Population structure and antimicrobial resistance patterns of Salmonella Typhi isolates in urban Dhaka, Bangladesh from 2004 to 2016
Population structure and antimicrobial resistance patterns of Salmonella Typhi isolates in urban Dhaka, Bangladesh from 2004 to 2016
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DOI：
10.1371/journal.pntd.0008036
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发表时间：
2020-02-01
影响因子：
3.8
通讯作者：
Qadri, Firdausi
中科院分区：
文献类型：
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作者：
Rahman, Sadia Isfat Ara;Dyson, Zoe A.;Qadri, Firdausi
背景：耐多药伤寒在低收入和中等收入国家仍然是一个巨大的公共卫生威胁。然而，我们仍然缺乏对许多地区伤寒沙门氏菌流行病学和基因组学的详细了解。在这里，我们对孟加拉国达卡城市的伤寒进行了详细的基因组分析，以揭示2004-2016年分离的伤寒沙门氏菌的种群结构和抗微生物药物耐药性模式。主要发现：对从达卡城市三个研究地点获得的202株伤寒沙门氏菌进行全基因组测序，揭示了多种多样的伤寒沙门氏菌基因型和抗菌素耐药性谱。达卡的细菌种群相对均匀，不同医疗机构或年龄组之间几乎没有分层。我们还观察到孟加拉国基因型与邻近南亚国家（印度、巴基斯坦和尼泊尔）交换的证据，表明这些基因型在整个地区传播。该分析显示，自2011年以来，H58（基因型4.3.1）分离株数量有所下降，与此同时，各种非H58基因型的数量有所增加，同时对氟喹诺酮类药物敏感性降低的分离株数量也有所增加，这可能反映了治疗方法的变化。我们发现了一种新的伤寒沙门氏菌基因型，亚支系3.3.2（以前仅在支系水平定义，3.3），它形成了两个局部集群(3.3.2。Bd1和3.3.2。Bd2)与基因gyrA喹诺酮类药物耐药决定区（QRDR）的不同突变相关。伤寒是由肠沙门氏菌血清型伤寒引起的，是发展中国家的一种急性且常常危及生命的发热性疾病。直到最近，对包括孟加拉国在内的资源贫乏环境中伤寒的流行病学和疾病负担进行了有限的研究。这项研究强调了迫切需要持续的基于基因组学的监测研究，以监测抗菌素耐药性的种群结构和持续进化。我们的数据揭示了从孟加拉国达卡三个城市地区收集的202株伤寒沙门氏菌基因型和抗菌素耐药性模式的多样性。此外，我们定义了一个新的基因型，亚支系3.3.2（以前只在支系水平上分型，3.3），其中有两个孟加拉国本地化的支系3.3.2。Bd1和3.3.2。Bd2对氟喹诺酮类药物的敏感性降低。我们的数据显示，从2012年起，携带QRDR突变的非H58基因型显著增加，取代了MDR H58基因型。我们的数据表明，除了在孟加拉国达卡城市引入疫苗接种计划和改善水环境卫生和个人卫生（WASH）外，将治疗实践转向使用第三代头孢菌素来控制伤寒可能是有益的。
BackgroundMulti-drug resistant typhoid fever remains an enormous public health threat in low and middle-income countries. However, we still lack a detailed understanding of the epidemiology and genomics of S. Typhi in many regions. Here we have undertaken a detailed genomic analysis of typhoid in urban Dhaka, Bangladesh to unravel the population structure and antimicrobial resistance patterns in S. Typhi isolated between 2004-2016.Principal findingsWhole genome sequencing of 202 S. Typhi isolates obtained from three study locations in urban Dhaka revealed a diverse range of S. Typhi genotypes and AMR profiles. The bacterial population within Dhaka were relatively homogenous with little stratification between different healthcare facilities or age groups. We also observed evidence of exchange of Bangladeshi genotypes with neighboring South Asian countries (India, Pakistan and Nepal) suggesting these are circulating throughout the region. This analysis revealed a decline in H58 (genotype 4.3.1) isolates from 2011 onwards, coinciding with a rise in a diverse range of non-H58 genotypes and a simultaneous rise in isolates with reduced susceptibility to fluoroquinolones, potentially reflecting a change in treatment practices. We identified a novel S. Typhi genotype, subclade 3.3.2 (previously defined only to clade level, 3.3), which formed two localized clusters (3.3.2.Bd1 and 3.3.2.Bd2) associated with different mutations in the Quinolone Resistance Determining Region (QRDR) of gene gyrA.Author summaryTyphoid fever, caused by Salmonella enterica serovar Typhi, is an acute and often life-threatening febrile illness in developing countries. Until recently, there have been limited studies focusing on the epidemiology and disease burden of typhoid in poor resource settings including Bangladesh. This study highlights the urgent need for sustained genomics based surveillance studies to monitor the population structure and ongoing evolution of AMR. Our data revealed a diverse range of S. Typhi genotypes and AMR patterns among 202 isolates collected from three urban areas in Dhaka, Bangladesh. Moreover, we defined a novel genotype, subclade 3.3.2 (previously typed only to clade level, 3.3) with two Bangladesh-localized clades 3.3.2.Bd1 and 3.3.2.Bd2 showing reduced susceptibility to fluoroquinolones. Our data shows a significant increase in non-H58 genotypes carrying QRDR mutations from 2012 onwards, replacing MDR H58 genotypes. Our data suggest that a shift in treatment practice towards third generation cephalosporins to control typhoid may be beneficial, in addition to the introduction of vaccination programs and improvements in water sanitation and hygiene (WASH) in urban Dhaka, Bangladesh.