Sample Essay Paper on Germany E. coli outbreak

Germany E. coli Outbreak

A large bacterial infection outbreak hit central Europe in the spring of 2011(Karch et al, 2012). The pathogen involved was a unique strain of Escherichia coli, O104:H4 belonging to the class enteroaggregative E. coli that leads to the development of hemolytic uremic syndrome (HUS). Preliminary reports indicated that the outbreak emanated from the consumption of contaminated salad sprouts, although the exact origin of the pathogen remains at large. The outbreak affected an estimated count of 4000 people and resulted in the death of 50 others. It caused a significant social and economic disturbance even with its record-time discovery and sequencing. This paper reviews the outbreak of the German strain and suggests measures aimed at preventing future occurrences of the pathogen.

Details of the outbreak

The outbreak of the Escherichia coli in during the late spring of 2011, early May to 22 June affected the majority of central European countries with a few cases reported in the United States(Karch et al, 2012). Germany happened to be the epicenter of the outbreak with the pinch of the outbreak hitting its peak around the 21st day of May. A total of about 4000 peoplewas infected with the disease mainly in Germany, more than 900 cases of hemolytic uremic syndrome (HUS) resulting in 54 deaths were reported(Karch et al, 2012). The table below shows the figures and analysis of the extent of the outbreak (WHO, 2011).

 

Country Deaths HUS cases Non-HUS cases
Austria 5000000000000000000 0 7000100000000000000 1 7000400000000000000 4
Canada 5000000000000000000 0 5000000000000000000 0 7000100000000000000 1
Czech Republic 5000000000000000000 0 5000000000000000000 0 7000100000000000000 1
Denmark 5000000000000000000 0 7001100000000000000 10 7001160000000000000 15
France 5000000000000000000 0 7000700000000000000 7 7000400000000000000 10
Germany 7001480000000000000 48 7002733000000000000 857 7003307800000000000 3078
Greece 5000000000000000000 0 5000000000000000000 0 7000100000000000000 1
Luxembourg 5000000000000000000 0 7000100000000000000 1 7000100000000000000 1
Netherlands 5000000000000000000 0 7000400000000000000 4 7000700000000000000 7
Norway 5000000000000000000 0 5000000000000000000 0 7000100000000000000 1
Poland 5000000000000000000 0 7000200000000000000 2 7000100000000000000 1
Spain 5000000000000000000 0 7000100000000000000 1 7000100000000000000 1
 Sweden 7000100000000000000 1 7001180000000000000 18 7001350000000000000 35
 Switzerland 5000000000000000000 0 7000500000000000000 5 5000000000000000000 0
United Kingdom 5000000000000000000 0 7000300000000000000 3 7000400000000000000 4
United States 7000100000000000000 1 7000400000000000000 4 7000200000000000000 2
Total 299990000000000000050 2999900000000000000908 29999000000000000003,167

 

The initial intervention measures were aimed at disclosing the source of the outbreak so as to prevent new infections. Initial reports from northern Germany postulated that the infection had probably been community-acquired and were not directly linked to the consumption of any particular food from a particular restaurant. This position, however, changed with time as microbiologic, epidemiologic, food trace-back and food trace-forward reports suggested otherwise. Initial reports suggested that raw food items in the form of tomatoes, cucumbers and leaf salad could have been the principal infection source with only a small percentage of interview subjects linking to outbreak to sprouts, which had previously been implicated with similar outbreaks in the US and Japan. Final reports from microbiologic, epidemiologic, food trace-back and food trace-forward investigations incriminated sprouts as the primary source of infection.

The German strain of E. coli exhibited unusual characteristics from other strains of the syndrome, these include;

 

  • A large proportion of case-patients with hemolytic uremic syndrome (HUS);

 

  • HUS in adults as opposed to children

 

  • Regular development of neurologic symptoms in patients when clinical and laboratory markers of HUS were improving(Scavia et al, 2011)

Another contrasting feature of O104:H4 from other enteroaggregative E. coli occurred in the differing incubation periods. According to a survey by Frank et al (2011) of 43 randomly sampled case patients, the median incubation period for the German pathogen was 8 days. A second survey of 79 case patients revealed the interval from the onset of diarrhea and diagnosis of HUS as 5 days. This differs from data on other strains of  E. coli, which is documented as 7 days the interval between onset of diarrhea and HUS diagnosis(Frank et al, 2011).It was characterized by diarrhea, vomiting and abdominal cramps(Kemper, 2012).

Features of the microorganism

The severity and unique characteristics of the GermanEscherichia coli forced researchers to hit the labs in attempts to uncover its identity.  E. colihas long been recognized as commensal organisms, although there is also knowledge of diarrheagenic pathotypes in existence(Rasko et al, 2011). Six strains of diarrheagenic  E. coli are known to exist, of these Shiga toxin producing pathotypes are the ones associated with diarrhea, hemolytic uremic syndrome and neurologic complications. Most of these strains have been classified as enterohemorrhagic due to the presence of the enterocyteeffacement pathogenicity island in them that aids their survival in the colon(Rasko et al, 2011). The second class of these strains, with rare occurrence, is enteroaggregative  E. coli. This strain has been linked to diarrhea especially with travelers, children and HIV/AIDS patients.

The German strain was establishedas a unique enteroaggregative  E. coli,which was contrary to the expectations as few of such cases had been documented before.This strain is among the few  E. coli strains known to invade the human intestines. It is known to result in serious disorders due to the ability to physically attach to the intestinalwalls and production of toxins furthered by the complication of the ability to develop resistance to antibiotics. This particular  E. coli was a unique strain as it exhibited an amalgamation both enteroaggregative  E. coli (EAEC) and enterohaemorrhagic  E. coli (EHEC) characteristics. In the light of its serotype for O and H antigens, the strain was classified as O104:H4(Karch et al, 2012). It contained the Stx2 encoding gene and reports from laboratories confirmed that this indeed was ahybrid strain that combined both EAEC and EHEC virulence factors.Prior to this spate, the sequencing of the EAEC genome had been limited to only three cases and therefore knowledge of its phylogeny was limited.

Virulence factors

The scale outbreak  of the O104:H4 was more severe than any of the previously reported cases in the country and elsewhere in the world. A critical review of the case reveals that this scenario was due to the ability of the strain to combine a number of virulence factors. Some of these include;

 

Unique assembly of genes

Reports from medical laboratories revealed that the  E. coli strain in question had evolved from another class of harmless  E. coli.  E. coli O104:H4 was traced from the harmless enterohemorrhagic class of  E. coli and developed Shiga toxin producing genes from the high-risk enteroaggregative  class  E. coli. The strain therefore not only possessed enteroaggregative  E. coli virulence factors, but also those of the less harmful enterohemorrhagic  E. coli(Bielaszewska et al, 2011). The more high-risk class of  E. coli is usually characterized by the encoding of spates, the german strain was however found to encode a combination of three SPATEs, SepA, SigA, and Pic, which is an unlikely occurrence in enteroaggregative  E. colistrains. The fact that it is very unusual for enterohemorrhagic  E. coli strains to encode two or more SPATEs and yet the German strain encoded three gives a reason for the increased virulence(Bielaszewska et al, 2011).

Increased adherence to the colon walls

The German strain of E. colidisplayed an increased rate of adherence to the intestinal walls than other known E. coli strains. Shiga toxin producing Escherichia coli (STEC) usually employs the attaching–effacing mechanism of adhesion to intestinal mucosa which is common with stark human illnesses. The German strain, however was mapped by genetic markers and an adhesion mechanism unique to EAEC. Reports indicate that this increased adherence was probably facilitated by facilitated by alleged adhesins that could possibly increase the absorption of Stx2 which could possibly explain the high frequency of patients developing HUS (Kemper, 2012). The increased adherence could also explain the reduction in the period between diarrheasto HUS develops from 7 days in other strains to 5 days.

 

Resistance to antibiotics

Reports from medical laboratories and scientific research showed that E. coliO104:H4 had developed antibiotic resistance in the course of its evolution due to possession of numerous genes coding for this resistance. This implies that the application of common antibiotics known to counter the effects of Escherichia coli yielded negative results and hence the infection continued to spread. The situation was worsened by the fact that toxin production by O104:H4 could have provoked by the use of a quinolone antibiotic. Thus, initial intervention measures to address the situation via the use of antibiotics could possibly have aggravated the conditions of the subjects.

 

An established human reservoir

 

Cattle had been previously identified as an alternate reservoir for EHEC; however, recent scientific reports indicate that this is not the case for O104:H4. Currently, human beings are the only known hosts for the strain ant it therefore seems to be well adapted to human beings(Karch et al, 2012). The reports are however not conclusive for humans to be the only reservoir of the virus since questions of its zoonotic origin cast a shadow of a potential existing carrier that possibly shelves the symptoms  making it an unsuspected source of spreading the virus.

 

 

Ineffective curative therapies

The adhesion of E. coli O104:H4 to the walls of the intestines resulted in difficult complications that were difficult to address. The toxin action of the virus leads to the destruction of the vascular endothelium; this is followed by the breaking down of blood vessels linings and results to internal bleeding. This sequence of events progresses to kidney failure and possibly the fatal HUS. Intervention measures require patients to receive supportive care aimed at monitoring body fluid levels and kidney functions followed by dialysis to get rid of the toxin. These options were however not available and patients in Germany were limited to plasmapheresis, eculizumab and immune-adsorption which could not effectively address the problem.

 

How the outbreak happened

Although the root source of the contamination still remains a mystery, epidemiologic reports suggested that salad sprouts were the source of contamination(Buchholz et al, 2011). These allegations are supported by the fact that a restaurant study showed that the consumption of sprouts accounted for 100% of confirmed patient cases. These sprouts were traced back to a supplier whose workforce, also frequent sprout consumers, tested positive for the bacteria strain in question. Further investigations showed that a similar outbreak had earlier occurred in France, trace-back investigations revealed that the vegetable sprouts in questions were from certain seed imported from Egypt and the contamination could have possibly occurred at the farm site. It is thus tempting to conclude that the German E. coli outbreak resulted from the consumption of contaminated fenugreek sprouts (Dempsey & Neuman, 2011). The situation was further aggravated by the application of certain antibiotics, which further aggravated the patient conditions as the pathogen had developed gene resistance to them.

Impact

When the scale of the effect of the E. coli O104:H4 is levelled against the impact of other diseases such as malaria, TB and HIV/AIDS, it is found that this outbreak had a very minor effect on the population. The public perception and media coverage that was given to the diseases could have served to blast its impact out of proportion. This was due to the fact that the pathogen was foodborne and to make matters worse, the origin of the contamination could not be clearly singled out. The combination of these reasons raised an alarm within the public creating an impression that the pathogen had caused a significant impact. Increased online searches on google concerning the pathogen species also served to heighten public anxiety of the outbreak.

The outbreak was also felt in terms of economic activities in central Europe. Initial warnings of possible contamination of some vegetables from local authorities in desperate measures to try to curb further spread of the pathogen greatly impacted vegetable sales in Europe (Dempsey & Neuman, 2011). The Spanish vegetable market was the most ill affected after preliminary reports suggested possible contamination. Although the Spanish vegetables were later confirmed to test negative of O104:H4, the damage had already been done.Official reports from Spanish authorities estimated the extend of the loss from produce to over 50 million Euros, although with other reports suggesting that close to 200 million Euros worth of production costs was lost. Spain government official even went a step ahead in attempts to salvage the situation by reassuring farmers that they would formally request the EU to aid those affected.

Other affected European countries include Austria, France and Portugal (WHO, 2011). As of 1st June, French and Austria cucumber sales had declined sharply, although authorities moved forward to reassure the public that all was well (Dempsey & Neuman, 2011). The European market shunned consumption of vegetables and fruits and during the period of the outbreak due to the standing warning from the German government against consumption of fruits and vegetable. EU farmers complained of losses incurred due to spoilage of unsold produce rotting in warehouse while others rotted in the fields. Aware of the extent of losses incurred, the EU set aside a budget to compensate farmers who had felt the pinch. It was said that farmers would receive up to 30% compensation for the unsold produce. The Spanish government was, however, reported to decline a compensation package from the European Commission on account that the level of damage was too small.

An analysis of the impact of the outbreak should also include the health care costs involved in terms of patient diagnostics, epidemiological analyses, hospital bills, dialysis and organ transplants that could be involved in addressing the aftermath of the  outbreak. The magnitude of these expenses remains unknown as an attempt to obtain the exact figures involved is a tricky undertaking. The impact of this outbreak should also be viewed in the light of the cost of the scientific studies and laboratory tests involved. Numerous scientists and medical experts rushed to research and laboratory tests in attempts to uncover the identity of the pathogen involved and suggest counteractive measures. All these efforts attracted financial costs that have not been accounted for therefore making the exact financial impact of the outbreak unknown.

What could be done to improve the situation

Investigative reports of the outbreak detail that the exact source of the contamination still remains at large. This is due to the fact the analysis of the contamination was done not on the vehicle of infection, but based on clinical samples of food leftovers and refuge. Another risky development is the fact that human beings are the only known reservoirs of the pathogen although questions of the zoonotic origin of the pathogen suggest the possibility of an existing carrier that is yet to be identified. Laboratory reports further suggested that antibiotics do little to address the situation, on the contrary, certain antibiotics were found to aggravate the situation by prompting the release of toxins by the E. coli bacteria. Based on these facts, further research into the subject seems to be the most appropriate alternative to prevent the recurrence of the outbreak in future.

  1. coli O157:H7 is bacterial pathogen to the same class as O104:H4 which is currently being addressed through vaccination to reduce cattle shedding(Karch et al, 2012). The strain is known to invade cattle and thus provides a direct source of infection to humans. Vaccination is aimed at preventing potential contamination of meat and dairy produce and thus reducing the risk of human infection. Vaccination for O157:H7 is currently available in the market and reports indicate that it currently commercially available in Canada. The synthesis of a similar vaccine for E. coli O104:H4 seems to be an unlikely event of the near future. This is due to the fact that human beings are the only known reservoirs of the pathogen and the primary reservoir of the pathogen still remains unknown.

An alternative preventive measure to the recurrence of such an outbreak should focus on research. Research of updated and exact channels of the evolution of E. coli to acquire details of its pathogenic factors and virulence factors that could lead to the development of new and complex strains of the bacteria needs to be done.  Due to the scarcity of reported cases of the high-riskE. colipathotype, there is limited knowledge of it and thus further research is necessary(Karch et al, 2012).

The isolated reported cases of E. coli O104:H4 patients reported in the US and other European countries were found with travelers from Germany. Health officials should therefore be wary of potential bacterial infections from other regions that could be spread via travelling populations.

 

Technologies used in the investigation

The success of the intervention methods for the German E. coli strain is attributed to the availability of new quick and effective sequencing technologies. Some of these technologies include(Mellmann et al, 2011);

 

Ion Torrent platform

This is a recent technology used for non-optical DNA sequencing of genomes(Quail et al, 2012). This platform has a number of advantages, mainly speed and use of moderately long read lengths that are significant for the sequencing and identification of new strains of bacteria. Through this patform the sequencing of E. coli samples were done in less than three days and the results provided insights into addressing the outbreak.

 

Pacific Biosciences platform

This is a platform that makes the real time single molecule sequencing possibleMellmann et al, 2011. The technique involves performing second strand DNA synthesis in the presence of γ-phosphate(Quail et al, 2012). Through the technique, the first whole-genome assembly of the German E. coli strain was accomplished within a week.

The outbreak of O104:H4 strain of E. coli in central Europe greatly exposed the limited bank of knowledge of some potentially catastrophic pathogens. They speed at which the matter was resolved also serves to show the levels of technology application in the field of medicine. The impact of this outbreak and the gaps in knowledge regarding the origin and pathogenicity of the bacteria involved should serve as a wakeup call for further research into this field if future occurrences of the deadly pathogen are to be avoided

 

 

 

 

 

 

 

 

 

 

 

 

References

Bielaszewska, M., Mellmann, A., Zhang, W., Köck, R., Fruth, A., Bauwens, A., … & Karch, H. (2011). Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. The Lancet infectious diseases, 11(9), 671-676.

Buchholz, U., Bernard, H., Werber, D., Böhmer, M. M., Remschmidt, C., Wilking, H., … & Kühne, M. (2011). German outbreak of Escherichia coli O104: H4 associated with sprouts. New England Journal of Medicine, 365(19), 1763-1770.

Dempsey, J., & Neuman, W. (2011, June 5). Deadly E. Coli Outbreak Linked to German Sprouts. The New York Times, p. Web.

Frank, C., Werber, D., Cramer, J. P., Askar, M., Faber, M., an der Heiden, M., … & Krause, G. (2011). Epidemic profile of Shiga-toxin–producing Escherichia coli O104: H4 outbreak in Germany. New England Journal of Medicine, 365(19), 1771-1780.

Karch, H., Denamur, E., Dobrindt, U., Finlay, B. B., Hengge, R., Johannes, L., … & Vicente, M. (2012). The enemy within us: lessons from the 2011 European Escherichia coli O104: H4 outbreak. EMBO molecular medicine, 4(9), 841-848.

Kemper, M. J. (2012). Outbreak of hemolytic uremic syndrome caused by E. coli O104: H4 in Germany: a pediatric perspective. Pediatric Nephrology, 27(2), 161-164.

Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR, et al. (2011) Prospective Genomic Characterization of the German Enterohemorrhagic Escherichia coli O104:H4 Outbreak by Rapid Next Generation Sequencing Technology. PLoS ONE 6(7): e22751. doi:10.1371/journal.pone.002275

Walker, Peter, Gabbatt , Adam and agencies (2011). “E coli: European commissioner suggests £135m payout for farmers | World news”. The Guardian (London). Retrieved 19October 2014

Quail, M. A., Smith, M., Coupland, P., Otto, T. D., Harris, S. R., Connor, T. R., … & Gu, Y. (2012). A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC genomics, 13(1), 341.

Rasko, D. A., Webster, D. R., Sahl, J. W., Bashir, A., Boisen, N., Scheutz, F., … & Waldor, M. K. (2011). Origins of the E. coli strain causing an outbreak of hemolytic–uremic syndrome in Germany. New England Journal of Medicine, 365(8), 709-717.

Scavia, G., Morabito, S., Tozzoli, R., Michelacci, V., Marziano, M. L., Minelli, F., … & Caprioli, A. (2011). Similarity of Shiga toxin-producing Escherichia coli O104: H4 strains from Italy and Germany. Emerg Infect Dis, 17(10), 1957-1958.

WHO. (2011, July 22). Outbreaks of E. coli O104:H4 infection: update 30. Retrieved from World Health Organization (WHO): http://www.euro.who.int/en/health-topics/disease-prevention/food-safety/news/news/2011/07/outbreaks-of-e.-coli-o104h4-infection-update-30