April-May-2015

SWINE FLU

Authors:Dr. Saurabh Suman

Swine flu (H1N1 and H3N2v influenza virus) facts
  • Swine flu is a respiratory disease caused by influenza viruses that infect the respiratory tract of pigs and result in a barking cough,decreased appetite, nasal secretions, and listless behavior; the virus can be transmitted to humans.
  • Swine flu viruses may mutate (change) so that they are easily transmissible among humans.
  • The 2009 swine flu outbreak (pandemic) was due to infection with the H1N1 virus and was first observed in Mexico.
  • Symptoms of swine flu in humans are similar to most influenza infections: fever (100 F or greater), cough, nasal secretions, fatigue, and headache.
  • Vaccination is the best way to prevent or reduce the chances of becoming infected with influenza viruses.
  • Two antiviral agents, zanamivir (Relenza) and oseltamivir (Tamiflu), have been reported to help prevent or reduce the effects of swine flu if taken within 48 hours of the onset of symptoms.
  • There are various methods listed in this article to help individuals from getting the flu.
  • The most serious complication of the flu is pneumonia.


What is the swine flu?

Swine flu (swine influenza) is a respiratory disease caused by viruses (influenza viruses) that infect the respiratory tract of pigs, resulting in nasal secretions, a barking cough, decreased appetite, and listless behavior. Swine flu produces most of the same symptoms in pigs as human flu produces in people.
Swine flu can last about one to two weeks in pigs that survive. Swine influenza virus was first isolated from pigs in 1930 in the U.S. and has been recognized by pork producers and veterinarians to cause infections in pigs worldwide. In a number of instances, people have developed the swine flu infection when they are closely associated with pigs (for example, farmers, pork processors), and likewise, pig populations have occasionally been infected with the human flu infection. In most instances, the cross-species infections (swine virus to man; human flu virus to pigs) have remained in local areas and have not caused national or worldwide infections in either pigs or humans. Unfortunately, this cross-species situation with influenza viruses has had the potential to change.
Investigators decided the 2009 so-called "swine flu" strain, first seen in Mexico, should be termed novel H1N1 flu since it was mainly found infecting people and exhibits two main surface antigens, H1 (hemagglutinin type 1) and N1 (neuraminidase type1). The eight RNA strands from novel H1N1 flu have one strand derived from human flu strains, two from avian (bird) strains, and five from swine strains.
Swine flu is transmitted from person to person by inhalation or ingestion of droplets containing virus from people sneezing or coughing; it is not transmitted by eating cooked pork products. The newest swine flu virus that has caused swine flu is influenza A H3N2v (commonly termed H3N2v) that began as an outbreak in 2011.
The "v" in the name means the virus is a variant that normally infects only pigs but has begun to infect humans. There have been small outbreaks of H1N1 since the pandemic; a recent one is in India where at least three people have died.

What causes swine flu?

The cause of the 2009 swine flu was an influenza A virus type designated as H1N1. In 2011, a new swine flu virus was detected. The new strain was named influenza A (H3N2)v. Only a few people (mainly children) were first infected, but officials from the U.S. Centers for Disease Control and Prevention (CDC) reported increased numbers of people infected in the 2012-2013 flu season. Currently, there are not large numbers of people infected with H3N2v.
Unfortunately, another virus termed H3N2 (note no "v" in its name) has been detected and caused flu, but this strain is different from H3N2v. In general, all of the influenza A viruses have a structure similar to the H1N1 virus; each type has a somewhat different H and/or N structure.

Why is swine flu now infecting humans?

Many researchers now consider that two main series of events can lead to swine flu (and also avian or bird flu) becoming a major cause for influenza illness in humans. First, the influenza viruses (types A, B, C) are enveloped RNA viruses with a segmented genome; this means the viral RNA genetic code is not a single strand of RNA but exists as eight different RNA segments in the influenza viruses.
A human (or bird) influenza virus can infect a pig respiratory cell at the same time as a swine influenza virus; some of the replicating RNA strands from the human virus can get mistakenly enclosed inside the enveloped swine influenza virus. For example, one cell could contain eight swine flu and eight human flu RNA segments. The total number of RNA types in one cell would be 16; four swine and four human flu RNA segments could be incorporated into one particle, making a viable eight RNA-segmented flu virus from the 16 available segment types.

Various combinations of RNA segments can result in a new subtype of virus (this process is known as antigenic shift) that may have the ability to preferentially infect humans but still show characteristics unique to the swine influenza virus (see Figure 1). It is even possible to include RNA strands from birds, swine, and human influenza viruses into one virus if a single cell becomes infected with all three types of influenza (for example, two bird flu, three swine flu, and three human flu RNA segments to produce a viable eight-segment new type of flu viral genome). Formation of a new viral type is considered to be antigenic shift; small changes within an individual RNA segment in flu viruses are termed antigenic drift (see figure 1) and result in minor changes in the virus.
However, these small genetic changes can accumulate over time to produce enough minor changes that cumulatively alter the virus' makeup over time (usually years). Second, pigs can play a unique role as an intermediary host to new flu types because pig respiratory cells can be infected directly with bird, human, and other mammalian flu viruses. Consequently, pig respiratory cells are able to be infected with many types of flu and can function as a "mixing pot" for flu RNA segments (see figure 1). Bird flu viruses, which usually infect the gastrointestinal cells of many bird species, are shed in bird feces. Pigs can pick these viruses up from the environment, and this seems to be the major way that bird flu virus RNA segments enter the mammalian flu virus population.
Figure 1 shows this process in H1N1, but the figure represents the genetic process for all flu viruses, including human, swine, and avian strains.

What are the symptoms of swine flu?

Symptoms of swine flu are similar to most influenza infections: fever (100 F or greater), cough, nasal secretions, fatigue, and headache, with fatigue being reported in most infected individuals. Some patients may also get a sore throat, rash, body aches, headaches, chills, nausea, vomiting, and diarrhea. In Mexico, many of the initial patients infected with H1N1 influenza were young adults, which made some investigators speculate that a strong immune response, as seen in young people, may cause some collateral tissue damage.The incubation period from exposure to first symptoms is about one to four days, with an average of two days.
The symptoms last about one to two weeks and can last longer if the person has a severe infection. Some patients develop severe respiratory symptoms and need respiratory support (such as a ventilator to breathe for the patient). Patients can get pneumonia (bacterial secondary infection) if the viral infection persists, and some can develop seizures.

Death often occurs from secondary bacterial infection of the lungs; appropriate antibiotics need to be used in these patients. The usual mortality (death) rate for typical influenza A is about 0.1%, while the 1918 "Spanish flu" epidemic had an estimated mortality rate ranging from 2%-20%. Swine (H1N1) flu in Mexico had about 160 deaths and about 2,500 confirmed cases, which would correspond to a mortality rate of about 6%, but these initial data were revised and the mortality rate worldwide was estimated to be much lower. Fortunately, the mortality rate of H1N1 remained low and similar to that of the conventional flu (average conventional flu mortality rate is about 36,000 per year; projected H1N1 flu mortality rate was 90,000 per year in the U.S. as determined by the president's advisory committee, but it never approached that high number).
Fortunately, although H1N1 developed into a pandemic (worldwide) flu strain, the mortality rate in the U.S. and many other countries only approximated the usual numbers of flu deaths worldwide. Speculation about why the mortality rate remained much lower than predicted includes increased public awareness and action that produced an increase in hygiene (especially hand washing), a fairly rapid development of a new vaccine, and patient self-isolation if symptoms developed.

How is swine flu diagnosed?

Swine flu is presumptively diagnosed clinically by the patient's history of association with people known to have the disease and their symptoms listed above. Usually, a quick test (for example, nasopharyngeal swab sample) is done to see if the patient is infected with influenza A or B virus. Most of the tests can distinguish between A and B types. The test can be negative (no flu infection) or positive for type A and B. If the test is positive for type B, the flu is not likely to be swine flu.
If it is positive for type A, the person could have a conventional flu strain or swine flu. However, the accuracy of these tests has been challenged, and the U.S. Centers for Disease Control and Prevention (CDC) has not completed their comparative studies of these tests. However, a new test developed by the CDC and a commercial company reportedly can detect H1N1 reliably in about one hour; the test was formerly only available to the military. In 2010, the FDA approved a commercially available test that could detect H1N1 within four hours. Most of these rapid tests are based on PCRtechnology.
Swine flu is definitively diagnosed by identifying the particular antigens (surface proteins) associated with the virus type. In general, this test is done in a specialized laboratory and is not done by many doctors' offices or hospital laboratories. However, doctors' offices are able to send specimens to specialized laboratories if necessary. Because of the large number of novel H1N1 swine flu cases that occurred in the 2009-2010 flu season (the vast majority of flu cases [about 95%-99%] were due to novel H1N1 flu viruses), the CDC recommended only hospitalized patients' flu virus strains be sent to reference labs to be identified. H3N2v flu strains and other flu virus strains are diagnosed by similar methods.

What is the treatment for swine flu?

The best treatment for influenza infections in humans is prevention by vaccination. Work by several laboratories has produced vaccines. The first H1N1 vaccine released in early October 2009 was a nasal spray vaccine that was approved for use in healthy individuals ages 2-49. The injectable vaccine, made from killed H1N1, became available in the second week of Oct. 2009. This vaccine was approved for use in ages 6 months to the elderly, including pregnant females.
Both of these vaccines were approved by the CDC only after they had conducted clinical trials to prove that the vaccines were safe and effective. A new influenza vaccine preparation is the intradermal (trivalent) vaccine is available; it works like the shot except the administration is less painful. It is approved for ages 18-64 years. Almost all vaccines have some side effects. Common side effects of H1N1 vaccines (alone or in combination with other flu viral strains) are typical of flu vaccines used over many years and are as follows:
  • Flu shot: Soreness, redness, minor swelling at the shot site, muscle aches, low-grade fever, and nausea do not usually last more than about 24 hours.
  • Nasal spray: runny nose, low-grade fever, vomiting, headache, wheezing, cough, and sore throat
  • Intradermal shot: redness, swelling, pain, headache, muscle aches, fatigue


The flu shot (vaccine) is made from killed virus particles so a person cannot get the flu from a flu shot. However, the nasal spray vaccine contains live virus that have been altered to hinder its ability to replicate in human tissue.
People with a suppressed immune system should not get vaccinated with the nasal spray. Also, most vaccines that contain flu viral particles are cultivated in eggs, so individuals with an allergy to eggs should not get the vaccine unless tested and advised by their doctor that they are cleared to obtain it. Like all vaccines, rare events may occur in some rare cases (for example, swelling, weakness, or shortness of breath). If any symptoms like these develop, the person should see a physician immediately.
Two antiviral agents have been reported to help prevent or reduce the effects of swine flu. They are zanamivir (Relenza) and oseltamivir (Tamiflu), both of which are also used to prevent or reduce influenza A and B symptoms. These drugs should not be used indiscriminately, because viral resistance to them can and has occurred. Also, they are not recommended if the flu symptoms already have been present for 48 hours or more, although hospitalized patients may still be treated past the 48-hour guideline. Severe infections in some patients may require additional supportive measures such as ventilation support and treatment of other infections like pneumonia that can occur in patients with a severe flu infection. The CDC has suggested in their guidelines that pregnant females can be treated with the two antiviral agents.
On Dec. 22, 2014, the FDA approved the first new anti-influenza drug (for H1N1 and other influenza virus types) in 15 years, peramivir injection (Rapivab). It is approved for use in the following settings: Diarrhea, skin infections, hallucinations, and/or altered behavior may occur as side effects of this drug.

  • Adult patients for whom therapy with an intravenous (IV) medication is clinically appropriate, based upon one or more of the following reasons:
  1. The patient is not responding to either oral or inhaled antiviral therapy, or
  2. drug delivery by a route other than IV is not expected to be d ependable or is not feasible, or
  3. the physician decides that IV therapy is appropriate due to other circumstances.
  • Pediatric patients for whom an intravenous medication clinically appropriate because:
  1. The patient is not responding to either oral or inhaled antiviral therapy, or
  2. drug delivery by a route other than IV is not expected to be dependable or is not feasible.


What are the risk factors for swine flu?

Vaccination to prevent influenza is particularly important for people who are at increased risk for severe complications from influenza or at higher risk for influenza-related doctor or hospital visits. When vaccine supply is limited, vaccination efforts should focus on delivering vaccination to the following people since these populations have a higher risk for H1N1 and some other viral infections according to the CDC:
  • All children 6 months to 4 years (59 months) of age
  • All people 50 years of age and older
  • Adults and children who have chronic pulmonary (including asthma) or cardiovascular (except isolated hypertension), renal, hepatic, neurological, hematologic, or metabolic disorders (including diabetes mellitus)
  • People who have immunosuppression (including immunosuppression caused by medications or by HIV)
  • Women who are or will be pregnantduring the influenza season
  • Children and adolescents (6 months to 18 years of age) who are receiving long-term aspirin therapy and who might be at risk for experiencingReye's syndrome after influenza virus infection
  • Residents of nursing homes and other long-term-care facilities
  • American Indians/Alaska natives
  • People who are morbidly obese (BMI ≥40)
  • Health-care professionals (doctors, nurses, health-care personnel treating patients)
  • Household contacts and caregivers of children under 5 years of age and adults 50 years of age and older, with particular emphasis on vaccinating contacts of children less than 6 months age
  • Household contacts and caregivers of people with medical conditions that put them at higher risk for severe complications from influenza


Can swine flu be prevented with avaccine?

The CDC recommends for the 2014-2015 flu season that everyone 6 months old and older should get a flu shot to prevent or reduce the chance of getting the flu. The best way to prevent novel H1N1 swine flu is vaccination. The 2014 CDC recommendations that apply to H1N1, H3N2, and other flu viruses are almost identical to those above-mentioned recommendations for patients at risk when vaccine doses are limited and are as follows:
  • Are aged 6 months through 4 years (59 months)
  • Are aged 50 years and older
  • Have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus)
  • Are immunosuppressed (including immunosuppression caused by medications or by human immunodeficiency virus)
  • Are or will be pregnant during the influenza season
  • Are aged 6 months through 18 years and receiving long-term aspirin therapy and who therefore might be at risk for experiencing Reye's syndrome after influenza virus infection
  • Are residents of nursing homes and other chronic-care facilities
  • Are American Indians/Alaska Natives
  • Are morbidly obese (body-mass index is 40 or greater)
  • Are health-care personnel
  • Are household contacts and caregivers of children aged younger than 5 years and adults aged 50 years and older, with particular emphasis on vaccinating contacts of children aged younger than 6 months
  • Are household contacts and caregivers of people with medical conditions that put them at higher risk for severe complications from influenza
  • As in previous recommendations, all children aged 6 months to 8 years of age who receive a seasonal influenza vaccine for the first time should receive two doses. Children who received only one dose of a seasonal influenza vaccine in the first influenza season should receive two doses rather than one in the following influenza season.
  • A newly approved inactivated trivalent vaccine containing 60 mcg of hemagglutinin antigen per influenza vaccine virus strain (Fluzone High-Dose [Sanofi Pasteur]) is an alternative inactivated vaccine for people 65 years of age and older.


The CDC occasionally makes changes and updates its information on vaccines and other recommendations about the current flu pandemic. The CDC states, "for the most accurate health information, visithttp://www.cdc.gov or call 1-800-CDC-INFO, 24/7." Caregivers should check the vaccine package inserts for more detailed information on the vaccines when they become available.
The CDC says that a good way to prevent any flu disease is to avoid exposure to the virus; this is done by frequent hand washing, not touching your hands to your face (especially the nose and mouth), and avoiding any close proximity to or touching any person who may have flu symptoms. Since the virus can remain viable and infectious for about 48 hours on many surfaces, good hygiene and cleaning with soap and water or alcohol-based hand disinfectants are also recommended. Some physicians say face masks may help prevent getting airborne flu viruses (for example, from a cough or sneeze), but others think the better use for masks would be on those people who have symptoms and sneeze or cough.
The use of Tamiflu or Relenza may help prevent the flu if taken before symptoms develop or reduce symptoms if taken within about 48 hours after symptoms develop. Some investigators say that administration of these drugs is still useful after 48 hours, especially in high-risk patient populations. However, taking these drugs is not routinely recommended for prevention for the healthy population because investigators suggest that as occurs with most drugs, flu strains will develop resistance to these medications.
During the H1N1 pandemic, the CDC made further suggestions about the use of these antiviral medications and developed the interim guidelines for use of Tamiflu and Relenza as follows, and this has not changed for the 2014-2015 flu season:
  1. Patients with high-risk factors should discuss flu symptoms and when to use antiviral medications; doctors should provide a prescription for the antiviral drug for the patient to use if the patient is exposed to flu or develops flu-like symptoms without having to go in to see the doctor.
  2. "Watchful waiting" was added as a response to taking antiviral medications, with the emphasis on the fact that those people who develop fever and have a preexisting health condition should then begin the antiviral medication.
  3. The antiviral medications are the first-line medicines for treatment of novel H1N1, H3N2, and H3N2v flu, and most cases are to date susceptible to Tamiflu and Relenza.


Feb. 16, 2015: Health authorities in India have reported that about 6,289 individuals have been diagnosed with swine flu (H1N1), with 485 deaths so far in 2015. In comparison, in 2014, there were only 937 individuals reported infected with H1N1 and 218 deaths in India.
The health officials can give no reason for the rise in numbers of infections and deaths this year. Again, the officials are hoping for a drop in the numbers of new infections and deaths as the winter weather abates in India. The officials state that they have the medical infrastructure and medicine to treat any swine-flu-infected individual in India. Feb. 9, 2015: According to India’s Health Ministry, total deaths from H1N1 influenza equaled 191 in January. This number of deaths is much higher than in January 2014.

The Ministry predicts that because there is at least one more month of winter weather, additional numbers of infected individuals will impact public health and have a negative effect on the economy for the next few months. Severe infections progress rapidly (three to five days) and oseltamivir (Tamiflu) seem to "have no effect at all." Some severely infected patients die within two days, according to one official.
Feb. 2, 2015: The BBC reported that over the last six weeks, at least 75 people in India have died from swine flu (H1N1). Although deaths have not reached the levels seen in 2012 (405) or 2013 (692), there is concern that because India is having a colder-than-normal winter (coldest in the last 20 years), the number of deaths may increase before the flu season abates. In addition, Indian health officials are investigating if the H1N1 virus has developed a "minor mutation." However, they indicate H1N1-infected patients are responding to current medicines.
Jan. 26, 2015: In New Delhi, India, another 18 people have tested positive for H1N1 swine flu virus. This brings the total number of people diagnosed to 179, with three deaths. However, officials suggest that there is no need for alarm as they expect the number of infected people to rapidly decline as the warmer weather begins to occur. New Delhi hospitals (22 hospitals) claim there are enough medicines in stock to treat individuals hospitalized with swine flu (H1N1).
Jan. 20, 2015: The H1N1 virus, commonly known as the swine flu virus, has begun to cause concern in India this year. Since Jan. 1, 2015, over 150 swine flu infections have been reported, along with seven deaths in India. In Dec. 2014, positive cases of swine flu were first reported. Telangana, a state in the southern region of India, has reported the most cases of H1N1 (over 120). Currently, 10 other states in India have reported H1N1 infections with a few deaths.
Because India has such a dense population and since H1N1 can be spread through the air via droplets, the Indian Health Ministry has asked their state officials to ensure sanitation and hygiene in all public places and to bring about awareness to people about the symptoms of swine flu. The concern is that rising numbers of swine flu infections may be the beginning of another H1N1 epidemic, although the current strain may not be as deadly as the 2009 H1N1 strain.

Where can I find more information about swine flu (H1N1 and H3N2v)?

For additional information see the following:
  • "Seasonal Influenza (Flu)," CDC
  • "Pregnant Women & Influenza (Flu)," CDC
  • "Influenza A (H3N2) Variant Virus," CDC


REFERENCES:

United States. Centers for Disease Control and Prevention. "Influenza (Flu)." Nov. 24, 2014. <http://www.cdc.gov/flu/protect/whoshouldvax.htm>. United States. Flu.gov. "H1N1." <http://www.flu.gov/about_the_flu/h1n1/>. http://www.medicinenet.com/swine_flu/article.htm