Monitoring the Efficacy and Safety of Artemisinin-Based Combination Therapies: A Review and Network Meta-analysis of Antimalarial Therapeutic Efficacy Trials in Cameroon

Abstract

Introduction: Artemisinin-based combination therapies (ACTs) are the first-line antimalarial drugs used to treat uncomplicated Plasmodium falciparum alaria in many endemic countries worldwide. The present work reviewed the therapeutic efficacy of ACT in Cameroon more than 10 years after the initial change in national drug policy in 2004.

Methods: A PubMed literature search was performed to analyse clinical trials conducted in Cameroon from 2001 to May 2017. Clinical studies that evaluated ACT for the treatment of uncomplicated falciparum malaria in children or adults, and reported efficacy and/or safety, were included. In addition, a small network meta-analysis (NMA) with a frequentist approach was performed.

Results: Six papers were selected from 48 articles screened and were full-text reviewed. The efficacy of both artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) ranged from moderate to high, with polymerase chain reaction-corrected cure rates ranging from 96.7 to 100% and 88.2 to 100%, respectively, in per-protocol analysis, and 86.2 to 96.7% and 74.0 to 90.6%, respectively, in intention-to-treat analysis. The malaria evidence network suggested that AL and ASAQ efficacies were comparable. The highest day 3 parasite positivity rate was 8.2% for ASAQ and 4% for AL. A novel ACT, artesunate-atovaquoneproguanil (ASATPG) was tested once and showed a cure rate of 100%. Based on an ITT approach, the NMA revealed that AL was more efficacious than ASAQ, but the difference was not statistical significant (706 participants, three randomised clinical trials (RCT); OR 1.25, 95%CI 0.78-2.00). Adverse events ranged from mild to moderate severity but were not directly attributed to drug intake.

Conclusion: ACTs are still effective and safe in Cameroon; however, there are insufficient data on their efficacy, safety and tolerability, therefore more RCTs should be conducted, including novel ACTs.

Fig. 1

Article selection process. A total of 48 published articles were identified and six were included in the present analysis

Fig. 2

Change in efficacy of ASAQ and AL during the study periods. Diamonds represent the ACPR (%) in the PP population, and squares represent the ACPR (%) in the ITT population. ACPR adequate clinical and parasitological response, ASAQ artesunate-amodiaquine, AL artemether-lumefantrine, PP per-protocol, ITT intention-to-treat

Fig. 3

Malaria evidence network in Cameroon. The thickness of the line joining two treatments is proportional to the number of clinical trials and the number of participants. The network provides the possibility of comparing ASATPG and DHPP, ASATPG and ASSP, ASATPG and AL, as well as AL and ASSP, and DHPP and ASSP, even if they were not directly compared, and these are represented by the dotted lines. Non-randomised clinical trials were excluded. The descriptions are based on the ITT outcomes. ASAQ artesunate-amodiaquine, ASATPG artesunate-atovaquone-proguanil, DHPP dihydroartemisinin-piperaquine, ASSP artesunate-sulfadoxine-pyrimethamine, ASCD artesunate-chlorproguanil-dapsone, AL artemether-lumefantrine, ITT intention-to-treat