You are presented with a 14-year-old mentally retarded male with a history of a seizure disorder. He came to his doctor in early January with a 5-day history of a fever, headache, nonproductive cough, nausea, vomiting, and lack of energy. He also had a loss of appetite, severe myalgias, and nasal congestion and shortness of breath. On the same day, his mother became ill, having headache, fever, and myalgias. His physical examination was noteworthy for a temperature of 39^oC and an increased respiratory rate of 35/min. He was dehydrated, and rales were heard at the base of his right lung. Laboratory data revealed normal electrolytes, creatinine, liver function tests, and complete blood count (CBC). His creatine kinase level (CPK) was slightly elevated. Analysis of arterial blood eases showed mild hypoxemia and respiratory alkalosis. A chest radiograph revealed a right lower lobe infiltrate. An induced sputum sample was obtained and sent for routine bacterial culture and viral culture. The sputum Gram stain was unremarkable.

He was admitted and given supplemental oxygen and intravenous hydration. Oral erythromycin therapy was begun pending culture results. He was also given antipyretics. Over the next 4 days, steady improvement was noted. On the fifth hospital day, a viral culture result revealed the diagnosis.

1. What is the differential diagnosis? What is the most likely etiology? Describe the functions of the two known virulence factors of this virus.

2. What is the least appropriate antipyretic to use in order to manage his fever? Why is antipyretic therapy an important consideration?

3. What strategies are available to prevent infection with this virus? Why are changes made in one of these preventative strategies each year?

4. Which conditions are necessary for an epidemic of this virus to occur?

DISCUSSION

1. The differential diagnosis of viral respiratory diseases in adolescents and adults includes the following: influenza virus, parainfluenza virus, respiratory syncytial virus, rhinovirus, adenovirus, measles virus, coronaviruses, coxsackievirus, and echoviruses, as well as varicella-zoster virus, cytomegalovirus (immunocompromised hosts), and herpes simplex virus (special circumstances).

This patient was not immunocompromised, and he developed an illness during the winter. Systemic symptoms were prominent, and he had evidence of lower respiratory tract involvement (pneumonia). His mother developed a similar illness. The most likely diagnosis is influenza, with parainfluenza a second possibility.

Influenza virus is one of the best-understood viruses in terms of pathogenesis. It is an RNA virus which has a segmented genome and belongs to the myxovirus group. Two virulence factors are recognized for this virus, hemagglutinin and neuraminidase. Hemagglutinin binds the virus to epithelial cells in the respiratory tract. The role of neuraminidase is less clear. It may help attach the virus by degrading mucins in the respiratory tract, thus allowing access of the hemagglutinin to the epithelial cell surface. It has also been suggested that this enzyme may play a role in the release of the virus from the infected cell.

2. Aspirin should never be used in children or young adults with viral illnesses such as influenza or varicella. There is an association of aspirin usage with the development of Reye's syndrome. This syndrome is often fatal and includes severe hepatic and central nervous system complications.

Acetaminophen is the appropriate antipyretic to use in this case.

3. There are two basic strategies for preventing influenza. First, annual vaccinations can prevent the majority of infections. Vaccines are made each year and include specific influenza A and B virus strains predicted to cause major illness. The need for yearly changes in the vaccine is due to the distinctive ability of this virus, especially influenza A. to change over time.

Influenza virus can undergo alterations in the antigenicity of its two major surface antigens, hemagglutinin and neuraminidase. Relatively minor changes in surface antigens which occur frequently are referred to as antigenic drift. Antigenic drift is believed to be due to point mutations in the RNA genome. it may lead to a selective advantage of the antigenically modified virus over the parent strain. Antibodies in patients exposed to the parent virus may be less protective against the mutated

strain, allowing for its greater transmission. Antigenic shift is defined as major changes in the antigenic structure of hemagglutinin or neuraminidase or both. Antigenic shift occurs as result of genetic reassortment, in which genomic RNA segments are exchanged between viruses, leading to major changes in the antigenic structure of the virus. It results in an antigenically new virus. Populations may have no immunity to the new virus, and influenza epidemics may occur as a result of these viral changes. Fortunately, antigenic shift occurs infrequently, historically at 10- to 20 year intervals.

Because the virus can undergo both major and minor antigenic variation, vaccines are produced each year based on the prevalent strains of the previous year to ensure induction of the best possible immunity in at-risk populations. Yearly vaccination is recommended for individuals with chronic respiratory and cardiac disease, for those with immunodeficiencies, the elderly, and health care providers.

Second, the use of the antiviral agent amantadine may prevent some infections with influenza A virus but not influenza B virus.

His father has preexisting respiratory compromise and is at high risk for developing severe illness if he acquires influenza.

He should receive annual influenza vaccinations. In tills particular situation he should also receive amantadine. If influenza B virus was isolated from his son, amantadine would be ineffective in preventing infection.