Background Artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DHA/PPQ) are the recommended first- and second-line treatments, respectively, for uncomplicated falciparum malaria in Somalia. The studies reported here were conducted to assess the efficacy of these artemisinin-based combinations and the mutations in Plasmodium falciparum K13-propeller ( Pfk13 ) domain and amplification in Pfplasmepsin 2 ( Pfpm2 ) gene in Somalia. Methods One-arm prospective studies were conducted to assess the clinical and parasitological responses to DHA/PPQ and AL at two sites in 2016 and 2017, respectively, using the standard WHO protocol. The patterns of molecular markers associated with artemisinin and PPQ resistance were investigated for the first time in Somalia. Results A total of 339 patients were enrolled with 139 for AL and 200 for DHA/PPQ. With AL, no parasite recurrence was observed among patients treated at either site, corresponding to 100% clinical and parasitological responses. For DHA–PPQ, an adequate clinical and parasitological response rate > 97% was observed. All study patients on both treatments at both sites were parasite-free on day 3. Of the 138 samples with interpretable results for the polymorphism in Pfk13 , only one (0.7%), from Bosaso, contained a non-synonymous mutation (R622I), which is not one of the known markers of artemisinin resistance. No Pfpm2 amplification was observed among the 135 samples with interpretable results. Conclusions AL and DHA/PPQ were highly effective in the treatment of uncomplicated falciparum malaria, and there was no evidence of resistance to artemisinin or PPQ. These two combinations are thus relevant in the chemotherapeutic strategy for malaria control in Somalia. Trial registration ACTRN12616001005448 (Jowhar DP study), ACTRN12616000553471 (Bosaso DP study), ACTRN12617001055392 (AL study in Bosaso and Jowhar)
The findings demonstrate a failing first-line treatment (AS + SP), with a failure rate above the threshold (10%) for policy change, and a high prevalence of quintuple mutations. In contrast, AL was highly efficacious. Based on these findings and the results from a previous AS + SP study, AL was selected to replace AS + SP as the first-line treatment for uncomplicated malaria in Somalia in 2016. Dihydroartemisinin + piperaquine (DHA + PPQ) has been recommended as the second-line treatment. Routine monitoring of recommended ACTs should continue to inform treatment policy.
Case management – rapid diagnosis and prompt administration of artemisinin-based combination therapy (ACT) – is a fundamental pillar of recommended malaria interventions in Somalia. Unfortunately, the emergence and spread of drug resistant falciparum parasites continues to pose a considerable threat to effective case management. With technical and financial support from WHO, the efficacy of recommended ACTs has been regularly monitored in sentinel sites since 2003. These studies provided evidence that supported the adoption of artesunate-sulfadoxine/pyrimethamine as first-line treatment in 2005 and artemether-lumefantrine as second-line treatment in 2011. Efficacy studies conducted between 2011 and 2015 showed high artesunate-sulfadoxine/pyrimethamine treatment failure rates of 12.3% - 22.2%, above the threshold (10%) for a change of treatment policy as recommended by WHO. This was also associated with high prevalence of quadruple and quintuple mutations in the dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, which are associated with sulfadoxine/pyrimethamine resistance. Based on these findings, national malaria treatment guidelines were updated in 2016, with artesunate-sulfadoxine/pyrimethamine replaced by artemether-lumefantrine as first-line treatment and dihydroartemisinin-piperaquine recommended as second-line treatment. Subsequent efficacy studies in 2016 and 2017 confirmed that both the current first- and second-line treatments remain highly efficacious (cure rate above 97%). Technical and financial support from WHO has been instrumental in generating evidence that informs malaria treatment policy and should therefore continue to ensure that effective treatments are available to malaria patients in the country.
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