Case 4

1. How is the virus transmitted? 

Inhalation or contact with respiratory secretions from an infected person.

2. How is the viral infection detected? 

During the acute phase of illness, influenza viruses can be readily isolated from respiratory tract specimens, such as nasopharyngeal and throat swabs. Most strains grow in primary monkey kidney cell cultures or in the amniotic cavity of embryonated hen's eggs, and they can be detected by hemadsorption or hemagglutination. Rapid diagnosis of infection is possible by direct immunofluorescence or immunoenzymatic detection of viral antigen in epithelial cells or secretions from the respiratory tract.

Serologic diagnosis is of considerable help epidemiologically and is usually made by demonstrating a fourfold or greater increase in complement-fixing or hemagglutination inhibition antibody titers in acute and convalescent specimens collected 10-14 day apart.

3. The woman received a vaccine last year, why wasn’t she still protected? Is a URI a contraindication to vaccination? 

The best available method of control is by use of killed viral vaccine prepared from those strains related most closely to the antigenic subtypes currently causing infections. (Viral strains change each year due to antigenic drift and shift). These inactivated vaccines may contain whole virions or "split" subunits composed primarily of hemagglutinin antigens. They are commonly used, in two doses given 1 month apart, to immunize children who may not have been immunized previously; otherwise, single annual doses are recommended just prior to influenza season. Used in this way, the virus vaccines may be 70 to 85% effective. 

It is recommended that vaccination be directed primarily toward the elderly, individuals of all ages who are at high risk (eg, those with chronic lung or heart disease), and their close contacts, including medical personnel and household members.

A URI is not contraindication for vaccination.

4. Are there any effective anti-viral agents that act against this virus? 

Yes. Oseltamivir and zanamivir has been shown to inhibit the replication of influenza A and B strains in vitro, in mice and in experientally induced infection in humans. Hayden et al. report that in a double-bind randomized, placebo-controlled trial conducted over a six-week period during the influenza season, 75 mg of oseltamivir administered once or twice daily (for a total dose of 75 or 150 mg daily) was well tolerated, and its efficacy as prophylaxis against laboratory-documented febrile influenza was 74 percent (95 percent confidence interval, 53 to 88 percent). Once-daily and twice-daily doses provided similar levels of efficacy. Likewise, Monto et al. found that another neuraminidase inhibitor, zanamivir, was approximately 84 percent effective (95 percent confidence interval, 55 to 94 percent) in preventing laboratory-confirmed illness associated with fever. Zanamirvir is an orally inhaled compound that has been approved for influenza treatment in Australia, Europe, and the United States.

These specific inhibitors of influenza neuraminidase have been discovered by analyzing the crystallographic structure of this molecule and applying the techniques of rational drug design. These compounds bind to the conserved active site of neuraminidase and appear to inhibit the release of viruses from infected cells and their subsequent spread to adjacent cells. The neuraminidase inhibitors for which data are currently available appear to be effective against both influenza A and influenza B infections. They seem to have less potential than amantadine or rimantadine for inducing resistance and are associated with fewer major side effects, but they are likely to cost more.

Amantadine hydrochloride, a symmetric amine, has been shown to be effective in short-term (several weeks) oral prophylaxis of Influenza A

INFECTIONS BUT NOT Influenza B. It appears to act by blocking the ion channel of the viral M2 protein, resulting in interference with its key role in early virus uncoating and also later virion assembly. Amantadine can produce side effects, however, and is recommended only for high-risk patient until vaccine-induced immunity can be achieved. A typical example of its use would be during an epidemic in which an elderly, potentially susceptible patient may become exposed to infection within a defined period. Oral amantadine prophylaxis may be initiated concurrently with administration of a vaccine containing the most current continued protection. It must be emphasized that amantadine has been proven effective for influenza A virus infections only; it is useless in other respiratory virus. A newer related drug, rimantadine, seems to be as efficacious as amantadine and may cause fewer adverse effects. Unfortunately, virus resistance to both drugs can develop. A single mutation in the membrane portion of the M2 protein is all that is necessary for this to occur.

5. What recommendation would you suggest for this woman for the next flu season? 

She should receive the vaccine each year.