Efficacy and Safety of Artemether- Lumefantrine, Artesunate-mefloquine Vs Dihydroartemisinin-piperaquine in the Treatment of P. Falciparum Malaria in Cameroon
Authors: Metoh Theresia Njuabe , Moyou-Somo Roger , Fon-Gah Philip , Zhou Xia , Tambo Ernest , Chen Jun-Hu , Zhou Xiaonong 
Published: January 2021

Abstract
Background: Artemisinin-based Combination Therapies (ACTs), have been reported to be effective against multidrug-resistant Plasmodium falciparum. There are controversies in the choice of the type of ACTs to be used at hospitals settings and health centres. This is mostly determined by the cost and less side effects reported for each drug leading to an over prescription and consumption of some ACTs compared to others and consequently to drug resistance. This situation highlight the importance for constant monitoring of ACTs efficacy to provide a guideline to the National Malaria Control Program (NMCP) in readjusting treatment policy when these ACTs are no longer effective and safe in the management of uncomplicated malaria. ACTs including Malacur® (DHAP), artequin® (ASMQ) and cofantrine® (AL) , have been reported to be effective against multidrug-resistant Plasmodium falciparum malaria in many countries including Cameroon and the efficacy may have another profile as the consumption increases in the treatment of any fever cases as malaria observed in meso to high malaria endemic countries. Methods: This open-label, randomized clinical trial was conducted from October 2012 to March 2013 at the Cameroon Development Corporation (CDC) health facilities in Cameroon. Patients who had P. falciparum mono-infection were randomized to receive Malacur® (DHAP), artequin® (ASMQ) and cofantrine® (AL) in the treatment of malaria in a high malaria transmission area. Out-patients from the clinics and hospital of the Cameroon Development Corporation having amongst other criteria, a pre-treatment parasite density of ≥2000 μL-1 of blood were enrolled for the study following the WHO protocol. Informed Consent was obtained from the parents/guardians of the participants and the drugs were given on days 0, 1 and 2. Each patient was followed up to day 42. Blood slides and filter paper samples for Polymerase Chain Reaction (PCR) were collected on days D0, D1, D2, D3, D14, D21, D28, and D42 post treatment.Findings: Results showed that of the one thousand five hundred and fifty five (1555) patients screened, two hundred and sixteen (216) meet the enrolment criteria, but 207 completed the trial. Baseline characteristics were similar in all three treatment groups. All of these participants were included in the per- protocol (PP) analysis. The overall crude adequate clinical and parasitological response (ACPR) were 84% (95%IC; 83.3- 84.7), 86.9% (95% IC; 86.1-87.7%), 92.1% (95% IC; 91.9-92.3%) in AL, ASMQ, and DHAP arms respectively. The PCR-corrected cure rates were generally higher than crude cure rates. The AL, ASMQ and DHAP PCR-corrected percentage cure rates were 95.6% (95% IC; 95.3-96.0%), 97.1% (IC95%; 96.8-97.4%) and 99.3% (IC95%; 99.1-99.6%) respectively with a significantly higher cure rate(p < 0.01) recorded for DHAP comparable to ASMQ and AL. The success rates, PCR-corrected for AL on D1, D2, D3, D7, D14, D28 and D42 were 88.90%, 99.97, 99.99, 100, 100, 97.10 and 94.20%, respectively. The success rates for the ASMQ group were 99.60, 99.93, 99.96, 100, 100, 97.10% and 97.10 %, respectively. The success rates for the DHAP group were 99.86, 99.98, 100, 100, 100, 100, 98.60 and 100% respectively. Parasite clearance time was shorter in the DHAP group 28.7± 9.64 hours as compare with AL, 34.33±18.40 hours (CI 95% 3.25-8.08；P=0.0001) and ASMQ 39.7± 21.4 hours (CI 95% 7.34-14.66）P=0.0001). The mean fever clearance times were 12.57, 11.25 and 11.02 hours, for AL, ASMQ and DHAP respectively. The DHAP and ASMQ exhibited marked antigametocyte activity, with a gametocyte clearance time of 48 and 51.0 hours respectively. The adverse reaction common to the three groups of treatment were cough, weakness, abdominal pain, loss of appetite. There were no major adverse reactions in the DHAP group. However, mild but higher frequency of abdominal pain, loss of appetite, vomiting and pruritus was observed in the AL group while mild hallucination and dizziness occurred only in the ASMQ group. It was equally observed that AL, ASMQ and DHAP have an impact in the improvement of Haematocrit rate. Conclusion: This finding provide evidence that DHAP is the most efficacious, safe and well tolerated ACT compared to ASMQ and AL. Its use is therefore recommended as alternative treatment of malaria in Cameroon and in meso to high malaria endemic countries in general.Trial registration This study is a randomized controlled trial approved by Cameroon National Ethics Committee and retrospectively registered with controlled-trials.com on the 28/11/2016 at the website: https://clinicaltrials.gov/ct2/show/NCT02974348 with the registration number NCT02974348.