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.

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 amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso. Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1

In Vivo Antiplasmodial Activity of Two Sahelian Plant Extracts on Plasmodium berghei ANKA Infected NMRI Mice

Up to now, the control of malaria remains a challenge. The World Health Organization (WHO) recommends the use of artemisinin-based combination therapies (ACTs) for uncomplicated malaria treatment. Despite this guideline, many people in Burkina Faso use herbal medicine as primary treatment against malaria. The aim of this study was to assess the in vivo activity of Guiera senegalensis J. F. Gmel and Bauhinia rufescens Lam. leaves extracts against Plasmodium berghei ANKA. A four-day treatment of leaves decoction of each plant was administrated orally to 7 groups of six NMRI (Naval Medical Research Institute) mice infected with Plasmodium berghei ANKA strain. The control group received distilled water as treatment while the treated groups each received daily 100, 250, and 500 mg extract/kg body weight. Thin blood smears were performed on day five and the percentage of reduction of parasitaemia was determined compared to the control. The percentages of reduction of the parasitaemia at the doses of 100, 250, and 500 mg extract/kg body weight were, respectively, 57.5%, 35.9%, and 44.9% for Guiera senegalensis and 50.6%, 22.2%, and 25.7% for Bauhinia rufescens. Our findings on antiplasmodial activity of these two plants justify the traditional use by local populations against malaria. Thus, the isolation of the active compounds from these two plants is suggested for possible antimalarial candidate drugs