Farm animal contact is associated with progression to Hemolytic uremic syndrome in patients with Shiga toxin-producing Escherichia coli - Indiana, 2012-2018

Background: Hemolytic uremic syndrome (HUS) is a life-threatening complication of Shiga toxin-producing Escherichia coli (STEC) infection. The relationship between STEC exposure and severity of clinical outcomes is not well documented. We examined whether direct contact with farm animals increased the likelihood of HUS among Indiana residents diagnosed with STEC. Methods: Exposure data for laboratory-confirmed STEC cases among Indiana residents during 2012-2018 were retrieved. Logistic regression and mediation analysis were performed to determine the extent to which a history of direct contact with farm animals was associated with post-diarrheal HUS independent of age and mediated by stx2 gene presence. Results: A total of 784 STEC cases were retrieved. Of these, 46 (6%) developed HUS. Complete exposure data were available for 600 (77%) cases. A total of 24 (52%) HUS patients reported direct contact with farm animals, while 114 (21%) STEC patients who did not develop HUS reported this exposure. Among all STEC cases, HUS was associated with direct farm animal contact after adjusting for age (OR = 3.40, 95% CI: 1.81, 6.40). Detection of stx2 genes mediated 12% of the association between farm animal contact and HUS. Conclusions: Direct farm animal contact was a risk factor for development of HUS among laboratory-confirmed STEC cases, independent of stx2 presence. Direct farm animal contact should be considered a potential predictor of progression to HUS when patients present for care and the mechanism for its effect on virulence investigated.