Missed Opportunities of Syndrome-Based Diarrhea Management Guidelines to Detect Non-Dysenteric Shigella Infections in Children: Findings from the Enteric for Global Health (EFGH)-Shigella Surveillance study in Kenya : 2022-2024

Shigella is a major cause of childhood diarrhea in sub-Saharan Africa. Current World Health Organization (WHO) guidelines recommend empiric antibiotics only for dysentery, yet non-dysenteric presentations account for 40-89% of Shigellainfections. We quantified the performance of existing guidelines to identify Shigella infection and evaluated enhanced syndromic criteria for improved management of Shigella cases. We leveraged data from the Enteric for Global Health (EFGH) Kenyan site, which enrolled children aged 6-35 months with medically attended diarrhea, collected rectal swabs at enrolment, and tested these for Shigella using both the culture and TaqMan-array cards (TAC). Shigella positivity was defined as either a culture-confirmed Shigella or a TAC-attributable result (CT <29.5). We compared categorical variables using the {chi}{superscript 2} test or Fishers exact as appropriate while continuous variables were compared between groups using the Wilcoxon rank-sum test. A logistic regression model was fitted to identify a parsimonious set of predictors. Out of the enrolled 1400 MAD cases, of whom 175 (12.5%) were Shigella positive, of which 134 (76.5%) being non-dysenteric. Among all enrolled children, 148 (10.6%) were dysenteric and 1,252 (89.4%) were non-dysenteric. Of the non-dysenteric cases, 57/1,252 (4.6%) and 129/1,251 (10.3%) of children were Shigella attributable by culture and TAC, respectively. Compared to Shigella negative cases, positive cases were older (Median age in months [Q1-Q3]: 20 [14-24] vs 13 [8-19], p<0.001), had higher stool frequency (5 [3-6] vs 4 [3-5], p<0.049) and were more likely to be dysenteric (42 [24%] vs 106 [8.7%], p<0.001). Contrarily, Shigella positive cases were less likely to present with vomiting (66 [37.7%] vs 587 [47.9%], p=0.014) and difficulty in breathing (0 (0%) vs 27 [2.2%], p<0.040). Dysentery alone had minimal predictive power to identify Shigella (area under the ROC curve (AUC) [95% CI]: 0.58 [0.54-0.61]), while Dysentery and Age binary (<17 months) (0.70 [0.66-0.74]), and Dysentery, Vomiting, Difficult breathing, and Age binary (0.72 [0.68-0.76]) had acceptable predictive performance. Our data shows that current guidelines miss up to 76.5% of Shigella-positive cases which are non-dysenteric. This suggests that dysentery alone has limited predictive power, but incorporating additional symptoms increases discriminatory ability by up to 14%, with age alone improving it by 12%. These findings support the need to re-evaluate the current syndromic based guidelines to better detect Shigellosis and strengthen antibiotic stewardship.