Analysis of Escherichia Coli O104:H4 Outbreak in Germany in 2011 Using Differentiation Method for Unusual Epidemiological Events.

INTRODUCTIONFrom 1 May to 5 July 2011 Germany faced the largest and the most severe food-borne outbreak of haemolytic- uremic syndrome (HUS) ever. It was reported to the World Health Organization (WHO) according to the International Health Regulations (1). The outbreak was caused by the unique serotype O104:H4 of Shiga toxin producing Escherichia coli, termed also as enterohaemorrhagic Escherichia coli (EHEC) (1). There were 2,987 cases of bloody diarrhoea (18 lethal) and 855 cases complicated with HUS (35 lethal). Additionally, 83 German Ec cases and 54 patients with HUS were recorded outside Germany, most of them linked to travelling to Northern Germany in May 2011 (2). German authorities and the European Food Safety Authority (EFSA) announced that the contaminated sprouts grown from fenugreek seeds imported from Egypt in 2009 were the most probable vehicle of the pathogen in this epidemic (1).Based on the results of a comparative study performed with three models for differentiation between natural and deliberate epidemics (3), the German Ec outbreak may be regarded as an unusual epidemiological event (UEE). This assumption is supported by the following epidemiological, demographical, biological, microbiological, pathological, and clinical features of German Hemolytic Uremic Syndrome/Enterohemorrhagic Escherichia Coli (GHUSEC): high pathogenicity and extended spectrum beta-lactamase antibiotic resistance of a chimeric (enterohaemorrhagic/enteroaggregative) O104:H4 strain (1, 4-10), sudden appearance and disappearance of the pathogen (1), suitability for genetic manipulation (11), long term carriage and excretion of the pathogen (9, 11, 12), easy pathogen spreading by different transmission routes (9, 12), longer incubation period than typical for known EHEC serotypes (1, 12), and no definite conclusions about the use of antibiotics in acute EHEC diarrhoea as well as for the causal therapy at all (2). There was a rapidly increasing number of patients with severe diarrhoea and unusually high proportion of patients with HUS, very fast supra-regional spread throughout Germany and in 13 other European countries plus cases in the USA and Canada and unexpectedly high incidence in adults and females (13-15). The causative role of fenugreek seeds exported from Egypt was questionable (12) due to difficulties to isolate the pathogen from fenugreek seeds and to identify sources of infection, reservoirs and modus of contamination of the food (1). The outbreak was unusually long-lasting, especially considering peaceful time without natural disasters in a highly developed country with a prominent healthcare system.One of the key points of the recent comparative study of the unique German Ec outbreak (3) was that the pathogen could have been introduced in the food chain deliberately. In order to further assess the probable origin of this epidemic we use a more detailed and subtle retrospective assessment.MATERIALS AND METHODSA literature review was performed in the database MEDLINE for the period 1999-2014 in order to obtain necessary data for a retrospective analysis of the German Ec outbreak with the following key words: outbreak, epidemic, Escherichia coli, EHEC O104:H4, STEC O104:H4, HUS, gastroenteritis, haemolytic uremic syndrome, HUS, sprouts, seeds, and Germany.We analysed the German Ec outbreak using a subtle and detailed differentiation method for four possible UEE scenarios: natural outbreak of a known endemic disease; natural outbreak of a new or re-emerging disease; outbreak by an accidental release of a pathogen; outbreak by a deliberate delivery of a biological agent. This method is based on 23 qualitative and 10 quantitative parameters (16-17). Parameters with its characterizing features were grouped in four components of the chain of infection (Table 1): Reservoir/source of infection vs. perpetrator: sophistication, motivation, intention, intelligence, secrecy, number of perpetrators, number of reservoirs? …