Prevalence and genetic relatedness of community-acquired methicillin-resistant Staphylococcus aureus in Israel.

The aims of the study presented here were to determine the prevalence of Staphylococcus aureus carriage and, specifically, community-acquired methicillin-resistant S. aureus (CA-MRSA) carriage in children and their parents in Israel and to determine the genetic relatedness of these isolates. S. aureus was isolated from 580 of 3,373 (17.2%) individuals screened. The predominant type identified by pulsed-field gel electrophoresis was strain ST45-MSSA (25%). Five MRSA isolates were detected, and two of these were classified as CA-MRSA, based on the following criteria: no previous contact with a healthcare facility, absence of a multidrug-resistant (MDR) phenotype, and presence of SCCmec type IV. Isolates were negative for pvl and were classified as ST-45-MRSA. Although CA-MRSA is still rare in Israel, the genetic relatedness of the strains found in this study to a successful MSSA clone warrants close follow up.

Normal D-dimer levels in patients with latent tuberculosis infection.

Studies have demonstrated a link between acute pulmonary tuberculosis and a hypercoagulable state, but there are no data on the coagulation state of patients with latent tuberculosis infection (LTI). The present prospective observational study was designed to help fill this gap. The sample included 84 patients (high school students and adults) with suspected LTI referred for the purified protein derivative (PPD) test. Results were read according to the criteria of the American Thoracic Society. Blood samples were collected at admission and assayed for D-dimer, the marker of the coagulation state, with the quantitative Miniquant test. D-dimer values were correlated with the PPD status and clinical parameters. Fifty-seven patients tested positive for LTI and 27 tested negative. There was no significant difference in D-dimer level between these groups (341 +/- 106 and 360 +/- 60 microg/ml, respectively). No significant correlation was found between D-dimer level and PPD status, patient age or occupation (health care worker or not), or clinical indication for the tuberculin test. The normal D-dimer levels in this series suggest that low-level inflammations such as LTI do not lead to a hypercoagulable state.

[Latent tuberculosis infection: diagnosis and treatment].

The essential component of tuberculosis elimination strategy is to identify and treat persons with latent tuberculosis infection (LTBI) who are at high risk for developing active tuberculosis. The tuberculin skin test is the only proven method for identifying LTBI. Although the specificity and the sensitivity are decreased by cross reaction with BCG vaccination and by non tuberculous mycobacteria, there is no better diagnostic tool. The test's positive predictive value is poor in populations with low risk for tuberculosis. Identification of persons with LTBI is focused on groups at high risk who would benefit from therapy (targeted tuberculin testing). The interpretation of the tuberculin skin test reaction is dependent on the risk factors and the immune status of the patient. For the past 30 years, Isoniazid has been the drug of choice for treating patients with LTBI, but its application has been limited by poor compliance and toxicity. Therefore, there has been interest in the development of shorter course treatments such as rifampin (4 months) or rifampin and pyrazinamide (2 months). We describe the new guidelines for targeted tuberculin testing and different treatment regimens for LTBI as recommend by the American Thoracic Society.

Using health outcomes data to inform decision-making: healthcare payer perspective.

Healthcare payers are charged with the responsibility of achieving maximum profits or output within their limited budget. As the demands are always greater than the budget, there is growing interest in tools that can inform decisions on the allocation of limited resources. Healthcare payers are using health outcomes data to assist the decision-making process, although the way in which such information is being used may differ between payers. From the perspective of the French sickness fund, there is a need for real-world information to supplement the results of clinical trials and inform negotiations on pricing. In the US, the large databases of healthcare insurers are being examined in order to carry out retrospective cohort studies that go some way towards providing such real-world information on outcomes with alternative treatments. Another approach to health outcomes information has been taken by an Israeli healthcare organisation, Maccabi Healthcare Services, which introduced a disease management programme in order to improve outcomes of asthma management. Clearly, healthcare payers are using health outcomes information in a variety of ways to inform decision-making. The extensive databases available to payers may be used to good effect, to obtain real-life information that supplements clinical trial data and economic models of outcomes and costs, and to enable the targeting of interventions.

Unexplained fever in neonates may be associated with hepatitis B vaccine.

AIM: To investigate whether hepatitis B vaccination has increased the number of cases of unexplained neonatal fever. METHOD: The files of all infants born from 1 January 1991 to 31 December 1992, in whom a diagnosis of "injected antibiotic" or "disease of temperature regulation" was recorded, were reviewed. Those who had unexplained fever of 38 degrees C or higher during the first three days of life were divided into two groups: infants who did not receive the hepatitis B vaccine (1991) and infants who did (1992). RESULTS: In 1992 the incidence of unexplained fever in hepatitis B vaccinated neonates was significantly higher than in the 1991 group of pre-vaccination neonates (35 out of 5819 (0.6%) vs 14 out of 5010 neonates (0.28%) respectively, p=0.013). CONCLUSIONS: The increase in the number of cases of unexplained neonatal fever seems to be associated with the introduction of routine hepatitis B vaccination on the first day of life. The possibility that an excess number of neonates will undergo unnecessary procedures and treatment to diagnose unexplained fever justifies planning a controlled study to determine whether these preliminary findings point to a significant problem.

Bovine herpesvirus-1 infection reduces bronchial epithelial cell migration to extracellular matrix proteins.

Repair of airway epithelium after viral infection involves migration of epithelial cells to cover injured, denuded areas. We determined whether viral infection reduces the capability of bronchial epithelial cells to migrate and to attach to extracellular matrix proteins. Inoculation of bovine bronchial epithelial cells in vitro with bovine herpesvirus-1 reduced their ability to migrate in two different assays of cell migration. When attachment assays were performed, fewer cells attached to both control wells and matrix protein-precoated wells, suggesting that general mechanisms of adherence to substrates were altered by viral infection. Focal contact points of epithelial cells with the underlying matrix were evaluated with epifluorescence microscopy and monoclonal antibodies to vinculin and alpha v, an integrin chain. Disruption of focal contact points was seen early after infection and was prevented by an inhibitor of viral DNA polymerase, phosphonoacetic acid. Cycloheximide did not cause similar disruptions of focal contacts at early time points. Viral infection thus has marked effects on the interactions of bronchial epithelial cells with extracellular matrix and the organization of matrix to cytoskeleton links. The effects appear to be dependent in part on viral replication in the cells and are not simply due to reductions in host cell protein synthesis.

Viral infection of bovine bronchial epithelial cells induces increased neutrophil chemotactic activity and neutrophil adhesion.

1. Acute bronchitis secondary to viral infection is associated with an influx of neutrophils. We hypothesized that bronchial epithelial cells are capable of releasing neutrophil chemotactic activity in response to viral infection. 2. To test this hypothesis, primary cultures of bovine bronchial epithelial cells were inoculated with a bovine respiratory pathogen, bovine herpes virus-1. 3. Supernatants collected from inoculated cells, before signs of toxicity, demonstrated significant neutrophil chemotactic activity using a blind well chamber neutrophil chemotaxis assay. Lipoxygenase inhibitors markedly reduced the amount of neutrophil chemotactic activity released after bovine herpes virus-1 inoculation. Analysis of arachidonic acid metabolites in cell supernatants by reverse-phase h.p.l.c. confirmed that leukotriene B4, a potent neutrophil chemoattractant, was released. 4. We also confirmed that adhesion of neutrophils to bovine herpes virus-1-inoculated bronchial epithelial cells was increased and mediated in part by the neutrophil integrin, LFA-1. 5. Thus, virally infected airway epithelial cells release leucocyte chemoattractants and hence adhesive interactions, functions that are likely to be important in the inflammatory acute response to viral infection.