Failure of Syndrome-Based Diarrhea Management Guidelines to Detect Shigella Infections in Kenyan Children

• Published in: Journal of the Pediatric Infectious Diseases Society 2016-12, Vol.5 (4), p.366-374
• Main Authors: Pavlinac, P B, Denno, D M, John-Stewart, G C, Onchiri, F M, Naulikha, J M, Odundo, E A, Hulseberg, C E, Singa, B O, Manhart, L E, Walson, J L
• Format: Article
• Language: English
• Subjects: Child, Preschool; Coinfection - epidemiology; Diagnostic Errors - statistics & numerical data; Dysentery, Bacillary - diagnosis; Dysentery, Bacillary - epidemiology; Dysentery, Bacillary - microbiology; Failure to Thrive - epidemiology; Female; HIV Infections - epidemiology; Humans; Infant; Kenya - epidemiology; Male; Original and Commentaries; Polymerase Chain Reaction; Practice Guidelines as Topic; Sensitivity and Specificity; Syndrome
• ISSN: 2048-7193; 2048-7207
• DOI: 10.1093/jpids/piv037

Shigella is a leading cause of childhood diarrhea mortality in sub-Saharan Africa. Current World Health Organization guidelines recommend antibiotics for children in non cholera-endemic areas only in the presence of dysentery, a proxy for suspected Shigella infection. To assess the sensitivity and specificity of the syndromic diagnosis of Shigella-associated diarrhea, we enrolled children aged 6 months to 5 years presenting to 1 of 3 Western Kenya hospitals between November 2011 and July 2014 with acute diarrhea. Stool samples were tested using standard methods for bacterial culture and multiplex polymerase chain reaction for pathogenic Escherichia coli. Stepwise multivariable logit models identified factors to increase the sensitivity of syndromic diagnosis. Among 1360 enrolled children, median age was 21 months (interquartile range, 11-37), 3.4% were infected with human immunodeficiency virus, and 16.5% were stunted (height-for-age z-score less than -2). Shigella was identified in 63 children (4.6%), with the most common species being Shigella sonnei (53.8%) and Shigella flexneri (40.4%). Dysentery correctly classified 7 of 63 Shigella cases (sensitivity, 11.1%). Seventy-eight of 1297 children without Shigella had dysentery (specificity, 94.0%). The combination of fecal mucous, age over 23 months, and absence of excessive vomiting identified more children with Shigella-infection (sensitivity, 39.7%) but also indicated antibiotics in more children without microbiologically confirmed Shigella (specificity, 82.7%). Reliance on dysentery as a proxy for Shigella results in the majority of Shigella-infected children not being identified for antibiotics. Field-ready rapid diagnostics or updated evidence-based algorithms are urgently needed to identify children with diarrhea most likely to benefit from antibiotic therapy.