An outbreak of hemolytic uremic syndrome due to Escherichia coli O157:H7: or was it?
An outbreak of hemolytic uremic syndrome due to Escherichia coli O157:H7: or was it?
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由大肠杆菌 O157:H7 引起的溶血性尿毒症综合征的爆发：或者是？
DOI：
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发表时间：
1996
影响因子：
11.8
通讯作者：
K. Bettelheim
中科院分区：
文献类型：
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作者：
P. Goldwater;K. Bettelheim
致编辑：自10多年前首次报道溶血性尿毒症综合征（HUS）及相关疾病暴发以来(1)，世界许多地区，特别是北美和欧洲都报道了由大肠杆菌O157引起的溶血性尿毒症暴发。虽然这些报告大多将O157:H7血清型的运动毒株归为犯罪，但非运动血清型（例如O157:H-）也与溶血性尿毒综合征有关；这两种血清型最常与溶血性尿毒综合征的暴发和散发病例及相关病症相关。在过去的十年中，已经开发了许多快速识别这些生物的技术。其中，山梨糖醇-麦康基琼脂(2)的使用可能是最有价值的。这项技术是基于这样一个事实，即这些微生物在初级分离时很少发酵山梨醇，而大多数其他大肠杆菌通常发酵这种底物。我们认为，由于调查这些暴发的技术有限，其他肠出血性大肠杆菌引起的暴发可能归因于O157血清群。在澳大利亚，尽管有由O157血清群引起的散在溶血性尿毒症病例，但未发生溶血性尿毒症暴发。在澳大利亚，其他血清型（特别是O111血清型：H-）与大多数溶血性尿毒综合征和相关疾病有关(3)。1995年1月，南澳大利亚报告了一次与食用受污染的发酵香肠（mettwurst，发酵香肠）有关的暴发，此后澳大利亚才报告了溶血性尿毒综合征暴发(4)。23名溶血性尿毒综合征患儿住院。最需要的血液透析；人死亡。从19例患者和mettwurst样本中分离到产志贺样毒素（SLT） I和II的大肠杆菌O111产胞毒素菌株。此外，从3名患者和metwurst中分离出产生SLT-I和SLT-II的大肠杆菌O157: h菌株。这些菌株没有在山梨糖醇-麦康基琼脂上发酵山梨糖醇，这有利于它们的分离。与最近被描述为山梨糖醇阴性的O111菌株不同，O111菌株主要呈山梨糖醇阳性(5)。除大肠杆菌O111:H-外还分离出O157: h株的患者的症状与仅分离出大肠杆菌O111:H-的患者的症状无显著差异。除O111（和O157）外，还从患者身上分离出其他血清型肠出血性大肠杆菌，包括血清群O23、O26和O91菌株。然而，在几乎所有患者中都检测到O111抗体，这表明该血清组在疫情中起主导作用。O157血清组的分离比较容易；因此，与O111和其他血清型相比，这些毒株被遗漏的可能性更小。尽管阴性结果永远不能被认为是结论性的，但我们认为无法分离O157血清组比其他血清型的相同结果更具结论性。经常有人认为，O157血清组可以相对较快地从患者体内清除，这使得很难或不可能将其分离出来。我们在其他肠出血性大肠杆菌血清型中发现了类似的情况。大多数患者引起O111抗体反应（而没有抗o157抗体）的事实几乎肯定证明了这种血清型在本次疫情中的因果作用。南澳大利亚的实验室在处理这种疾病爆发方面做得特别好，因为它正在进行的一些研究项目包括对肠出血性大肠杆菌和相关有机体的研究。立即使用了最先进的分子生物学技术，以准确调查疫情并确认有关共同来源的流行病学线索。聚合酶链反应（Polymerase chain reaction， PCR）不仅在鉴定患者粪便中产生SLT-I、SLT-II以及SLT-I和SLT-II的细菌中发挥了重要作用，而且在鉴定可疑来源（mettwurst）中也发挥了重要作用。此外，利用O111血清组特异性序列的PCR方法能够在患者粪便样本和疑似源材料中快速鉴定出该血清组。如果没有这项技术，疫情不可能如此迅速地得到控制。另一方面，如果实验室必须依靠传统的微生物培养程序，包括山梨糖醇-麦康基琼脂，那么就可以从三名患者以及流行病学上的mettwurst中鉴定出血清群O157菌株。实验室不会发现O111菌株，因为它们都很容易发酵山梨醇，并且会像其他肠出血性大肠杆菌血清型一样被作为正常菌群丢弃。这次爆发将被报道为另一次O157爆发，其中只有约15%的患者产生了可定罪的菌株。这次暴发可被认为是由多种不同的肠出血性大肠杆菌血清型引起的，其中血清型O111:Hand O157: h0最为突出。信
To the Editor: Since the first reported outbreaks of hemolytic uremic syndrome (HUS) and related conditions more than 10 years ago (1), outbreaks of HUS due to Escherichia coli O157 have been reported from many parts of the world, particularly North America and Europe. While most of these reports have incriminated the motile strains of serotype O157:H7, nonmotile serotypes (e.g., O157:H-) have also been associated with HUS; these two serotypes are most commonly associated with both outbreaks and sporadic cases of HUS and related conditions. Over the last decade, a number of techniques for the rapid identification of these organisms have been developed. Of these, the use of sorbitol-MacConkey agar (2) has perhaps been the most valuable. This technique is based on the fact that these organisms rarely ferment sorbitol on primary isolation, while most other E. coli usually ferment this substrate. We believe that outbreaks due to other enterohemorrhagic E. coli may have been attributed to serogroup O157 because of the limited technology used in investigating these outbreaks. No outbreaks of HUS due to serogroup O157 have occurred in Australia despite sporadic cases of HUS caused by such strains. Other serogroups (particularly serotype O111:H-) have been associated with most cases of HUS and related conditions in Australia (3). No outbreak of HUS had been reported in Australia until January 1995, when an outbreak associated with the consumption of contaminated mettwurst (fermented sausage) was reported from South Australia (4). Twenty-three children with HUS were hospitalized. Most required hemodialysis; one died. Verocytotoxigenic strains of E. coli O111 producing Shiga-like toxin (SLT) I and II were isolated from 19 patients and from samples of mettwurst. In addition, strains of E. coli O157:Hthat produced SLT-I and SLT-II were isolated from three of the patients and the mettwurst. These strains did not ferment sorbitol on the sorbitol-MacConkey agar, which facilitated their isolation. The predominant O111 strains were sorbitol-positive, unlike the O111 strains, recently described as being sorbitolnegative (5). Symptoms of the patients from whom the O157:Hstrains were isolated, in addition to E. coli O111:H-, were not significantly different from those of the patients whose specimens yielded only E. coli O111:H-. In addition to O111 (and O157), other serotypes of enterohemorrhagic E. coli, including strains of serogroup O23, O26, and O91, were isolated from the patients. However, antibodies to O111 were detected in nearly all patients, which indicates the serogroup’s leading role in the outbreak. The isolation of serogroup O157 is comparatively easy; therefore, it is less likely that these strains would have been missed, than it is that O111 and other serotypes would have been. Even though a negative finding can never be considered conclusive, we consider the inability to isolate serogroup O157 more conclusive than the same result for other serotypes. It has frequently been suggested that the O157 serogroup is cleared from the patient relatively rapidly, which makes its isolation difficult or impossible. We found a similar situation with other enterohemorrhagic E. coli serotypes. The fact that most patients elicited an O111 antibody response (and no anti-O157) almost certainly proves this serotype’s causal role in this outbreak. The laboratory in South Australia was particularly well disposed to deal with such an outbreak because some of its ongoing research programs included studies on aspects of enterohemorrhagic E. coli and related organisms. The most sophisticated molecular biologic techniques were immediately available to investigate the outbreak accurately and confirm epidemiologic leads regarding a common source. Polymerase chain reaction (PCR) played a major role not only in identifying SLT-I, SLT-II, and SLT-I and SLT-II producing bacteria in the stool of patients, but also in identifying the suspected source (mettwurst). In addition, PCR, utilizing sequences specific for the O111 serogroup, enabled this serogroup to be rapidly identified in patients’ feces samples and suspected source material. Without this technology, the outbreak would not have been contained so rapidly. On the other hand, if the laboratory had to rely on conventional microbiologic culture procedures, including sorbitol-MacConkey agar, strains of serogroup O157 would have been identified from three patients, as well as from the epidemiologically incriminated mettwurst. The laboratory would not have found the O111 strains because they all fermented sorbitol readily and would have been discarded as normal flora as would the other enterohemorrhagic E. coli serotypes. The outbreak would have been reported as another O157 outbreak, from which only about 15% of the patients yielded the incriminating strains. This outbreak could be recognized as one caused by a number of different enterohemorrhagic E. coli serotypes, of which serotypes O111:Hand O157:Hwere the most prominent. Letters