The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

Background  

Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib_2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib_2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib_2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Multiplex PCR assay to aid in the identification of the highly transmissible Mycobacterium tuberculosis strain CDC1551.

SETTING: Mycobacterium tuberculosis strain CDC1551 outbreak area in Tennessee and Kentucky and selected locations in the USA. OBJECTIVE: Develop a PCR assay to distinguish the highly transmissible CDC1551 from strains which have similar 4-band IS6110 fingerprints. DESIGN: Compare the IS6110 insertion sites in CDC1551 with those in 10 isolates which have similar 4-band IS6110 fingerprints. Utilize unique characteristics of insertion sites in CDC1551 to design a multiplex PCR to identify this strain. RESULTS: A multiplex PCR was developed which targets an IS6110 insertion conserved in most IS6110 low copy number strains and a deletion within the direct repeat region adjacent to an IS6110 insertion. Of 139 isolates with similar 4-band fingerprints, the CDC1551 PCR pattern was generated by only the 14 outbreak associated isolates. Of 154 isolates with different fingerprints, only four generated the CDC1551 pattern and these could be distinguished from CDC1551 by their IS6110 fingerprint. CONCLUSIONS: The multiplex PCR used in conjunction with the IS6110 fingerprint should be a useful tool to aid in the continued surveillance of the outbreak area and follow the spread of this highly transmissible strain of M. tuberculosis.     

Pityriasis alba: a study of pathogenic factors

BACKGROUND: The aetiology of pityriasis alba (PA), a common dermatosis in childhood, is still controversial. The objective of this study was to assess the possible aetiopathogenic factors of this disease in infants. METHODS: Forty-four patients with PA and 31 healthy children were examined and compared. Personal hygiene habits, sun exposure, presence of Staphylococcus aureus in nasal fossae and presence of major or minor signs of atopy were assessed during anamnesis and physical examination. Susceptibility to ultraviolet (UV) B radiation was measured by the onset of a contact hypersensitivity reaction to diphenylcyclopropenone in individuals sensitized in previously irradiated areas. RESULTS: The prevalence of PA was higher in individuals with darker skin, in high phototype categories, as well as in males. The number of daily baths and sun exposure between 10.00 h and 15.00 h were significantly higher in the PA group when compared with controls (P = 0.03 and P = 0.0015, respectively). The presence of atopy signs was more common in pityriasis patients (P = 0.002). Susceptibility to UVB radiation was 29.6% in the PA group vs. 29.0% in the control group; nevertheless, important differences were found after stratification in order to control possible confounding factors. The presence of S. aureus in the nostrils was equal in both groups. CONCLUSIONS: Our results confirm that PA, in our population, is more prevalent in males and in individuals in higher phototype categories. In those with inadequate personal hygiene and sun exposure habits the disease is more accentuated, demonstrating that the xerosis presenting in individuals with atopic diathesis is an important element in the development of the disease. S. aureus is not an important aetiopathogenic factor in PA. Susceptibility to UVB becomes important when related to the patient's phototype.     

Tuberculosis subunit vaccine development: impact of physicochemical properties of mycobacterial test antigens

Tuberculosis caused by Mycobacterium tuberculosis continues to be one of the major public health problems in the world. The eventual control of this disease will require the development of a safe and effective vaccine. One of the approaches receiving a great deal of attention recently is subunit vaccination. An efficacious antituberculous subunit vaccine requires the identification and isolation of key components of the pathogen that are capable of inducing a protective immune response. Clues to identify promising subunit vaccine candidates may be found in their physicochemical and immunobiological properties. In this article, we review the evidence that the physicochemical properties of mycobacterial components can greatly impact the induction of either protective or deleterious immune response and consequently influence the potential utility as an antituberculous subunit vaccine.     

Sporadic community-acquired Legionnaires' disease in the United States. A case-control study.

One hundred patients with sporadic, community-acquired, serologically confirmed Legionnaires' disease were matched with control subjects known by the patients (acquaintance controls) and control subjects chosen from among patients with negative serodiagnostic tests for Legionnaires' disease (clinical controls). Each clinical control subject was also matched with an acquaintance control of his own. Legionnaires' disease patients had smoked more cigarettes, consumed more alcohol, and were more likely to have resided near excavation sites than acquaintance or clinical control subjects. Parallel differences between clinical controls and their acquaintances were not seen. Legionnaires' disease patients had traveled away from home for more time during the 2 weeks before onset of illness than had their acquaintances. The difference was of greater magnitude than that between clinical control subjects and their acquaintances. Legionnaires' disease patients were more likely to have resided near construction sites than clinical controls, and there were more construction workers among patients than among clinical control subjects.     

Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells

Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU- E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti- HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity.