Swine flu

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

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Overview

Swine flu (also swine influenza) refers to influenza caused by any virus of the family Orthomyxoviridae, that is endemic to pig (swine) populations. Strains endemic in swine are called swine influenza virus (SIV), and all known strains of SIV are classified as Influenzavirus A (common) or Influenzavirus C (rare). Influenzavirus B has not been reported in swine. All three clades, Influenzavirus A, B, and C, are endemic in humans.

People who work with poultry and swine, especially people with intense exposures, are at risk of infection from these animals if the animals carry a strain that is also able to infect humans. SIV can mutate into a form that allows it to pass from human to human. The strain responsible for the 2009 swine flu outbreak is believed to have undergone this mutation.

In humans, the symptoms of swine flu are similar to those of influenza and of influenza-like illness in general.

Classification

SIV strains isolated to date have been classified either as Influenzavirus C or one of the various subtypes of the genus Influenzavirus A.

Influenza A

Swine influenza is known to be caused by influenza A subtypes H1N1, H1N2, H3N1, H3N2, and H2N3.

In swine, three influenza A virus subtypes (H1N1, H3N2, and H1N2) are circulating throughout the world. In the United States, the H1N1 subtype was exclusively prevalent among swine populations before 1998; however, since late August 1998, H3N2 subtypes have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants, containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages.

Interaction With H5N1

Avian influenza virus H3N2 is endemic in pigs in China and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. Health experts say pigs can carry human influenza viruses, which can combine (i.e. exchange homologous genome sub-units by genetic reassortment) with H5N1, passing genes and mutating into a form which can pass easily among humans. H3N2 evolved from H2N2 by antigenic shift. In August 2004, researchers in China found H5N1 in pigs.

Swine Flu in Humans

Can humans catch swine flu?

Swine flu viruses do not normally infect humans. However, sporadic human infections with swine flu have occurred. Most commonly, these cases occur in persons with direct exposure to pigs (e.g. children near pigs at a fair or workers in the swine industry). In addition, there have been documented cases of one person spreading swine flu to others. For example, an outbreak of apparent swine flu infection in pigs in Wisconsin in 1988 resulted in multiple human infections, and, although no community outbreak resulted, there was antibody evidence of virus transmission from the patient to health care workers who had close contact with the patient.

How common is swine flu infection in humans?

In the past, CDC received reports of approximately one human swine influenza virus infection every one to two years in the U.S., but from December 2005 through February 2009, 12 cases of human infection with swine influenza have been reported.

What are the symptoms of swine flu in humans?

The symptoms of swine flu in people are expected to be similar to the symptoms of regular human seasonal influenza and include fever, lethargy, lack of appetite and coughing. Some people with swine flu also have reported runny nose, sore throat, nausea, vomiting and diarrhea.

Can people catch swine flu from eating pork?

No. Swine influenza viruses are not transmitted by food. You can not get swine influenza from eating pork or pork products. Eating properly handled and cooked pork and pork products is safe. Cooking pork to an internal temperature of 160°F kills the swine flu virus as it does other bacteria and viruses.

How does swine flu spread?

Influenza viruses can be directly transmitted from pigs to people and from people to pigs. Human infection with flu viruses from pigs are most likely to occur when people are in close proximity to infected pigs, such as in pig barns and livestock exhibits housing pigs at fairs. Human-to-human transmission of swine flu can also occur. This is thought to occur in the same way as seasonal flu occurs in people, which is mainly person-to-person transmission through coughing or sneezing of people infected with the influenza virus. People may become infected by touching something with flu viruses on it and then touching their mouth or nose.

What do we know about human-to-human spread of swine flu?

In September 1988, a previously healthy 32-year-old pregnant woman was hospitalized for pneumonia and died 8 days later. A swine H1N1 flu virus was detected. Four days before getting sick, the patient visited a county fair swine exhibition where there was widespread influenza-like illness among the swine.

In follow-up studies, 76% of swine exhibitors tested had antibody evidence of swine flu infection but no serious illnesses were detected among this group. Additional studies suggest that one to three health care personnel who had contact with the patient developed mild influenza-like illnesses with antibody evidence of swine flu infection.

How can human infections with swine influenza be diagnosed?

To diagnose swine influenza A infection, a respiratory specimen would generally need to be collected within the first 4 to 5 days of illness (when an infected person is most likely to be shedding virus). However, some persons, especially children, may shed virus for 10 days or longer. Identification as a swine flu influenza A virus requires sending the specimen to CDC for laboratory testing.

What medications are available to treat swine flu infections in humans?

There are four different antiviral drugs that are licensed for use in the US for the treatment of influenza: amantadine, rimantadine, oseltamivir and zanamivir. While most swine influenza viruses have been susceptible to all four drugs, the most recent swine influenza viruses isolated from humans are resistant to amantadine and rimantadine. At this time, CDC recommends the use of oseltamivir or zanamivir for the treatment and/or prevention of infection with swine influenza viruses.

What other examples of swine flu outbreaks are there?

Probably the most well known is an outbreak of swine flu among soldiers in Fort Dix, New Jersey in 1976. The virus caused disease with x-ray evidence of pneumonia in at least 4 soldiers and 1 death; all of these patients had previously been healthy. The virus was transmitted to close contacts in a basic training environment, with limited transmission outside the basic training group. The virus is thought to have circulated for a month and disappeared. The source of the virus, the exact time of its introduction into Fort Dix, and factors limiting its spread and duration are unknown. The Fort Dix outbreak may have been caused by introduction of an animal virus into a stressed human population in close contact in crowded facilities during the winter. The swine influenza A virus collected from a Fort Dix soldier was named A/New Jersey/76 (Hsw1N1).

Is the H1N1 swine flu virus the same as human H1N1 viruses?

No. The H1N1 swine flu viruses are antigenically very different from human H1N1 viruses and, therefore, vaccines for human seasonal flu would not provide protection from H1N1 swine flu viruses.

Signs and Symptoms

According to the Centers for Disease Control and Prevention (CDC), in humans the symptoms of swine flu are similar to those of influenza and of influenza-like illness in general. Symptoms include fever, cough, sore throat, body aches, headache, chills and fatigue. A few more patients than usual have also reported diarrhea and vomiting.

Because these symptoms are not specific to swine flu, a differential diagnosis of probable swine flu requires not only symptoms but also a high likelihood of swine flu due to the person's recent history. For example, during the 2009 swine flu outbreak in the United States, CDC advised physicians to "consider swine influenza infection in the differential diagnosis of patients with acute febrile respiratory illness who have either been in contact with persons with confirmed swine flu, or who were in one of the five U.S. states that have reported swine flu cases or in Mexico during the 7 days preceding their illness onset." A diagnosis of confirmed swine flu requires laboratory testing of a respiratory sample (a simple nose and throat swab).

Main symptoms of swine flu in humans.

General Management and & Treatment

The aim is to provide interim guidance on the use of antiviral agents for treatment and chemoprophylaxis of swine influenza A (H1N1) virus infection. This includes patients with confirmed or suspected swine influenza A (H1N1) virus infection and their close contacts.

Case Definitions for Infection with Swine Influenza A (H1N1) Virus

A confirmed case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests:

1. real-time RT-PCR

2. viral culture

Infectious period

The infectious period for a confirmed case of swine influenza A (H1N1) virus infection is defined as 1 day prior to the case’s illness onset to 7 days after onset.

A probable case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness who is:

• positive for influenza A, but negative for H1 and H3 by influenza RT-PCR, or
• positive for influenza A by an influenza rapid test or an influenza immunofluorescence assay (IFA) plus meets criteria for a suspected case

A suspected case of swine influenza A (H1N1) virus infection is defined as a person with acute febrile respiratory illness with onset

• within 7 days of close contact with a person who is a confirmed case of swine influenza A (H1N1) virus infection, or
• within 7 days of travel to community either within the United States or internationally where there are one or more confirmed swine influenza A (H1N1) cases, or
• resides in a community where there are one or more confirmed swine influenza cases.

Close contact is defined as: within about 6 feet of an ill person who is a confirmed or suspected case of swine influenza A (H1N1) virus infection during the case’s infectious period.

Acute respiratory illness is defined as: recent onset of at least two of the following: rhinorrhea or nasal congestion, sore throat, cough (with or without fever or feverishness)

High-risk group for complications of influenza is defined as: a person who is at high-risk for complications of seasonal influenza: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e717a1.htm.However, it too early to ascertain what persons are at high-risk for complications of swine influenza A(H1N1) virus infection. This guidance will be updated as new information is available.

Clinicians should consider swine influenza A (H1N1) virus infection in the differential diagnosis of patients with febrile respiratory disease and who 1) live in areas in the U.S. with confirmed human cases of swine influenza A (H1N1) virus infection or 2) who traveled recently to Mexico or were in contact with persons who had febrile respiratory illness and were in the areas of the U.S. with confirmed swine influenza cases or Mexico in the 7 days preceding their illness onset.

Special Considerations for Children

Aspirin or aspirin-containing products (e.g. bismuth subsalicylate – Pepto Bismol) should not be administered to any confirmed or suspected ill case of swine influenza A (H1N1) virus infection aged 18 years old and younger due to the risk of Reye syndrome. For relief of fever, other anti-pyretic medications are recommended such as acetaminophen or non steroidal anti-inflammatory drugs.

Antiviral Resistance

This swine influenza A (H1N1) virus is sensitive (susceptible) to the neuraminidaseinhibitor antiviral medications zanamivir and oseltamivir. It is resistant to the adamantane antiviral medications amantadine and rimantadine.

Seasonal influenza A and B viruses continue to circulate at low levels in the U.S. and in Mexico. Currently circulating human influenzaA (H1N1) viruses are resistant to oseltamivir and sensitive (susceptible) to zanamivir, amantadine and rimantadine. Currently circulating human influenza A (H3N2) viruses are resistant to amantadine andrimantadine, but sensitive (susceptible) to oseltamivir and zanamivir. Therefore,at this time antiviral treatment recommendations for suspected cases of swineinfluenza A (H1N1) virus infection need to consider potential infection with swine influenza A (H1N1) virus as wellas human influenza viruses, andtheir different antiviral susceptibilities.

Antiviral Treatment

Suspected Cases

Empiric antiviral treatment is recommended for any ill person suspected to have swine influenza A (H1N1) virus infection. Antiviral treatment witheither zanamivir alone or with a combination of oseltamivir and either amantadine or rimantadine should be initiated as soon as possible after theonset of symptoms. Recommended duration of treatment is five days.Recommendations for use of antivirals may change as data on antiviral susceptibilities become available. Antiviral doses and schedules recommended for treatment of swine influenza A (H1N1) virus infection are the same as those recommended for seasonal influenza: http://www.cdc.gov/flu/professionals/antivirals/dosagetable.htm#table

Confirmed Cases

For antiviral treatment of a confirmed case of swine influenza A (H1N1) virus infection, either oseltamivir or zanamivir may be administered. Recommended duration of treatment is five days.These same antivirals should be considered for treatment of cases that test positive for influenza A but test negative for seasonal influenza viruses H3 and H1 by PCR.

Pregnant Women

Oseltamivir, zanamivir, amantadine, and rimantadine are all “PregnancyCategory C" medications, indicating that no clinical studies have beenconducted to assess the safety of these medications for pregnant women. Onlytwo cases of amantadine use for severe influenza illness during the thirdtrimester have been reported. However, both amantadine and rimantadine havebeen demonstrated in animal studies to be teratogenic and embryotoxic whenadministered at substantially high doses. Because of the unknown effects ofinfluenza antiviral drugs on pregnant women and their fetuses, these four drugsshould be used during pregnancy only if the potential benefit justifies thepotential risk to the embryo or fetus; the manufacturers' package insertsshould be consulted. However, no adverse effects have been reported among womenwho received oseltamivir or zanamivir during pregnancy or among infants born to such women.

Antiviral Chemoprophylaxis

For antiviral chemoprophylaxis of swine influenza A (H1N1) virus infection,either oseltamivir or zanamivir are recommended. Duration of antiviralchemoprophylaxis is 7 days after the last known exposure to an ill confirmedcase of swine influenza A (H1N1) virus infection. Antiviral dosing and schedules recommended for chemoprophylaxis of swine influenza A(H1N1) virus infection are the same as those recommended for {http://www.cdc.gov/flu/professionals/antivirals/dosagetable.htm#table seasonal influenza]:

Antiviral chemoprophylaxis (pre-exposure or post-exposure) with eitheroseltamivir or zanamivir is recommended for the followingindividuals:

• Household close contacts who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly) of a confirmed or suspected case.
• School children who are at high-risk for complications of influenza (persons with certain chronic medical conditions) who had close contact (face-to-face) with a confirmed or suspected case.
• Travelers to Mexico who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly).
• Border workers (Mexico) who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly).
• Health care workers or public health workers who had unprotected close contact with an ill confirmed case of swine influenza A (H1N1) virus infection during the case’s infectious period.

Antiviral chemoprophylaxis (pre-exposure or post-exposure) with either oseltamivir or zanamivir can be considered for the following:

• Any health care worker who is at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly) who is working in an area with confirmed swine influenza A (H1N1) cases, and who is caring for patients with any acute febrile respiratory illness.

8 Non-high risk persons who are travelers to Mexico, first responders, or border workers who are working in areas with confirmed cases of swine influenza A (H1N1) virus infection.

Prevention

Swine Influenza A (H1N1) Virus Biosafety Guidelines for Laboratory Workers

This guidance is for laboratory workers who may be processing or performing diagnostic testing on clinical specimens from patients with suspected swine influenza A (H1N1) virus infection, or performing viral isolation.

Diagnostic laboratory work on clinical samples from patients who are suspected cases of swine influenza A (H1N1) virus infection should be conducted in a BSL2 laboratory. All sample manipulations should be done inside a biosafety cabinet (BSC).

Viral isolation on clinical specimens from patients who are suspected cases of swine influenza A (H1N1) virus infection should be performed in a BSL2 laboratory with BSL3 practices (enhanced BSL2 conditions).

Additional precautions include

• Recommended Personal Protective Equipment (based on site specific risk assessment )
• Respiratory protection – fit-tested N95 respirator or higher level of protection.
• Shoe covers
• Closed-front gown
• Double gloves
• Eye protection (goggles or face shields)

Waste

• All waste disposal procedures should be followed as outlined in your facility standard laboratory operating procedures.

Appropriate disinfectants

• 70% Ethanol
• 5% Lysol
• 10% Bleach

All personnel should self monitor for fever and any symptoms. Symptoms of swine influenza infection include cough, sore throat, vomiting, diarrhea, headache, runny nose, and muscle aches. Any illness should be reported to your supervisor immediately.

For personnel who had unprotected exposure or a known breach in personal protective equipment to clinical material or live virus from a confirmed case of swine influenza A (H1N1), antiviral chemoprophylaxis with zanamivir or oseltamivir for 7 days after exposure can be considered.

Infection Control of Ill Persons in a Healthcare Setting

Patients with suspected or confirmed case-status should be placed in a single-patient room with the door kept closed. If available, an airborne infection isolation room (AIIR) with negative pressure air handling with 6 to 12 air changes per hour can be used. Air can be exhausted directly outside or be recirculated after filtration by a high efficiency particulate air (HEPA) filter. For suctioning, bronchoscopy, or intubation, use a procedure room with negative pressure air handling.

The ill person should wear a surgical mask when outside of the patient room, and should be encouraged to wash hands frequently and 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 to the environmental management of swine influenza. More information can be found at http://www.cdc.gov/ncidod/dhqp/gl_environinfection.html.

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. Maintain adherence to hand hygiene by washing with soap and water or using 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 suspected or confirmed cases should wear disposable non-sterile gloves, gowns, and eye protection (e.g., goggles) to prevent conjunctival exposure.

Masks and respirators: Until additional, specific information is available regarding the behavior of this swine influenza A (H1N1), the guidance in the October 2006 "Interim Guidance on Planning for the Use of Surgical Masks and Respirators in Healthcare Settings during an Influenza Pandemic" http://www.pandemicflu.gov/plan/healthcare/maskguidancehc.htmlExternal Web Site Policy. should be used. These interim recommendations will be updated as additional information becomes available.

Interim recommendations

• Personnel engaged in aerosol generating activities (e.g., collection of clinical specimens, endotracheal intubation, nebulizer treatment, bronchoscopy, and resuscitation involving emergency intubation or cardiac pulmonary resuscitation) for suspected or confirmed swine influenza A (H1N1) cases should wear a fit-tested disposable N95 respirator.
• Pending clarification of transmission patterns for this virus, personnel providing direct patient care for suspected or confirmed swine influenza A (H1N1) cases should wear a fit-tested disposable N95 respirator when entering the patient room.

• Respirator use should be in the context of a complete respiratory protection program in accordance with Occupational Safety and Health Administration (OSHA) regulations. Information on respiratory protection programs and fit test procedures can be accessed at www.osha.gov/SLTC/etools/respiratory. Staff should be medically cleared, fit-tested, and trained for respirator use, including: proper fit-testing and use of respirators, safe removal and disposal, and medical contraindications to respirator use.

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