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

Malaria Journal

Research

Shambhu Prasad¹  Amit Kumar²  Pradeep Baghel³  Jai P. Malaiya⁴  Usha Gahlot⁵  Pascal Ringwald⁶  Leonard I. Ortega⁶  Jaiprakash Vadadi⁷  Sri Krishna⁸  Man M. Shukla⁸  Pushpendra P. Singh⁸  Praveen K. Bharti⁸  Neeru Singh⁸  Ajay Yadav⁸  Sweta Mishra⁸  Mrigendra P. Singh⁹  Sher S. Kashyotia^1,10  Gagan S. Sonal^1,10  Mohan Singh^1,11  Maria Dorina G. Bustos^1,12  Eva-Maria Christophel^1,13 

[1] Community Health Centre Bano, District Simdega, Jharkhand, India;Community Health Centre Jaldega, District Simdega, Jharkhand, India;Community Health Centre Kilepal, District Bastar, Chhattisgarh, India;Community Health Centre Rajendragram, District Anuppur, Madhya Pradesh, India;Community Health Centre Ranapur, District Jhabua, Madhya Pradesh, India;Global Malaria Programme World Health Organization, Geneva, Switzerland;Indravati Bhawan, Raipur, Chhattisgarh, India;National Institute for Research in Tribal Health (NIRTH), 482003, Jabalpur, Madhya Pradesh, India;National Institute of Malaria Research (NIMR) Field Station, Jabalpur, MP, India;National Vector Borne Disease Control Programme (NVBDCP), New Delhi, India;Satpura Bhawan, Bhopal, Madhya Pradesh, India;World Health Organization, Country Office for Thailand, Bangkok, Thailand;World Health Organization, Regional Office for South-East Asia, New Delhi, India;

关键词: Therapeutic efficacy;    Artemether–lumefantrine;    Plasmodium falciparum;    Malaria;    India;   

DOI  :  10.1186/s12936-016-1555-4

 received in 2016-07-28, accepted in 2016-10-04,  发布年份 2016

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2016