机构：[1]Science and Technology Park, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, People’s Republic of China.[2]School of Medicine, Jinan University, Guangzhou 510632, Guangdong, People’s Republic of China.[3]Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.[4]State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, People’s Republic of China.[5]The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, People’s Republic of China.[6]Guangdong Newsouth Artepharm Co., Ltd, Guangzhou 510405, Guangdong, People’s Republic of China.[7]National Malaria Control Programme, BP 500 Moroni, Union of Comoros.[8]Ministry of Health Comoros, BP 403 Moroni, Union of Comoros.[9]Research Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, People’s Republic of China.[10]Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, People’s Republic of China.
In Comoros, the widespread of chloroquine (CQ)-resistant Plasmodium falciparum populations was a major obstacle to malaria control, which led to the official withdrawal of CQ in 2004. Continuous monitoring of CQ-resistant markers of the P. falciparum CQ resistant transporter (pfcrt) and the P. falciparum multiple drug resistance 1 (pfmdr-1) is necessary inder to obtain first-hand information on CQ susceptibility of parasite populations in the field. The objective of this study is to assess the prevalence and evolution of CQ-resistance in the P. falciparum populations on the Comoros' Grande Comore island after withdrawal of CQ.
A total of 207 P. falciparum clinical isolates were collected from the island, including 118 samples from 2006 to 2007 and 89 samples from 2013 to 2014. Nucleotide substitutions in the pfcrt and pfmdr-1 genes linked to CQ response in parasite isolates were assessed using nested PCR and DNA sequencing.
From the pfcrt gene segment sequenced, we detected C72S, M74I, N75E, and K76T substitutions in the parasite isolates collected from both 2006-2007 to 2013-2014 periods. Significant decline of pfcrt resistant alleles at C72S (42.6 to 6.9 %), M74I (39.1 to 14.9 %), N75E (63.5 to 18.3 %), and K76T (72.2 to 19.5 %) from 2006-2007 to 2013-2014 were observed, and the frequency of pfcrt wild type allele was significantly increased from 19.1 % in 2006-2007 to 75.8 % in 2013-2014. Sequence analysis of pfmdr-1 also detected point mutations at codons N86Y, Y184F, and D1246Y, but not S1034C and N1042D, in the isolates collected from both examined periods. An increasing trend in the prevalence of the pfmdr-1 wild type allele (NYD, 4.3 % in 2006-2007; and 28.7 % in 2013-2014), and a decreasing trend for pfmdr-1 N86Y mutation (87.0 % in 2006-2007; and 40.2 % in 2013-2014) were observed in our samples.
The present data indicate that the prevalence and patterns of mutant pfcrt and pfmdr-1 dramatically decreased in the Grande Comore isolates from 2006 to 2014, suggesting that the CQ-sensitive P. falciparum strains have returned after the withdrawal of CQ. The data also suggests that the parasites with wild type pfcrt/pfdmr-1 genes may have growth and/or transmission advantages over the mutant parasites. The information obtained from this study will be useful for developing and updating anti-malarial treatment policy in Grande Comore island.
基金：
This work was supported in part by grants from Natural Science Foundation
of China [Grant Number 81273643] and Guangdong Provincial Science and
Technology Program [Grant Number 2014B050502013] to JS, China Postdoctoral
Science Foundation [Grant Number 2015M570699 and 2016T90773],
Guangdong Provincial Science Foundation [Grant Number 2015A030310107],
and Guangdong Provincial Medicine Science Foundation [Grant Number
A2016315] to BH, Foundation of Traditional Chinese Medicine Bureau of
Guangdong Province [Grant Number 20141074] to QW, Science and Technology
Program of Guangzhou [2014J4500037] to YG, and by the Division of
Intramural Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health (XzS).
第一作者机构：[1]Science and Technology Park, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, People’s Republic of China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Bo Huang,Qi Wang,Changsheng Deng,et al.Prevalence of crt and mdr-1 mutations in Plasmodium falciparum isolates from Grande Comore island after withdrawal of chloroquine.[J].MALARIA JOURNAL.2016,15:doi:10.1186/s12936-016-1474-4.
APA：
Bo Huang,Qi Wang,Changsheng Deng,Jianhua Wang,Tao Yang...&Jianping Song.(2016).Prevalence of crt and mdr-1 mutations in Plasmodium falciparum isolates from Grande Comore island after withdrawal of chloroquine..MALARIA JOURNAL,15,
MLA：
Bo Huang,et al."Prevalence of crt and mdr-1 mutations in Plasmodium falciparum isolates from Grande Comore island after withdrawal of chloroquine.".MALARIA JOURNAL 15.(2016)
