Influenza

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Influenza

Introduction

Disease History, Characteristics, and Transmission

Treatment and Prevention

Scope and Distribution

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

Influenza is a viral disease that has plagued humans since the time of learning to walk upright. The medical writings of antiquity contain evidence that implicates influenza in causing epidemics of death and disease. A form of the influenza virus exists in nearly all animals, including domesticated birds and pigs, and these animal viruses bear a close genetic relationship to human influenza viruses.

A typical attack of influenza starts with high fever, chills, muscle aches, a dry cough, and feeling distinctly ill. Soon a sore throat with nasal congestion and a runny nose develops. The cough worsens and misery results. In healthy adults and children, a case of influenza lasts about a week and recovery is complete. Many think the illness is nothing more than a particularly severe “cold.” However, influenza can be unpredictable, and can kill healthy adults and children.

Disease History, Characteristics, and Transmission

Most often, influenza primarily attacks the nose, throat, and lungs, but any part of the body can be infected. Sometimes influenza will cause abdominal pain, nausea, and diarrhea. Rarely, the muscles will be infected and can be severely damaged. Infants may develop a severe form of viral pneumonia with the heart and lungs struggling to sustain life. Influenza can infect the brain as well, resulting in seizures and coma. Influenza is predictably unpredictable in how severe the disease may be in any one person.

Other diseases can take advantage of the weakened state of the body after a case of influenza and cause a secondary infection. Bacteria such as group A streptococcus, Staph aureus, and strep pneumonia are particularly efficient at causing a lethal pneumonia after influenza damages the lungs. About 10% of children will develop a secondary infection while recovering from influenza, and ear infections frequently afflict infants and young children just as they are trying to recover from influenza. The secondary infections often cause another visit to the doctor when parents discover their child, who seemed to be recovering, is ill again.

Influenza is highly contagious and primarily spreads person to person in virus-laden droplets produced by sneezing or coughing. Alternatively, the droplets land on a surface and contaminate the hands that, if not washed, carry the virus to the mouth or nose. Schoolaged children are the main culprits in spreading influenza. Usually 10–40% of school-aged children will get influenza in any one season. They swap virus at school and bring it home to infect family members. Children are contagious before they even appear or feel ill, and the virus is present in nasal mucous and cough droplets for over a week after apparent recovery from influenza.

The microbiology of the influenza virus is quite complex. Influenza viruses consist of three different major types known as A, B, and C. Of the three types, only A and B cause significant disease in humans. Both A and B types cause the seasonal epidemics around the world, but at any one time there may be hundreds of different variations of each type circulating the globe. This multitude of subtly different varieties presents a challenge to the human immune system.

Both influenza A and B virus change their structure often enough such that the immune system can never develop long-lasting immunity. Influenza B virus changes much more slowly than influenza A and usually causes milder illness compared to influenza A. However, influenza B can cause severe disease in the elderly, those with impaired immunity, or those with chronic lung or heart disease.

Influenza A generally causes more severe disease and is the most unpredictable. The yearly season epidemics of the “flu” are primarily the result of influenza A. The virus has two specific proteins on its surface, which are important for infecting humans. These proteins, known as antigens, bear the names hemagglutinin (HA) and neuraminidase (NA). The HA and NA proteins vary in their chemical structure from year to year. This process, termed antigenic drift, results in virus particle proteins with subtle variations in structure. Fifteen different HA subtypes are known to exist while there are nine NA subtypes. These slightly different proteins get different number designations, and the various influenza strains are named by the specific HA and NA proteins on the virus. The H3N1 virus contains HA protein 3 and NA protein 1.

Influenza A employs an additional means of evading the immune system. When two different viral strains infect someone at the same time, the two viral variants will swap component genes and create yet another slightly different form of influenza. The new virus will contain some proteins of one variety of influenza A and some proteins of the other variety. This sloppy way of making new virus particles extends to swapping genetic material with animal or bird influenza viruses. This process, termed antigenic shift, will sometimes create an influenza virus for which humans have no immunity at all. A novel virus produced this way has the potential to spread worldwide, resulting in a pandemic.

Three influenza pandemics have occurred in the twentieth century. The influenza pandemic in 1918 killed at least twenty million people, and some experts think there were fifty million deaths within a period of 24 weeks. Nearly as many United States soldiers died of influenza in 1918 as died in battle in all of World War I. In the United States, the 1957 pandemic resulted in 70,000 deaths while in 1968 about 30,000 died. During influenza pandemics, a larger proportion of healthy adults die than during the yearly “flu season” outbreaks.

WORDS TO KNOW

ANTIGEN: Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of anti-bodies (each with a unique genetic sequence).

ANTIGENIC SHIFT: Antigenic shift describes an abrupt and major genetic change (e.g. in genes coding for surface proteins of a virus).

DROPLET TRANSMISSION: Droplet transmission is the spread of microorganisms from one space to another (including from person to person) via droplets that are larger than 5 microns in diameter. Droplets are typically expelled into the air by coughing and sneezing.

PANDEMIC: Pandemic, which means all the people, describes an epidemic that occurs in more than one country or population simultaneously.

STRAIN: A subclass or a specific genetic variation of an organism.

Treatment and Prevention

Medicine has developed weapons with which to combat influenza, specifically the adamantanes and the neuraminidase inhibitor drugs. The adamantanes treat only influenza A while the neuraminidase inhibitors will treat both influenza A and B. Both of these classes of medicines interfere with the ability of the influenza virus to make more virus particles. They either stop production of the viral genetic material or prevent the viral particles from escaping from infected cells to infect other cells. In order to help relieve symptoms or shorten the course of influenza, one must take these drugs early in the course of influenza. Once the illness is established and new influenza virus particles have replicated, the medications are largely ineffective. Many of the symptoms of influenza are due to the damage the virus does to the body during the making of new virus particles so stopping the virus early provides the greatest relief in symptoms.

Until effective medications became available to treat influenza, determining who has influenza rather than one of a similar multitude of viral respiratory illnesses was of little use. Treatment involved decreasing the fever, resting, and drinking plenty of fluids. This treatment is appropriate for most viral illnesses, but now with medications available, there is a difference whether the illness is a “cold” or the “flu” and testing for influenza is often done.

Several rapid tests are available to detect the influenza virus. These tests, often run in a doctor's office, use a sample of mucus taken from the nose or from the back of the throat. The tests are rapid usually taking only five minutes and will detect influenza virus accurately about 75-85% of the time if properly done.

Contrary to popular belief, antibiotics are not effective treatment for influenza. Antibiotics are useful in the treatment of bacterial infections and have no benefit during viral illnesses. Antibiotics may be helpful if secondary bacterial infections develop during the course of influenza.

Drugs provide a treatment option unavailable in past decades, but they do not provide the best option for control of influenza. Many will not realize their illness is influenza until it is too late for medications to be effective. Additionally they have usually already spread influenza to family members and co-workers.

Influenza vaccination provides the most effective treatment by preventing the disease, but the influenza virus poses a challenge for vaccine development. Since the virus changess lightly year to year and changes dramatically at unpredictable intervals, vaccines also need altering from year to year. Each year, public health officials make an educated guess as to what will be the prevalent strains circulating in the next season, and vaccine preparation commences targeting those strains.

Influenza vaccines provide excellent protection when administered at least two weeks before exposure to the influenza virus, and vaccination is needed each year. The vaccine itself does not cause influenza, but depending on the exact form of vaccine administered, side effects may include soreness at the injection site, muscle aches, runny nose, or sore throat. Young children often need two doses of vaccine for full protection. In the United States, the current vaccine recommendations include everyone older than 65 years, those between six months and five years, and everyone with chronic health problems involving the lungs or heart.

Scope and Distribution

Every year about 35,000 deaths occur in the United States due to influenza. Most of these deaths are those older than 65 years, but more children die of influenza or its complications each year than all the deaths due to whooping cough and measles combined. The World Health Organization credits influenza with causing between 250,000 and 500,000 deaths yearly throughout the world. For example, in 2002, an influenza outbreak started in Madagascar. Over a period of three months, 27,000 people developed influenza, and despite rapid medical intervention, 800 deaths occurred.

Impacts and Issues

Unless a family member or close friend dies of influenza, many people do not really give much thought to the impact influenza has on their health and pocketbook. Influenza ranks far behind heart disease and cancer as a worldwide cause of death, yet its economic impact is considerable. Public health experts have estimated a cost of $60-$4,000 for every case of influenza in a healthy adult in the United States. These costs include direct medical expenses, lost wages, and lost productivity at work. For parents, the cost often includes lost work while caring for the sick child, and afterwards, lost work from the case of influenza caught from the child.

A pandemic raises great concern for public health officials worldwide. Influenza pandemics occur several times a century but are unpredictable as to the exact timing. Each of the past three influenza pandemics (in 1918, 1957, and 1968) resulted from human influenza virus sharing genetic material with a bird influenza virus. Human immune systems had never encountered the new virus, and everyone was susceptible to the new form of influenza. As a result, the new virus swept through countries throughout the globe.

The pandemic of 1918 deserves further explanation as medical history warns that a similar event at some point in the future is highly likely. In the 1918 pandemic, about one third of the world's population suffered a severe case of influenza, and nearly 3% of those infected with the virus died. An unusually high percentage of the young and healthy died during this pandemic. All current strains of influenza A virus are descended from the 1918 virus, but the current strains have weakened considerably. Now less than 0.1% of people die when infected by today's forms of influenza.

Given that the medical system has advanced since 1918, what would be the impact of a new, more lethal influenza virus today? The answer is that the impact could be devastating. Public health experts predict an estimated 90,000–200,000 deaths, over 700,000 hospital admissions, and about forty million visits to doctors in the United States alone. The estimated economic impact exceeds $160 billion, not including the disruptions due to illness in the police, transportation workers, and the health workers themselves.

Over the past several years, a particularly vicious strain (type) of avian (bird) flu, known as H5N1 influenza, has caused many cases of disease and death in humans. Presently, transmission of this virus from human to human does not readily occur. Close contact with infected birds is required to catch this form of influenza. If this bird virus ever acquires the ability to infect humans from one person to another, a new pandemic could occur. The Center for Disease Control and the World Health organization recognize this possibility, and planning for the potential pandemic continues.

Primary Source Connection

Scientists at the Centers for Disease Control and Prevention play a key role in accessing influenza viruses and formulating vaccines for them. In order to prepare for a future pandemic influenza, CDC scientists studied the characteristics of the 1918 pandemic flu virus. The CDC press release below, released in February 2007, relates that by manipulating the 1918 virus, CDC scientists have found a way to render it less capable of spreading among animals that were in close contact with each other. This type of research could prove beneficial in reducing the ability of future influenza viruses to spread rapidly across heavily populated regions and cause a pandemic.

Small Changes in 1918 Pandemic Virus Knocks Out Transmission: Research Provides Clues for Assessing Pandemic Potential of New Influenza Viruses

Press Release

Embargoed Until 2 p.m. EST: February 1, 2007

Contact:

CDC Media Relations

(404) 639-3286

Experts at the Centers for Disease Control and Prevention have shown that a molecular change in the 1918 pandemic influenza virus stops its transmission in ferrets that were in close proximity, shedding light on the properties that allowed the 1918 pandemic virus to spread so quickly and potentially providing important clues that could help scientists assess emerging influenza viruses, such as H5N1.

The study, which is published in the Feb. 5 issue of Science, showed that a modest change of two amino acids in the main protein found on the surface of the 1918 virus did not change the virus's ability to cause disease, but stopped respiratory droplet transmission of the virus between ferrets placed in close proximity. The experiments were conducted with ferrets because their reaction to influenza viruses closely mimics how the disease affects humans.

“With this vital research, we are learning more about what may have contributed to the spread and deadliness of the 1918 pandemic,” said CDC Director Dr. Julie Gerberding. “By better understanding how this virus spreads, we can be better positioned to slow down or stop the spread of the pandemic virus and hence be better prepared for the next pandemic.”

To spread and cause illness, the influenza virus must first bind to host cells found in humans and animals. The Science study suggests that the hemagglutinin (HA), a type of protein found on the surface of influenza viruses, plays an important role in the 1918 virus's ability to transmit from one host to another efficiently. This research suggests that, for an influenza virus to spread efficiently, the virus's HA must prefer attaching to cells that are found predominately in the human upper airway instead of cells found predominately in the gastrointestinal tracts of birds. Other changes may be necessary as well. Current H5N1 viruses prefer attaching to avian cells, suggesting the virus would need to make genetic changes before it could pass easily between humans.

“Work on the 1918 virus is providing clues that are helping us evaluate other influenza viruses with pandemic potential, such as H5N1, that may emerge,” said Dr. Terrence Tumpey, lead author of the paper and a CDC senior microbiologist. “Though we still don't know what changes might be necessary for H5N1 to transmit easily among people, it's likely that changes in more than one virus protein would be required for the H5N1 virus to be transmitted among humans.”

Influenza pandemics occur when a new strain emerges to which people have little or no immunity. Most experts argue another pandemic will occur, but it is impossible to predict which strain will emerge as the next pandemic strain, when it will occur or how severe it will be.

The 1918 pandemic caused an estimated 675,000 deaths in the United States and up to 50 million worldwide, in the worst pandemic of the past century.

The research was done in collaboration with Mount Sinai School of Medicine and the Southeast Poultry Research Laboratory. All laboratory work with 1918 virus was conducted at CDC in a high containment Biosafety Level 3 laboratory with enhancements, using stringent biosecurity precautions to protect both laboratory workers and the public from exposure to the virus. Currently available antiviral drugs have been shown to be effective against the 1918 influenza virus and similar viruses.

Centers for Disease Control and Prevention (CDC)

CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC). “SMALL CHANGES IN 1918 PANDEMIC VIRUS KNOCKS OUT TRANSMISSION.” PRESS RELEASE. FEBRUARY 1, 2007. <HTTP://WWW.CDC.GOV/OD/OC/MEDIA/PRESSREL/2007/R070201.HTM> (ACCESSED JUNE 4, 2007).