Swine Influenza A (H1N1) Virus

Author: Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine,
University of Oklahoma Health Science Center
Contributor Information and Disclosures
Updated: Apr 30, 2009

Introduction

Swine influenza is a highly contagious respiratory disease in pigs caused by one of several swine influenza
A viruses. In addition, influenza C viruses may also cause illness in swine. Current strategies to control
swine influenza virus (SIV) in animals typically include one of several commercially available bivalent swine
influenza virus vaccines.

Transmission of swine influenza viruses to humans is uncommon. However, the swine influenza virus can
be transmitted to humans via contact with infected pigs or environments contaminated with swine influenza
viruses. Once a human becomes infected, he or she can then spread the virus to other humans,
presumably in the same way as seasonal influenza is spread (ie, via coughing or sneezing).

This preliminary negative stained transmission electron micrograph depicts some of the
ultrastructural morphology of the A/CA/4/09 swine flu virus. Courtesy of CDC/ C. S.
Goldsmith and A. Balish.

This preliminary negative stained transmission electron micrograph depicts some of the
ultrastructural morphology of the A/CA/4/09 swine flu virus. Courtesy of CDC/ C. S.
Goldsmith and A. Balish.

History
The ability to trace outbreaks of swine flu in humans dates back to investigation of the 1918 Spanish
influenza pandemic, which infected one third of the world’s population (an estimated 500 million people)
and caused approximately 50 million deaths. In 1918, the cause of human influenza and its links to avian
and swine influenza was not understood. The answers did not begin to emerge until the 1930s, when
related influenza viruses (now known as H1N1 viruses) were isolated from pigs and then humans.1

In humans, the severity of swine influenza can vary from mild to severe. From 2005 until January 2009, 12
human cases of swine flu were reported in the United States. None were fatal. In 1988, however, a
previously healthy 32-year-old pregnant woman in Wisconsin died of pneumonia as a complication of swine
influenza.

A 1976 outbreak of swine influenza in Fort Dix, New Jersey, involved more than 200 cases, some of them
severe, and one death.2 The first discovered case involved a soldier at Fort Dix who complained of feeling
weak and tired. He died the next day.

The fear of an influenza pandemic in 1976 led to a national campaign in the United States designed to
immunize nearly the entire population. In October, 1976, approximately 40 million people received the
A/NewJersey/1976/H1N1 vaccine (ie, swine flu vaccine) before the immunization initiative was halted
because of the strong association between the vaccine and Guillain-Barré syndrome (GBS).3,4 About 500
cases of GBS were reported, with 25 deaths due to associated pulmonary complications.5

A recent investigation sought to determine the link between GBS and the 1976 swine flu vaccine, since
subsequent influenza vaccines did not have this strong association. Nachamkin et al (2008) found that
inoculation of the 1976 swine flu vaccine, as well as the 1991-1992 and 2004-2005 influenza vaccines, into
mice prompted production of antibodies to antiganglioside (anti-GM1), which are associated with the
development of GBS. They proposed that further research regarding influenza vaccine components is
warranted to determine how these components elicit antiganglioside effects.6

Current swine influenza outbreak

Human cases of swine influenza A (H1N1) have been reported worldwide. In 2009, cases of influenzalike
illness were first reported in Mexico on March 18; the outbreak was subsequently confirmed as swine
influenza A.7 Investigation is continuing to clarify the spread and severity of swine influenza in Mexico.
Suspected clinical cases have been reported in 19 of the country's 32 states. Although only 97 of the
Mexican cases have been laboratory-confirmed as Swine Influenza A/H1N18 (12 of them genetically
identical to Swine Influenza A/H1N1 viruses from California7 ) approximately 1,600 cases and over 150
deaths have been attributed to swine influenza in Mexico.9

According to the WHO, as of April 30, 2009, swine flu has been laboratory-confirmed in 11 countries: the
United States, Mexico, Austria (1 case), Canada (19 cases), Germany (3 cases), Israel (2 cases), the
Netherlands (1 case), New Zealand (3 cases), Spain (13 cases), Switzerland (1 case), and the United
Kingdom (8 cases).8 Cases are also suspected in Brazil.

On April 26, 2009, the US Department of Health and Human Services declared a national public health
emergency involving swine influenza A, citing its significant potential to affect national security.10 In the
United States, 91 confirmed cases of swine flu have been reported as of April 30, 2009, in Arizona (1 case),
California (14 cases), Indiana (1 case), Kansas (2 cases), Massachusetts (2 cases), Michigan (2 cases),
Nevada (1 case), New York (51 cases), Ohio (1 case), and Texas (16 cases).11 All affected patients have
had mild influenzalike illness, with only two requiring brief hospitalization. As of April 30, 2009, only one
death attributed to swine flu has been reported in the United States, involving a 23-month-old child.

Unlike typical influenza, most cases of swine influenza have occurred in previously healthy young adults.7
Government and public health officials are monitoring this situation worldwide to assess the threat from
swine influenza and to provide guidance to health care professionals and the public. Because the situation
is changing rapidly, it is important to check regularly for changes in recommendations as new information
becomes available. Online resources for daily guidance include the Centers for Disease Control and
Prevention (CDC), World Health Organization (WHO), and Medscape's Swine Flu Alert Center.

Morbidity and Mortality

Swine influenza tends to cause high morbidity but low mortality rates (1%-4%). At the time of this writing
during the 2009 outbreak (April 30, 2009), 149 deaths in Mexico have been attributed to swine influenza,
with 9 of those deaths confirmed as resulting from the infection. One death has been reported in the United
States (in Texas).

Symptoms

Manifestations of swine influenza are similar to those of seasonal influenza. Patients present with
symptoms of acute respiratory illness, including at least 2 of the following:

• Fever
• Cough
• Sore throat
• Body aches
• Headache
• Chills and fatigue
• Diarrhea and vomiting (possible)

Persons with these symptoms should call their health care provider promptly. If an antiviral agent is
warranted, it should ideally be initiated with 48 hours from the onset of symptoms (see Medications). The
duration of illness is typically 4-6 days. The infectious period for a confirmed case is defined as 1 day prior
to the onset of symptoms to 7 days after onset.

In children, signs of severe disease include apnea, tachypnea, dyspnea, cyanosis, dehydration, altered
mental status, and extreme irritability.12

Viral Strain and Testing

Outbreaks of swine influenza are common in pigs year-round. Historically, when humans have become
infected, it is a result of close contact with infected pigs. However, the current virus is a novel influenza A
(H1N1) virus not previously identified in humans, and it appears to be spread by human-to-human
transmission. The WHO has raised its pandemic alert level for swine influenza to phase 5, which is a strong
signal that a pandemic is imminent and that the time to finalize the organization, communication, and
implementation of the planned mitigation measures is short.

Phase 5 is characterized by human-to-human spread of the virus into at least two

countries in one WHO region. While most countries will not be affected at this stage, the
declaration of Phase 5 is a strong signal that a pandemic is imminent and that the time
to finalize the organization, communication, and implementation of the planned
mitigation measures is short. Courtesy of the WHO.

In the current 2009 outbreak in the United States, preliminary testing has shown that, in all cases, the
viruses have the same genetic pattern. The virus is being described as a new subtype of influenza A/H1N1
not previously detected in swine or humans.

Clinicians should consider the possibility of swine influenza virus infections in patients who present with
febrile respiratory illness. The CDC criteria for suspected swine influenza are as follows13 :

• Onset of acute febrile respiratory illness within 7 days of close contact with a person who has a
confirmed case of swine influenza A (H1N1) virus infection, or
• Onset of acute febrile respiratory illness within 7 days of travel to a community (within the United
States or internationally) where one or more swine influenza A (H1N1) cases have been confirmed,
or
• Acute febrile respiratory illness in a person who resides in a community where at least one swine
influenza case has been confirmed.
If swine flu is suspected, the clinician should obtain a respiratory swab for swine influenza testing and place
it in a refrigerator (not a freezer). Once collected, the clinician should contact his or her state or local health
department to facilitate transport and timely diagnosis at a state public health laboratory.

Laboratories should send all influenza A specimens that they are unable to subtype to the Viral Surveillance
and Diagnostic Branch of the CDC's Influenza Division as soon as possible for further diagnostic testing.14

Treatment Recommendations

Treatment is largely supportive and consists of bedrest, increased fluid consumption, cough suppressants,
and antipyretics and analgesics (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) for fever and
myalgias. Severe cases may require intravenous hydration and other supportive measures. Antiviral agents
may also be considered for treatment or prophylaxis (see Medications).

Patients should be encouraged to stay home if they become ill, to avoid close contact with people who are
sick, to wash their hands often, and to avoid touching their eyes, nose, and mouth. The CDC recommends
the following actions when human infection with swine flu is confirmed in a community13 :

Home isolation

• Patients who develop flulike illness (ie, fever with either cough or sore throat) should be strongly
encouraged to self-isolate in their home for 7 days after the onset of illness or at least 24 hours
after symptoms have resolved, whichever is longer.
• To seek medical care, patient should contact their health care providers to report illness (by
telephone or other remote means) before seeking care at a clinic, physician's office, or hospital.
• Patients who have difficulty breathing or shortness of breath or who are believed to be severely ill
should seek immediate medical attention.
• If the patient must go into the community (eg, to seek medical care), he or she should wear a face
mask to reduce the risk of spreading the virus in the community when coughing, sneezing, talking,
or breathing. If a face mask is unavailable, ill persons who need to go into the community should
use tissues to cover their mouth and nose while coughing.
 • While in home isolation, patients and other household members should be given infection control
instructions, including frequent hand washing with soap and water. Use alcohol-based hand gels
(containing at least 60% alcohol) when soap and water are not available and hands are not visibly
dirty. Patients with swine influenza should wear a face mask when within 6 feet of others at home.
Household contacts who are not ill

• Remain home at the earliest sign of illness.

• Minimize contact in the community to the extent possible.
• Designate a single household family member as caregiver for the patient to minimize interactions
with asymptomatic persons.
School dismissal and childcare facility closure

• Strong consideration should be given to close schools upon a confirmed case of swine flu or a
suspected case epidemiologically linked to a confirmed case.
• Decisions regarding broader school dismissal within these communities should be left to local
authorities, taking into account the extent of influenzalike illness within the community.
• Cancelation of all school or childcare related gatherings should also be announced.
• Encourage parents and students to avoid congregating outside of the school if school is canceled.
• Duration of schools and childcare facilities closings should be evaluated on an ongoing basis
depending on epidemiological findings.
• Consultation with local or state health departments is essential for guidance concerning when to
reopen schools. If no additional confirmed or suspected cases are identified among students (or
school-based personnel) for a period of 7 days, schools may consider reopening.
• Schools and childcare facilities in unaffected areas should begin preparation for possible school
closure.
Social distancing

• Large gatherings linked to settings or institutions with laboratory-confirmed cases should be

canceled (eg, sporting events or concerts linked to a school with cases); other large gatherings in
the community may not need to be canceled at this time.
• Additional social distancing measures are currently not recommended.
• Persons with underlying medical conditions who are at high risk for complications of influenza
should consider avoiding large gatherings.
Patient education

Patients should be referred to the eMedicine Health article Swine Flu.

Preventive measures for health care personnel

The CDC has issued interim recommendations for controlling the spread of swine influenza in health care
settings.15 Recommended measures for care of patients with suspected or confirmed swine influenza
include the following:

• Place patients in a single-patient room with the door kept closed.

• An airborne-infection isolation room with negative-pressure air handling can be used, if
available. Air can be exhausted directly outside or can be recirculated after filtration by a
high efficiency particulate air (HEPA) filter.
 • Suctioning, bronchoscopy, or intubation should be performed in a procedure room with negative-
pressure air handling.
• Patients should wear a surgical mask when outside their room.
• Encourage patients to wash their hands frequently and to follow respiratory hygiene practices.
Cups and other utensils used by the ill person should be washed with soap and water before use
by other persons.
• Routine cleaning and disinfection strategies used during influenza seasons can be applied.

• Standard, droplet, and contact precautions should be used for all patient care activities and
maintained for 7 days after illness onset or until symptoms have resolved.
• Health care personnel should wash their hands with soap and water or use hand sanitizer
immediately after removing gloves and other equipment and after any contact with respiratory
secretions.
• Personnel providing care to or collecting clinical specimens from patients should wear disposable
nonsterile gloves, gowns, and eye protection (eg, goggles) to prevent conjunctival exposure.
• As per previous recommendations regarding mask and respirator use during influenza pandemics,
personnel engaged in aerosol-generating activities (eg, collection of clinical specimens,
endotracheal intubation, nebulizer treatment, bronchoscopy) and/or resuscitation involving
emergency intubation or cardiac pulmonary resuscitation should wear a fit-tested disposable N95
respirator.
• Pending clarification of transmission patterns for the 2009 swine influenza A (H1N1) virus,
personnel providing direct patient care for suspected or confirmed cases should wear a fit-tested
disposable N95 respirator when entering the patient's room.
Swine influenza in pregnancy

Pregnant women with suspected swine influenza should should receive empiric antiviral treatment.16

Medications

Laboratory testing has found the swine influenza A (H1N1) virus susceptible to the prescription antiviral
drugs oseltamivir and zanamivir, and the CDC has issued interim guidance for the use of these drugs to
treat and prevent infection with swine influenza viruses.17,18 As part of its preparation for the emergency, the
US Department of Homeland Security is releasing 25% of stockpiled antiviral agents (ie, oseltamivir
[Tamiflu], zanamivir [Relenza]).

The usual vaccine for influenza administered at the beginning of the flu season is not effective for this viral
strain. Also, other antiviral agents (eg, amantadine, rimantadine) are not recommended because of recent
resistance to other influenza strains documented over the past several years.

Basic supportive care (ie, hydration, analgesics, cough suppressants) should be prescribed. Empiric
antiviral treatment should be considered for confirmed, probable, or suspected cases of swine influenza.
Treatment of hospitalized patients and patients at higher risk for influenza complications should be
prioritized.

Initiation of antiviral agents within 48 hours of symptom onset is imperative for providing treatment efficacy
against influenza virus. In studies of seasonal influenza, evidence for benefits of treatment is strongest
when treatment is started within 48 hours of illness onset. However, some studies of treatment of seasonal
influenza have indicated benefit, including reductions in mortality or duration of hospitalization, even in
patients in whom treatment was started more than 48 hours after illness onset. The recommended duration
of treatment is 5 days.17,18
 • Prophylaxis with antiviral agents should also be considered in the following individuals (pre-
exposure or postexposure):
○ Close household contacts of a confirmed or suspected case who are at high risk for
complications (eg, chronic medical conditions, persons >65 y or <5 y, pregnant women)
○ School children at high risk for complications who have been in close contact with a
confirmed or suspected case
○ Travelers to Mexico who are at high risk for complications (eg, chronic medical conditions,
persons >65 y or <5 y, pregnant women)
○ Health care providers or public health workers who were not using appropriate personal
protective equipment during close contact with a confirmed or suspected case
• Pre-exposure prophylaxis can be considered in the following persons:
○ Any health care provider who is at high risk for complications (eg, persons with chronic
medical conditions, adults >65 y, pregnant women)
○ Individuals not considered to be at high risk but who are nonetheless traveling to Mexico,
first responders, or border workers who are working in areas with confirmed cases
Antiviral Agents
Drugs indicated for treatment of swine influenza A (H1N1) virus include neuraminidase inhibitors (ie,
oseltamivir and zanamivir).

Oseltamivir (Tamiflu)

Oseltamivir inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys
an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, this agent decreases
the release of viruses from infected cells and, thus, viral spread. Oseltamivir is effective in the treatment of
influenza A or B and must be administered within 48 hours of symptom onset. The sooner the drug is
administered after symptom onset, the better the likelihood of a good outcome. Oseltamivir reduces the
length of illness by an average of 1.5 days. (In a subgroup of high-risk patients, illness was reduced by 2.5
d.) In addition, the severity of symptoms is also reduced.

Oseltamivir is available as 30-mg, 45-mg, and 75-mg oral capsules and as a powder for suspension that
contains 12 mg/mL after reconstitution.

• Adult dose
○ Treatment for acute illness: 75 mg PO bid for 5 d
○ Prophylaxis: 75 mg PO qd
• Pediatric dose
○ Treatment for acute illness and age <1 year

 <3 months: 12 mg PO bid

 3-5 months: 20 mg PO bid
 6-11 months: 25 mg PO bid
○ Treatment for acute illness and age >1 year

 <15 kg: 30 mg PO bid

 15-23 kg: 45 mg PO bid
 23-40 kg: 60 mg PO bid
  >40 kg: Administer as in adults
○ Prophylaxis and age <1 year

 <3 months: Data limited; not recommended unless situation judged critical
 3-5 months: 20 mg PO qd
 6-11 months: 25 mg PO qd
○ Prophylaxis and age >1 year

 <15 kg: 30 mg PO qd
 15-23 kg: 45 mg PO qd
 23-40 kg: 60 mg PO qd
 >40 kg: Administer as in adults
Zanamivir (Relenza)

Zanamivir inhibits neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys
the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from
infected cells and viral spread are decreased. Zanamivir is effective against both influenza A and B. The
preparation of zanamivir is in powder form for inhalation via the Diskhaler oral inhalation device. Circular
foil discs that contain 5-mg blisters of drug are inserted into the supplied inhalation device. Individuals with
asthma or other respiratory conditions that may decrease ability to inhale drug should be given oseltamivir.

• Adult dose
○ Treatment for acute illness: 10 mg inhaled orally bid for 5 d
○ Prophylaxis of household contact: 10 mg inhaled orally qd for 10 d (initiate within 36 h)
○ Prophylaxis for community outbreak: 10 mg inhaled orally qd for 28 d (initiate within 5 d of
outbreak)
• Pediatric dose
○ Treatment for acute illness

 <7 years: Not established

 >7 years: Administer as in adults
○ Prophylaxis in household contact

 <5 years: Not established

 >5 years: Administer as in adults
○ Prophylaxis in community outbreak

 Adolescents 12-16 years: Administer as in adults

Additional pediatric considerations

Aspirin or aspirin-containing products (eg, bismuth subsalicylate [Pepto Bismol]) should not be included in
the treatment of confirmed or suspected viral infection in persons aged 18 years or younger because of the
risk of Reye syndrome. For relief of fever, other antipyretic medications (eg, acetaminophen, nonsteroidal
anti-inflammatory drugs) are recommended.

Pregnant women

Oseltamivir and zanamivir are "Pregnancy Category C" medications, indicating that no clinical studies have
been conducted to assess the safety of these medications in pregnant women. Because of the unknown
effects of influenza antiviral drugs on pregnant women and their fetuses, oseltamivir or zanamivir should be
used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus; the
manufacturers' package inserts should be consulted. However, no adverse effects have been reported
among women who received oseltamivir or zanamivir during pregnancy or among infants born to women
who have received oseltamivir or zanamivir. Pregnancy should not be considered a contraindication to
oseltamivir or zanamivir use. Because zanamivir is an inhaled medication and has less systemic
absorption, some experts prefer zanamivir over oseltamivir for use in pregnant women, when feasible.17,19

Multimedia
Media file 1: Swine influenza virus. Colorized transmission electron
micrograph (37,800X) of the A/New Jersey/76 (Hsw1N1) virus under
plate magnification. Image taken during the virus' first developmental
passage through a chicken egg. Courtesy of the CDC/Dr. E. Palmer;
R.E. Bates.

(Enlarge Image)
Media file 2: Phase 5 is characterized by human-to-human spread
of the virus into at least two countries in one WHO region. While
most countries will not be affected at this stage, the declaration of
Phase 5 is a strong signal that a pandemic is imminent and that
the time to finalize the organization, communication, and
implementation of the planned mitigation measures is short.
Courtesy of the WHO.

(Enlarge Image)
Media file 3: Negative stained transmission electron micrograph of
recreated 1918 influenza virions. Courtesy of CDC/ Dr. Terrence
Tumpey.

(Enlarge Image)
 Media file 4: This preliminary negative stained transmission electron
micrograph depicts some of the ultrastructural morphology of the
A/CA/4/09 swine flu virus. Courtesy of CDC/ C. S. Goldsmith and A.
Balish.

(Enlarge Image)
Media file 5: This preliminary negative stained transmission
electron micrograph depicts some of the ultrastructural
morphology of the A/CA/4/09 swine flu virus. Courtesy of CDC/ C.
S. Goldsmith and A. Balish.

(Enlarge Image)
Keywords

swine flu, swine influenza, swine influenza virus, swine influenza A (H1N1) virus, human swine flu,
influenza A, influenza (H1N1), SIV, swine flu symptoms, swine flu diagnosis, swine flu treatment, swine flu
antiviral, swine flu pandemic