A multicenter study into the diarrhea causing bacteria entero-invasive Escherichia coli (EIEC) and Shigella species

The invasive bacteria Shigella species and entero-invasive E. coli (EIEC) can cause gastroenteritis, and share a similar invasive nature. From results of food related outbreaks, a few in-vitro and in-vivo experiments with a limited number of strains, it appears that the symptoms of infections with Shigella and EIEC are comparable, only EIEC has a higher infection dose. Shigella species and EIEC are not compared with each other in a large prospective study, to our knowledge. Little is known about the incidence and course of infection of EIEC. Infections with Shigella species are notifiable in the Netherlands and infections with EIEC are not, even though differences between them are not clear. Next to this, diagnostics poses a problem, because Shigella species and EIEC are genetically related, they are difficult to distinguish with commonly used molecular diagnostics. Culturing, extensive phenotypic identification and serotyping are needed for identification. These labor-intensive and not cost-effective techniques are only performed by reference laboratories.



The IBESS study is started to gain insight into diagnostic algorithms, prevalence, patient and strain bound risk factors, clinical relevance, spread and impact on public health of infections with EIEC and Shigella species, and how these variables of the two genera relate to each other. A secondary objective is to perform molecular epidemiology to investigate genetic relatedness of EIEC and Shigella species in the Netherlands.



The study was submitted to the MERC of UMC Utrecht. As the study does not require extra procedures for the patients, but uses fecal samples from routine diagnostic procedures, the committee has ruled that the Medical Research Involving Human Subjects Act (WMO) does not apply to the IBESS study and that therefore an official approval of this study by the MERC UMC Utrecht is not required under the WMO.



In IBESS, results of laboratory tests of feces samples and deriving bacterial strains will be combined with epidemiological and clinical data of patients. The fecal samples are submitted to a participating laboratory as part of regular patient diagnostics. The IBESS study group will perform additional laboratory testing and will conduct a single survey for patients by telephone to collect the patient data.



It is estimated that 1100 samples can be included during two year, of which the IBESS group can derive approximately 700 bacterial strains.



Outcomes of the study are:
ƒ{ The effects of the different diagnostic laboratory results on patient bound risk factors, incidence, spread, clinical relevance and economic consequences of infection.

ƒ{ The effect of certain strain bound characteristics, both phenotypically and genotypically, on severity and spread of infection.

ƒ{ Results of molecular epidemiology: the source and relatedness of Shigella and EIEC strains in the Netherlands.

ƒ{ If applicable: recommendations for diagnostics to medical microbiological laboratories in the Netherlands.

ƒ{ If applicable: recommendations about improvements of national guidelines for control of infectious diseases caused by Shigella species or EIEC.

The invasive bacteria Shigella and entero-invasive E.coli (EIEC) that cause gastro-enteritis, are genetically related and share an infection mechanism. In the Netherlands, Shigellosis is a notifiable disease, while infections with EIEC are not. With commonly used molecular diagnostics it is not possible to distinguish the two bacteria. Culturing, phenotypic identification and serotyping, which are all labor-intensive and not cost-effective, are needed for identification. The main objectives of IBESS are to gain insight into prevalence, patient and strain bound risk factors, clinical relevance, spread of disease and impact on public health of infections with EIEC and Shigella species. For evidence-based evaluation of guidelines for Shigellosis and infections with EIEC, the above-mentioned variables of the two genera are compared to each other. Secondary objectives are to optimize diagnostics and to perform molecular epidemiology for investigation of genetic relatedness within EIEC and Shigella species in the Netherlands.

After a two year inclusion period, the outcomes can be analyzed.

The intervention in the IBESS is a noninvasive single survey assessed by telephone for inquiry of epidemiological and clinical data of the patient. In case of a minor, one of the parents or caretakers will be asked to participate in the survey on behalf of the child.