Human influenza overview

# Overview
Influenza, commonly known as flu, is an infectious disease of birds and mammals caused by  RNA viruses of the biological family Orthomyxoviridae (the influenza viruses). In humans, common symptoms of influenza infection are fever, sore throat, muscle pains, severe headache, coughing, weakness and general discomfort. In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children and the elderly. Sometimes confused with the common cold, influenza is a much more severe disease and is caused by a different type of virus. Although nausea and vomiting can be produced, especially in children, these symptoms are more characteristic of the unrelated gastroenteritis.

# Historical Perspective
Influenza-like symptoms have been reported for many thousandth of years, but the first pandemic outbreak was in Asia, Europe and Africa in 1580.  Since then, several outbreaks have been reported, including the Spanish flu pandemic in 1918, the Asian flu pandemic in 1957, and the Hong Kong flu pandemic in 1968.   The first vaccine against influenza was developed in 1940s to prevent the US military to develop the disease in World War II.

# Classification
Influenza virus can be classified into 3 main types: A, B and C.  Based on the surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), influenza type A is subclassified into several subtypes and can infect many species, including humans.  Type B can only infect humans and type C is not that common and causes mild illness.

# Pathophysiology
Influenza virus is under constant evolutionary change.  These genetic changes may be small and continuous or large and abrupt.  Small genetic changes happen continuously in Type A and Type B influenza as the virus makes copies of itself.  This process is called antigenic drift.  Drifting happens frequently enough to make new strains of virus unrecognizable to the human immune system.  Type A influenza also undergoes infrequent and sudden changes known as antigenic shift.  Antigenic shift occurs when two different flu strains infect the same cell and combine portions of their genetic material.  The novel assortment of HA and/or NA proteins in a shifted virus may create a new influenza A subtype.    Influenza viruses spread mainly through tiny droplets expelled when people with the disease cough, sneeze, or talk. These droplets can land in the mouths or noses of people who are nearby or be inhaled into the lungs.

# Causes
Influenza infection is caused by the influenza virus that belong to the family Orthomyxoviridae.  Three types of influenza virus  have been reported to cause clinical illness in humans: types A, B, and C.  Influenza virus can be found in humans, as well as in poultry, pigs, and bats.

# Differentiating Influenza from other Diseases
Influenza should be differentiated from other conditions that cause fever, cough, myalgias, headache and fatigue, such as RSV infection, dengue fever, parainfluenza virus infection, ebola infection adenovirus infection, rhinovirus infection, and legionella infection.

# Epidemiology and Demographics
The CDC estimates that 5 to 20 percent of Americans are affected by the flu during each flu season, which typically lasts from October to March. Children are 2 to 3 times more likely than adults to get sick with the flu, and children frequently spread the virus to others.  For elderly people, newborn babies, pregnant women, and people with certain chronic illnesses, the flu and its complications can be life-threatening.  Although most people recover from the illness, between 3,000 and 49,000 US citizens die from the flu and its complications every year.

# Risk Factors
Risk factors for influenza are for those patients that are exposed to the disease, such as healthcare workers, residents of nursing homes or children. However, there are certain groups that are at risk for severe disease and complications, such as children younger than 2 years old, adults aged 65 or older, pregnant women, patients with comorbidities, asthmatic patients, and patients with a weakened immune system.

# Natural History, Complications and Prognosis
Influenza is a viral respiratory infection spread from person to person chiefly through droplet transmission. The incubation period period is 1 to 4 days. The uncomplicated influenza can present with constitutional symptoms and can resolve in 3-7 days; while others can develop into pneumonia, ear infection, encephalitis and sepsis.

# Diagnosis

## History and Symptoms
Influenza illness can include several non-specific symptoms, such as fever, muscle aches, headache, lack of energy, dry cough, sore throat, and runny nose. The fever and body aches can last 3-5 days and the cough and lack of energy may last for 2 or more weeks. The symptoms of the flu are more severe than their common-cold equivalents.

## Physical Examination
During the physical examination in a patient with influenza, findings can include fever, tachycardia, tachypnea, sore throat, and fatigue.   Complications can worsen the patient's condition and findings in the lung examination may include dry cough, rales and focal wheezing.

## Laboratory Findings
Diagnostic tests available for influenza include viral culture, serology, rapid antigen testing, polymerase chain reaction (PCR), immunofluorescence assays, and rapid molecular assays. Sensitivity and specificity of any test for influenza might vary by the laboratory that performs the test, the type of test used, and the type of specimen tested.  Among respiratory specimens for viral isolation or rapid detection, nasopharyngeal specimens are typically more effective than throat swab specimens.  As with any diagnostic test, results should be evaluated in the context of other clinical and epidemiologic information available to health-care providers.

## Chest X Ray
Chest X-ray is not routinely done in patients with influenza.  A chest X-ray is useful to assess complications of influenza infection, such as a superimposed bacterial pneumonia.

## Other Diagnostic Studies
Other diagnostic test for influenza include molecular assays, such as RT-PCR. New technologies being pursued include those that examine influenza viruses at the molecular level.  By examining the genetic makeup of influenza viruses, such tests could identify both the virus type and subtype simultaneously.

# Treatment

## Medical Therapy
Antiviral drugs can diminish symptoms and shorten the time of the disease by 1 or 2 days.  They also can prevent serious flu complications, such as pneumonia.  For people with a high risk medical condition, treatment with an antiviral drug can mean the difference between having milder illness instead of very serious illness that could result in a hospital stay.  The two main antivirals used in the treatment and prevention of influenza are oseltamivir and zanamivir.   Symptomatic therapy is also important to overcome the symptoms of influenza, this include analgesics, antihistamines, decongestants and cough suppressants.

## Primary Prevention
Vaccination and chemoprophylaxis are the two most important methods for preventing influenza among patients.  Routine annual influenza vaccination is recommended for all persons aged 6 months who do not have contraindications.  Annual influenza vaccination is the best way to prevent influenza because vaccination can be given well before influenza virus exposures occur, and can provide safe and effective immunity throughout the influenza season.  Chemoprophylaxis is not recommended in all patients and should only be administered for certain populations who are at risk of complications.

## Cost-Effectiveness of Therapy
Influenza produces direct costs due to lost productivity and associated medical treatment, as well as indirect costs of preventative measures. In the United States, influenza is responsible for a total cost of over $10 billion per year, while it has been estimated that a future pandemic could cause hundreds of billions of dollars in direct and indirect costs. However, the economic impact of past pandemics have not been intensively studied, and some authors have suggested that the Spanish influenza actually had a positive long-term effect on per-capita income growth, despite a large reduction in the working population and severe short-term depressive effects. Other studies have attempted to predict the costs of a pandemic as serious as the 1918 Spanish flu on the U.S. economy, where 30% of all workers became ill, and 2.5% were killed. A 30% sickness rate and a three-week length of illness would decrease gross domestic product by 5%. Additional costs would come from medical treatment of 18 million to 45 million people, and total economic costs would be approximately $700 billion.

## Future or Investigational Therapies
Other antiviral drugs are being developed to treat influenza infection, such as peramivir.  Vaccines are manufactured every year according to the subtype of influenza virus that causes the outbreak in that specific year.