High relatedness of invasive multi-drug resistant non-typhoidal Salmonella genotypes among patients and asymptomatic carriers in endemic informal settlements in Kenya
High relatedness of invasive multi-drug resistant non-typhoidal Salmonella genotypes among patients and asymptomatic carriers in endemic informal settlements in Kenya
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DOI：
10.1371/journal.pntd.0008440
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发表时间：
2020-08-01
影响因子：
3.8
通讯作者：
Dougan, Gordon
中科院分区：
文献类型：
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作者：
Kariuki, Samuel;Mbae, Cecilia;Dougan, Gordon
撒哈拉以南非洲幼儿的血流感染导致高发病率和死亡率。在肯尼亚，非伤寒沙门氏菌（NTS）血清型鼠伤寒沙门氏菌和肠炎沙门氏菌在引起血液感染方面尤为重要。在这项病例对照研究中，我们共检测了4201名有潜在血流感染的儿童，并将他们的NTS基因型与6326名年龄匹配的无症状对照组粪便样本中发现的基因型进行了比较。从系统发育分析中，我们观察到在病例和对照组中携带率很高的多药耐药沙门氏菌基因型与引起侵袭性疾病的基因型相似。我们推测无症状人群中的高携带率可能有助于NTS疾病在脆弱人群儿童中的维持和传播。侵袭性非伤寒沙门氏菌（iNTS）疾病是一个主要的公共卫生挑战，特别是在撒哈拉以南非洲（SSA）。在肯尼亚，如果不及时治疗，死亡率很高（20 - 25%）。最常见的血清型是沙门氏菌（Salmonella entericaserotype Typhimurium）。鼠伤寒沙门氏菌（S.肠道）。在肯尼亚内罗毕Mukuru非正式定居点的儿童中进行的一项为期5年的病例对照研究中，研究了来自疑似iNTS病例的4201份血液培养物和来自年龄匹配对照的6326份粪便样本。从实验室培养物中，我们总共获得了133S。其中83株（62.4%）来自病例（53株血液和30株粪便），50株（37.6%）来自对照（粪便）。共120个S。肠道感染包括70例（58.3%）病例（43例血液和27例粪便）和50例（41.7%）对照（粪便）。帖前鼠伤寒菌群分为两个不同的ST 19谱系，占36.1%，以及ST 313谱系I（27.8%）和ST 313谱系II（36.1%）分离株。帖前肠道病毒分离株分为全球流行谱系（46.6%）、中非/东非谱系（30.5%）、新的肯尼亚特异性谱系（12.2%）和遗传学异常谱系（10.7%）。详细的系统发育分析显示，来自病例和对照的血液和粪便的NTS之间存在高度相关性，表明有一个共同的来源池。多药耐药在整个过程中很常见，其中8.5%的此类分离株对超广谱β内酰胺类抗生素耐药。人群中无症状携带率高是传播给脆弱个体的一个问题，如果iNTS疫苗可用，这一群体可能成为疫苗接种的目标。
Author summary Blood-stream infections in young children in Sub-Saharan Africa cause high levels of morbidity and mortality. Non-typhoidalSalmonella(NTS) serovars Typhimurium and Enteritidis are especially important in causing blood-stream infections in Kenya. In this case-control study we examined a total of 4201 children with potential blood-stream infections and compared their NTS genotypes with those found in fecal samples of 6326 asymptomatic age-matched controls. From a phylogenetic analysis, we observed a high rate of carriage in cases and controls of multidrug resistantSalmonellagenotypes with similarity to those causing invasive disease. We hypothesize that the high carriage rates in asymptomatic population may be contributing to maintenance and transmission of NTS disease among vulnerable population of children.Invasive Non-typhoidalSalmonella(iNTS) disease is a major public health challenge, especially in Sub-Saharan Africa (SSA). In Kenya, mortality rates are high (20-25%) unless prompt treatment is instituted. The most common serotypes areSalmonella entericaserotype Typhimurium (S. Typhimurium) andSalmonella entericaserotype Enteritidis (S. Enteritidis). In a 5 year case-control study in children residing in the Mukuru informal settlement in Nairobi, Kenya, a total of 4201 blood cultures from suspected iNTS cases and 6326 fecal samples from age-matched controls were studied. From the laboratory cultures we obtained a total of 133S. Typhimurium isolates of which 83(62.4%) came from cases (53 blood and 30 fecal) and 50(37.6%) from controls (fecal). A total of 120S. Enteritidis consisted of 70(58.3%) from cases (43 blood and 27 fecal) and 50(41.7%) from controls (fecal). TheS. Typhimurium population fell into two distinct ST19 lineages constituting 36.1%, as well as ST313 lineage I (27.8%) and ST313 lineage II (36.1%) isolates. TheS. Enteritidis isolates fell into the global epidemic lineage (46.6%), the Central/Eastern African lineage (30.5%), a novel Kenyan-specific lineage (12.2%) and a phylogenetically outlier lineage (10.7%). Detailed phylogenetic analysis revealed a high level of relatedness between NTS from blood and stool originating from cases and controls, indicating a common source pool. Multidrug resistance was common throughout, with 8.5% of such isolates resistant to extended spectrum beta lactams. The high rate of asymptomatic carriage in the population is a concern for transmission to vulnerable individuals and this group could be targeted for vaccination if an iNTS vaccine becomes available.