High antibiotic prescription rates in hospitalized children with human metapneumovirus infection in comparison to RSV infection emphasize the value of point-of-care diagnostics.

BACKGROUND: Respiratory infections are the main causes for hospitalization in children and a common reason for the initiation of antibiotic treatment. Rapid antigen detection tests and point-of-care mPCR-based assays provide a fast detection of viral pathogens. Nonetheless, the prescription rate of antibiotics for respiratory infections is exceedingly high. In particular, human metapneumovirus (hMPV) infections frequently cause antibiotic treatment. METHODS: Children hospitalized in our clinic with an acute respiratory infection between January 2008 and January 2013 were included in the present study. Data of 3799 children were analyzed retrospectively for clinical symptoms, laboratory findings, and antibiotic and inhalation treatment. We performed an in-house m-RT-PCR-ELISA method for pathogen detection. RESULTS: Pathogen detection was possible in 2464 patients. In 6.3%, hMPV and, in 24.0%, RSV were detected. Patients positively tested for hMPV received inhalation therapy in 62.9%; patients positive for RSV in 73.8%. Patients positive for hMPV were treated with antibiotics in 62.3%. Patients with RSV infection received antibiotic treatment in 44.4%; all others in 43.5%. Notably, a positive result in RSV-RADT was associated with reduced number of antibiotic treatment. CONCLUSION: hMPV infections inherit a two times higher probability of antibiotic treatment. There was no significant difference in laboratory findings or body temperature between hMPV infection and infections caused by other pathogens. Clinical symptoms seem not to differ from those in RSV illness. Nonetheless, RSV infections triggered significantly lower antibiotic prescription rates. A considerate application of a POC-mPCR for patients with RSV-like symptoms and age of 1 year and older with a negative RSV-RADT might lead to higher detection rates of hMPV and a reduction in prescription of antibiotics.

The influence of major histocompatibility complex class II genes and T-cell Vbeta repertoire on response to immunization with HBsAg.

Nonresponsiveness to HBsAg vaccination is observed in 5-10% of vaccine recipients and is possibly caused by a defect in the T helper cell compartment. The immune response to HBsAg is influenced by genes of the major histocompatibility complex. We have investigated MHC class I and class II antigens in 53 adult responders and 73 nonresponders. Results obtained in this first study were tested in a second study with 56 responders and 62 nonresponders from an infant vaccination trial. In addition, the peripheral Vbeta-chain T-cell receptor repertoire was investigated using monoclonal antibodies and flow-cytometry in 26 adult responders and 38 nonresponders. As previously reported, nonresponsiveness to HBsAg vaccination was associated with DRB1*3 and DRB1*7. In addition, DRB1*13 was significantly increased among vaccine responders (35.2% vs 5.4%;p < 0.0001) suggesting an immune response promoting effect for this allele whereas the closely related allele DRB1*14 was associated with nonresponse in the infant study. There was no evidence for a hole in the T cell receptor Vbeta repertoire. In conclusion, in agreement with results obtained in mice there appears to be a hierarchy of DRB1* genes in the HBsAg immune response. The possible differential association of DRB1*13 and DRB1*14 may allow the identification of differences between responsiveness and nonresponsiveness to a few amino acid differences in the beta1-domain of the class II heterodimer.

PID-ARI.net - a pediatric infectious diseases network on acute respiratory infections and the added value of a multilevel research network.

BACKGROUND: PID-ARI.net was one of three infectious disease epidemiological research networks funded by the German Ministry of Education and Research (BMBF). Its objectives were to strengthen the national initiative on infectious diseases epidemiology and to focus on a health care problem of high relevance. PATIENTS AND METHODS: A research network on the epidemiology of ARI in children was formed to generate data on several levels. Key structure was a centrally organized active surveillance system in three areas of Germany from north to south. RESULTS: In the 6 years of funding by the BMBF, an integrated research network with a known population denominator was formed. In the laboratory-based surveillance of up to 19 respiratory pathogens, 18,899 samples were analyzed. The added value is utilization of data on time, place, person and pathogen of a disease episode at several levels - from surveillance and online publication via a website to descriptive, analytical and molecular epidemiology and further specialized projects. Its wide age range including children up to 16 years of age, an extensive panel of pathogens, a known population denominator and the diversity of 3 distant geographical areas should considerably reduce vulnerability due to bias. CONCLUSIONS: Active surveillance systems for ARI are superior to passive systems. If a surveillance system such as the one used in PID-ARI.net is part of a research network which can utilize the data on several levels, the expenditure for such a system should be worthwhile and such a system would be an asset to any health care system.

Long-term humoral and cell-mediated immunity after acellular pertussis vaccination compares favourably with whole-cell vaccines 6 years after booster vaccination in the second year of life.

Humoral and cell-mediated immune responses (CMI) were evaluated in subjects 3 and 6 years after primary and booster vaccination with either three-component acellular (Pa) or whole-cell (Pw) vaccines. Low anti-pertussis toxin (PT) antibody levels confirmed the absence of pertussis disease, consistent with ongoing protection. Anti-pertactin (PRN) antibodies, remained at higher levels in Pa-vaccinated subjects. At year 6, CMI responses continued to be present and were higher in Pa-vaccinated than Pw-vaccinated subjects. Long-term protection with Pa vaccines can be expected to be at least as good as that provided by efficacious Pw vaccines.

Cell mediated and antibody immune response to inactivated hepatitis A vaccine.

The humoral and cellular immune response to inactivated hepatitis A vaccine was investigated dynamically in a time elapse study over 1 year. Fourty-five healthy volunteers, seronegative for anti-HAV, were vaccinated with 1440 enzyme-linked immunosorbent assay units (EU) of formalin-inactivated hepatitis A virus following a 0--6-month schedule. Serum anti-HAV levels and HAV-specific proliferation of peripheral blood mononuclear cells were measured at several time points over a 26- and 28-week period after the first and second injection, respectively. Distinct B and T cell responses were determined within 14 days after primary vaccination. The booster vaccination-induced immediate peak levels for the humoral (anti-HAV GMC=5376mIU/ml) as well as the cellular (median Deltacpm=14173cpm) response.

RSV-prevention in children guided by a web-based early warning system.

BACKGROUND: Passive immunization with palivizumab is expensive and requires considerable logistic effort. So far 5 monthly injections from November to March are recommended. The RSV season onset and its duration, however, shows considerable variation. In many countries on the northern hemisphere a dual rhythm is described. METHOD: A web-based early warning system within the research network PID-ARI.net is in place since 2002. The surveillance data are published online weekly via www.pid-ari.net. This enables physicians to carry out interventions, like passive immunization for RSV, synchronously with the epidemiology of a given pathogen instead of a rigid schedule. The surveillance of PID-ARI.net is based on a 19 valent multiplex RT-PCR on naso-pharyngeal aspirates. The samples are provided by hospitals and offices in Freiburg, Mainz and Schleswig-Holstein (north, middle, south of Germany). Children with lower airway infections are prospectively enrolled. RESULTS: In the time period from July 1999 to June 2003 with 20 months of recommended palivizumab application, 5 months (25 %) would have been not on target. In two seasons the start of the vaccine campaign would have been too early (waste of two months). In one season the application would have started one month too late and in two seasons the vaccine campaign would have been stopped two months too early leaving the vaccinees on risk for acquiring RSV. CONCLUSIONS: The web-based early warning system of PID-ARI.net is the first, pathogen-specific, comprehensive and fast surveillance-system for airway pathogens in Europe. It facilitates the epidemic-synchronous use of the passive immunization with palivizumab and by this increases its efficiency and should safe costs.

Tubulin gene expression during growth and maturation of leaves with different developmental patterns.

Changes in the tubulin-protein and -poly(A) +RNA contents were monitored by means of Western and Northern blot analyses, respectively, during growth and maturation of leaves of a dicotyledonous (tobacco) and monocotyledonous (barley) plant. It was recently argued from immunofluorescence and preliminary biochemical data that the density of microtubular networks and concomitantly the tubulin content are distinctly reduced after cessation of cell growth in leaves [Jung et al., 1993]. The results presented now confirm and extend this view. There appeared to be clear differences between the monocot and the dicot: (1) the loss of tubulin during leaf development was much slower in the dicot than in the monocot leaves (within months instead of days); (2) the degree of loss was more dramatic in the monocot leaf and only very low threshold levels of tubulin were retained in fully differentiated tissues; and (3) the loss of tubulin in the monocot leaf tissue appeared to be correlated with the decrease in the mRNA content, whereas the high level of tubulin-RNA in fully differentiated or even almost senescent dicot leaves indicated a gene expression control at the posttranscriptional level. The comparatively rapid and very distinct tubulin-protein and -RNA disappearance during development of the monocot leaf tissues confirm at the molecular level that differentiation proceeds much faster and is much more determinative in these leaves, as was postulated from histological and physiological data.(ABSTRACT TRUNCATED AT 250 WORDS)