在印度中央邦乌贾因引入青蒿琥酯加磺胺多辛/乙胺嘧啶 3 至 4 年后，恶性疟原虫对磺胺多辛/乙胺嘧啶的耐药相关突变频率仍然很高且不存在 K13 突变。
Stable high frequencies of sulfadoxine-pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine-pyrimethamine in Ujjain, Madhya Pradesh, India.
机构信息
Department of Pediatrics, R D Gardi Medical College, Surasa, 456010, Ujjain, India.
Department of Women and Children's Health, International Maternal and Child Health Unit, Uppsala University, 751 85, Uppsala, Sweden.
出版信息
Malar J. 2020 Aug 14;19(1):290. doi: 10.1186/s12936-020-03274-w.
BACKGROUND
Artesunate plus sulfadoxine-pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associated with increased drug tolerance, but not overt resistance to sulfadoxine and pyrimethamine were 9% and > 80%, respectively, in 2009 and 2010, just prior to the introduction of ASP. The frequency of drug resistance associated mutations in Ujjain in 2015-2016 after 3-4 years of ASP use, are reported.
METHODS
Blood samples from patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons pfdhfr 16-185, pfdhps 436-632 and K13 407-689 were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism.
RESULTS
Sulfadoxine-pyrimethamine resistance-associated pfdhfr 108 N and 59R alleles were found in 100/104 (96%) and 87/91 (96%) samples, respectively. Pfdhps 437G was found in 10/105 (10%) samples. Double mutant pfdhfr 59R + 108 N were found in 75/81 (93%) samples. Triple mutant pfdhfr 59R + 108 N and pfdhps 437G were found in 6/78 (8%) samples. Chloroquine-resistance-associated pfcrt 76T was found in 102/102 (100%). Pfmdr1 N86 and 86Y were identified in 83/115 (72%) and 32/115 (28%) samples, respectively.
CONCLUSION
The frequency of P. falciparum with reduced susceptibility to sulfadoxine-pyrimethamine remained high, but did not appear to have increased significantly since the introduction of ASP. No polymorphisms in K13 associated with decreased artemisinin susceptibility were found. ASP probably remained effective, supporting continued ASP use.
背景
青蒿琥酯加磺胺多辛-乙胺嘧啶（ASP）是印度大部分地区治疗无并发症恶性疟原虫的一线药物，但在东北部的六个省份，治疗失败率很高。在印度中央乌贾因地区，与增加药物耐受性相关的突变频率在 2009 年和 2010 年分别为 9%和>80%，但与磺胺多辛和乙胺嘧啶的明显耐药性无关，就在引入 ASP 之前。本文报告了在使用 ASP 3-4 年后，2015-2016 年乌贾因地区与药物耐药性相关的突变频率。
方法
在乌贾因市的 9 个主要病理实验室，用滤纸收集显微镜验证的恶性疟原虫单感染患者的血液样本。通过测序确定 codons pfdhfr 16-185、pfdhps 436-632 和 K13 407-689。通过限制性片段长度多态性鉴定 Pfcrt K76T 和 pfmdr1 N86Y。
结果
在 104 例样本中发现磺胺多辛-乙胺嘧啶耐药相关 pfdhfr 108N 和 59R 等位基因分别为 100/104（96%）和 87/91（96%）。在 105 例样本中发现 pfdhps 437G。在 81 例样本中发现双突变体 pfdhfr 59R+108N。在 78 例样本中发现三突变体 pfdhfr 59R+108N 和 pfdhps 437G。在 102 例样本中发现氯喹耐药相关的 pfcrt 76T。在 115 例样本中分别发现 pfmdr1 N86 和 86Y，分别为 83/115（72%）和 32/115（28%）。
结论
恶性疟原虫对磺胺多辛-乙胺嘧啶的敏感性降低的频率仍然很高，但自引入 ASP 以来，似乎并没有显著增加。没有发现与青蒿素敏感性降低相关的 K13 多态性。ASP 可能仍然有效，支持继续使用 ASP。
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