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Is it the Flu or Another Virus? Diagnosing and Treating Influenza

Isaacs, Lawrence MD

ID Rounds

Dr. Isaacs is a clinical assistant professor of emergency medicine at the Temple University School of Medicine, and the assistant director of the emergency department at Virtua Hospital in Voorhees, NJ.

With winter in full swing, we all see many patients complaining of having the flu, but who really has influenza and not one of the many other viruses in the community? Historically, there are reports of influenza outbreaks going back at least 400 years, with the first reliably recorded pandemic occurring in 1580. The most infamous pandemic occurred in 1918–1919 when there were 21 million deaths worldwide. By the middle of the 20th century, three types of the virus were identified, which are classified influenza A, B, or C.

Each type is then given a label depending on type, place of initial isolation, strain designation, and year of isolation (i.e., A/Moscow/7/65). Furthermore, the virus is given a “HN” designation depending on what glycoprotein surface antigens are present, resulting in more specific designations such as A/Moscow/87/H3N2. We share influenza A and C with non-humans (swine, birds), influenza B is only found in humans, and C does not cause significant disease in humans.

Influenza is spread primarily through coughing and sneezing; the incubation period is one to four days. The illness is characterized by abrupt onset of fever, chills, cough, sore throat, and rhinitis. Other signs and symptoms include watery, red eyes, myalgias (including the extraocular muscles), and headache. The fever rises very quickly, sometimes reaching 104°F to 106°F, and may last three to four days.

In addition to this syndrome, children may have calf muscle myalgias, a croup-like cough, higher fevers, otitis media, and tender cervical adenopathy. Gastrointestinal symptoms are not common in adults, but are found more frequently in children. The illness typically lasts for seven to 10 days, but the cough and malaise may remain for up to two weeks.

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Although most cases of influenza are uncomplicated, the infection may result in a variety of complications, with the very young, old, or chronically ill more likely affected. First, there is the pulmonary complication, pneumonia. This may be a primary viral or secondary bacterial pneumonia. In primary viral pneumonia, the pulmonary signs and symptoms (cough, shortness of breath, and hypoxia) begin early in the disease. Pregnancy and cardiovascular disease are the two risk factors to develop the primary pneumonia. The chest x-ray will look like ARDS with diffuse, bilateral infiltrates.

In secondary pneumonia, the patient, who is more likely elderly with COPD or other chronic diseases, will have shown improvement from the primary illness, then develop a “typical” pneumonia: fever, shortness of breath, and sputum production. Although historically Staphylococcus aureus was the most likely pathogen, more recent outbreaks have shown a predominance of pneumococcus or H. influenzae. (Arch Intern Med 1971;127[6]:1037.) Interestingly, the mortality from the primary pneumonia is higher than from the secondary. In children, pneumonia is less common than in adults, but in the 2003–2004 season, of the 93 children who died, 25 had pneumonia, and 15 of those had a bacterial co-infection. (MMWR 2004;52:1286.)

Children can present with croup or a bronchiolitis-like picture. Febrile seizures can occur, and in one study did so in approximately 10 percent of all cases. (Clin Infect Dis 2003;36:299.) Other possible complications include encephalitis, Guillain-Barre syndrome, myositis, toxic shock syndrome, and Reye's syndrome (which is uncommon these days.)

Although most cases of influenza are uncomplicated, the infection may result in a variety of complications, especially in the young, old, or chronically ill

Differentiating influenza from a nonspecific virus can be challenging. It is important for several reasons, the first being reducing unnecessary antibiotic use. Secondly, if the diagnosis is made early in the disease, antiviral therapy is of use. The third reason is to give the patient realistic expectations on the length of his illness. There are several methods of making the diagnosis. Clinically, it can be challenging, but during the fall or winter, if the patient has an abrupt onset of high fever, chills, malaise, and myalgias, he is more likely to have influenza than a nonspecific virus. This is far from reliable, however, and if one needs to know for the above reasons, laboratory testing is the next step.

There are several ways to test for the influenza virus, each having its limitations. Viral culture, PCR, DFA, IFA, and ELISA are all available tests. Samples are obtained from throat swabs, nasopharyngeal washes, or sputum. Although they have a turnaround time of two to four hours, unfortunately the DFA and IFA have sensitivities in the 60% to 70% range. There are several commercially available tests that have 10- to 30-minute result times with sensitivities in the 70% to 90% range. Some of these also can differentiate between A and B type. (Pediatr Infect Dis 2003;22:164.) If confirmation is necessary, a viral culture should be sent.

Table. D

Table. D

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Influenza Treatment

Amantadine has been approved for treatment of influenza for approximately 30 years. It treats influenza A, decreasing the length of illness by about one day, frequency of GI symptoms, and viral shedding. Unfortunately, there is a high incidence of viral resistance, a relatively high incidence of side effects, it does not treat the B type, and it does not prevent influenza-related complications. Rimantadine is similar to amantadine, treating only influenza A. Like amantadine, it must be started in the first 24 to 48 hours from onset of symptoms, but has fewer side effects, and is approved for chemoprophylaxis in children.

Oseltamavir (Tamiflu) treats both influenza A and B. It is approved for treatment of patients over a year old and for chemoprophylaxis over age 13. If begun within the first 48 hours of illness, it decreases the length of illness by 36 hours and the incidence of otitis media by 44 percent. (Pediatr Infect Dis J 2000;19:410.) Used for prophylaxis, it has a protective efficacy of 89%. Oseltamavir has a low incidence of side effects, and there is no significant resistance. The last drug used in the treatment on influenza A and B is zanamivir (Relenza). It is not approved for prophylaxis, and is administered via an inhaler, which has raised concerns about its use in patients with pulmonary disease (asthma or COPD). It is approved for patients over age 7, and like oseltamavir, is used for five days. All the antivirals are pregnancy category C.

The final issue concerning influenza is the vaccine. As everyone is aware, we are short of vaccine this season. This was a result of the British authority's halting the production of approximately half of the United States' supply. The vaccination should be given in the late fall, and confers immunity to the susceptible strains through the season, which lasts until spring. The vaccine is developed by predicting which strains the northern hemisphere will get by typing the strains from influenza patients' serum in the southern hemisphere. The serum is injected into hen's eggs and grown, then typed. The efficacy of the vaccine depends on how accurately the Centers for Disease Control and Prevention has predicted the influenza type. The contraindications to receiving it are just two: allergy to eggs and a history of Guillain-Barre after receiving a prior vaccine.

© 2004 Lippincott Williams & Wilkins, Inc.