Hebbelstrup Jensen Betina, Poulsen Anja, Hebbelstrup Rye Rasmussen Stig, Struve Carsten, Engberg Jørgen H, Friis-Møller Alice, Boisen Nadia, Jønsson Rie, Petersen Randi F, Petersen Andreas M, Krogfelt Karen A
Department of Bacteria, Parasites and Fungi, Statens Serum InstitutCopenhagen, Denmark.
Department of Gastroenterology, Copenhagen University Hospital HvidovreCopenhagen, Denmark.
Front Cell Infect Microbiol. 2017 May 30;7:230. doi: 10.3389/fcimb.2017.00230. eCollection 2017.
Enteroaggregative (EAEC) is frequently found in diarrheal stools worldwide. It has been associated with persistent diarrhea, weight loss, and failure to thrive in children living in developing countries. A number of important EAEC virulence genes are identified; however, their roles in acute and persistent diarrhea have not been previously investigated. The aim of this study was to identify specific EAEC virulence genes associated with duration and type of diarrhea in Danish children. We aimed to improve the current diagnostics of EAEC and enable targeting of strains with an expected severe disease course. Questionnaires answered by parents provided information regarding duration of diarrhea and presence of blood or mucus. A total of 295 EAEC strains were collected from children with acute (≤7 days) and persistent diarrhea (≥14 days) and were compared by using multiplex PCR targeting the genes , and . Furthermore, the distribution of EAEC genes in strains collected from cases of bloody, mucoid, and watery diarrhea was investigated. The classification and regression tree analysis (CART) was applied to investigate the relationship between EAEC virulence genes and diarrheal duration and type. Persistent diarrhea was associated with strains lacking the gene ( = 0.002) and with the combination of the genes , and absence of the gene ( = 0.05). Prolonged diarrhea was associated with the combination of the genes and ( = 0.03). Non-mucoid diarrhea was associated with strains lacking the gene ( = 0.004). Acute diarrhea was associated with the genes , and by individual odds ratios. Resistance toward gentamicin and ciprofloxacin was observed in 7.5 and 3% of strains, respectively. Multi-drug resistance was observed in 38% of strains. Genetic host factors have been associated with an increased risk of EAEC-associated disease. Therefore, we investigated a panel of risk factors in two groups of children-EAEC-positive and EAEC-negative-to identify additional factors predisposing to disease. The duration of breastfeeding was positively correlated with the likelihood of belonging to the EAEC-negative group of children.
肠集聚性大肠杆菌（EAEC）在全球腹泻粪便中经常被发现。它与发展中国家儿童的持续性腹泻、体重减轻和发育不良有关。已鉴定出许多重要的EAEC毒力基因；然而，它们在急性和持续性腹泻中的作用此前尚未被研究。本研究的目的是确定与丹麦儿童腹泻持续时间和类型相关的特定EAEC毒力基因。我们旨在改进当前对EAEC的诊断，并能够针对预期有严重病程的菌株。家长填写的问卷提供了有关腹泻持续时间以及是否有血便或黏液便的信息。从患有急性腹泻（≤7天）和持续性腹泻（≥14天）的儿童中总共收集了295株EAEC菌株，并使用针对基因、和的多重PCR进行比较。此外，还研究了从血性、黏液性和水样腹泻病例中收集的菌株中EAEC基因的分布情况。应用分类与回归树分析（CART）来研究EAEC毒力基因与腹泻持续时间和类型之间的关系。持续性腹泻与缺乏基因的菌株相关（P = 0.002），也与基因、的组合以及缺乏基因相关（P = 0.05）。腹泻时间延长与基因和的组合相关（P = 0.03）。非黏液性腹泻与缺乏基因的菌株相关（P = 0.004）。急性腹泻分别通过个体优势比与基因、相关。分别在7.5%和3%的菌株中观察到对庆大霉素和环丙沙星的耐药性。在38%的菌株中观察到多重耐药性。遗传宿主因素与EAEC相关疾病风险增加有关。因此，我们在两组儿童（EAEC阳性和EAEC阴性）中调查了一组风险因素，以确定导致疾病的其他因素。母乳喂养持续时间与属于EAEC阴性儿童组的可能性呈正相关。
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