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“I believe the HUS cases are the real tip of the iceberg.”

– Dr. Michael T. Osterholm, PhD, MPH, Director of the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP), the publisher of CIDRAP News.

One puzzling aspect of the E. coli O104:H4 outbreak has been the very high number of cases of hemolytic uremic syndrome (HUS) and the large number of deaths in comparison to the total number of reported infections.

The World Health Organization, as of July 7th, reported a total of 3,941 cases worldwide, including 909 cases of HUS and 52 deaths. This tally actually dropped from the previously reported total (on July 1st) of 4,137 cases. The change was due to a redefinition of outbreak-related cases issued by the European Union.

Determining the actual number of outbreak victims in a foodborne disease investigation is rarely easy. I’ve wondered for some time how many mild and/or asymptomatic illnesses have gone unreported. On July 5th, I gave voice to my suspicion that many cases of E. coli O104:H4 have gone unreported, saying, “It’s likely that an unknown number of milder gastrointestinal illnesses also can be blamed on this outbreak strain.”

It is now clear that my hunch was well-founded. The European Centre for Disease Prevention and Control (ECDC) and the European Food Safety Authority (EFSA) have released an updated “Risk Assessment”which includes the following paragraph:

“The most significant development since June 29 relates to the preliminary results of the screening of children and staff in a school in Kreis Paderborn (Paderborn county), Germany, where three cases of HUS STEC and one case of non-HUS STEC infection have been identified since 13 June 2011 and onwards. In 22 of the 30 children tested (including the three HUS STEC cases, and the non-HUS STEC case), the epidemic strain of E. coli was isolated, indicating a significant level of asymptomatic infection. Asymptomatic carriage of STEC infection was also found in three kitchen workers at the school, in four guardians in four different child care centres in the district, and in three staff members of a supplying catering company. Further investigations of this cluster are ongoing.”

So, how big is the E. coli O104:H4 iceberg? Let’s do the math. First, we must decide on our multiplier. Let’s look at the two extreme cases.

  • The conservative estimate. The ECDC/EFSA report of asymptomatic cases documented a total of 22 children and 10 adults who were carriers of E. coli O104:H4 in its investigation of the Kreis Paderborn cluster of illnesses. Of these 32 carriers, only 4 developed active illnesses – including 3 cases of HUS. This gives us a multiplier of 8 (i.e., each reported case represents 8 actual infections).
  • The opposite extreme. In January 2011, CDC released its latest estimates of foodborne disease illness in the USA. The report details the multipliers that the authors developed for each pathogen to extrapolate actual illnesses from the numbers of reported illnesses. For non-O157 strains of enterohemorrhagic E. coli – the category into which E. coli O104:H4 falls – this multiplier is 106.8 (see Table 2 of report).

Taking these two multipliers and applying them to the most recent numbers reported by the World Health Organization, we arrive at the following:

  • The conservative estimate: 3,941 reported cases worldwide x 8 = 31,528 estimated symptomatic and asymptomatic infections.
  • The opposite extreme: 3,941 reported cases worldwide x 106.8 = 420,899 estimated symptomatic and asymptomatic infections.

The truth, no doubt, lies somewhere in between these two extremes.

Why is this important? Simply, the more people who have been infected – especially those who show no symptoms of illness – the more likely that E. coli O104:H4 will establish itself as thoroughly as E. coli O157:H7 already has done.

As for the “most probable source” of the outbreak, the Egyptian fenugreek seeds have been tracked forward to 25 countries so far – Austria, Belgium, Bulgaria, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Luxembourg, the Netherlands, Norway, Poland, Portugal, Slovenia, Spain, Sweden, Switzerland and the United Kingdom.

As for the German outbreak investigation, the Federal Office of Consumer Protection and Food Safety has released its final Task Force report.

The German investigation may be complete, and the present outbreak winding down, but this is not the last we’ve heard from E. coli O104:H4.

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