intake of AL. Conclusions AL was well tolerated and efficacious in treating uncomplicated falciparum malaria in HIV co-infected adults on efavirenz-based ART. However, a higher than anticipated proportion of participants experienced malaria re-infection, which highlights the need for additional malaria prevention measures in this sub-population after treatment with AL. Trial registration Pan African Clinical Trials Registry (PACTR): PACTR201311000659400. Registered on 4 October 2013. https://pactr.samrc.ac.za/Search.aspx Electronic supplementary material The online version of this article (10.1186/s12936-019-2818-7) contains supplementary material, which is available to authorized users.

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“…Eight studies [ 33 – 40 ] did not report the PCR corrected ACPR. However, except two studies [ 41 , 42 ], the rest reported PCR uncorrected ACPR and included for this group of analysis. Using meta-analysis, the PCR uncorrected ACPR of AL for the treatment of uncomplicated malaria was 87% (95% CI: 85-90%).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Efficacy of Artemether-Lumefantrine (Coartem®) for the Treatment of Uncomplicated Falciparum Malaria in Africa: A Systematic Review

Derbie

Mekonnen

Adugna

et al. 2020

Journal of Parasitology Research

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Background. Africa still bears the largest burden of malaria as the majority of infections in the continent are caused by P. falciparum. Artemether-lumefantrine (AL, Coartem®) is the most widely used artemisinin-based combination therapy (ACT), for treating uncomplicated falciparum malaria globally. However, the development of resistance to antimalarial drugs is a major challenge for malaria control. In this review, the efficacy of AL for the treatment of uncomplicated falciparum malaria in Africa was evaluated. Methods. Articles published between January 2015 and July 2019 were systematically searched using comprehensive search strings from PubMed/Medline, SCOPUS, and grey literature from Google Scholar. Interventional studies that followed patients for at least 28 days were included. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. All the included articles were measured to be good quality. While computing the efficacy of AL, polymerase chain reaction (PCR)–corrected cure rate (adequate clinical and parasitological response, ACPR) at day 28 was considered as the main endpoint. Meta-analysis was computed using STATA v 15 to calculate the pooled ACPR. Results. In this review, 39 articles that reported the treatment outcome of 8,320 patients were included. After 28 days of follow-up, the pooled PCR uncorrected and corrected APCR was at 87% (95% CI: 85-90%) and 97.0% (95% CI: 96-98%), respectively. Moreover, the proportion of early treatment failure (ETF) was almost 0%, while most of the included articles reported <8% late treatment failures. The reinfection and recrudescence rate was less than 10% and 2.6%, respectively, within 28 days. We noted rapid fever and parasite clearance in which greater than 93% and 94% patients were parasite and fever free at day three following AL treatment. Conclusions. This review discovered that despite more than a decade since its introduction, Coartem® remains effective and thus could continue to be the drug of choice for the treatment of uncomplicated falciparum malaria for all age groups in Africa. However, the risk of new emerging resistance for this combination warrants regular monitoring of its efficacy across the continent.

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

Cited by 26 publications

References 27 publications

In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso

In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso

Efficacy and safety of artemether–lumefantrine as treatment for Plasmodium falciparum uncomplicated malaria in adult patients on efavirenz-based antiretroviral therapy in Zambia: an open label non-randomized interventional trial

Therapeutic Efficacy of Artemether-Lumefantrine (Coartem®) for the Treatment of Uncomplicated Falciparum Malaria in Africa: A Systematic Review

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