Therapeutic efficacy of artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria from three highly malarious states in India

Abstract

BackgroundAnti-malarial drug resistance continues to be a leading threat to malaria control efforts and calls for continued monitoring of waning efficacy of artemisinin-based combination therapy (ACT). Artesunate + sulfadoxine/pyrimethamine (AS + SP) is used for the treatment of uncomplicated Plasmodium falciparum malaria in India. However, resistance against AS + SP is emerged in northeastern states. Therefore, artemether–lumefantrine (AL) is the recommended first line treatment for falciparum malaria in north eastern states. This study investigates the therapeutic efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in three malaria-endemic states in India. The data generated through this study will benefit the immediate implementation of second-line ACT as and when required.MethodsThis was a one-arm prospective evaluation of clinical and parasitological responses for uncomplicated falciparum malaria using WHO protocol. Patients diagnosed with uncomplicated mono P. falciparum infection were administered six-dose regimen of AL over 3 days and subsequent follow-up was carried out up to 28 days. Molecular markers msp-1 and msp-2 were used to differentiate recrudescence and re-infection and K13 propeller gene was amplified and sequenced covering the codon 450–680.ResultsA total of 402 eligible patients were enrolled in the study from all four sites. Overall, adequate clinical and parasitological response (ACPR) was 98 % without PCR correction and 99 % with PCR correction. At three study sites, ACPR rates were 100 %, while at Bastar, cure rate was 92.5 % on day 28. No early treatment failure was found. The PCR-corrected endpoint finding confirmed that one late clinical failure (LCF) and two late parasitological failures (LPF) were recrudescences. The PCR corrected cure rate was 96.5 %. The mean fever clearance time was 27.2 h ± 8.2 (24–48 h) and the mean parasite clearance time was 30.1 h ± 11.0 (24–72 h). Additionally, no adverse event was recorded. Analysis of total 186 samples revealed a mutation in the k13 gene along with non-synonymous mutation at codon M579T in three (1.6 %) samples.ConclusionAL is an efficacious drug for the treatment of uncomplicated falciparum malaria. However, regular monitoring of AL is required in view of malaria elimination initiatives, which will be largely dependent on therapeutic interventions, regular surveillance and targeted vector control.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1555-4) contains supplementary material, which is available to authorized users.

Pharmacotherapy follow-up: Role in active malaria surveillance in a travel medicine centre outside the transmission area in Brazil

“…According to WHO recommendations, several studies on antimalarial therapeutic monitoring are designed as therapeutic efficacy studies. Therapeutic monitoring studies on artemisinin derivatives for P. falciparum treatment in Africa demonstrated therapeutic success higher than 95% . Similar high treatment success was reported in therapeutic efficacy studies for vivax malaria with chloroquine and primaquine in the African continent and in Brazil .…”

“…Therapeutic monitoring studies on artemisinin derivatives for P. falciparum treatment in Africa demonstrated therapeutic success higher than 95%. 35,36 Similar high treatment success was reported in therapeutic efficacy studies for vivax malaria with chloroquine and primaquine in the African continent and in Brazil. [37][38][39] Despite differences in study design, therapeutic success rates were similar in this and previous studies, underscoring the importance of pharmacotherapy follow-up of patients with malaria.…”

Surveillance of genetic markers associated with Plasmodium falciparum resistance to artemisinin-based combination therapy in Pakistan, 2018-2019

“…AL, on the other hand, remains efficacious in the North Eastern region of the India [41,42], and is currently the recommended first line treatment for P. falciparum in the whole of the WHO Eastern Mediterranean Region, covering Afghanistan, Djibouti, Pakistan, Somalia and Sudan [1]. The efficacy of AL has been monitored in each of these countries, except in Djibouti.…”

Efficacy of Artemisinin-lumefantrine for the treatment of uncomplicated malaria after more than a decade of its use in Kenya

“…The World Health Organization recommends that malaria-endemic countries should monitor the efficacy of nationally recommended ACT to guide national treatment guidelines [11]. The Artemisinin-based combination reduces both malaria-associated morbidity and mortality as well as the transmission of P. falciparum by acting on gametocytes, decreasing the likelihood of drug resistance development [11,21]. To date, approximately 40 countries in Africa and six in South America are using AL as their first or second-line treatments [2,22].…”