A study of excess mortality during influenza epidemics in the Czech Republic, 1982-2000.

Influenza related mortality rates have been established in many countries; nevertheless, studies focusing on the Central European population have been rare to date. We assess mortality attributable to influenza by comparing all cause mortality and mortality due to diseases of the circulatory system during influenza epidemic and non-epidemic periods, as defined by acute respiratory infection surveillance data. Data on total mortality, mortality due to diseases of the circulatory system and surveillance data for influenza and other respiratory infections were used in a general linear model with a logarithmic link for dependence of left censored mortality data over time, and week as a categorical factor. Results of the analysis show statistically significant (p <0.001) differences in excess mortality rates between influenza epidemic and non-epidemic periods in the Czech Republic between 1982 and 2000. We estimate that 2.17% of all cause mortality, and 2.57% of mortality due to diseases of the circulatory system throughout the study period was attributable to influenza, with an estimated annual average of 2661 and 1752 deaths respectively. The highest numbers of deaths were reported during seasons when influenza A/H3N2 was the predominant circulating strain. Improving vaccination coverage against influenza is considered to be the primary strategy for prevention of influenza associated mortality.

Influence of the parental virus strain on the virulence and immunogenicity of recombinant vaccinia viruses expressing HBV preS2-S protein or VZV glycoprotein I.

Five triple-plaque purified vaccinia virus (VV) lines generated from smallpox Sevac VARIE vaccine (strain Praha) and three VV virus lines similarly derived from Wyeth DRYVAX vaccine were used for preparation of recombinants expressing the hepatitis B virus preS2-S gene. The same five Praha-derived virus lines were used to construct recombinants expressing the varicella-zoster virus (VZV) glycoprotein I (gpI) gene. Recombinants and their parental viruses were tested for the residual neurovirulence in mice. The virus lines and the recombinants derived therefrom differed markedly in this respect. Immunization of mice resulted in high levels of anti-HBsAg antibodies only in the case of recombinants derived from the relatively virulent viruses. In contrast, the levels of VZVgpI antibodies in mice were similar with all VV-VZV recombinants irrespective of the virulence of the parental virus line.

Search for optimal parent for recombinant vaccinia virus vaccines. Study of three vaccinia virus vaccinal strains and several virus lines derived from them.

Three vaccinia virus strains (Praha, DD--a DRYVAX Wyeth vaccine-derived virus-and LIVP) were examined for growth in various cell cultures and for virulence and immunogenicity in mice. The viruses did not differ by their growth rates in monkey kidney cells (CV-1), human diploid cells (LEP), rat TK cells (RAT 2) or primary dog kidney cells. The immunogenicity of Praha and DD viruses was similar, the virus LIVP was somewhat more immunogenic. In terms of virulence in 3-day-old mice, the DD virus was the most attenuated. Single-plaque progenies were derived from the original smallpox vaccines VARIE Sevac (strain Praha) and DRYVAX Wyeth and tested for the above markers and DNA restriction patterns. The results obtained demonstrated biological and molecular heterogeneity of the original virus populations. Close linkage was observed between immunogenic activity and virulence in 3-day but not in 3-week mice. The results indicate that smallpox vaccine preparations may serve as an abundant source of virus mutants.

Evaluation of various virulence tests with low virulence vaccinia virus in mice.

Two vaccinia virus (VV) clones, denoted P20 and P21 were derived from the parental VV strain Praha. The residual virulence of these two viruses in mice was compared. Intracerebral inoculation of 21-day-old mice did not reveal any marked difference between the two viruses. Tests using intracerebral inoculation of 10-day-old mice showed that their LD50 differed by 2 log10 pfu, P20 being the more attenuated. The difference between the two viruses increased further when intranasal and intracerebral inoculations of 3-day-old mice were employed. Their LD50 differed by 4 and 5 log10 pfu, respectively. Thus, these tests proved to be the most sensitive for determining residual virulence of VV in mice and thus the most suitable for differentiating among the low virulence VVs. The antibody tests carried out in the surviving mice suggested that the more attenuated virus was less immunogenic than the more virulent virus.

[Problems associated with the development of vaccines based on recombinant vaccinia virus]. / Nekteré problémy vývoje vakcín zalozených na rekombinantním viru vakcínie.

A collection of single and double vaccinia virus recombinants was prepared. The recombinants contained either genes for different forms of surface protein or core protein of HBV or the gene for glycoprotein I of varicella-zoster virus. Cells infected with the recombinants produced the respective foreign antigens. Specific antibodies against the heterologous antigens were induced in mice immunized with the recombinants. The insertion of the second foreign gene into the genome of single recombinants did not influence either the extent of production of the first protein in vitro or its immunogenicity for mice.

An attempt to analyse the functional difference between various mumps virus strains.

Enzymatic activity of N-acetylneuraminidase of ten various strains of mumps virus was compared. From the viewpoint of their biological properties, these strains could be classified as laboratory, neurovirulent, and vaccinal (attenuated) ones. The enzymatic activity was evaluated by Scatchard's plot which enables to interpret it according to polarity of the cooperativity of enzymes' binding sites. Laboratory strains of the mumps virus demonstrated an independent type of cooperativity, while vaccinal (attenuated) ones showed a positive type of cooperation.

Two sites of oxygen control in induced synthesis of respiratory nitrate reductase in Escherichia coli.

The time course of appearance of respiratory nitrate reductase in Escherichia coli after induction by nitrate was analyzed under different conditions, and the inhibitory effects of oxygen, chloramphenicol, and rifampin were compared. Oxygen appeared to inhibit the synthesis of nitrate reductase at the level of transcription. In addition, the translation or some later steps of enzyme formation were blocked.