A definition for influenza pandemics based on historical records.

OBJECTIVE: To analyse the records of past influenza outbreaks to determine a definition for pandemics. METHODS: Analysis of publications of large outbreaks of influenza which have occurred since 1889/90, and to match the results against the current definitions of an influenza pandemic. RESULTS: According to the general understanding of a pandemic, nine outbreaks of influenza since 1889/90 satisfy the definition; however, for two of these, occurring in 1900 and 1933, the data are limited. The special condition for an influenza pandemic requires, in one definition, that the virus strain responsible could not have arisen from the previous circulating strain by mutation; and in the second, that the new strain be a different subtype to the previously circulating strain. Both these restrictions deny pandemic status to two, and possibly three, influenza outbreaks which were pandemics according to the more general understanding of the term. These observations suggest that a re-evaluation of the criteria which define influenza pandemics should be carried out. CONCLUSION: The contradiction outlined above brings the previous definitions of an influenza pandemic into question; however, this can be resolved by defining an influenza pandemic by the following criteria. Thus, an influenza pandemic arises at a single, specific place and spreads rapidly to involve numerous countries. The haemagglutinin (HA) of the emergent virus does not cross-react serologically with the previously dominant virus strain(s), and there is a significant lack of immunity in the population against the emergent virus. These three criteria are interlinked and can be determined early to alert authorities who could respond appropriately. Other criteria associated with pandemics are necessarily retrospective, although important and valid. The implications of this definition are discussed.

Analysis of modulated gene expression in a model of Interferon-gamma-induced persistence of Chlamydia trachomatis in HEp-2 cells.

BACKGROUND: Chlamydia trachomatis is an important pathogen, being the commonest sexually transmitted bacterial disease in the Western world and is also implicated in a number of acute and chronic diseases. Persistent infections of C. trachomatis are particularly associated with chronic infections, which although eliciting an immune response, result in tissue damage leading to complications such as pelvic inflammatory disease. Interferon (IFN)-gamma is known to induce persistent infections of C. trachomatis both in vitro and in vivo. METHODS: A model of IFN-gamma-induced persistence containing aberrant inclusions of C. trachomatis was developed in the HEp-2 cell line. Morphological changes to inclusions were assessed by fluorescence immunocytochemistry and transcript levels determined by Real-Time RT-PCR. To assess infectivity of C. trachomatis in an IFN-gamma-induced persistent state, cultures containing aberrant inclusions were inoculated onto fresh HEp-2 monolayers. RESULTS: IFN-gamma induced aberrant inclusion formation at 0.01 ng/ml. Doses from 0.05 to 100 ng/ml did not significantly increase numbers of aberrant inclusions, and some normal inclusions were observed at the highest dose of IFN-gamma. Transfer of IFN-gamma-treated C. trachomatis onto fresh cultures confirmed the infectivity of these cultures. Real-Time RT-PCR identified apparent increased expression of the C. trachomatis heat-shock response genes ct604 and ct755 at 96-h post-infection. However comparisons with control cultures suggest that this more likely reflects a failure to down regulate gene expression as observed in untreated cultures. CONCLUSIONS: These data show that whereas IFN-gamma induces aberrant inclusion formation, many normal inclusions are still observed at high doses of IFN-gamma, and that the infectivity of such cultures is presumably from these. Transcriptional changes observed in response to IFN-gamma suggest a failure of the C. trachomatis life cycle in response to IFN-gamma, however IFN-gamma-induced transcriptional changes may be masked by the presence of normal inclusions. The implications of these observations in relation to models of persistence of C. trachomatis are discussed.

Raised inflammatory markers in semen from men with asymptomatic chlamydial infection.

The aim of this study was to determine whether interleukin (IL)-6 and IL-8 concentrations, as well as numbers of seminal leukocytes in a population of infertile men, some of whom were Chlamydia trachomatis positive, were related to chlamydial infection. Our patient group included 255 men attending for diagnostic semen analysis as part of infertility investigations. Significantly raised levels of IL-8, but not IL-6, were found in C trachomatis-infected patients but not in uninfected patients. Raised IL-8 levels in semen were also associated with an increase in semen volume. There was a relationship between C trachomatis infection and lower progressive motile sperm, as well as an increase in seminal leukocytes. The overall prevalence rate for C trachomatis was 6.2%, and more infections were detected in semen than in first void urine. This study supports the suggestion that IL-8 might be used as a marker for male genital tract infection, especially when due to C trachomatis. In this study, there was a relationship between the presence of C trachomatis in semen and alterations of some semen parameters. Further investigations should be performed to understand the disparities of first void urine and semen testing for detection of C trachomatis in males.

Effective nasal influenza vaccine delivery using chitosan.

Nasal influenza vaccination may prove to be a good alternative to parenteral injection because of the enhancement of the mucosal immune response and the ease of vaccine administration. This study investigated the use of chitosan, a bioadhesive polymer, as a nasal delivery system with inactivated, subunit influenza vaccine. Subjects received nasally 15 or 7.5 microg of the standard inactivated trivalent influenza vaccine with chitosan or 15 microg of the same vaccine intramuscularly. Serum haemagglutination inhibition (HI) titres for all three vaccine components were measured prior to, and at time points up to 14 weeks after dosing. Serum HI titres following intranasal vaccination with the nasal chitosan-influenza vaccine met the criteria set by the Committee for Proprietary Medicinal Products in terms of seroprotection rate, seroconversion rate and mean fold increase of HI titre for at least one of the three antigens in the vaccination schedules used. These data show that nasal immunisation with chitosan plus trivalent inactivated influenza is a potentially effective, easily-administered form of vaccination.

Large-scale comparison of experimental adjuvants with herpes simplex virus vaccine reveals a correlation of protection with IgG2a and IgG2b responses.

The potential of a large number of commercial and experimental adjuvant preparations to enhance the immunogenicity of an HSV-1 glycoprotein subunit vaccine was investigated. Evaluation was based on toxicity, HSV-specific antibody production, and protection against lethal challenge. All adjuvants tested increased the titer of antigen specific Ig levels when compared to subunit vaccine alone. However, following challenge, a broad range of protective responses were noted. Statistically significant correlations were observed between IgG antibody levels post immunization and the observed protection and these were particularly associated with antibodies of the IgG2a and IgG2b subclasses. The results emphasize the requirement of adjuvants for vaccine formulation when using subunit preparations, and demonstrate that the magnitude and efficacy of the induced immune response varies greatly with the choice of adjuvant.

Adenovirus, parainfluenza virus and respiratory syncytial virus antibodies in the sera of Jamaicans

Surveys for respiratory virus antibodies in the Jamaican population have shown that adenovirus, respiratory syncytical virus and parainfluenza types 1 and 3 virus antibodies are acquired early in life. The incidence of haemagglutination-inhibiting antibodies to parainfluenza viruses increases rapidly with age and almost all adults possess parainfluenza type 3 antibody, usually in high titre. Parainfluenza type 1 antibodies are only slightly less common. Complement-fixing antibodies to the adenovirus group were also observed to increase in incidence with age. Complement-fixing antibody to respiratory syncytial virus was less common in Jamaican sera than antibody to the other respiratory viruses described here. The highest titres were observed in the youngest age-group. (Summary)

Respiratory viruses in Jamaica: a virologic and seriologic study. 3. Hemagglutination-inhibiting antibodies to type B and C influenza viruses in the sera of Jamaicans

The results presented in this paper described a survey for hemagglutination-inhibiting antibodies to one type C and 2 type B influenza viruses in Jamaica sera. Antibodies to all 3 strains were found to be very common and the distribution by age of influenza B antibodies indicates that infections by the type B viruses occur in Jamaica primarily in the 5-to 9-year and 10- to 14 year age groups. A fairly widespread immunity to influenza B infection is evident in early adult life. The incidence and titer levels of hemagglutination-inhibiting antibodies to type C influenza virus increase throughout life. Primary infections is acquired during childhood and the increasing antibody titer levels with age suggest that reinfections are not uncommon. (AU)

Respiratory viruses in Jamaica: a virological and serological study. 2. Hemagglutination-inhibiting antibodies to influenza A viruses in the sera of Jamaicans

The incidence and level of hemagglutination-inhibiting antibodies to 4 group A infleunza viruses in the population of Jamaica has shown that there is an approximately similar age distribution of antibodies to the different infleunza strains as has been encountered else-where. Antibody titres to A/Swine/1976/31 were highest in sera from older Jamaicans; antibodies titres to A1/Fort Manmouth/1/47 were maximal in the younger segment of the population and antibody titres to A/Puerto Rico/8/34 reached their highest levels in sera from intermediate age groups. The greatest incidences and levels of hemagluttination-inhibiting antibody in almost all age groups were observed against infleunza A2/Jamaica/2/63, a locally recovered type A2 strain.(Summary)

Respiratory viruses in Jamaica: a virologic and serologic study. 1. Virus isolations and serological studies on clinical specimens

A survey of respiratory viruses and their antibodies in the Caribbean island of Jamaica has revealed that infleunza A, B and C viruses, parainfleunza type 1 and 3 viruses, respiratory syncytial virus and several types of adenovirus are causing respiratory infections in the Jamaican population. Respiratory virus infections were detected in Jamaica more frequently in the cooler months of the year, October through March, than in the warmer months. Adenoviruses were observed to be causing infections at all times of the year, but some evidence that parainfleunza type 1 infections are occurring at intervals only was obtained. Almost all infections by respiratory syncytial virus were obtained in infants and young children with severe lower respiratory tract disease.(Summary)

The role of respiratory viruses in Jamaica

This thesis describes a survey for respiratory viruses and their antibodies carried out at the Department of Microbiology, U. W. I., Mona from January, 1964 to June, 1966. The thesis is designed to show that representatives of the newer groups of viruses known to be associated with respiratory infections in humans are present in Jamaica, and to give indication of the prevalence of these viruses and their epidemiological behaviour in a tropical area. Two different approaches were made to the problem. Specimens from over 500 patients of ll ages and both sexes, suffering from both mild and severe respiratory infections were examined for the presence of respiratory viruses and their antibodies. Virus infection was detected in 67 (12.14 percent ) of these patients. Members of all the major groups of respiratory viruses, except rhinoviruses, were cultivated and serological conversions to many of them were also observed. Infections in children were found to be fairly common. Secondly, a series of surveys for antibodies to respiratory viruses in the general population were undertaken. Particular attention was paid to group A influenza viruses and their epidemic behaviour. Antibodies to type A2/Jamaica/2/63 influenza virus were widespread in the population, and there was a definite age-distribution of haemagglutination-inhibiting antibodies to certain other influenza strains. Antibodies to type C influenza virus were very common in the population of Jamaica. Antibodies to the parainfluenza viruses were also not infrequent in the sera of Jamaicans and evidence was obtained to show that these viruses and also respiratory syncytial virus caused frequent infections in infants and young children. Similarly, adenovirus antibodies were found to be acquired by the population at an early age (AU)

Aetiology of respiratory virus infections in Jamaica

Several viral agents were involved. Influenza A and B were isolated during epidemic periods, and there have been recent isolations of Adenovirus, para-influenza and Respiratory Syncytial viruses from clinical cases (AU)

Isolation of adenovirus in Jamaica

A brief report on the isolation in Jamaica of five strains of Adenovirus, since February 1964, included a description of the techniques being used routinely, details of the Adenoviruses so far isolated and studied, together with some indication of other work being carried out in the field of respiratory virology in Jamaica (AU)