Shiga Toxin-Producing E. Coli Infections Associated with Flour

Published - Written by Karen Sokal-Gutierrez, MD, MPH, FAAP

A 35-year-old woman presents to the emergency department with low-grade fever, stomachache, and bloody diarrhea for 2  days. She explains that she is a pastry chef, specializing in cookies. She says, “I always taste my raw cookie dough. Might that be the cause of my diarrhea? Is it safe for me to eat raw dough? Is it okay to give it to my children?”

Gastroenteritis can be caused by viral, parasitic, and bacterial pathogens including toxin-producing bacterial strains. Although raw meat, poultry, and eggs are often implicated in bacterial gastroenteritis, raw flour is rarely suspected of contamination with Shiga toxin-producing Escherichia coli (STEC). Symptoms of STEC infection — mild fever, abdominal pain, vomiting, and diarrhea (sometimes bloody) — typically arise 3 to 4 days after ingestion of the contaminated item. Rarely, STEC also causes hemolytic uremic syndrome (HUS). In the U.S. each year, STEC causes an estimated 265,000 infections, 3600 hospitalizations, and 30 deaths.

This week, NEJM published a report from the Centers for Disease Control and Prevention (CDC) investigation of a 2016 multistate outbreak of STEC infections. STEC cases were defined as patients with the onset of gastroenteritis during a specified period, with identification of the STEC bacterial strain from stool specimens by molecular subtyping and genome sequencing. Initial interviews of STEC patients with the standard CDC questionnaire on food consumption patterns during the week before the illness failed to identify any significant food exposure. Subsequently, in-depth, open-ended interviews with 10 STEC patients revealed that all patients frequently baked or regularly consumed home-baked goods, 80% reported that they had or may have baked in the week before the illness, and 80% of those who remembered baking also recalled tasting or eating raw batter or cookie dough. Investigators then developed a detailed questionnaire, including history of baking and exposure to or ingestion of raw flour and dough. To determine the odds for specific exposures associated with STEC gastroenteritis, the investigators conducted a case-case analysis of data from the second questionnaire  completed by 33 STEC cases and 84 non-STEC gastroenteritis “control” cases (e.g., salmonella) reported to state health department and matched by age group, gender, and state of residence.

Between December 2015 and September 2016, 56 STEC cases were identified in 24 states (55 patients infected with STEC O121 and 1 patient with STEC O26). STEC cases ranged in age from 1 to 95 years (median age, 18 years) and 77% were female. Sixteen patients were hospitalized, one adolescent developed HUS, and no deaths were reported. In the case-case analysis, univariable logistic regression indicated that use of one specific flour brand (odds ratio, 21.0) and tasting unbaked homemade dough or batter (OR, 36.0) were significantly associated with STEC infection. Laboratory testing isolated the outbreak strains from flour samples and whole-genome sequencing showed that clinical and food isolates were closely related genetically. Traceback investigation identified a common flour production facility. In response, the U.S. Food and Drug Administration (FDA) inspected the factory, the company issued recalls of flour produced there, and 250 products containing flour were recalled. Although the specific source of contamination was not identified, investigators posited that cow manure used to fertilize the wheat fields led to contamination of the wheat. The authors concluded that raw flour was the source of the outbreak of STEC infections and ingestion of raw flour should be avoided.

As Lindsey R Baden, Deputy Editor at NEJM noted, “Molecular sequencing has substantially increased our ability to connect cases of illness to a potential point source, thus identifying an outbreak. This should lead to earlier outbreak detection and control. As seen in this investigation, even dry flour can be a potential vehicle for foodborne illness.” 

Returning to the patient who is a baker, work-up should include analysis of stool samples and treatment as needed. She should be advised to refrain from preparing food while ill with gastroenteritis; avoid eating raw cookie dough because the raw flour and raw eggs can carry bacterial pathogens; and wash her hands well after handling raw flour, eggs, and dough. In addition, she should not let her young children eat raw cookie dough or handle raw flour and dough because children may be particularly vulnerable to complications of STEC infection, including HUS. Following the conclusion of the investigation, three children in three states were identified with STEC infection after eating at restaurants that gave children raw dough to play with while waiting for their food to be served.

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Karen is a 2017-2018 NEJM Editorial Fellow, Clinical Professor at UC Berkeley-UCSF Joint Medical Program and UC Berkeley School of Public Health, researcher on children’s nutrition and oral health, and member of American Academy of Pediatrics.