Swine Flu (Novel H1N1 Influenza and H3N2v)

Mutations in swine flu viruses allow for easy transmission to humans.

Influenza viruses are small RNA viruses that infect many mammals, including humans, birds, and swine. Before 2009, swine influenza predominately affected swine and was not transmitted often or easily to people. Even in the isolated instances in which swine influenza-infected people, it had a very limited ability to spread from person to person. Most cases were directly linked to contact with swine through farming or at fairs. Since 2009, the interactions and understanding of the role of swine and flu viruses in human infections have been markedly changed.

Swine flu was first noticed to have influenza-like illnesses in 1918 during the human influenza pandemic. The term pandemic means that an infection has spread to many countries around the world, causing widespread human disease. Swine influenza did not cause the 1918 pandemic. Rather, pigs apparently acquired the infection from humans or from an undiscovered source. For decades, the swine virus remained relatively unchanged. In the 1990s, however, swine influenza viruses became more diverse and new strains appeared. The reason for this change is not clear but may have been related to overcrowding on large swine farms.

Before 2009, there was only one swine influenza outbreak in people that caused public health concerns. This outbreak occurred in 1979, in soldiers at Fort Dix, N.J. One recruit died, and approximately 12 were hospitalized with influenza. Further testing showed that more than 200 recruits had acquired the virus, although most had few or no symptoms. The infecting strain was found to be strongly related to the swine influenza virus, raising concerns that a new pandemic might occur. In response, public health officials began a massive public vaccination program. Up to 25% of people in the United States were vaccinated. Unfortunately, the 1979 vaccine was associated with a small increased risk of Guillain-Barré syndrome, a serious neurological condition, with the risk estimated to be one to nine excess cases per million doses. Importantly, the 1979 strain did not spread easily from person to person and there was no epidemic. Human cases outside of Fort Dix were uncommon. Moreover, the 1979 vaccine was made using an old-fashioned process that is no longer utilized.

The lessons learned from the 1979 swine influenza event were applied in dealing with pandemic threats, including the severe acute respiratory syndrome (SARS) outbreak of 2003 and the 2009 influenza outbreak. Key lessons included ensuring adequate communication with the public, producing a rapid but measured response to potential threats, and ensuring that any new strain fulfills the criteria to cause a pandemic before large-scale vaccination was undertaken.

There is no commercially available vaccine for H3N2v flu.

In March and April 2009, hundreds of cases of human respiratory illness were reported in Mexico that was suspected or confirmed to be caused by a novel swine-type influenza virus. By April, confirmed cases were also reported in the United States. The first reported cases in the U.S. came from San Diego County and Imperial County in California and Guadalupe County in Texas. Reports from other states rapidly followed, and the disease spread rapidly around the globe. The World Health Organization (WHO) officially declared the 2009 swine flu to be a pandemic. The U.S. Centers for Disease Control and Prevention (CDC) estimated that more than 1 million Americans were infected with swine influenza by June 2009. By August 2009, more than 170 countries and territories reported swine flu cases. By October, 46 U.S. states were reporting widespread outbreaks. By late October, the virus had been confirmed to have caused more than 1,000 deaths in the U.S., with almost 100 of the deaths in children. Approximately 6% of deaths were in pregnant women, although only 1% of the population was pregnant. Physician visits, hospitalizations, and deaths in the fall of 2009 all exceeded seasonal thresholds. On Oct. 25, 2009, President Obama declared a national emergency as a result of the outbreak. This allowed public health officials additional power to allow waive some regulations to facilitate patient care and allowed hospitals to set up separate facilities to isolate sick patients.

A new vaccine was emergency made against the H1N1 virus, and while during the first several months of the pandemic it was in short supply, it eventually became available worldwide. As the H1N1 pandemic began to wane, the statistics suggested that the H1N1 infections more closely resembled a potent seasonal flu outbreak. However, an H1N1 virus strain has been included in all of the seasonal trivalent vaccines since the 2011-2012 flu season.

In 2011, the CDC reported a new assortment of genetic material from H1N1 and H3N2 influenza A viruses that resulted in a new strain of swine virus termed influenza A (H3N2)v (also termed H3N2v) that was similar to viruses that infected pigs in the 1990s. However, this strain genetically picked up an M gene from H1N1 that researchers suggest allowed the viral strain to more easily infect humans. In the fall of 2011, the CDC reported that about 12 confirmed human infections were detected in young people who often had some association with pigs or pig farming. In July 2012, the CDC noted a rapid rise in these H3N2v infections that again occurred with people associated with pigs and pig farming. In addition, a new virus with the same H and N designations but antigenically different from H3N2v also caused flu; it is designated as H3N2. This outbreak also was noted in 2011 and infected many people worldwide but was not a pandemic. The newest seasonal flu shots and nasal spray vaccines now contain H3N2 antigens to offer protection against the H2N2 flu virus, but the resultant vaccine is not effective against H3N2v.

In 2017, a large outbreak of H1N1 happened in India, and from about January to August, there were over 1,000 deaths. Doctors encouraged individuals to get vaccinated at clinics and hospitals; the vaccine cost is about 500-560 rupees (about $7-$8 U.S. dollars), which is fairly high if your average income is 40 cents per hour. This outbreak in India seemed worse than the previous 2015-2016 outbreak. From Jan. 1, 2020, to Feb. 24, 2020, there have been 884 reported cases of H1N1 in India with 14 deaths.

Influenza viruses are named according to the types of proteins on the outer surface of the virus. The two main proteins are hemagglutinin (H) and neuraminidase (N). The swine influenza virus in the 2009 outbreak was an H1N1 virus. In fact, although the term swine flu is often used to describe the outbreak, the official term for the 2009 virus is novel H1N1 influenza.

It is important to realize that the influenza virus changes (mutates) constantly so that there are many strains of H1N1 that differ subtly from each other. Swine flu is caused by one strain of H1N1, but there are many other strains. Some H1N1 strains only infect pigs. Others infect humans, pigs, and birds. These subtle differences matter because the human body makes antibodies that are tailored to a single strain of influenza. If a person recovers from novel H1N1 (swine) flu, they are probably protected against infection from the same swine flu strain but are not protected against infections from variations on the strain or from other strains of influenza.

The 2009 novel H1N1 swine influenza strain appeared to be a result of a genetic shift, meaning that it contains pieces of influenza from many different sources. The 2009 virus included genes that come from bird influenza viruses, swine influenza viruses, and human influenza viruses. This strain had not previously caused infections in humans or pigs. Thus, it was unlikely that most humans had preexisting immunity to this new strain. The diagram below shows how the gene assortment can happen.

Although the diagram shows the genetic shift and drift of various flu virus genes, this diagram represents the mechanisms used by all influenza A viruses that result in "new" viral antigenic types, such as the newest swine flu virus, H3N2v, that is being transmitted from pigs to humans. This new type was first detected in 2011 with an M gene acquired from the H1N1 virus.

Swine influenza (novel H1N1 and H3N2v) spreads from person to person, either by inhaling the virus or by touching surfaces contaminated with the virus, then touching the mouth or nose. Infected droplets are expelled into the air through coughing or sneezing. H3N2v does not spread as easily from person to person as H1N1. This poor transmission rate is likely why there have been so few individuals infected with H3N2v.

Research suggested that H1N1 swine influenza is about as contagious as the usual human influenza. If one person in a household gets swine flu, anywhere from 8%-19% of household contacts likely will get infected. Reports from the southern hemisphere suggest that swine influenza caused slightly more infections than would be normal for an influenza season.

However, the newest swine flu virus, H3H2v, is not being spread very easily from human to human. The majority of infections to date occurred as a result of the swine virus H3N2v being transmitted directly from pigs to humans since most of the reported infected people were associated with pig farms or state fairs with pigs as predominant competition entries. However, the CDC is concerned because this situation could easily change if H3N2v acquires genes that allow easy viral transmission between humans.

Swine flu, both H1N1 and H3N2v, causes respiratory infection. The CDC recommends that swine influenza be considered in people who have a fever and respiratory symptoms, especially cough or a sore throat. People may also have fatigue, chills, headache, or body aches. Nausea, vomiting, or diarrhea has also occurred in people with swine flu. Very young children may not complain of fever or cough but rather have listlessness or shortness of breath as their main symptom.

Children and young adults (ages 0-24 years) had the highest rate of infection with the 2009 H1N1 flu. Older adults (>65 years) were less likely to have infections, leading some to speculate that older individuals might have "partial immunity." Partial immunity occurs when people make antibodies against one virus that have some effect on another virus. Thus, older people who were exposed to a similar virus may have been partly protected against swine flu. The keywords here are may and partly. There is no guarantee that an older person is protected, and if they do get infected, they are at risk for complications requiring hospitalization. One recent study showed that 33% of people over age 59 have antibodies that might help protect against novel H1N1. However, if older people do get infected, the disease may be more severe, as is true of most influenza infections.

Although the infection is usually mild, some people with swine flu have experienced serious respiratory illness, including pneumonia or respiratory failure leading to death. Pregnant women are at high risk for severe disease. Of concern, most deaths early in the pandemic occurred in adults under age 65, including people under age 25. This was the opposite of what happens in a normal influenza season when most deaths occur in the elderly.

People with chronic medical conditions are always at higher risk for complications from influenza and this is also true of swine flu. These chronic medical conditions include asthma, chronic lung disease, heart disease, diabetes, suppressed immune systems (including from chemotherapy), and kidney failure.

People with swine influenza are assumed to be contagious from one day before getting sick until at least 24 hours after symptoms resolve. Children and people with weak immune systems may be infectious for longer periods (for example, 10 days).

Currently, the new H3N2v swine flu produces about the same symptoms as the more benign strains of H1N1.

People with fever and mild respiratory symptoms should call their physician for guidance. If you live in an area that is not currently reporting any cases of swine influenza, your physician may direct you to come into the clinic to be evaluated. If you live in an area where swine influenza is circulating already, your physician may decide to treat you over the phone. The CDC recommends this approach to minimize the number of sick people who go out into the community or into a clinic once cases have been confirmed.

People who are seriously ill should seek medical attention immediately through an emergency room or other settings.

• This includes people with shortness of breath, confusion, dizziness, or alterations in consciousness.
• Small children may not be able to describe their symptoms, and parents should look for signs of rapid breathing, bluish skin, or reduced level of responsiveness, which should prompt immediate medical attention.

Swine influenza can be confirmed by culturing respiratory secretions such as sputum or nasal/throat secretions, but this is expensive and not often done. Rapid tests are available to give a general idea if an influenza strain is present, but they are far from perfect and may not pick up swine influenza or even regular seasonal influenza (regular flu). In fact, the CDC does not recommend the use of rapid tests because the results are often inaccurate. Specific testing for the genetic material of the virus, such as the test called polymerase chain reaction or PCR, may be done at state health departments or at the CDC. Your local laboratory will have a procedure in place to send specimens to the health department when necessary. H1N1 and H3N2v strains are detected with similar methods, and new tests are being produced to detect these strains quickly and economically in hospitals and clinics (most will test only for H1N1 and possibly H3N2 but not for bird flu strains or MERS-CoV or other respiratory diseases).

It is not possible or economically feasible to test every symptomatic patient for swine flu once a community has multiple cases. If there are large numbers of cases of swine flu present in the community, the laboratory will usually stop doing specific tests for swine flu and will simply recommend that patients with symptoms be assumed to have the infection.

Laboratory testing has shown that the swine influenza strains are sensitive to three antiviral medicines that are used to treat human influenza. They are

• oseltamivir (Tamiflu),
• zanamivir (Relenza), and
• peramivir (Rapivab).

Oseltamivir is given in pill form. Zanamivir is an inhaled medication, and Peramivir is given intravenously. All three medications require a prescription. The drugs should be given to people who appear to have swine influenza if they have chronic medical conditions that put them at risk for complications (see above) or if they are unusually ill.

These drugs can be used for patients with either H1N1 or H3N2v infections. A few drug-resistant H1N1strains have been reported, but most swine flu strains remain sensitive.

Older drugs like amantadine (Symmetrel) are not effective. Some physicians think that antiviral drugs are not effective.

People who are suspected of having novel H1N1 or H3N2v (swine) influenza should stay home from work and not go into the community, including attending school or going to work. The CDC recommends that people with influenza-like illnesses remain at home until at least 24 hours after they are free of fever.

• Over-the-counter medicines like ibuprofen (Advil) or acetaminophen (Tylenol) may be used to reduce fever or aches.
• Aspirin or aspirin-containing products should not be given to children 18 years of age or younger, due to the risk of liver damage (Reye's syndrome).
• Always follow the package directions for any over-the-counter cold or flu remedy.

Simple measures have been shown to reduce the risk of transmission of influenza. These include frequent hand washing with soap and water or disinfection with alcohol. People should try to avoid touching their faces or mucous membranes. The influenza virus can live about two hours on surfaces that become contaminated. During coughs and sneezes, the mouth should be covered with a tissue or a sleeve. In areas with large numbers of cases, it is best to minimize nonessential exposure to crowds. Sick people should stay home whenever possible.

To reduce the risk of spreading the flu to other family members, everyone in the household should wash their hands frequently. Alcohol-based sanitizing gels are available in stores and may be used instead of soap and water when hands are not visibly soiled. The most significant risk factor for the flu is contact with virus particles, usually hand-to-mouth contact, or contact with particles spread by coughing and sneezing.

Rarely, if a person has been exposed to a confirmed case of any type of swine influenza, a physician may recommend a course of medications to reduce the risk of disease. This is called "prophylaxis" and is usually reserved for people at very high risk for complications, such as pregnant women. The CDC has issued guidelines for prophylaxis in special circumstances (https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm).

For the first time during the 2013-2014 flu season, one seasonal flu vaccine was composed of four different flu virus antigens instead of the usual three. However, the trivalent (three virus strains) vaccine was also available. The CDC indicated the following: The 2013-14 U.S. trivalent influenza vaccines contained an A/California/7/2009 (H1N1)-like virus, an H3N2 virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011, and a B/Massachusetts/2/2012-like virus. Quadrivalent (containing four viral types) vaccines included an additional vaccine virus, a B/Brisbane/60/2008-like virus. The CDC speculated that the quadrivalent vaccine would replace the trivalent vaccine in the future. In addition, a quadrivalent nasal vaccine is now available and is expected to replace the current trivalent live attenuated vaccine. This vaccine is used for people 2-49 years of age and not for pregnant women or people with any immune-compromising factors (cancer or chemotherapy, for example). A nasal mist vaccine was utilized in the past, but the CDC recommended stopping its use in 2016. For the 2017-2018 flu season, the CDC recommends either a trivalent (three-component) or quadrivalent (four-component) vaccine. The strength and dosage methods may vary according to age and other factors; your medical caregiver can help in selecting the best vaccine for you.

It is important to point out that the 2009 novel H1N1 vaccine was not related to the 1976 vaccine. The 2009 vaccine was made using a more modern process, and the 2009 virus was very dissimilar to the 1976 virus; consequently, the problems seen with the 1976 vaccine (neurologic problems) do not occur with the newer vaccines.

Some people have died from bacterial infections that attack lungs already damaged by influenza. For this reason, the CDC recommends that the pneumococcal vaccine (against Pneumococcus bacteria that may cause pneumonia) be offered to all people with underlying chronic illnesses and all people over 65 years of age. In addition, people who survive novel H1N1 (swine) flu are still at risk for the regular seasonal flu. For this reason, the CDC continues to recommend the seasonal influenza vaccine be used as recommended. Currently, there is no commercially available vaccine for H3N2v strains. However, a pilot vaccine in preliminary clinical studies may lead to a significant (protective) immune response.

The results of ongoing investigations may answer several key questions about current swine flu viruses and how strains appear and then seem to disappear. So far, the H1N1 virus has not changed much since it first appeared in 2009. The newer vaccine seems effective against the virus and H3N2. Each year has brought new information to researchers and that information is used to help design new vaccines.

The following are the CDC recommendations for avoiding H3N2v flu. The CDC suggests that these actions can reduce the risk of influenza viruses spreading from pigs to people since there is no commercially available vaccine for H3N2v flu.

• Don't take food or drink into pig areas; don't eat, drink or put anything in your mouth in pig areas.
• Don't take toys, pacifiers, cups, baby bottles, strollers, or similar items into pig areas.
• Wash your hands often with soap and running water before and after exposure to pigs. If soap and water are not available, use an alcohol-based hand rub.
• Avoid close contact with pigs that look or act ill.
• Take protective measures if you must come in contact with pigs that are known or suspected to be sick. This includes minimizing contact with pigs and wearing personal protective equipment like protective clothing, gloves, and masks that cover your mouth and nose when contact is required.
• To further reduce the risk of infection, minimize contact with pigs in the pig barn and arenas.
• Watch your pig (if you have one) for signs of illness and call a veterinarian if you suspect it might be sick.
• Avoid contact with pigs if you have flu-like symptoms. Wait seven days after your illness started or until you have been without fever for 24 hours without the use of fever-reducing medications, whichever is longer. If you must have contact with pigs while you are sick, take the protective actions listed above.

The 2009 influenza pandemic caused significant economic, social, and health problems. Although the number of deaths was not high for a pandemic influenza virus, it is concerning that death rates in pregnant women and otherwise healthy young people were disproportionately high.

• Simple infection-control measures (covering coughs, and washing hands) will help reduce the risk of any flu infection.
• Vaccination is an effective method of controlling H1N1 and H3N2 viral disease and should be given whenever indicated and available.
• For most people, the prognosis is good, but for a few others in whom the disease progresses more severely, the prognosis ranges from good to poor.