Avian Flu: Why All the Squawk?

February 1, 2006
Linda S. Nield, MD

Deepak M. Kamat, MD, PhD

Physicians around the country are being bombarded with questions about avian flu. This brief review of the current status of the avian flu outbreak and its treatment and prevention provides the information you will need to answer the most pressing patient questions.

Physicians around the country are being bombarded with questions about avian flu. This brief review of the current status of the avian flu outbreak and its treatment and prevention provides the information you will need to answer the most pressing patient questions.

What is avian flu-and what's all the fuss?

Avian flu, or "bird flu," is a predominantly respiratory illness caused by influenza viruses normally found in birds. These viruses are genetically distinct from influenza viruses that infect humans. The avian influenza A viral strain of H5N1 is the focus of media attention for a number of reasons:

•H5N1-1 of 15 avian virus subtypes-mutates rapidly.

•It has the propensity to acquire genes from influenza viruses that affect other species.

•It can cause severe disease in humans.

•Infected birds can spread it through saliva and feces.

The first cases of known human infection occurred in 1997 in Hong Kong.1 Since then, more reports have surfaced. Between January 2004 and April 2005, avian flu killed more than 50 people in Vietnam, Cambodia, and Thailand.2

Wild, migratory birds are a natural reservoir for H5N1. Infection of domestic poultry in Southeast Asia, western China, Turkey (most recently), and possibly, Romania, has heightened the attention given to this infection. The avian H5N1 virus is spread easily from bird to bird; reports of the spread of this virus from birds to humans are increasing. Human-to-human spread-which is very rare-probably occurred in a cluster of cases in a family from Thailand.3 So far, however, human-to-human transmission has not been observed beyond a single person and therefore is not sustained. As the number of cases of human infection increases, however, the opportunities for the virus to evolve into a strain that is more easily transmissible from human to human will increase.

The influenza virus genome can change frequently; it has a high mutation rate and can segment into 8 separate RNA molecules.2 This segmentation allows genetic exchange (reassortment) in hosts who are coinfected with 2 different influenza viruses. Reassortment could result in a human-avian hybrid that has the ability to spread easily from person to person.

To date, there is no evidence that the 2004-2005 H5N1 isolates have acquired nonavian influenza genes by reassortment. However, the recent isolate circulating in Vietnam appears to be much more virulent than the 1997 isolate.4

Human influenza pandemics have occurred at irregular intervals (in 1918, 1957, and 1968), and it is unknown when the next one will occur. There is worry that the world is overdue for another influenza pandemic and that the potentially life-threatening avian flu virus, to which humans have no past immunity, may become more easily transmissible from person to person. This will be particularly true as the number of cases of bird-to-human transmission increases and another human influenza pandemic may be just around the corner.

Who gets the avian flu-and how do you get it?

At the time of this publication, no human cases of avian flu have occurred in the United States. However, persons of all ages can become infected. Age greater than 13 years may be a risk factor for more severe disease.1

Infected birds shed virus in saliva, nasal secretions, and feces. Exposure to these birds in an area with high infection rates is the greatest risk factor for contracting avian flu. Humans may become infected through contact with the diseased bird in a live market or during preparation for its consumption. Defeathering causes aerosolization of virus particles, which may land on exposed mucosal surfaces of the mouth, eyes, and nose and subsequently be inhaled into the lungs. Bridges and colleagues5 found that the butchering of infected birds is associated with the development of anti-H5 antibodies.

Although ingestion of contaminated poultry is an unlikely mode of transmission (it was not associated with infection in the earliest cases), fecal-oral spread by direct contact of a person's mucous membranes with the contaminated poultry is possible.6 Isolation of H5N1 from fecal specimens of a 4-year-old Vietnamese boy who presented with severe diarrhea and no respiratory symptoms was reported.6

As noted, human-to-human spread is rare but is more likely when one has been in close contact with the index case.3 Contaminated environmental surfaces may also pose a substantial risk.6

What is the clinical presentation of avian flu?

An "influenza-like" illness with fever, malaise, myalgias, and respiratory tract symptoms is the likely presentation. GI symptoms are not typical, but diarrhea as well as coma have occurred secondary to avian flu, as described in the 4-year-old Vietnamese boy.6

A progressive primary viral pneumonia may be accompanied by lymphopenia, elevated serum liver enzyme levels, and reactive hemophagocytosis. Children younger than 5 years may display milder symptoms, but infants in the first several months of life are at greater risk for complications when infected with human influenza viruses. Along with age greater than 13 years, factors associated with severe disease include a delay in hospitalization, lower respiratory tract involvement, low total peripheral white blood cell count, and lymphopenia.1

How is avian flu diagnosed?

The patient's history and clinical scenario should alert you to the possibility of avian flu. Testing for avian H5N1 should be considered on a case-by-case basis in consultation with state and local health departments, as advised by the CDC.7 The CDC recommends testing in persons who have all of the following:

•A documented fever (temperature higher than 38ºC [100.4ºF]).

•One or more of the following symptoms: cough, sore throat, shortness of breath.

•A history of contact with poultry or with persons who are known to have or suspected of having avian flu in an affected area within 10 days of symptom onset.

Viral culture, polymerase chain reaction, and antigen testing applied directly to specimens are possible methods of diagnosis. Laboratories must meet the specified safety requirements to process specimens suspected of harboring the H5N1 virus. A local infectious disease expert, the local health department, and the CDC can offer guidance about proper diagnostic testing.

How is avian flu treated?

Supportive measures-oxygen, adequate hydration, and close monitoring-are the mainstay of treatment for patients with all types of flu. Neuraminidase inhibitors (oseltamivir and zanamivir) are effective antiviral drugs against human influenza viruses. All the recent isolates of avian H5N1 from humans have been sensitive to the neuraminidase inhibitors but have been resistant to amantadine and rimantadine.2 Because of the risk of Reye syndrome, aspirin should not be given to a child in whom any type of influenza is suspected.

Most important, how is it prevented?

As always, good hand washing and avoidance of close contact with sick persons is important in controlling the spread of infection. Educating children and parents about respiratory hygiene and cough etiquette is crucial in helping prevent the spread of infection. During periods of increased respiratory infections in the community, patients who are coughing should be provided with masks.

At this time, there are no recommendations to avoid eating poultry. However, poultry throughout the world are under close surveillance.

When a patient is admitted because H5N1 infection is suspected or has been diagnosed, he or she should be hospitalized in a negative-air-pressure room. In addition to standard hand hygiene, health care workers should wear gloves and a gown during all patient contact. Eye protection and a fit-tested respirator are recommended for those who come within 3 feet of the patient.

The standard flu vaccine is recommended for all eligible persons to control the spread of human influenza.8 This is especially true for those who have come in contact with patients in whom avian flu is confirmed or suspected.

In May 2004, the National Institute of Allergy and Infectious Diseases announced contracts for the development of a vaccine against avian H5N1. Trials are currently under way: reports in August 2005 indicated that a vaccine had been shown to produce a robust immune response.9

We encourage readers to keep abreast of this situation. The CDC, the NIH, and the World Health Organization offer up-to-date information about the vaccine and about the status of avian and human influenza outbreaks.2




Yuen KY, Chan PK, Peiris M, et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus.




The World Health Organization Global Influenza Program Surveillance Network. Evolution of H5N1 avian influenza viruses in Asia.

Emerg Infect Dis

[serial online]. Available at: www.cdc.gov/ncidod/EID/ vol11no10/05-0644.htm. Accessed October 18, 2005.


Ungchusak K, Auewarakul P, Dowell SF, et al. Probable person-to-person transmission of avian influenza A (H5N1).

N Engl J Med.



Li KS, Guan Y, Wang J, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia.




Bridges CB, Lim W, Hu-Primmer J, et al. Risk of influenza A (H5N1) infection among poultry workers, Hong Kong, 1997-1998.

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Ahmad K. Vietnamese cases suggest avian flu has been underestimated.

Lancet Infect Dis.



Centers for Disease Control and Prevention. Update on Avian Influenza A (H5N1). February 4, 2005. Available at: http://www.cdc.gov/flu/avian/ professional/han020405.htm. Accessed October 18, 2005.


Nield LS, Kamat D. "Flu" season: are you ready?

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