Laboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy
Laboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy
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DOI：
10.1371/journal.pntd.0006408
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发表时间：
2018-04-01
影响因子：
3.8
通讯作者：
Pollard, Andrew J.
中科院分区：
文献类型：
--
作者：
Britto, Carl D.;Dyson, Zoe A.;Pollard, Andrew J.
背景在包括尼泊尔在内的大多数疾病负担高的环境中，儿童受到肠道热的严重影响。然而，病原体种群结构和传播动力学在幼儿中的描述很差，这是免疫规划的拟议目标群体。在这里，我们提出了198 S的全基因组测序和抗菌药物敏感性数据。伤寒和66 S. 2008- 2016年尼泊尔帕坦医院血培养监测期间从2个月至15岁儿童中分离出的甲型副伤寒。伤寒是主要病原体，包括几种不同的基因型，以4.3.1（H58）为主。与2005-2006年的数据相比，5岁以下儿童的基因型异质性降低，这归因于H58的持续克隆扩增。大多数分离株（86%）对氟喹诺酮类药物不敏感，主要与沙门氏菌相关。伤寒H_（58）Ⅱ型和S.在喹诺酮耐药决定区（QRDR）中携带突变的甲型副伤寒;来自这些群体的非敏感菌株占所有分离株的50%和25%。多药耐药（MDR）少见（占3.5%）。伤寒，0 S。甲型副伤寒），并限于染色体插入的耐药基因在H58谱系I菌株。时间分析显示，优势从H58谱系I转移到H58谱系II，后者在2010年后明显更常见。与全球数据集的比较表明，当地的S。伤寒和沙门氏菌。甲型副伤寒菌株在其他南亚国家有密切的遗传亲缘关系，表明区域菌株循环。从印度进口的耐环丙沙星的H58谱系II菌株被确定，但这些是罕见的，没有证据表明当地的S。这些数据表明，尼泊尔的肠热病仍然是一个主要的公共卫生问题，在国家间和国家内不断传播，并突出表明有必要对干预战略进行区域协调。缺少S。甲型副伤寒疫苗是引起关注的原因，因为它作为一种氟喹诺酮耐药的肠热病剂在这种情况下的流行。
BackgroundChildren are substantially affected by enteric fever in most settings with a high burden of the disease, including Nepal. However pathogen population structure and transmission dynamics are poorly delineated in young children, the proposed target group for immunization programs. Here we present whole genome sequencing and antimicrobial susceptibility data on 198 S. Typhi and 66 S. Paratyphi A isolated from children aged 2 months to 15 years of age during blood culture surveillance at Patan Hospital, Nepal, 2008-2016.Principal findingsS. Typhi was the dominant agent and comprised several distinct genotypes, dominated by 4.3.1 (H58). The heterogeneity of genotypes in children under five was reduced compared to data from 2005-2006, attributable to ongoing clonal expansion of H58. Most isolates (86%) were non-susceptible to fluoroquinolones, associated mainly with S. Typhi H58 lineage II and S. Paratyphi A harbouring mutations in the quinolone resistance-determining region (QRDR); non-susceptible strains from these groups accounted for 50% and 25% of all isolates. Multi-drug resistance (MDR) was rare (3.5% of S. Typhi, 0 S. Paratyphi A) and restricted to chromosomal insertions of resistance genes in H58 lineage I strains. Temporal analyses revealed a shift in dominance from H58 Lineage Ito H58 Lineage II, with the latter being significantly more common after 2010. Comparison to global data sets showed the local S. Typhi and S. Paratyphi A strains had close genetic relatives in other South Asian countries, indicating regional strain circulation. Multiple imports from India of ciprofloxacin-resistant H58 lineage II strains were identified, but these were rare and showed no evidence of clonal replacement of local S. Typhi.SignificanceThese data indicate that enteric fever in Nepal continues to be a major public health issue with ongoing inter-and intra-country transmission, and highlights the need for regional coordination of intervention strategies. The absence of a S. Paratyphi A vaccine is cause for concern, given its prevalence as a fluoroquinolone resistant enteric fever agent in this setting.