Case Report of Attenuated-Responsiveness to Coartem® in Western Kenya

Abstract

ABSTRACT We describe a case of attenuated-responsiveness to Artemether-Lumefantrine (AL) in western Kenya. A 4-year old patient with 14% parasitemia was treated with Coartem® but on day 7 still had 5% parasitemia. Parasite genetic profile had similar genetic polymorphism as that selected for when AL is administered. In vitro analysis revealed elevated IC 50 s for AL components compared to the reference P. falciparum clone 3D7 and samples collected at this site over the last 5 years. There is need for continued global surveillance to effectively manage emergence and spread of artemisinin drug resistance which has now been found in Southeast Asia. Keywords: Coartem; resistance; malaria; artemether-lumefantrine; treatment-failure. 1. INTRODUCTION malaria and are Artemether-Lumefantrine (AL) is the Artemisinin Combination Therapy (ACT) currently recommended first-line therapy for falciparum malaria since 2006 by Kenyan Ministry of Health (MoH). Artemether -lumefantrine is used in more than 80 countries worldwide and was the first World Health Organization (WHO) prequalified ACT anti-malarial drug, manufactured by Novartis under the brand name Coartem®. Artemether half-life is ~ 1.5 h and lumefantrine is 4 to 6 days, both for the hard and dispersible tablets. AL is administered twice daily for three days as tablets containing 20 mg of artemether plus 120 mg of lumefantrine as follows: 1 tablet (for patients weighing 5–14 kg), 2 tablets (for patients weighing 15–24 kg), 3 tablets (for patients weighing 25–34 kg) and 4 tablets (for patients weighing ≥35 kg). The efficacy of AL has remained > 95% with mild adverse events, most commonly GI (vomiting and diarrhea) and hematologic (anemia and eosinophilia). Although ACTs continue to have excellent cure rates in Africa, there are now confirmed reports of artemisinin-resistance malaria in Southeast Asia [1,2]. A recent report from the coast of Kenya showed that responsiveness to ACTs is declining [3]. This report was the first showing declining responsiveness to artemisinin outside Southeast Asia. The US Army Medical Research Unit – Kenya (USAMRU-K) has an approved active study protocol to study the epidemiology of malaria and drug sensitivity patterns in Kenya. The primary objective of the study is to describe the molecular and