Interrupting the transmission of respiratory tract infections: theory and practice.
Interruption of transmission has always been one of the most attractive approaches for infection control. The technologies available were severely limited before the development of appropriate vaccines. Mathematically, the proportion of those who need to be immune to interrupt transmission can be derived from the Ro, which represents the number of new cases infected by a single case when all contacts are susceptible. Purely respiratory infections have critical characteristics affecting transmission that are different from key childhood vaccine-preventable diseases spread by the respiratory route. They include frequent reinfections and antigenic changes of the agents. Pragmatic approaches to understanding their potential effect can be found in experimental and programmatic use of vaccines such as those for Haemophilus influenzae type b and influenza virus infections. Results of these experiences can in turn strengthen the development of transmission theory. (+info)
Potential advantages of DNA immunization for influenza epidemic and pandemic planning.
Immunization with purified DNA is a powerful technique for inducing immune responses. The concept of DNA immunization involves insertion of the gene encoding the antigen of choice into a bacterial plasmid and injection of the plasmid into the host where the antigen is expressed and where it induces humoral and cellular immunity. The most effective routes and methods for DNA immunization are bombardment with particles coated with DNA ("gene gun" technique), followed by the intramuscular and intradermal routes. DNA immunization technology has the potential to induce immunity to all antigens that can be completely encoded in DNA, which therefore include all protein, but not carbohydrate, antigens. DNA immunization results in presentation of antigens to the host's immune system in a natural form, like that achieved with live-attenuated vaccines. The DNA immunization strategy has the potential to rapidly provide a new vaccine in the face of an emerging influenza pandemic. (+info)
Evaluation of clinical case definitions of influenza: detailed investigation of patients during the 1995-1996 epidemic in France.
Using clinical predictors, we evaluated clinical case definitions of influenza during the 1995-1996 outbreak in France. Thirty-five general practitioners collected virological specimens and clinical data. Predictors of influenza virus infection were selected with logistic regression models. The results varied with the influenza virus subtype: temperature of >38.2 degrees C, stiffness or myalgia, rhinorrhea, and cough were predictive of influenza A/H3N2, whereas fatigue, lacrimation or conjunctival injection, and the absence of stiffness or myalgia were predictive of influenza A/H1N1. On the basis of this analysis and data from the literature, 12 clinical case definitions were evaluated for their abilities to diagnose influenza virus infection. They were associated with positive predictive values of 27% to 40% and negative predictive values of 80% to 91%. We conclude that focused studies evaluating clinical case definitions of influenza with use of subsets of patients should accompany population-based disease surveillance for optimal estimates of the disease burden associated with influenza epidemics. (+info)
Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong.
An H5N1 avian influenza A virus was transmitted to humans in Hong Kong in 1997. Although the virus causes systemic infection and is highly lethal in chickens because of the susceptibility of the hemagglutinin to furin and PC6 proteases, it is not known whether it also causes systemic infection in humans. The clinical outcomes of infection in Hong Kong residents ranged widely, from mild respiratory disease to multiple organ failure leading to death. Therefore, to understand the pathogenesis of influenza due to these H5N1 isolates, we investigated their virulence in mice. The results identified two distinct groups of viruses: group 1, for which the dose lethal for 50% of mice (MLD50) was between 0.3 and 11 PFU, and group 2, for which the MLD50 was more than 10(3) PFU. One day after intranasal inoculation of mice with 100 PFU of group 1 viruses, the virus titer in lungs was 10(7) PFU/g or 3 log units higher than that for group 2 viruses. Both types of viruses had replicated to high titers (>10(6) PFU/g) in the lungs by day 3 and maintained these titers through day 6. More importantly, only the group 1 viruses caused systemic infection, replicating in nonrespiratory organs, including the brain. Immunohistochemical analysis demonstrated the replication of a group 1 virus in brain neurons and glial cells and in cardiac myofibers. Phylogenetic analysis of all viral genes showed that both groups of Hong Kong H5N1 viruses had formed a lineage distinct from those of other viruses and that genetic reassortment between H5N1 and H1 or H3 human viruses had not occurred. Since mice and humans harbor both the furin and the PC6 proteases, we suggest that the virulence mechanism responsible for the lethality of influenza viruses in birds also operates in mammalian hosts. The failure of some H5N1 viruses to produce systemic infection in our model indicates that multiple, still-to-be-identified, factors contribute to the severity of H5N1 infection in mammals. In addition, the ability of these viruses to produce systemic infection in mice and the clear differences in pathogenicity among the isolates studied here indicate that this system provides a useful model for studying the pathogenesis of avian influenza virus infection in mammals. (+info)
Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays.
From May to December 1997, 18 cases of mild to severe respiratory illness caused by avian influenza A (H5N1) viruses were identified in Hong Kong. The emergence of an avian virus in the human population prompted an epidemiological investigation to determine the extent of human-to-human transmission of the virus and risk factors associated with infection. The hemagglutination inhibition (HI) assay, the standard method for serologic detection of influenza virus infection in humans, has been shown to be less sensitive for the detection of antibodies induced by avian influenza viruses. Therefore, we developed a more sensitive microneutralization assay to detect antibodies to avian influenza in humans. Direct comparison of an HI assay and the microneutralization assay demonstrated that the latter was substantially more sensitive in detecting human antibodies to H5N1 virus in infected individuals. An H5-specific indirect enzyme-linked immunosorbent assay (ELISA) was also established to test children's sera. The sensitivity and specificity of the microneutralization assay were compared with those of an H5-specific indirect ELISA. When combined with a confirmatory H5-specific Western blot test, the specificities of both assays were improved. Maximum sensitivity (80%) and specificity (96%) for the detection of anti-H5 antibody in adults aged 18 to 59 years were achieved by using the microneutralization assay combined with Western blotting. Maximum sensitivity (100%) and specificity (100%) in detecting anti-H5 antibody in sera obtained from children less than 15 years of age were achieved by using ELISA combined with Western blotting. This new test algorithm is being used for the seroepidemiologic investigations of the avian H5N1 influenza outbreak. (+info)
Influenza vaccination among the elderly in Italy.
This article surveys the attitudes and perceptions of a random sample of the elderly population in three regions of Italy on the use and efficacy of influenza vaccine. The data were collected by direct interviews using a standard questionnaire. The results show that vaccination coverage against influenza is inadequate (26-48.6%). The major reasons for nonvaccination were lack of faith in the vaccine and disbelief that influenza is a dangerous illness. These data emphasize the need for a systematic education programme targeted at the elderly and the provision of influenza vaccination, with the increased cooperation of general practitioners. (+info)
Influenza A virus accelerates neutrophil apoptosis and markedly potentiates apoptotic effects of bacteria.
Neutrophils are recruited into the airway in the early phase of uncomplicated influenza A virus (IAV) infection and during the bacterial superinfections that are a significant cause of morbidity and mortality in IAV-infected subjects. In this report, we show that IAV accelerates neutrophil apoptosis. Unopsonized Escherichia coli had similar effects, although apoptotic effects of opsonized E coli were greater. When neutrophils were treated with both IAV and unopsonized E coli, a marked enhancement of the rate and extent of neutrophil apoptosis occurred as compared with that caused by either pathogen alone. Treatment of neutrophils with IAV markedly increased phagocytosis of E coli. Simultaneous treatment of neutrophils with IAV and E coli also elicited greater hydrogen peroxide production than did either pathogen alone. IAV increased neutrophil expression of Fas antigen and Fas ligand, and it also increased release of Fas ligand into the cell supernatant. These findings may have relevance to the understanding of inflammatory responses to IAV in vivo and of bacterial superinfection of IAV-infected subjects. (+info)
A mathematical approach to epidemic control.
A mathematical model of an influenza epidemic which occurred in 1961 is suggested. The mathematics imply conclusions on the practical control of similar outbreaks. This is a technique applicable to one general practice. (+info)