Influenza Infection Control Research Articles

Influenza

Influenza (flu) is an acute contagious viral infection characterized by inflammation of the respiratory tract that every winter affects more than 100 million people in Europe, Japan and the United States of America, also being responsible for several thousand of excess deaths (data from the United States reveal between 20,000 to 40,000 excess deaths annually). The Mixovirus influenzae is the agent that causes influenza, commonly called flu. There are 3 types of influenza virus: A, B, C, and only types A and B are perceived to be clinically relevant in humans. Due to the segmented nature of its genetic material, the influenza virus is highly mutagenic, causing frequent insertion of new antigenic strains into the community, against which the population presents no immunity. Presently, there are few options for the control of influenza and annual immunization is the most effective means to prevent disease and its complications. In Brazil, according to data collected by the VigiGripe's Project - linked to the Federal University of Sao Paulo -, circulation of the influenza virus also has a seasonal pattern, with peak activity occurring between May and September. Yearly vaccination is, therefore, best indicated on March and April. Currently, there are four medications available for the treatment of influenza viruses: amantadine and rimantadine, and two second generation pharmaceutical products, the neuraminidase inhibitors, oseltamivir and zanamivir. The latter two drugs have set the stage for a new approach to the management and control of influenza infections.

Development of a DIVA (Differentiating Infected from Vaccinated Animals) strategy using a vaccine containing a heterologous neuraminidase for the control of avian influenza

The present paper reports of the development and validation of a control strategy for avian influenza infections in poultry. The "DIVA" (Differentiating Infected from Vaccinated Animals) strategy is based on the use of an inactivated oil emulsion vaccine containing the same haemagglutinin (H) subtype as the challenge virus, but a different neuraminidase (N). The possibility of using the heterologous N subtype, to differentiate between vaccinated and naturally infected birds, was investigated through the development of an "ad hoc" serological test based on the detection of specific anti-N1 antibodies. This was achieved using a baculovirus expressing a recombinant N1 protein. The A/ck/Pakistan/H7N3 virus was used as a vaccine and birds were challenged with the HPAI A/ty/Italy/4580/V99/H7N1 strain. The homologous H group ensured a clinical protection of 93% regardless of the vaccination scheme used, and was able to prevent viraemia and muscle colonization in the clinically healthy challenged birds. However, it was not able to prevent viral shedding. The "ad hoc" serological assay was developed as an indirect immunofluorescence test, and was validated using 608 field sera, and showed an "almost perfect agreement" (Kappa value) with the HI test, with relative sensitivity and specificity values of 98.1 and 95.7, respectively. The results of the present investigation suggest that the "DIVA" control strategy may represent a tool for the control of avian influenza infections in poultry.

Mucosal Immunity to Influenza Without IgA: An IgA Knockout Mouse Model

IgA knockout mice (IgA-/-) were generated by gene targeting and were used to determine the role of IgA in protection against mucosal infection by influenza and the value of immunization for preferential induction of secretory IgA. Aerosol challenge of naive IgA-/- mice and their wild-type IgA+/+ littermates with sublethal and lethal doses of influenza virus resulted in similar levels of pulmonary virus infection and mortality. Intranasal and i.p. immunization with influenza vaccine plus cholera toxin/cholera toxin B induced significant mucosal and serum influenza hemagglutinin-specific IgA Abs in IgA+/+ (but not IgA-/-) mice as well as IgG and IgM Abs in both IgA-/- and IgA+/+ mice; both exhibited similar levels of pulmonary and nasal virus replication and mortality following a lethal influenza virus challenge. Monoclonal anti-hemagglutinin IgG1, IgG2a, IgM, and polymeric IgA Abs were equally effective in preventing influenza virus infection in IgA-/- mice. These results indicate that IgA is not required for prevention of influenza virus infection and disease. Indeed, while mucosal immunization for selective induction of IgA against influenza may constitute a useful approach for control of influenza and other respiratory viral infections, strategies that stimulate other Igs in addition may be more desirable.

A Perspective from Controlled Investigations on Chemotherapy for Viral Respiratory Infections

Failure to translate discoveries about the etiology of viral respiratory infections into effective vaccines has stimulated research into antiviral chemotherapy. Volunteers whose antibody status before challenge is known and who have been exposed to a known dose of virus at a defined time provide an objective system for controlled observation of antiviral chemotherapy. A perspective on experience with drugs of five different categories of mechanisms of action is presented. Prophylactic and possibly therapeutic control of influenza and rhinovirus infections is possible. Field trials have confirmed that some regimens have beneficial effects and have shown the clinical restrictions of others. Chemotherapy is enhanced by immunoprophylaxis, and vice versa. If the potential of antiviral chemotherapy for clinical use is to be realized, complex virologic problems (some related to drugs and others unrelated) must be overcome. The groundwork is laid for new directions and new successes in the prevention and treatment of viral respiratory diseases with antiviral drugs.