H5N1 bird flu

Introduction
Background

Influenza virus infection, one of the most common infectious diseases, is a highly contagious airborne disease that causes an acute febrile illness and results in variable degrees of systemic symptoms, ranging from mild fatigue to respiratory failure and death. These symptoms contribute to significant loss of workdays, human suffering, mortality, and significant morbidity. The 1918-1919 H1N1 type influenza pandemic killed an estimated 20-50 million persons, with 549,000 deaths in the United States alone.

Accurately diagnosing influenza A or B infection based solely on clinical criteria is difficult because of the overlapping symptoms caused by the various viruses associated with upper respiratory tract infection (URTI). In addition, several serious viruses, including adenoviruses, enteroviruses, and paramyxoviruses, may initially cause influenzalike symptoms. The early presentation of mild or moderate cases of flavivirus infections (eg, dengue) may initially mimic influenza. For example, some cases of West Nile fever acquired in New York in 1999 were clinically misdiagnosed as influenza.

Patients with influenza frequently present with various symptoms shared by many other viral infections. In the northern and southern hemispheres, these symptoms are more common in the winter months. As a result, during the winter, clinics and emergency department waiting rooms fill with patients who have influenza or other URTIs.

For supplementary information, see Medscape’s Influenza Resource Center.


Pathophysiology

Influenza results from infection with 1 of 3 basic types of influenza virus—A, B, or C—which are classified within the family Orthomyxoviridae. These single-stranded RNA viruses are structurally and biologically similar but vary antigenically.

The RNA core consists of 8 gene segments surrounded by a coat of 10 (influenza A) or 11 (influenza B) proteins. Immunologically, the most significant surface proteins include hemagglutinin and neuraminidase. The viruses are typed based on these proteins. For example, influenza A subtype H3N2 expresses hemagglutinin 3 and neuraminidase 2.

The most common prevailing influenza A subtypes that infect humans are H1N1 and H3N2. Each year, the trivalent vaccine used worldwide contains A strains from H1N1 and H3N2, along with an influenza B strain.

Influenza virus infection occurs after transfer of respiratory secretions from an infected individual to a person who is immunologically susceptible. If not neutralized by secretory antibodies, the virus invades airway and respiratory tract cells. Once within host cells, cellular dysfunction and degeneration occur, along with viral replication and release of viral progeny. Systemic symptoms result from inflammatory mediators, similar to other viruses. The incubation period of influenza ranges from 18-72 hours.

Influenza A is generally more pathogenic than influenza B. Influenza A is a zoonotic infection, and more than 100 types of influenza A infect most species of birds, pigs, horses, dogs and seals. Indeed, the 1918 pandemic that resulted in millions of human deaths worldwide is believed to have originated from a virulent strain of H1N1 from pigs or birds. Recently, scientists obtained and sequenced the 1918 H1N1 strain from a frozen corpse found in Alaska. The virus was reconstructed at the Centers for Disease Control and Prevention (CDC) laboratory in Atlanta and was found to be highly lethal when tested in mice; the virus was also found to be lethal to chicken embryos. This unique N1 neuraminidase is being studied in order to provide better insight into the N1 found in H5N1, the type responsible for avian influenza (also known as bird flu).

H5N1 bird flu
In 1997, an avian subtype of influenza A, H5N1, was first described in Hong Kong. Infection was confirmed in only 18 individuals, but 6 died. Since then, sporadic cases of H5N1 infection have continued to be described in southern China. In January 2004, an epidemic occurred among domesticated birds in Southeast Asia, initially in Vietnam. In nearly all cases of H5N1 bird flu in humans, the virus is transmitted from birds. As of fall 2008, more than 390 human cases had been documented and more than 246 persons had died following H5N1 outbreaks among poultry and resulting bird-to-human transmission. Most human deaths due to bird flu have occurred in Indonesia. Sporadic outbreaks among humans have continued elsewhere, including China, Egypt, Thailand, and Cambodia.

Experts are concerned that a slight mutation could convert H5N1 to a strain that would be easily transferred from human to human. Such a strain has the potential to spread rapidly and precipitate a catastrophic worldwide pandemic. Because of this concern, efforts to develop an effective vaccine are currently underway. In addition, studies to expand the number of drugs that are effective against influenza are underway. Ribavirin has shown activity in animal models.

Other types of avian influenza
In March 1999, infection with another avian influenza subtype, H9N2, was described in 2 young children. Despite concern, no additional cases of H9N2 infection were reported. As with the H5N1 influenza, experts are concerned that a virulent strain of H9N2 influenza may mutate to allow human-to-human infection and that such a strain may possess the triad of infectivity, lethality, and transmissibility.

H1N1 swine flu
On April 26, 2009, the US Department of Health and Human Services issued a nationwide public health emergency regarding swine influenza A (H1N1) virus infections in humans.1 Over the past several weeks, an outbreak of a new strain of influenza virus, which contains a combination of swine, avian, and human influenza virus genes, has been reported in Mexico (approximately 1600 cases) and in the United States (40 cases, according to the CDC as of the time of this writing on April 27, 2009). In Mexico, 103 deaths are suspected to have been caused by the recent swine influenza outbreak. The infection has been confirmed in patients in California (7), Kansas (2), New York City (28), Ohio (1), and Texas (2). No deaths attributable to the swine influenza virus have been confirmed in the United States.2 Internationally, confirmed cases have also been reported in Canada, New Zealand, Spain, and the United Kingdom (Scotland), with suspected cases in Brazil, Israel, and France.3

Upon suspicion of swine flu, clinicians should obtain a respiratory swab for swine influenza testing and place it in a refrigerator (not a freezer). Once collected, the clinician should contact the state or local health department to facilitate transport and timely diagnosis at a state public health laboratory.4

The new virus is resistant to the antiviral agents amantadine and rimantadine but sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza). Initiation of antiviral agents within 48 hours of symptom onset is imperative to provide treatment efficacy against influenza virus. The usual vaccine for influenza administered at the beginning of the flu season is not effective for this viral strain.

Initial symptoms of swine influenza include high fever, myalgias, rhinorrhea, and sore throat. Nausea, diarrhea, and vomiting have also been reported. Infection control precautions (ie, handwashing, covering mouth with tissue when sneezing or coughing) are encouraged. If suspected swine flu occurs, isolation is recommended for infected individuals and household contacts. For more information, see updated information from the US Centers for Disease Control and Prevention.

Viral shedding

Viral shedding occurs at the onset of symptoms or just before the onset of illness (0-24 h). Shedding continues for 5-10 days. Young children may shed virus longer, placing others at risk for contracting infection with the virus.


Frequency

United States

Influenza epidemics typically occur in winter months and vary in severity and attack rates depending on the virus subtype involved. Millions of people may develop infection during a given year. The pandemics of 1918-1919 and 1957, which resulted in higher infection rates and profound morbidity and mortality rates, demonstrate the impact of the disease.

In the United States, significant influenza activity occurred during the winter of 1999-2000 and 2003-2004. Influenza A/Fujian/411/2002 (H3N2) was the major strain involved in 2003-2004. During the 2000-2003 and 2004-2005 seasons, influenza activity was relatively low in the United States. However, the activity increased during the 2007-2008 season to the highest levels in years.

International
In tropical areas, influenza occurs throughout the year.

Mortality/Morbidity

The CDC estimates that influenza is responsible for an average of more than 20,000 deaths annually.

Sex
Women in the third trimester of pregnancy are at higher risk for complications of influenza A and B.

Age
•Elderly people are at higher risk for complications of influenza A and B.
•For more information on pediatric influenza, see the Influenza article in eMedicine’s Pediatrics: General Medicine volume.
Clinical
HistoryThe presentation of influenza virus infection varies; however, it usually includes many of the symptoms described below. Patients with influenza who have pre-existing immunity or who have received vaccine may have milder symptoms.



•Abrupt onset of illness is common. Many patients with influenza are able to report the time when the illness began.
•Fever may vary widely among patients, with some having low fevers (in the 100°F range) and others developing fevers as high as 104°F. Some patients report feeling feverish and a feeling of chilliness.
•Sore throat may be severe and may last 3-5 days. The sore throat may be a significant reason why patients seek medical attention.
•Myalgias are common and range from mild to severe.
•Frontal/retro-orbital headache is common and is usually severe. Ocular symptoms develop in some patients with influenza and include photophobia, burning sensations, and/or pain upon motion.
•Some patients with influenza develop rhinitis of varying severity but is generally not the chief symptom.
•Weakness and severe fatigue may prevent patients from performing their normal activities or work. In some cases, patients with influenza may find activity difficult and may require bedrest.
•Cough and other respiratory symptoms may be initially minimal but frequently progress as the infection evolves. Patients may report nonproductive cough, cough-related pleuritic chest pain, and dyspnea. In children, diarrhea may be a feature.
•Acute encephalopathy has recently been associated with influenza A virus. In a case series of 21 patients, Steininger et al described clinical, CSF, MRI, and EEG findings.5 Clinical features included altered mental status, coma, seizures, and ataxia. Of those who underwent further testing, most had abnormal CSF, MRI, and EEG findings.

Physical
The general appearance varies among patients who present with influenza. Some patients may appear acutely ill, with some weakness and respiratory findings, while others may appear only mildly ill. Upon examination, patients may have some or all of the following findings:



•Fever may range from 100-104°F. The fever in elderly patients is not generally as severe as that in young adults.
•Tachycardia most likely results from hypoxia, fever, or both.
•Pharyngitis may be present. Even in patients who report a severely sore throat, findings vary from minimal infection to more severe inflammation.
•Eyes may be red and watery.
•Nasal discharge is absent in most patients.
•Skin may be warm-to-hot, as reflected by the temperature status. Patients who have been febrile with poor fluid intake may show signs of mild volume depletion with dry skin.
•Pulmonary findings during the physical examination may include dry cough with clear lungs or rhonchi.