Systematic review of the global epidemiology, clinical and laboratory profile of enteric fever.

BACKGROUND: Children 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. METHODS: We 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. RESULTS: 96% 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. CONCLUSIONS: Our 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.

Challenges in measuring complications and death due to invasive Salmonella infections.

Despite the highest burden of Typhoid fever in children globally, exact estimates of morbidity and mortality are lacking due to scarcity of published data. Despite a high prevalence and a socioeconomic burden in developing countries, published data with morbidity and mortality figures are limited especially Africa and South American regions. Data from the community is insufficient and most case fatality estimates are extrapolations from hospital based studies that do not cover all geographical regions, and include cases which may or not be culture confirmed, MDR resistant or sensitive cases, or from mixed populations of age (adults and children). Complications of typhoid such as intestinal perforation, bone marrow suppression, and encephalopathy are dependent on MDR/Fluoroquinolone resistant Salmonella infection, comorbidities such as malnutrition, and health-care access. Data is again insufficient to estimate the true burden of Typhoid Fever in different regions and groups of populations. Although there has been a rapid decline in cases in developed countries with the advent of improved sanitization, timely and easy access to health care and laboratories, this is still not the case in the developing countries where Typhoid deaths are still occurring. The way forward is to develop rapid and cost effective point of care diagnostic tests, put in place validated clinical algorithms for suspected clinical cases, and design prospective, and community based studies in different groups, implement maintenance of electronic health records in large public sector hospitals and regions to identify populations that will benefit most from the implementation of vaccine. Policies on public health education and typhoid vaccine may help to reduce morbidity and mortality due to the disease.

A three-year review of antimicrobial resistance of Salmonella enterica serovars Typhi and Paratyphi A in Pakistan.

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) between 2009 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.

A comparison of fluoroquinolones versus other antibiotics for treating enteric fever: meta-analysis.

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 (1966-2007), Embase (1974-2007), LILACS (1982-2007), 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.

Prevalence of behavioural and psychological problems in working children.

OBJECTIVE: To determine the prevalence and screen the nature and types of behavioural and psychological problems among working children in Karachi. METHODS: A cross sectional study was conducted in three urban squatter settlements of Karachi from May to June 2006, targeting working children aged 11-16 years. Behavioural Problems of these children were estimated by using the self reported Urdu version of the Strengths and Difficulty Questionnaire. The results were cross-tabulated using SPSS 13.0 with the identified risk-factors. RESULTS: Out of a total of 225 respondents, 94.2% (n = 212) males and 5.8% (n = 13) females, the prevalence of Behavioural Problems among working children was found to be 9.8%. Peer problems were most prevalent (16.9%) seconded by Conduct problems (16.7%). Adverse family environment and work environment were closely associated with Behavioural Problems in these children. CONCLUSION: Our study reinforces the need for measures to improve the environment of the children and prevent the psychological and behavioural problems associated with working children. Gradual, long-term policies are required to decrease the need for working children, though sudden abolishment would cause more detrimental effects.

Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).

BACKGROUND: Fluoroquinolones are recommended as first-line therapy for typhoid and paratyphoid fever (enteric fever), but how they compare with other antibiotics and different fluoroquinolones is unclear. OBJECTIVES: To evaluate fluoroquinolone antibiotics for treating enteric fever in children and adults compared with other antibiotics, different fluoroquinolones, and different durations of fluoroquinolone treatment. SEARCH STRATEGY: In November 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, LILACS, mRCT, conference proceedings, and reference lists. SELECTION CRITERIA: Randomized controlled trials of fluoroquinolones in people with blood or bone marrow culture-confirmed enteric fever. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trials' methodological quality and extracted data. We calculated odds ratios (OR) for dichotomous data with 95% confidence intervals (CI). We analysed trials with greater than 60% children separately from trials of mostly adults. MAIN RESULTS: Of 38 included trials, 22 had unclear allocation concealment and 34 did not use blinding. Four trials included exclusively children, seven had both adults and children, and three studied outpatients. ADULTS: Among primary outcomes (clinical failure, microbiological failure, and relapse), compared with chloramphenicol, fluoroquinolones were not statistically significantly different for clinical failure (594 participants) or microbiological failure (378 participants), but they reduced clinical relapse (OR 0.14, 95% CI 0.04 to 0.50; 467 participants, 6 trials). We detected no statistically significant difference versus co-trimoxazole (82 participants, 2 trials) or azithromycin (152 participants, 2 trials). Fluoroquinolones reduced clinical failure compared with ceftriaxone (OR 0.08, 95% CI 0.01 to 0.45; 120 participants, 3 trials), but not microbiological failure or relapse. Versus cefixime, fluoroquinolones reduced clinical failure (OR 0.05, 95% CI 0.01 to 0.24; 238 participants; 2 trials) and relapse (OR 0.18, 95% CI 0.03 to 0.91; 218 participants, 2 trials). CHILDREN: In children with high proportions of nalidixic acid-resistant strains, older fluoroquinolones increased clinical failures compared with azithromycin (OR 2.67, 95% CI 1.16 to 6.11; 125 participants, 1 trial), with no differences using newer fluoroquinolones (285 participants, 1 trial). Fluoroquinolones and cefixime were not statistically significantly different (82 participants, 1 trial). Trials comparing different durations of fluoroquinolone treatment were not statistically significantly different (889 participants, 9 trials). Norfloxacin had more clinical failures than other fluoroquinolones (417 participants, 5 trials). AUTHORS' CONCLUSIONS: 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.