Edition: September 2002 - Vol 10 Number 09
Author: Laura Thill
Not worried about that pesty little flu bug? After all, it’s nothing more than a bad cold, and flu season isn’t even upon us.
Wrong: Flu – or influenza – actually is a lung disease capable of causing pneumonia. Up to 114,000 people are hospitalized in the United States each year due to influenza, according to the Centers for Disease Control and Prevention (CDC). About 20,000 of these individuals will die this year alone.
True, peak flu season doesn’t hit until closer to late December or January. But, October is the time to consider a flu vaccination, particularly for those in high-risk categories. And, with the range of diagnostic tools available for early detection of flu, patients can assume an active role in preventing adverse consequences to their health.
A Respiratory Illness
Like a cold, influenza is a respiratory illness. Both illnesses are caused by viruses, and both trigger similar symptoms, according to the CDC. A cold usually begins two or three days following infection by the virus, and generally lasts up to a week. Symptoms include a scratchy, sore throat, sneezing and a runny nose. Adults and older children tend not to develop a fever, but younger children and infants may run a temperature as high as 102˚ F (39˚ C).
Flu symptoms include a dry cough, runny nose and sore throat. Muscles tend to ache, and the patient can become exhausted. Fevers as high as 104˚ F are possible. While the worst symptoms might diminish after a day or two, the exhaustion and cough can persist for over two weeks, according to the CDC.
Although children sometimes present stomach symptoms (i.e. nausea, vomiting and diarrhea) in addition to the respiratory ones, these symptoms are uncommon and are not considered “stomach flu.” In fact, there is no such thing as stomach flu. Usually, symptoms involving the stomach are caused by other viruses, bacteria or parasites.
Most people develop symptoms within a couple of days from exposure to the influenza virus. But symptoms can also appear in a day, or they can take as long as four days to surface. Whereas adults tend to be contagious for three to seven days, children can be contagious for over a week. Generally, the disease is transmitted when an ill person coughs, sneezes or speaks, and others inhale the virus that has been sent into the air. The virus enters the victim’s nose, throat or lungs, and multiplies. Infrequently, one might contract the flu after touching an infected surface and then touching his or her nose or mouth.
Flu-related complications can arise in the form of bacterial pneumonia or dehydration. Existing medical conditions, such as congestive heart failure, asthma or diabetes, can worsen from the flu, according to the CDC.
There are three categories of influenza viruses – types A, B and C. Influenza types A and B are responsible for the typical winter epidemics of respiratory illness, and are often linked to increased hospitalizations and death. Type C differs in that it usually causes a respiratory illness that is very mild or has no symptoms at all. Type C does not cause epidemics as do types A and B. Hence, most efforts to control the impact of influenza are directed at types A and B.
Types A and B
Influenza type A viruses fall into two categories, depending on variations in the viral proteins (hemagglutinin and neuraminidase) they contain. The current subtypes of influenza A are A(H1N1) and A(H3N2). These two strains, along with influenza B strains, are included in the influenza vaccine offered annually.
Influenza type A viruses are capable of changing in two different ways. One type of change is gradual, involving a series of mutations over time. Named the antigenic ‘drift,’ this constant pattern of change allows the virus to evade the immune system of its host. This is why people are susceptible to influenza virus infection throughout life, according to the CDC. A person infected with influenza virus develops antibody against that virus. But, as the virus changes, the original antibody no longer recognizes, or protects against, the mutated virus. The original antibody still, however, offers partial protection against reinfection.
The second type of mutation – antigenic ‘shift’ – involves an abrupt change in the hemagglutinin and/or neuraminidase proteins. In an antigenic shift, a new subtype of the virus suddenly emerges. While type A viruses undergo both antigenic drifts and shifts, type B viruses change only by the more gradual antigenic drift. CDC flu surveillance tracks mutating characteristics of influenza, ensuring that the vaccine composition is changed annually to target new mutations of the virus.
While there is no cure for the flu, antiviral drugs can diminish the duration of the illness when administered within the first two days, notes the CDC. Drugs approved for flu treatment include amantadine, rimantadine, zanamivir and oseltamivir. All but zanamivir have been FDA-approved for flu prevention, but the CDC maintains that they are no substitute for the vaccine, especially for high-risk individuals. It is important to note that aspirin should never be administered to a flu patient, as it can lead to Reye syndrome.
Sometimes, a test administered within the first two or three days after the onset of symptoms can provide the physician with information that can aid in diagnosis and treatment. For instance, testing for influenza can be helpful during a respiratory illness outbreak to help determine if flu has been the cause.
Samples for influenza testing (i.e. collected via throat swab, nasal wash or nasal aspirates) must be obtained within the first four days of illness, according to the CDC. This is especially important, since therapeutics are only effective if administered within the first 36-48 hours. Rapid test results are available within 24 hours, while viral culture results take three to 10 days. Most rapid tests can be completed in the doctor’s office, with approximately 70 percent sensitivity and 90 percent specificity.
Serum samples also can be tested for the influenza antibody, although these tests require more time. Two samples must be collected from the patient: One within the first week of illness and the second sample two to four weeks later. An increase in antibody levels from the first test to the second indicates the presence of influenza infection. In spite of its long waiting period, viral testing is useful, particularly in determining influenza subtype strains and for surveillance of new strains, notes the CDC.
Rapid Flu Diagnostics
There are two rapid detection methods for point-of-care and clinical lab assessment, according to ZymeTx (Oklahoma City):
• Influenza virus antigen detection with antibodies, or viral antigen detection. This method uses antibodies from mice immunized with influenza.
• Influenza neuraminidase enzyme activity (NA) detection, or viral enzyme detection. This method employs a more stable target and recognizes the viral enzyme active site inside the NA enzyme that cannot be touched by antibodies.
• Rapid diagnostic tests available on today’s market include: Flu-OIA™ (Biostar), Directigen-Flu A and B™ (Becton Dickinson), Quick Vue™ (Quidel), and ZstatFlu™ (ZymeTx). One example of how these tests function is ZymeTx’s ZstatFlu™,
an NA detection method that employs a technology called Endogenous Viral-encoded Enzyme Assay (EVEA). The test takes less than two minutes to complete and does not require refrigeration. Another example of rapid diagnostic technology is Becton Dickenson’s Directigen Flu A and B, which can distinguish influenza A viral antigens form those of influenza B. This is useful since certain antiviral therapies are effective only for the A strain, while others can be used to treat both influenza A and B.
A recent article about rapid influenza testing of infants and toddlers (Miller, Karl E., M.D., “Rapid Influenza Testing in Febrile Infants and Toddlers,” American Family Physician, June 1, 2002), considers the benefit of rapid testing, suggesting that early diagnosis may reduce the need for pediatric patients to require further testing and therapy.
The researchers investigated rapid diagnostic testing, given the current emphasis on reducing antibiotic use and unnecessary diagnostic testing. They employed a rapid detection test using an enzyme-linked immunosorbent assay (ELISA), which is as spec-ific and sensitive as viral cultures, according to the researchers.
The study group included 72 infants, 47 of whom were placed in the early diagnosis group and 25 of whom were placed in the late diagnosis group. Both groups were comparable in terms of age, temperature and triage. Infant in the early diagnosis group were much less likely to undergo urine testing and complete blood counts than those in the late group, noted the researchers. Early diagnosis group members also were less likely to receive therapy with ceftriaxone sodium.
Because influenza viruses change so often, the vaccine must be updated annually. Last year’s flu vaccine will not protect against this year’s viruses. The FDA Vaccines and Related Biological Products Advisory Committee made the following recommendations in March 2002 for the influenza virus strains to be included in the 2002-03 influenza vaccine:
• H1N1, A/New Caledonia/20/99.
• H3N2, A/Panama/2007/99 (an A/Moscow/10/99-like virus).
• B/Hong Kong/330/2001-like virus strain.
Vaccinated individuals should be protected after about two weeks of receiving the shot, according to the CDC. And, while some vaccinated individuals may still get the flu, they should develop a much milder case than those who have not been vaccinated.
In contrast to past seasons, which saw flu vaccine distribution delays, the CDC projects an increased availability in vaccine – as many as 97 million doses, compared to 87 million doses produced in the 2001-02 flu season. Still, the CDC recommends that healthcare providers order influenza vaccine as soon as possible to ensure that they have it on hand for higher-risk patients by October. At press time, the CDC offered the following update on availability:
• Aventis-Pasteur (1-800-822-2463) has indicated that its total influenza vaccine supply for the 2002-03 flu season has been booked, but the company’s waiting list remains open.
• The Evans Vaccines brand of flu vaccine is available from Henry Schein (800-772-4346) and its GIV (800-521-7468) and Caligor (888-225-4467) divisions. Evans vaccine also has added two distributors: FFF Enterprises and AmerisourceBergen. FF Enterprises can be contacted at (800) 843-7477, www.fluvaccine.net, or FAX (800) 418-4333. It is accepting orders for small quantities of 10-dose vials and continues to pre-book single-dose syringes. AmerisourceBergen has pre-filled syringes available through two of its subsidiaries. Hospitals, home infusion pharmacies and dialysis clinics can reach them through ASD Specialty Healthcare at (800) 746-6273. All others may call Besse Medical Supply at (877) 462-3773, or e-mail them at email@example.com
• Wyeth Vaccines has pre-booked all of it projected flu vaccine production, but continues to accept names on a waiting list. They may be contacted at (800) 358-7443.
Providers should not be intimidated by the prospect of being waitlisted. Last year, despite vaccine shortages, Henry Schein (Melville, NY) was able to fill orders by the first week of October for over 80 percent of customers who pre-booked with the company, according to Medical Group President Mike Racioppi in an earlier interview with Repertoire. And, this year’s outlook for flu vaccine availability is more positive.
The Advisory Committee on Immunization Practices (ACIP) voted in February 2002 on influenza vaccine recommendations for the 2002-03 season. The Committee will prioritize vaccination efforts in October and earlier to target individuals at high risk for flu complications, healthcare workers and children under nine years who are receiving the vaccine for the first time, since they require a booster dose one month following the initial dose, according to the CDC. Others, including household members of high-risk individuals, healthy people between 50 and 64 years, and others interested in receiving vaccine should begin vaccination in November.
The Committee also encourages that healthy children between six and 23 months receive the influenza vaccination, since they are at increased risk for influenza-related hospitalizations. The CDC expects the committee to make a full recommendation to this effect within one to three years.
This year, the committee encourages those who put off being vaccinated to receive it at a later date. Waiting until after November – even as late as January – is not too late, says the CDC. In recent years, the flu season hasn’t peaked until late December through early March. Since patients develop maximum antibody protection against influenza two weeks following vaccination, the months of December or January are not too late to receive it. Extending the window for vaccination should also ensure that lesser amounts of influenza vaccine go unused, as they have over the past two flu seasons.