Multidrug resistant invasive non-typhoidal Salmonella disease in children: The role of carriage in humans and environmental contamination in an endemic setting in Kenya

儿童多重耐药侵袭性非伤寒沙门氏菌病:肯尼亚流行环境中携带的人类和环境污染的作用

基本信息

项目摘要

While textbook knowledge divides between invasive typhoidal and non-invasive enteric non-typhoidal Salmonellosis (NTS), in Sub-Saharan Africa so far neglected and threatening infectious disease has emerged as a prominent cause of bloodstream infection. This disease is caused by invasive strains of NTS (iNTS). The largest number of cases annually is found in children less than 5 years of age with an associated case fatality of 20–25%. Further, increasing antimicrobial resistance (AMR) in iNTS is of great global concern, with low and middle-income countries suffering mostly as alternative drugs for effective treatment of life-threatening invasive disease are eroding rapidly. Worryingly, iNTS infections are also found in Germany with increasing prevalence. Carriage of pathogens often contributes to disease transmission, but in contrast to the well-documented prolonged carriage of typhoidal Salmonella in humans, carriage of non-typhoidal Salmonellae is far less studied. Therefore, we here aim to establish in an endemic disease setting if carriage of NTS at the household level and environmental contamination play a major role in iNTS infection occurring in vulnerable children in the community and what drives this escalating problem of antimicrobial resistance. Further, a comprehensive genome analysis of African iNTS strains in comparison to German strains from invasive infections will be performed. Specific objectives of the proposed project are: 1) To determine the prevalence, host, environmental and pathogen factors associated with persistent carriage of NTS strains in apparently healthy individuals. 2) To describe the epidemiology and genomics of multi-drug resistant iNTS strains from patients, carriers and environment and their association with persistent carriage of iNTS strains. To further compare strain genomes to those isolated from infections in Germany. 3) To determine AMR genes in homestead and environment (open sewers and water sources) as potential donors of resistance determinants to iNTS. 4) To develop simple PCR tools which can be easily adapted to improve detection and engage local community to minimize risk factors for carriage and transmission of iNTS and AMR. 5) To establish a comprehensive research training program on Salmonella classification, subtyping, genome sequencing, genome and metagenome analysis with the goal to enable African scientists to perform molecular detection and characterization of project samples.
虽然教科书中对侵袭性伤寒沙门氏菌病和非侵袭性肠非伤寒沙门氏菌病(NTS)的认识有所不同,但在撒哈拉以南非洲地区,迄今为止被忽视和威胁的传染病已成为血流感染的主要原因。这种疾病是由 NTS (iNTS) 入侵菌株引起的。每年发现的病例数最多的是 5 岁以下儿童,相关病死率为 20-25%。此外,iNTS 中抗生素耐药性 (AMR) 的增加引起了全球的高度关注,低收入和中等收入国家深受其害,因为有效治疗危及生命的侵袭性疾病的替代药物正在迅速消失。令人担忧的是,德国也发现了 iNTS 感染,而且患病率不断上升。病原体的携带通常会导致疾病传播,但与有据可查的伤寒沙门氏菌在人类中的长期携带相比,非伤寒沙门氏菌的携带研究却少得多。因此,我们的目标是在地方病环境中确定家庭水平的 NTS 携带和环境污染是否在社区弱势儿童发生 iNTS 感染中起主要作用,以及是什么导致了抗菌素耐药性问题的升级。此外,还将对非洲 iNTS 菌株与德国侵袭性感染菌株进行全面的基因组分析。拟议项目的具体目标是: 1) 确定与表面健康个体中持续携带 NTS 菌株相关的流行率、宿主、环境和病原体因素。 2) 描述来自患者、携带者和环境的多重耐药 iNTS 菌株的流行病学和基因组学及其与 iNTS 菌株持续携带的关系。进一步将菌株基因组与从德国感染中分离出的菌株基因组进行比较。 3) 确定宅基地和环境(开放式下水道和水源)中的 AMR 基因作为 iNTS 抗性决定因素的潜在供体。 4) 开发简单的 PCR 工具,这些工具可以轻松适应以改进检测,并让当地社区参与其中,以最大限度地减少 iNTS 和 AMR 携带和传播的风险因素。 5) 建立关于沙门氏菌分类、亚型、基因组测序、基因组和宏基因组分析的综合研究培训计划,目标是使非洲科学家能够对项目样本进行分子检测和表征。

项目成果

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Professorin Dr. Antje Flieger其他文献

Professorin Dr. Antje Flieger的其他文献

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{{ truncateString('Professorin Dr. Antje Flieger', 18)}}的其他基金

Significance of Legionella pneumophila phospholipases for modification of lipids within the phagosomal membrane
嗜肺军团菌磷脂酶对吞噬体膜内脂质修饰的意义
  • 批准号:
    198259546
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
    Priority Programmes
Characterization of Legionella pneumophila genes with impact on bacterial uptake into host cells and on bacterial virulence
嗜肺军团菌基因对细菌摄取宿主细胞和细菌毒力的影响的表征
  • 批准号:
    45258236
  • 财政年份:
    2007
  • 资助金额:
    --
  • 项目类别:
    Priority Programmes
Analysis of export and membrane association of PlaB - a surface-associated phospholipase A and virulence factor of Legionella pneumophila
PlaB(一种表面相关磷脂酶 A 和嗜肺军团菌毒力因子)的输出和膜关联分析
  • 批准号:
    16256777
  • 财政年份:
    2005
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Charakterisierung von Patatin-ähnlichen Phospholipasen A des Lungenpathogens Legionella pneumophila
肺部病原体嗜肺军团菌的 patatin 样磷脂酶 A 的表征
  • 批准号:
    5437147
  • 财政年份:
    2004
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Phospholipasen A von Legionella pneumophila
来自嗜肺军团菌的磷脂酶 A
  • 批准号:
    5269980
  • 财政年份:
    2000
  • 资助金额:
    --
  • 项目类别:
    Research Fellowships
Function of Legionella pneumophila phospholipases in vacuole and host egress
嗜肺军团菌磷脂酶在液泡和宿主出口中的功能
  • 批准号:
    446411117
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Priority Programmes

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