Abstract
SummaryBackgroundShigella infections are a leading cause of diarrhoeal death among children in low-income and middle-income countries. WHO guidelines reserve antibiotics for treating children with dysentery. Reliance on dysentery for identification and management of Shigella infection might miss an opportunity to reduce Shigella-associated morbidity and mortality. We aimed to systematically review and evaluate Shigella-associated and dysentery-associated mortality, the diagnostic value of dysentery for the identification of Shigella infection, and the efficacy of antibiotics for children with Shigella or dysentery, or both.MethodsWe did three systematic reviews (for mortality, diagnostic value, and antibiotic treatment of Shigella and dysentery), and meta-analyses where appropriate, of studies in resource-limited settings. We searched MEDLINE, Embase, and LILACS database for studies published before Jan 1, 2017, in English, French, and Spanish. We included studies of human beings with diarrhoea and accepted all study-specific definitions of dysentery. For the mortality and diagnostic value searches, we excluded studies that did not include an effect estimate or data necessary to calculate this estimate. The search for treatment included only randomised controlled trials that were done after Jan 1, 1980, and assessed antibiotics in children (aged <18 years) with dysentery or laboratory-confirmed Shigella. We extracted or calculated odds ratios (ORs) and 95% CIs for relative mortality and did random-effects meta-analysis to arrive at pooled ORs. We calculated 95% CIs assuming a binomial distribution and did random-effects meta-regression of log-transformed sensitivity and specificity estimates for diagnostic value. We assessed the heterogeneity of papers included in these meta-analyses using the I2 statistic and evaluated publication bias using funnel plots. This review is registered with PROSPERO (CRD42017063896).Findings3649 papers were identified and 60 studies were included for analyses: 13 for mortality, 27 for diagnostic value, and 20 for treatment. Shigella infection was associated with mortality (pooled OR 2·8, 95% CI 1·6–4·8; p=0·000) whereas dysentery was not associated with mortality (1·3, 0·7–2·3; p=0·37). Between 1977 and 2016, dysentery identified 1·9–85·9% of confirmed Shigella infections, with sensitivity decreasing over time (p=0·04). Ten (50%) of 20 included antibiotic trials were among children with dysentery, none were placebo-controlled, and two (10%) evaluated antibiotics no longer recommended for acute infectious diarrhoea. Ciprofloxacin showed superior microbiological, but not clinical, effectiveness compared with pivmecillinam, and no superior microbiological and clinical effectiveness compared with gatifloxacin. Substantial heterogeneity was reported for meta-analyses of the Shigella-associated mortality studies (I2=78·3%) and dysentery-associated mortality studies (I2=73·2%). Too few mortality studies were identified to meaningfully test for publication bias. No evidence of publication bias was found in this analysis of studies of diagnostic value.InterpretationCurrent WHO guidelines appear to manage dysentery effectively, but might miss opportunities to reduce mortality among children infected with Shigella who present without bloody stool. Further studies should quantify potential decreases in mortality and morbidity associated with antibiotic therapy for children with non-dysenteric Shigella infection.FundingBill & Melinda Gates Foundation and the Center for AIDS Research International Core.
Highlights
WHO diarrhoea guidelines[7,8] focus on rehydration, and the provision of zinc, and they address Shigella infections by recommending ciprofloxacin be given to children with dysentery, defined as observed presence or caregiver report of blood in the patient’s stool
Added value of this study Through systematic reviews and meta-analyses of evidence available form MEDLINE, Embase, and LILACs database, this study suggests that current international guidelines might not be addressing the full burden of Shigella-associated mortality
Because of the ongoing contribution of Shigella to childhood diarrhoeal morbidity and mortality, and the changing epidemiology of Shigella globally, we aimed to examine evidence supporting dysentery-based Shigella management and to systematically review the available literature to assess associations between symptomatic Shigella infection, dysentery, and death
Summary
In resource-limited settings, Shigella species (Shigella) are a leading cause of childhood diarrhoea[1,2] and have case-fatality rates of up to 28% in children with severe disease.[3,4] The manifestations of Shigella can include watery diarrhoea, dysentery, and complications such as encephalopathy.[5,6] WHO diarrhoea guidelines[7,8] focus on rehydration, and the provision of zinc, and they address Shigella infections by recommending ciprofloxacin be given to children with dysentery, defined as observed presence or caregiver report of blood in the patient’s stool. Evidence before this study We did a preliminary literature search of MEDLINE in October, 2015, using the search terms “dysentery” and “Shigella”. This search revealed studies from sub-Saharan Africa where a large proportion of children infected with Shigella do not present with dysentery. Restriction of antibiotic treatment to these children is a pragmatic stewardship measure in settings where diagnostics are rarely available, but might result in an appreciable amount of unaddressed Shigella-associated morbidity and mortality
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
