Failure of Syndrome-Based Diarrhea Management Guidelines to DetectShigellaInfections in Kenyan Children

Abstract

Background. 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. Methods. 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. Results. 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%). Conclusions. 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.

Use of antibiotics in children younger than two years in eight countries: a prospective cohort study

“…Interventions to promote rational antibiotic use are critical for preserving the effectiveness of available drugs 9 – 11 . Conversely, in low-resource settings, the high burden of bacterial causes of diarrhoea in children 12 , 13 has led to proposals for antibiotics to be used more widely for the treatment of diarrhoea even in the absence of dysentery 14 – 16 . Antibiotics may also be a potential intervention for malnutrition and environmental enteropathy 17 …”

A double-blind placebo-controlled trial of azithromycin to reduce mortality and improve growth in high-risk young children with non-bloody diarrhoea in low resource settings: the Antibiotics for Children with Diarrhoea (ABCD) trial protocol

“…More recently, global data suggest that multiple bacterial and parasitic diarrhoeal pathogens are significantly associated with death, particularly in sub-Saharan Africa [1]. In low -resource settings, the high burden of bacterial causes of diarrhoea [1,3,5] has led to suggestions that antibiotics be used more widely, even in the absence of dysentery, as most children with these infections do not have bloody stools [6,7].…”

“…Stratified randomisation (by site) will be carried out in permuted blocks (block size 4,6,8). A computergenerated randomisation list will be converted into unique serial numbers for each enrolled child at each site.…”

“…These studies suggest a significant role for bacterial pathogens in diarrhoea-associated deaths [1]. Other studies have also demonstrated that visible blood in the stool is a poor indicator of a bacterial aetiology in children with diarrhoea [6,7], suggesting that the use of blood in the stool as a proxy for Shigella spp. may be inadequate and that the indications for antibiotic use in young children with acute diarrhoea could be expanded.…”

A double-blind placebo-controlled trial of azithromycin to reduce mortality and improve growth in high risk young children with non-bloody diarrhoea in low resource settings: The Antibiotic for Children with Diarrhoea (ABCD) Trial Protocol

“…These studies suggest a significant role for bacterial pathogens in diarrhoea associated deaths [1]. Other studies have also demonstrated that visible blood in stool is a poor indicator of a bacterial aetiology in children with diarrhoea [6,7], suggesting that the use of blood in stool as a proxy for Shigella may be inadequate and that the indications for antibiotic use in young children with acute diarrhoea could be expanded.…”