Cytokine kinetic profiles in children with acute lower respiratory tract infection: a post hoc descriptive analysis from a randomized control trial.

OBJECTIVES: Standard inflammatory markers and chest radiography lack the ability to discriminate bacterial from non-bacterial lower respiratory tract infection (LRTI). Cytokine profiles may serve as biomarkers for LRTI, but their applicability to identify aetiology, severity of disease and need for antibiotic prescription in children remains poorly defined. Objectives were to determine the cytokine kinetic profiles over 5 days in paediatric patients with LRTI, to investigate the relationship between cytokine patterns, and clinical and laboratory variables. METHODS: We included patients aged 1 month to 18 years, with febrile LRTI and three consecutive cytokines measurements on days 1, 3 and 5 of a randomized controlled trial (ProPAED study). We evaluated differences in cytokine concentrations between days and associations with clinical and laboratory variables. RESULTS: A total of 181 patients (median age 4.1 years) were included; 72/181 (40%) received antibiotics. Serum concentrations of interferon (IFN)-γ, interleukin (IL)-1ra, IL-6, IL-10, IFN-γ-inducible protein (IP)-10 and tumor necrosis factor-α were elevated on day 1 and decreased subsequently, with the greatest decline between day 1 and 3 (by -8 to >-94%). Procalcitonin (PCT) and C-reactive protein (CRP) values showed a protracted decrease with the most prominent reduction in concentrations between days 3 and 5. Significantly elevated IL-6 concentrations were associated with hospital admission, antibiotic treatment, and prolonged antibiotic treatment. Bacteraemic LRTI patients had higher concentrations of IL-1ra (p <0.0055) and IL-6 (p <0.0055) on day 1. CONCLUSIONS: We observed an earlier decrease of elevated cytokines compared to PCT or CRP. Both pro- and anti-inflammatory cytokines may serve as markers for severity of LRTI.

Combining multiple healthcare databases for postmarketing drug and vaccine safety surveillance: why and how?

A growing number of international initiatives (e.g. EU-ADR, Sentinel, OMOP, PROTECT and VAESCO) are based on the combined use of multiple healthcare databases for the conduct of active surveillance studies in the area of drug and vaccine safety. The motivation behind combining multiple healthcare databases is the earlier detection and validation, and hence earlier management, of potential safety issues. Overall, the combination of multiple healthcare databases increases statistical sample size and heterogeneity of exposure for postmarketing drug and vaccine safety surveillance, despite posing several technical challenges. Healthcare databases generally differ by underlying healthcare systems, type of information collected, drug/vaccine and medical event coding systems and language. Therefore, harmonization of medical data extraction through homogeneous coding algorithms across highly different databases is necessary. Although no standard procedure is currently available to achieve this, several approaches have been developed in recent projects. Another main challenge involves choosing the work models for data management and analyses whilst respecting country-specific regulations in terms of data privacy and anonymization. Dedicated software (e.g. Jerboa) has been produced to deal with privacy issues by sharing only anonymized and aggregated data using a common data model. Finally, storage and safe access to the data from different databases requires the development of a proper remote research environment. The aim of this review is to provide a summary of the potential, disadvantages, methodological issues and possible solutions concerning the conduct of postmarketing multidatabase drug and vaccine safety studies, as demonstrated by several international initiatives.

Lemierre syndrome and nosocomial transmission of Fusobacterium necrophorum from patient to physician.

BACKGROUND: Human-to-human transmission of Fusobacterium necrophorum has not been described before. CASE PRESENTATION: We present the case of a 15-year-old girl with Lemierre Syndrome and possible nosocomial transmission of F. necrophorum to her treating physician in hospital. CONCLUSION: Early diagnosis and treatment of anaerobic pharyngitis is critical to prevent Lemierre Syndrome. Respiratory precautions should be recommended to medical staff caring for patients with suspected Lemierre Syndrome to prevent nosocomial transmission.

Immunisation of premature infants.

Premature infants are at increased risk of vaccine preventable infections, but audits have shown that their vaccinations are often delayed. Early protection is desirable. While the evidence base for immunisation of preterm infants is limited, the available data support early immunisation without correction for gestational age. For a number of antigens the antibody response to initial doses may be lower than that of term infants, but protective concentrations are often achieved and memory successfully induced. A 2-3-4 month schedule may be preferable for immunisation of preterm infants in order to achieve protection as early as possible, but an additional dose may be required to achieve persistence of protection. This update focuses on the use of routine childhood vaccines in premature infants.

The role of Bordetella infections in patients with acute exacerbation of chronic bronchitis.

BACKGROUND: Acute exacerbations of chronic bronchitis (AECB) are associated with a variety of viral and bacterial infectious agents, some of which are potentially preventable by immunization. Bordetella pertussis, which causes whooping cough, has not been studied in this context. We aimed to assess the role of Bordetella infections in patients with AECB. PATIENTS AND METHODS: Patients with AECB, who presented to participating private practices in Basel, Switzerland, between October 2000 and June 2002, were evaluated by a standardized questionnaire, nasopharyngeal swabs for culture (Bordetella spp.), and PCR (Bordetella spp. and selected other respiratory pathogens) and paired blood samples for serologic diagnosis of Bordetella infection. RESULTS: A total of 26 patients (34-86 years of age) were recruited. All culture and PCR samples were negative. Serology revealed Bordetella infection in eight (31%) patients. Duration of cough was shorter in patients with Bordetella infection compared to those without Bordetella infection (mean 15 days vs 41 days, p = 0.04). Cough > or = 21 days duration was present in three (43%) of seven patients with evidence of Bordetella infection compared to 17 (94%) of 18 controls (p = 0.012). Progression to convalescence from initial to follow-up visit after 4-6 weeks was comparable between both groups. CONCLUSION: Bordetella infections appear to play a significant role in AECB and preventive measurements such as immunization with acellular pertussis vaccines should be considered. Extended investigations are necessary to confirm our preliminary and provocative findings.

Reporting of vaccine safety data in publications: systematic review.

PURPOSE: To assess current reporting practices of immunisation safety data in the scientific literature. METHODS: Systematic literature search for recent prospective clinical studies on vaccines in humans. The main outcome measures were methodological differences in the assessment, definition, analysis and presentation of 'adverse events following immunisation' (AEFI). RESULTS: In total, 182 published articles possibly satisfied defined inclusion criteria, of which 149 were included. Overall, the presentation of data on AEFI was inadequate: 45% of articles did not mention AEFI at all; if mentioned, case definitions of AEFI were not specified in the majority of articles; there was inconsistency of AEFI reporting between 'Methods' and 'Results' in up to 24% of articles; the observation period following immunisation and the method of follow-up with study subjects was not reported in 28% and 32% of studies respectively. CONCLUSIONS: We identified a lack of reporting of AEFI data as well as a heterogeneity of case definitions and methods for data collection, analysis and presentation of AEFI in recently published articles. Guidelines for standardised collection, analysis and publication of such data and standardised case definitions for AEFI are needed. Ideally, journal editors would agree on a minimum set of guidelines for structured presentation of vaccine safety data in publications.

Diagnosis of acute haematogenous osteomyelitis and septic arthritis: 20 years experience at the University Children's Hospital Basel.

OBJECTIVE: To review the diagnostic experience with acute haematogenous osteomyelitis (AHOM) and/or septic arthritis at our institution. METHODS: Retrospective review of the medical records of those patients with a bacteriologically and/or radiologically confirmed diagnosis, hospitalised in the University Children's Hospital Basel, Switzerland between January 1980 and July 2000. RESULTS: 90 patients (61% males), 4 weeks to 14 years of age, met the inclusion criteria. Median duration of disease prior to hospitalisation was 3 days (range 0-14); 88% were admitted during the first week after onset of complaints. 81 patients received no antimicrobial therapy prior to hospitalisation and are the subject of this presentation. ESR (1st hour in mm; median 36; range 11-124), CRP (mg/l; median 64; range 0-221) and WBC (x 10(9)/l; median 13; range 5-34) were elevated in 100%, 82% and 58% of patients, respectively. Blood cultures (BC) and/or tissue cultures (TC) were performed in 79 (98%) patients. Overall, bacteria were isolated from 53 patients (65%) with Staph. aureus as the most frequent organism (n = 31; 50%). BC were performed in 67 patients and yielded 35 (52%) positive cultures; TC (n = 47) yielded 27 (57%) isolates. In 34 patients with both BC and TC performed, only 12 (35%) were positive in both tests. Diagnostic findings were observed in 23 (59%) of 39 plain radiographs, 31 (56%) of 55 sonograms, 39 (89%) of 44 99mTc-labeled bone scans and 4 (100%) of 4 MRI. 41 patients with diagnostic radiological findings had consecutive TC yielding 30 (73%) bacteriological isolates. Median duration of hospitalisation was 15 days (range 2-66). CONCLUSION: Our data indicate that the diagnostic procedures of choice should be 1) early bone scan or MRI, 2) BC and 3) TC. Of supportive laboratory parameters, ESR and CRP were most valuable in our hands.