Kavishe Reginald A, Kaaya Robert D, Nag Sidsel, Krogsgaard Camilla, Notland Jakob Ginsbak, Kavishe Adellaida A, Ishengoma Deus, Roper Cally, Alifrangis Michael
Kilimanjaro Christian Medical University College, Moshi, Tanzania.
Centre for Medical Parasitology, Department of International Health, Immunology & Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Malar J. 2016 Jun 23;15:335. doi: 10.1186/s12936-016-1387-2.
Sulfadoxine-pyrimethamine (SP) is recommended for prophylactic treatment of malaria in pregnancy while artemisinin combination therapy is the recommended first-line anti-malarial treatment. Selection of SP resistance is ongoing since SP is readily available in health facilities and in private drug shops in sub-Saharan Africa. This study reports on the prevalence and distribution of Pfdhps mutations A540E and A581G in Tanzania. When found together, these mutations confer high-level SP resistance (sometimes referred to as 'super-resistance'), which is associated with loss in protective efficacy of SP-IPTp.
DNA samples were extracted from malaria-positive blood samples on filter paper, used malaria rapid diagnostic test strips and whole blood collected from eight sites in seven administrative regions of Tanzania. PCR-RFLP and SSOP-ELISA techniques were used to genotype the A540E and A581G Pfdhps. Data were analysed using SPSS version 18 while Chi square and/or Fischer Exact tests were used to compare prevalence between regions.
A high inter-regional variation of Pfdhps-540E was observed (χ(2) = 76.8, p < 0.001). High inter-regional variation of 581G was observed (FE = 85.3, p < 0.001). Both Tanga and Kagera were found to have the highest levels of SP resistance. A high prevalence of Pfdhps-581G was observed in Tanga (56.6 %) in northeastern Tanzania and in Kagera (20.4 %) in northwestern Tanzania and the 540-581 EG haplotype was found at 54.5 and 19.4 %, respectively. Pfdhps-581G was not detected in Pwani and Lindi regions located south of Tanga region.
Selection of SP super-resistant Pfdhps A581G is highest in northern Tanzania. Variation in distribution of SP resistance is observed across the country: northeastern Tanga region and northwestern Kagera region have highest prevalence of SP super-resistance markers, while in Pwani and Lindi in the southeast the prevalence of super-resistance was zero. More studies should be conducted to understand the factors underlying the remarkable heterogeneity in SP resistance in the country.
磺胺多辛-乙胺嘧啶（SP）被推荐用于孕期疟疾的预防性治疗，而青蒿素联合疗法是推荐的一线抗疟治疗方法。由于在撒哈拉以南非洲的医疗机构和私人药店中SP很容易获得，对SP耐药性的选择一直在进行。本研究报告了坦桑尼亚Pfdhps突变A540E和A581G的流行情况和分布。当这两种突变同时出现时，会产生高水平的SP耐药性（有时称为“超级耐药性”），这与SP-IPTp的保护效力丧失有关。
从坦桑尼亚七个行政区八个地点使用疟疾快速诊断试纸条检测为疟疾阳性的滤纸血样和全血中提取DNA样本。采用PCR-RFLP和SSOP-ELISA技术对Pfdhps的A540E和A581G进行基因分型。使用SPSS 18版软件进行数据分析，同时使用卡方检验和/或费舍尔精确检验比较各地区的流行率。
观察到Pfdhps-540E存在较高的地区间差异（χ(2)=76.8，p<0.001）。观察到581G存在较高的地区间差异（FE=85.3，p<0.001）。坦噶和卡盖拉被发现具有最高水平的SP耐药性。在坦桑尼亚东北部的坦噶（56.6%）和坦桑尼亚西北部的卡盖拉（20.4%）观察到Pfdhps-581G的高流行率，540-581 EG单倍型分别为54.5%和19.4%。在坦噶地区以南的滨海和林迪地区未检测到Pfdhps-581G。
在坦桑尼亚北部，对SP超级耐药的Pfdhps A581G的选择最为常见。在全国范围内观察到SP耐药性分布的差异：坦桑尼亚东北部的坦噶地区和西北部的卡盖拉地区SP超级耐药标志物的流行率最高，而在东南部的滨海和林迪地区超级耐药性的流行率为零。应该进行更多的研究以了解该国SP耐药性显著异质性的潜在因素。
