Artemether 20mg / Lumefantrine 120mg tablets

BackgroundMalaria remains a significant public health concern in Mozambique. Early diagnosis and the prompt use of effective drugs are essential for malaria control in endemic regions. This review aims to synthesize the existing evidence concerning the efficacy of artemether-lumefantrine (AL) in treating uncomplicated Plasmodium falciparum malaria in Mozambique.MethodsThis systematic review and meta-analysis include studies evaluating the efficacy of AL using the World Health Organization standard protocol in Mozambique across children under 5 years of age and adults, regardless of publication year. The main outcome was efficacy, defined as the proportion of participants who had an adequate clinical and parasitological response, without or with Polymerase Chain Reaction (PCR) correction. Other outcomes included day 3 positivity rate, early treatment failure, late clinical failure and late parasitological failure. Data were obtained from electronic searches of PubMed and ScienceDirect citations. The Rayyan software assessed the adherence of all studies to the stipulated inclusion criteria. The studies' risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Pooled efficacy was calculated based on the per-protocol population. The heterogeneity between studies was assessed using Cochran's Q statistic, the τ2, and the I2 statistic, and all statistical analyses were performed using the R software.ResultsSix studies, comprising 20 single-arm trials and including 1862 participants, were included in the analysis. Studies were conducted across Mozambique and enrolled both children and adults from the country's three main regions (South, Centre, and North). The pooled uncorrected efficacy of AL was 91.0% (95% CI 84.2-94.6), while the PCR-corrected efficacy was 98.3% (95% CI 96.9-99.1). During the 28-day follow-up period, early treatment failure was observed in 0.05% (95% CI 0.01-0.38) of participants. Late clinical failure and late parasitological failure occurred in 2.73% (95% CI 1.65-4.50) and 5.3% (95% CI 3.10-8.96) of participants, respectively. Recrudescence was observed in 1.8% (95% CI 1.20-2.70) of cases, whereas new infections accounted for 8.6% (95% CI 7.30-10.10). The day 3 parasite positivity rate remained low, at about 0.78% (95% CI 0.21-2.81).ConclusionsAL remains efficacious for the treatment of uncomplicated malaria with an efficacy above 90%, and may consequently continue to be used as the first-line treatment option in Mozambique among all vulnerable groups. Registration number prospero: 369991.

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Background The development and spread of drug-resistant parasites continue to threaten the move toward malaria elimination. Therapeutic efficacy and resistant marker studies are needed to guide national control programs. In African settings, evidence of partial resistance to artemisinin combination therapies associated with Kelch13 is accumulating as World Health Organization (WHO) recommends a regular monitoring of first line antimalarial drugs to early detection of resistant parasites. In our study, we evaluated the efficacy of artemether-lumefantrine (AL) combined with a single low dose of primaquine (PQ) for treating uncomplicated Plasmodium falciparum malaria in a co-endemic area where P. falciparum is predominant. Methods and findings One hundred twenty-three cases with P. falciparum mono-infection were enrolled and treated with artemether-lumefantrine (AL) plus single low dose primaquine (PQ) as per the national guideline and followed up over 28 days. Pfmsp2 capillary electrophoresis (CE) genotyping was used to differentiate recrudescence from new infection and we found seven recrudescence as true treatment failure. More than half (56.1%) of the participants had high (>10,000 parasites/μL) parasitemia at enrollment. At day 3, 17% (20/118) remained parasitemic and of the 10 individuals with detectable gametocytes at enrollment, only 1 remained gametocytemic on day 3, and 100% parasite clearance was achieved on day 7 respectively, indicating no early treatment failure. Multiplicity of infection was 3.8 and 1.7 before treatment and the day of recurrence respectively. The adequate clinical and parasitological responses, the PCR uncorrected at 28-day was 73.7% (95% CI 65.6 - 82.9), while the PCR adjusted efficacy was 91.3% (95% CI 85.3 – 97.7). In our study assessment, no serious adverse event was recorded as AL plus single low-dose PQ is safe for the treatment of uncomplicated falciparum malaria in the study setting. Conclusions The low efficacy found in our study is concerning, which might pos a challenge for malaria control in the study setting and beyond. We suggest that regular monitoring and conducting further research using advanced molecular techniques such as next-generation sequencing (NGS) to enable early detection of mutant variants that reduce treatment efficacy. Author Summary Since 2022, Ethiopia’s progress toward malaria elimination has been challenged by a nationwide surge in malaria cases, prompting intensified efforts by the national malaria control program to address this upsurge (Fig 1). Of the factors attributed to the widespread outbreak include the emergence and spread of diagnostic and drug resistance mutations. Due to the spread of the HRP2/3 deletion, the region is moving away from a rapid diagnostic test that has high sensitivity and specificity. On top, of the emergence and spread of the Pfkelch13 mutation implicated in partial resistance to artemisinin-based combination, the first line regimen could be an impending challenge (Fig 2). The WHO recommends a regular therapeutic efficacy study to monitor antimalarial drugs with a target of 90% threshold for first line regimens. Western Ethiopia has the highest malaria burden in the country. The Artemisinin Lumefantrine based combination is the first line for the treatment of uncomplicated falciparum malaria since the 2000s. In our study, we evaluated the efficacy of artemether-lumefantrine (AL) combined with a single low dose of primaquine (PQ) for treating uncomplicated P. falciparum malaria in a coendemic area where P. falciparum is predominant. A single arm partially directly observed 28days of follow up for one hundred twenty-three microscopically mono-infection were enrolled a therapeutic efficacy study, at Bambasi Health Center, Northwest Ethiopia. We found 91.3% PCR based adjusted efficacy (CE), a lower efficacy reported so far to the best of our knowledge in Ethiopia. The PCR-corrected efficacy of 91.3%, just above the WHO’s 90% threshold, raises concerns about the declining effectiveness of artemether-lumefantrine (AL) in this high-transmission setting. We observed a high multiplicity of infection (MOI), with 98 Pfmsp2 allelic variants detected and an initial MOI of 3.8 at recruitment, which reduced to 1.7 on the day of recurrence, suggesting a complex parasite population that may contribute to treatment challenges. The WHO recommends amplicon-based sequencing in high MOI settings to distinguish recrudescence from new infections. Our findings, using Pfmsp2 CE genotyping, revealed a 28-day PCR-corrected efficacy of 91.3% for AL plus single low-dose PQ, which is below the 98.7% pooled efficacy reported in Ethiopian systematic reviews. Despite achieving 100% parasite clearance by day 7, the combination of AL and PQ showed enhanced gametocyte clearance compared to AL alone, though clearance was delayed, with one participant remaining gametocytemic on day 3. Pretreatment parasite density and hemoglobin levels likely influenced these outcomes. Notably, the high initial parasite load in 56.1% of participants (geometric mean of 13,513 parasites/μL) may have contributed to delayed clearance and elevated treatment tolerance risk. The efficacy of single low dose primaquine as WHO-recommended transmission blocking strategy requires further evaluation in a powered study, given the reduced efficacy observed in our study.

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The combinations of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) are used as first-line treatments for uncomplicated malaria in the Ivory Coast. Different studies document the efficacy of two artemisinin-based combination therapies (ACTs) (AL and ASAQ) in the Ivory Coast. However, there is no meta-analysis examining the data set of these studies. The purpose of this work was to determine the prevalence of malaria treatment failure cases in randomized control trials with two artemisinin-based combination therapies (AL versus ASAQ) in the Ivory Coast between 2009 to 2016. This study is a meta-analysis of data from the results of four previous multicenter, open-label, randomized clinical trial studies evaluating the clinical and parasitological efficacy of artemether-lumefantrine and artesunate-amodiaquine conducted between 2009 and 2016 following World Health Organization (WHO) protocol at sentinel sites in the Ivory Coast. These drug efficacy data collected between 2009 and 2016 were analyzed. During these studies, to distinguish between recrudescence and new infection, molecular genotyping of genes encoding merozoite surface protein 1 and 2 was carried out using nested polymerase chain reaction (PCR). A total of 1575 patients enrolled in the four studies, including 768 in the AL arm and 762 in the ASAQ arm, which were fully followed either for 28 days or 42 days according to WHO protocol. The adequate clinical and parasitological response (ACPR) was higher than 95% in the two groups (intention to treat (ITT): AL = 96.59% and ASAQ = 96.81; Per Protocol (PP): AL = 99.48% and ASAQ = 99.61%) after PCR correction at day 28. Aggregate data analysis (2009-2016) showed that at day 28, the proportions of patients with recurrent infection was higher in the AL group (ITT: 3.79%, PP: 3.9%) than in the ASAQ group (ITT: 2.17%, PP: 2.23%). After PCR correction, most treatment failures were classified as new infections (AL group (ITT: 0.13%, PP: 0.13%); ASAQ group (ITT: 0.39%, PP: 0.39%). The recrudescent infections rate was high, at 0.39% compared to 0.13% for ASAQ and AL, respectively, for both ITT and PP, no significant difference. However, the Kaplan-Meier curve of cumulative treatment success showed a significant difference between the two groups after PCR from 2012-2013 (p = 0.032). Overall, ASAQ and AL have been shown to be effective drugs for the treatment of uncomplicated P. falciparum malaria in the study areas, 14 years after deployment of these drugs.

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