Influenza
A digitally colorized, negative-stained transmission electron micrograph depicting several influenza A virus particles.
Credit: F. A. Murphy/CDC
Influenza
The “flu” has become a popular catchall term to describe anything from a bad cold to stomach distress. But real flu, influenza, is the defined illness that many public health officials dread most. Between 1976 and 2006, annual estimates of deaths from flu-related complications in the United States ranged from 3,000 to 49,000, and more than 200,000 people are hospitalized each year.
The hardy influenza virus can survive on environmental surfaces, such as doorknobs and countertops, for 2 to 8 hours—one of the reasons that hand washing and surface hygiene is an important part of most flu control strategies.
Of even greater concern is a flu pandemic—a worldwide epidemic of a new strain of influenza virus from which the human population has no immunity. Depending on its severity, an influenza pandemic could result in 200,000 to 2 million deaths in the United States alone. In 2009, the World Health Organization (WHO) declared the H1N1 “swine flu” a pandemic; deaths were estimated between 151,700 and 575,400 worldwide. Unlike typical seasonal influenza epidemics, however, where the majority of deaths occur in people age 65 and older, 80 percent of the deaths during the 2009 H1N1 epidemic occurred in people younger than 65, including pregnant women, highlighting a different type of impact many were not expecting.
How the Flu Spreads
Influenza viruses mainly spread when droplets from the cough or sneeze of an infected person are propelled through the air and land on the mouth or nose of someone nearby. Flu viruses may also spread when a person touches respiratory droplets on another person or on an object and then touches his or her own mouth or nose. The hardy influenza virus can survive on environmental surfaces such as doorknobs and countertops for 2 to 8 hours—one of the reasons why hand washing and surface hygiene is an important part of most flu control strategies.
Once the flu virus makes contact with mucous membranes in the eyes and nose, it heads to the cells along the upper and lower respiratory tract where it swiftly multiplies. Scientists believe flu symptoms arise because growth of the virus damages the cells into which it has inserted itself and because the immune system, in trying to limit the damage, responds in ways that cause familiar discomfort: It sends out white blood cells that release chemicals called cytokines, causing muscle and joint pain, and it produces a fever, which is one of the body’s ways of mobilizing its defenses against invaders.
Seasonal Versus Pandemic Flu
The success of the influenza virus lies in its ability to alter itself. The virus uses RNA rather than DNA as its genetic material. RNA viruses make frequent mistakes while copying themselves. Their high mutation rate means that RNA viruses evolve far more rapidly than DNA viruses, because every successive generation contains new variants from the previous one, and some of these will be better adapted to new conditions. The flu virus’s surface proteins—hemagglutinin (H) and neuraminidase (N)—are also changeable. These proteins have a role in making it possible for a virus to invade and hijack cells. Hemagglutinin permits virus particles to gain access to the cell’s interior and neuraminidase helps newly produced copies of the virus break free of the cell in quest of other cells to invade.
The extent and severity of a pandemic depend on the specific characteristics of the virus. While rare, pandemics sweep the world like wildfire.
There are three types of influenza viruses: A, B, and C. Only influenza type A viruses are further classified by subtype on the basis of the H and N surface proteins. Influenza type A subtypes and type B viruses are further classified by strains. Among influenza type A viruses, there are 18 known subtypes of hemagglutinin and 9 of neuraminidase. Many different combinations of these H and N proteins are possible, each representing a different subtype.
According to the Centers for Disease Control and Prevention (CDC), the subtypes of influenza circulating among people worldwide in 2016 include A H1N1, A H3N2, and B strains. Influenza type C infections cause mild respiratory illnesses but usually do not cause epidemics. In a given flu season, usually only one subtype predominates. Epidemics break out every year because of slight genetic mutations in a virus subtype’s surface proteins that result in a new strain of the virus—a process known as antigenic drift. New combination vaccines are formulated annually to protect against the three circulating strains of seasonal flu that experts predict will cause the most illness in the coming season. It is very difficult to make accurate predictions in time for vaccines to be manufactured on a worldwide scale, so mismatches may occur. This took place during the 2014–2015 flu season, resulting in a lower rate of efficacy for the vaccine than is typically seen.
Sometimes the virus’s surface proteins undergo a radical change—a process known as antigenic shift—resulting in an altogether new influenza subtype against which most humans have no immunity. The result can be a pandemic. The extent and severity of a pandemic depend on the specific characteristics of the virus. While rare, pandemics sweep the world like wildfire. In addition to the recent H1N1 pandemic, three major pandemics broke out in the 20th century: an H1N1 in 1918 (the misnamed “Spanish” flu), an H2N2 in 1957 (the “Asian” flu), and an H3N2 in 1968 (the “Hong Kong” flu). Of these pandemics, the 1918–1919 virus was the most severe, killing 50 million to 100 million people worldwide (or between 0.5 and 1 percent of the global population at that time). Many of those deaths were due to the effects of pneumococcal pneumonia, a secondary bacterial complication of flu for which no antibiotics existed in 1918. Diagnosis and treatment of this complication continue to be key to survival and recovery for flu patients.
Where Does Flu Virus Come From?
All flu strains contain genes that originated in migrating aquatic birds such as wild ducks, wild geese, and terns. Domestic birds such as chickens, geese, and ducks also carry a large variety of flu strains. New flu strains enter human populations in several ways. Sometimes genetic material is exchanged between mammal (including human) and avian flu viruses when a human or other mammal is infected with both viruses. Often this mixing and matching of viral genes happens in pigs, which are uniquely susceptible to both mammalian and avian flu viruses. The process of swapping genes is called reassortment. The 2009 H1N1 pandemic, for instance, was a triple reassortant virus containing genetic materials from avian, swine, and human viruses.
The source of all flu strains is migrating aquatic birds, such as wild ducks, geese, and terns.
Another process, known as adaptive mutation, is more gradual. In this case, the longer an avian flu virus infects humans, the more it is able to bind to human cells as the virus adapts to its new host. Recent investigations suggest that the 1918 flu virus was a bird virus that became a human virus by slowly accumulating genetic mutations that helped it survive in a human host.
On rare occasions, flu viruses leap directly from birds to humans. In 1997 a highly fatal H5N1 bird flu broke out in Hong Kong, infecting 18 individuals and causing 6 deaths—a potential pandemic that was averted when authorities ordered the slaughter of more than 1.5 million domestic birds. If H5N1 were to acquire the ability to spread easily from person to person, a new influenza pandemic could be possible.
Vaccines
Vaccines provide an effective means to prevent infection by the influenza virus. But, as the world learned with the 2009 H1N1 “swine flu” pandemic, making a vaccine is a time-consuming process that normally takes 5 to 6 months. For more than 50 years, the flu vaccine has been produced by injecting the whole virus into fertilized hens’ eggs. The virus is harvested, purified, chemically treated, and then weakened (attenuated) so that it cannot trigger infections. Despite appeals from scientists, governments have been slow to invest in newer and faster methods of producing flu vaccines such as recombinant technologies or tissue-culture–based production methods that bypass the need to grow a whole virus in eggs or cells. Nevertheless, recent moves by the U.S. government and vaccine manufacturers toward utilizing some of these new technologies provide hopeful signs. Scientists are also exploring ways to make a vaccine that is effective against all flu strains—a so-called universal vaccine. Such a development could dramatically improve the public’s protection against influenza infection.
Using cutting-edge technology, researchers may be closer to realizing this goal, but there is still much work to be done. Scientists manipulated a protein called hemagglutinin to create a vaccine fully effective when tested in mice against H5N1. More testing is needed, but this is a step in the right direction. Researchers hope to expand protection against other flu strains by taking advantage of technological advances.
As new vaccines become available, it may be difficult to determine which should be considered the top priority in light of limited funding, competing demands, and uncertainty regarding which virus presents the highest risk. A decision-support model with accompanying software is being developed to help make this task easier.
How to Protect Yourself
To reduce the likelihood of coming down with or spreading the flu:
- Get vaccinated against influenza each year. Vaccines are one of the best ways to reduce the morbidity and mortality associated with the disease. They themselves do not cause influenza in any form.
- Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use it.
- Wash your hands often with soap and water, especially after coughing or sneezing. Alcohol-based hand sanitizers are also effective.
- Avoid touching your eyes, nose, or mouth, which can spread germs.
- Stay home from work or school if you do get sick and limit your contact with others to keep from infecting them.
- Ask your doctor whether you should take an anti-influenza drug such as Tamiflu (oseltamivir), which can be effective if taken within 48 hours of developing flu symptoms.
