BackgroundChildren suffer the highest burden of enteric fever among populations in South Asian countries. The clinical features are non–specific, vary in populations, and are often difficult to distinguish clinically from other febrile illnesses, leading to delayed or inappropriate diagnosis and treatment. We undertook a systematic review to assess the clinical profile and laboratory features of enteric fever across age groups, economic regions, level of care and antibiotic susceptibility patterns.MethodsWe searched PubMed (January 1964–December 2013) for studies describing clinical features in defined cohorts of patients over varying time periods. Studies with all culture–confirmed cases or those with at least 50% culture–confirmed cases were included. 242 reports were screened out of 4398 relevant articles and 180 reports were included for final review.Results96% of studies were from an urban location, 96% were hospital–based studies, with 41% of studies were from South Asia. Common clinical features in hospitalized children include high–grade fever, coated tongue, anaemia, nausea/vomiting, diarrhea, constipation, hepatomegaly, splenomegaly neutrophilia, abdominal distension and GI bleeding. In adults’ nausea/vomiting, thrombocytopenia and GI perforation predominate. The case–fatality rate in children under 5 years is higher than school aged children and adolescents, and is highest in Sub Saharan Africa and North Africa/Middle East regions. Multi–drug resistant enteric fever has higher rates of complications than drug sensitive enteric fever, but case fatality rates were comparable in both.ConclusionsOur findings indicate variability in disease presentation in adults compared to children, in different regions and in resistant vs sensitive cases. Majority of studies are from hospitalized cases, and are not disaggregated by age. Despite higher complications in MDR enteric fever, case fatality rate is comparable to sensitive cases, with an overall hospital based CFR of 2%, which is similar to recent global estimates. This review underscores the importance of further epidemiological studies in community settings among children and adults, and the need for further preventable measures to curtail the burden of disease.

Introduction: Enteric fever is among the most common bacteraemic illnesses in South Asia. Multidrug resistance as well as fluoroquinolone resistance has severely limited therapeutic options in high disease burden countries such as Pakistan. This review was conducted to determine the frequency of drug-resistant Salmonella enterica serovar Typhi (S.Typhi) and Salmonella enterica serovar Paratyphi A (S. Paratyphi A) between2009 and 2011. Methodology: This study was a review of laboratory data. The antibiotic susceptibility of typhoidal Salmonellae isolated from blood cultures submitted to the Aga Khan University Hospital's laboratory from all over Pakistan between January 2009 and December 2011 were reviewed. Results: The sensitivity data of 4,323 positive isolates of S. Typhi and S. Paratyphi A isolated during the three-year period were reviewed. The majority of isolates were S. Typhi (59.6%).Over three years, the incidence of multidrug-resistant (MDR) S.Typhi remained high, ranging from 64.8%-66.0%, while MDR S. Paratyphi A decreased from 4.2% to 0.6%.Fluoroquinolone resistance increased for S. Typhi from 84.7% to 91.7%.Cefixime-and ceftriaxone-resistant S. Typhi were isolated in two children. Conclusions: Our results show high rates of multidrug and fluoroquinolone resistance among S. Typhi and S. Paratyphi. The occurrence of two cases of ceftriaxone resistance is alarming.

Objectives To review evidence supporting use of fluoroquinolones as first line agents over other antibiotics for treating typhoid and paratyphoid fever (enteric fever). Design Meta-analysis of randomised controlled trials. Data sources Cochrane Infectious Diseases Group specialised register, CENTRAL (issue 4, 2007), Medline , Embase , LILACS , selected conferences, reference lists, and ongoing trial register (November 2007). Review methods Trials comparing fluoroquinolones with chloramphenicol, cephalosporins, or azithromycin in culture-proven enteric fever were included. Two reviewers extracted data and assessed methodological quality. Odds ratios with 95% confidence intervals were estimated. Trials recruiting over 60% children were analysed separately from trials on adults. Primary outcomes studied were clinical failure, microbiological failure, and relapse. Results Twenty trials were included. Trials were small and often of limited methodological quality. Only 10 trials concealed allocation and only three were blinded. In trials on adults, fluoroquinolones were not significantly different from chloramphenicol for clinical failure (594 participants) or microbiological failure (n=378), but reduced clinical relapse (odds ratio 0.14 (95% confidence interval 0.04 to 0.50), n=467, 6 trials). Azithromycin and fluoroquinolones were comparable (n=152, 2 trials). Compared with ceftriaxone, fluoroquinolones reduced clinical failure (0.08 (0.01 to 0.45), n=120, 3 trials) but not microbiological failure or relapse. Compared with cefixime, fluoroquinolones reduced clinical failure (0.05 (0.01 to 0.24), n=238, 2 trials) and relapse (0.18 (0.03 to 0.91), n=218, 2 trials). In trials on children infected with nalidixic acid resistant strains, older fluoroquinolones (ofloxacin) produced more clinical failures than azithromycin (2.67 (1.16 to 6.11), n=125, 1 trial), but there were no differences with newer fluoroquinolones (gatifloxacin, n=285, 1 trial). Fluoroquinolones and cefixime were not significantly different (n=82, 1 trial). Conclusions In adults, fluoroquinolones may be better than chloramphenicol for preventing clinical relapse. Data were limited for other comparisons, particularly for children. INTRODUCTIONEnteric fever (typhoid or paratyphoid fever) caused by Salmonella serotype Typhi (S Typhi) or Salmonella serotype Paratyphi (S Paratyphi) remains endemic in many areas of the developing world, causing over 26 million infections and over 200 000 deaths annually.

No abstract

Trials were small and methodological quality varied. In adults, fluoroquinolones may be better for reducing clinical relapse rates compared to chloramphenicol. Data are limited for other comparisons, particularly in children.