Meta-Analysis of Data from Four Clinical Trials in the Ivory Coast Assessing the Efficacy of Two Artemisinin-Based Combination Therapies (Artesunate-Amodiaquine and Artemether-Lumefantrine) between 2009 and 2016.

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.

Efficacy and tolerability of artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria at two sentinel sites across Côte d'Ivore

Malaria remains a major public health problem in Côte d'Ivoire. The aim of this study is to compare the efficacy and tolerability of artesunate-amodiaquine (ASAQ) versus artemether-lumefantrine (AL) for the treatment of uncomplicated malaria, at two malaria surveillance sites in Côte d'Ivoire. The World Health Organization 2003 protocol was used for this multicenter open randomized clinical trial with a 42-day follow-up. We recruited 240 patients (120 per arm), of whom 114 (ASAQ group) and 112 (AL group) were fully followed-up. According to intention-to-treat statistical analysis, PCR-corrected cure rates for ASAQ and AL treatments were 95.8% and 92.5% on day 28, and 95% and 92.5% on day 42, respectively. Based on per-protocol statistical analysis, ASAQ and AL treatment rates reached 100% and 99.1%, respectively, on day 28 and remained the same on day 42. Overall, both drugs were well-tolerated at the clinical and biological level. This study shows that ASAQ and AL are still effective and well-tolerated. Accordingly, they can continue being used to treat uncomplicated malaria in Côte d'Ivoire. However, monitoring of their efficacy should remain a priority for health authorities.

Efficacy and Safety of Artesunate-Amodiaquine versus Artemether-Lumefantrine in the Treatment of Uncomplicated Plasmodium falciparum Malaria in Sentinel Sites across Côte d'Ivoire.

Two years after the introduction of free Artesunate-Amodiaquine (ASAQ) and Artemether-Lumefantrine (AL) for the treatment of uncomplicated malaria in public health facilities in Côte d'Ivoire, we carried out this study to compare their efficacy and tolerability in three surveillance sites. It was a multicentre open randomised clinical trial of 3-day ASAQ treatment against AL for the treatment of 2 parallel groups of patients aged 2 years and above. The endpoints were (1) Adequate Clinical and Parasitological Response (ACPR) at day 28 and (2) the clinical and biological tolerability. Of the 300 patients who were enrolled 289, with 143 (49.5%) and 146 (50.5%) in the ASAQ and AL groups, respectively, correctly followed the WHO 2003 protocol we used. The PCR-corrected ACPR was 99.3% for each group. More than 94% of patients no longer showed signs of fever, 48 hours after treatment. Approximately 78% of the people in the ASAQ group had a parasite clearance time of 48 hours or less compared to 81% in the AL group (p = 0.496). Both drugs were found to be well tolerated by the patients. This study demonstrates the effectiveness and tolerability of ASAQ and AL supporting their continuous use for the treatment of uncomplicated P. falciparum malaria infection in Côte d'Ivoire.

Coverage of intermittent prevention treatment with sulphadoxine-pyrimethamine among pregnant women and congenital malaria in Côte d'Ivoire.

BACKGROUND: The World Health Organization (WHO) recommends using insecticide-treated mosquito nets (ITNs) and intermittent preventive treatment with sulphadoxine-pyrimethamine (IPT-SP) to prevent malaria in sub-Saharan Africa. Data on IPT-SP coverage and factors associated with placental malaria parasitaemia and low birth weight (LBW) are scarce in Côte d'Ivoire. METHODS: A multicentre, cross-sectional survey was conducted in Côte d'Ivoire from March to September 2008 at six urban and semi-urban antenatal clinics. Standardized forms were used to collect the demographic information and medical histories of women and their offspring. IPT-SP coverage (≥2 doses) as well as placental and congenital malaria prevalence parasitaemia were estimated. Regression logistics were used to study factors associated with placental malaria and LBW (birth weight of alive babies < 2,500 grams). RESULTS: Overall, 2,044 women with a median age of 24 years were included in this study. Among them 1017 (49.8%) received ≥2 doses of IPT-SP and 694 (34.0%) received one dose. A total of 99 mothers (4.8%) had placental malaria, and of them, four cases of congenital malaria were diagnosed. Factors that protected from maternal placental malaria parasitaemia were the use of one dose (adjusted odds ratio (aOR), 0.32; 95%CI: 0.19-0.55) or ≥2 doses IPT-SP (aOR: 0.18; 95%CI: 0.10-0.32); the use of ITNs (aOR: 0.47; 95%CI: 0.27-0.82). LBW was associated with primigravidity and placental malaria parasitaemia. CONCLUSION: IPT-SP decreases the rate of placental malaria parasitaemia and has a strong dose effect. Despite relatively successful IPT-SP coverage in Côte d'Ivoire, substantial commitments from national authorities are urgently required for such public health campaigns. Strategies, such as providing IPT-SP free of charge and directly observing treatment, should be implemented to increase the use of IPT-SP as well as other prophylactic methods.