Novel H1N1 Influenza (Swine Flu)

Last updated March 5, 2010

Agent
Swine Influenza in Pigs
Swine-Origin Influenza in Humans: Historic Perspective
2009-10 Pandemic: Case Counts and Clinical Features
Pandemic Perspective
Laboratory Testing for the Novel H1N1 Virus in Humans
Community Mitigation Measures
Recommendations for Use of Influenza A H1N1 2009 Monovalent Vaccine
Vaccine Development
Use of Antiviral Agents
Infection Control Considerations
Food Safety Issues
References

Note: Information on avian influenza is available in the overviews "Avian Influenza (Bird Flu): Implications for Human Disease" and "Avian Influenza (Bird Flu): Agricultural and Wildlife Considerations" in the Avian Flu section of this Web site. General information on pandemic influenza is available in the overview "Pandemic Influenza" in the Pandemic Influenza section of this Web site.

Agent

General Information about Influenza A Viruses

Swine influenza (illness in pigs) is caused by influenza A viruses. Influenza A viruses of swine origin can cause influenza in humans. General information about influenza A viruses is presented in the bullet points below.

Descriptive information

Influenza A viruses are negative-sense single-stranded RNA viruses and belong to the family Orthomyxoviridae and the genus Influenzavirus A.
Enveloped virions are 80 to 120 nm in diameter, are 200 to 300 nm long, and may be filamentous. They consist of spike-shaped surface proteins, a partially host-derived lipid-rich envelope, and matrix (M) proteins surrounding a helical segmented nucleocapsid (6 to 8 segments).
The virus envelope glycoproteins (hemagglutinin [HA] and neuraminidase [NA]) are distributed evenly over the virion surface, forming characteristic spike-shaped structures; antigenic variations in these proteins form the basis of the classification system for influenza A virus subtypes.

Influenza A virus subtypes

There are 16 different HA antigens (H1 to H16) and nine different NA antigens (N1 to N9) for influenza A.
Human disease historically has been caused by three subtypes of HA (H1, H2, and H3) and two subtypes of NA (N1 and N2). More recently, human disease has been recognized to be caused by additional HA subtypes, including H5, H7, and H9 (all from avian origin).
All of these subtypes have been found in birds, and birds are the primordial reservoir for influenza A viruses.
Several subtypes have been found in pigs (see section below for more information).

Information about the 2009 Novel H1N1 Virus

The 2009 novel A H1N1 virus appears to be of swine origin and contains a unique combination of gene segments that has not been identified in the past (see References: Garten 2009, Zimmer 2009).

The NA and M gene segments are in the Eurasian swine genetic lineage; they were originally derived from a wholly avian influenza virus and likely entered the Eurasian swine population in 1979. Until emergence of the current novel H1N1 strain, these gene segments had not been identified outside Eurasia.
The HA, NP, and NS gene segments are in the classical swine lineage; they likely entered the swine population around 1918 and are common in North America.
The PB2 and PA gene segments are in the swine triple reassortant lineage; viruses of this lineage entered pigs in North America around 1998. Viruses that seeded this lineage were originally of avian origin.
The BP1 gene segment is in the swine triple reassortant lineage and was seeded in pigs from humans also around 1998; this virus was also originally from an avian source.

A recent molecular analysis of the novel H1N1 virus demonstrates that the virus possesses a distinctive evolutionary trait (genetic distinctness) that may be characteristic in pig-human interspecies transmission of influenza A (reported cases of similar reassortant viruses of swine origin occurred in Iowa, Maryland, and Wisconsin between 1991 and 2006) (see References: Nava 2009).

Swine Influenza in Pigs

Virus Subtypes

Influenza A was first recognized as a clinical illness in swine in 1918, which coincided with the 1918-19 influenza pandemic in humans. H1N1 influenza A virus was first isolated from pigs in the United States in 1930.

Swine influenza is considered endemic in swine in the United States, and animal outbreaks occur with regular frequency (usually in the fall and winter months). Key information about swine influenza viral subtypes in North America includes the following (see References: Olsen 2002):

From 1930 through 1998 swine influenza in North America was primarily caused by viruses of the classical H1N1 lineage.
Since 1998, H3N2 viruses with genes derived from human, swine, and avian viruses (triple reassortant viruses) have become an important cause of swine influenza in North America, along with classical H1N1.
H1N2 viruses that resulted from reassortment between the triple reassortant H3N2 viruses and classical H1N1 swine viruses also have been isolated in swine in the United States.
Avian H4N6 virus was recognized in swine in Canada in 1999, but spread beyond the original farm of detection was not identified.
A novel H3N1 influenza virus was isolated from swine in the United States in the mid 2000s; this virus may have risen from reassortment of an H3N2 turkey isolate, a human H1N1 isolate, and currently circulating swine influenza viruses (see References: Lekcharoensuk 2006).

Influenza viruses also have been identified in swine in South America, Europe (including the United Kingdom, Sweden, and Italy), Africa (Kenya), and in parts of eastern Asia (see References: WHO: Swine influenza frequently asked questions).

Clinical Illness in Swine

Swine influenza is an upper respiratory disease that causes outbreaks in herds. The incubation period in swine is usually 1 to 3 days. Clinical signs include fever, loss of appetite, weight loss, lethargy, coughing, sneezing, nasal discharge, labored breathing, conjunctivitis, and spontaneous abortion (see References: AVMA 2007). The mortality rate is relatively low (1% to 3%), and most affected animals recover within 5 to 7 days after illness onset. Some pigs exhibit severe viral pneumonia, which is the major cause of death. Secondary bacterial or viral infections also can occur. Pigs begin excreting the virus within 24 hours after infection, and may shed the virus for 7 to 10 days. A carrier state can exist for up to 3 months.

2009 Novel H1N1 Strain in Swine

To date, H1N1 has not been identified in swine herds in the United States. In May 2009, however, the Canadian Food Inspection Agency (CFIA) indicated that it had found the novel H1N1 influenza virus in a swine herd in Alberta (see References: CFIA 2009: An Alberta swine herd investigated for H1N1 flu virus). Initially, the agency believed that the pigs were exposed to the virus from a Canadian who had recently returned from Mexico and had an influenza-like illness (ILI). Signs of illness were subsequently observed in the pigs; the herd was placed under quarantine and later destroyed. The Canadian subsequently tested negative for the virus, and the source of exposure for the pigs remains unknown. According to the CFIA, herds in which the virus is detected will not be quarantined or destroyed, but will be monitored to verify that infected animals recover before they are sent to slaughter (see References: CFIA 2009: Management of pandemic H1N1 in swine herds).

In mid-June 2009, an outbreak of novel H1N1 in a swine herd in Argentina was reported to the World Organization for Animal Health (OIE). Approximately 30% of the herd developed symptoms, but none of the animals died. According to the report, in early June two workers on the farm had ILI, but their illnesses were not confirmed as H1N1 influenza (see References: OIE 2009).

In July 2009, outbreaks of H1N1 influenza were recognized in several swine herds in Australia (see References: Australian Government Department of Agriculture, Fisheries, and Forestry 2009).

Novel H1N1 in Poultry

In August 2009, the novel H1N1 strain was isolated from domestic turkeys on two farms in Chile (see References: FAO 2009). A temporary quarantine was established and the birds were allowed to recover before going to market (rather than being culled). This incident raises the possibility that other poultry flocks around the globe could become infected with H1N1. The major concern is that if the novel H1N1 virus and the H5N1 virus coinfect poultry, a new reassortant strain could emerge that could be much more lethal to humans than the current H1N1 pandemic strain.

Swine-Origin Influenza in Humans: Historic Perspective

Cases Identified in Civilians Before February 2009

A 2007 report identified 37 civilian swine-origin influenza cases reported in the medical literature between 1958 and 2005 (see References: Myers 2007). Of these cases, 19 occurred in the United States, six in Czechoslovakia, four in the Netherlands, three in Russia, three in Switzerland, one in Canada, and one in Hong Kong. Twenty-two (61%) reported recent exposure to pigs. The overall case fatality rate was 17%. Possible or probably limited human-to human transmission was reported in several situations.

Between December 2005 and February2009, 11 sporadiccases of infection in humans with triple-reassortant swine influenzaA H1 viruses were reported to the Centers for Disease Control and Prevention (CDC) (see References: Shinde 2009, Newman 2008). Ten of the infections were caused by triple reassortant H1N1 viruses and one by triple reassortant H1N2 virus. Seven cases involved either direct exposure to pigs or close proximity to pigs (ie, within 6 feet) shortly before illness onset. In two other cases the patients were in the general vicinity of pigs before illness onset, one was epidemiologically linked to a possible case, and one had no pig exposure. All patients survived the illness, although four were hospitalized and two required mechanical ventilation. Among the 10 patients with known clinical symptoms,nine reported fever, all had cough, six had a headache, and three reported diarrhea.

An additional swine-origin influenza case occurred in Spain in 2008 (see References: Adiego 2009, Van Reeth 2009).

Swine-Origin Influenza Outbreak at Fort Dix, New Jersey, 1976

An outbreak of swine-origin influenza was recognized in early 1976 among military personnel at Fort Dix, New Jersey. Thirteen clinical cases occurred with one death; the cause of the outbreak remains unknown, and no exposure to pigs was identified (see References: Gaydos 2006). Retrospective serologic testing subsequently demonstrated that up to 230 soldiers had been infected with the novel virus, which was an H1N1 strain. The outbreak did not spread beyond Fort Dix.

The US Swine-Origin Influenza Vaccination Campaign, 1976

Following the Fort Dix outbreak, the federal government embarked upon a universal vaccination campaign aimed at vaccinating the United States population against the H1N1 swine-origin influenza strain because of concerns that the novel strain could cause a pandemic (see References: Sencer 2006). A vaccine was developed and vaccinations began in the fall of 1976. By late in the year, more than 40 million Americans had been vaccinated. Soon after vaccinations began, however, reports of Guillain-Barre syndrome (GBS) associated with vaccination began to surface. By December 1976, the federal government decided to halt the vaccination campaign since no evidence of H1N1 transmission had been detected during the course of the year and there was concern regarding an association between GBS and the H1N1 vaccine. A subsequent epidemiologic study demonstrated a slightly elevated risk for acquiring GBS among persons who received the H1N1 swine-origin influenza vaccine (see References: Schonberger 1979) .

2009-10 Pandemic: Case Counts and Clinical Features

Current Case Status

Cases of novel H1N1 influenza were first identified in mid-April 2009 in California and soon thereafter in Texas and Mexico (see References: CDC 2009: Swine influenza A [H1N1] infection in two children—southern California, March-April 2009; CDC 2009: Update: swine influenza A [H1N1] infections—California and Texas). The earliest recognized case occurred in Mexico with illness onset on Mar 17, 2009 (see References: CDC: Outbreak of swine-origin influenza A (H1N1) virus infection—Mexico, March-April 2009). Since that time, the virus has spread across the globe, and on Jun 11, 2009, the World Health Organization (WHO) declared the onset of an influenza pandemic. Case summaries for the United States and countries affected across the world are presented below. A recent analysis of global air traffic patterns illustrates how the virus spread via air travel from its likely source in Mexico to other areas of the world, most notably the United States (see References: Khan 2009).

The CDC discontinued reporting the number of individual cases of novel H1N1 influenza as of Jul 24, 2009. The agency now reports weekly the cumulative number of US laboratory-confirmed influenza-associated hospitalizations and deaths since Aug 30, 2009. The numbers as of March 2, 2010, were 40,805 hospitalizations (187 more than the previous week's total) and 2,009 deaths (an increase of 15 from previous week) (see References: CDC: H1N1 flu situation updates). No states are reporting widespread flu activity.

The WHO ceased regular reporting of specific case counts Jul 16, 2009, saying many countries were having difficulty tracking individual numbers and that their time would be better spent on investigating severe cases and other exceptional events (see References: WHO 2009: Pandemic [H1N1] 2009 briefing note 3). In all, 213 countries and territories have reported H1N1 activity. The cumulative number of deaths from pandemic H1N1 influenza reported to WHO regional offices as of Feb 28, 2010, was at least 16,455 (an increase of 229 from the week before), a number WHO acknowledges significantly understates the actual number. The countries and territories shown in the table below have been affected by the virus (see References: WHO 2009: Situation updates). An interactive map showing the timeline of events is available on the WHO Web site (see References: WHO 2009: Timeline of influenza A (H1N1) cases).

Countries/Territories Reporting Cases of Novel H1N1 Influenza A Virus Infection
Western Hemisphere	Europe	Africa	Middle East	Asia/Pacific
Antigua & Barbuda Argentina Bahamas Barbados Belize Bermuda Bolivia Brazil British Virgin Islands Canada Cayman Islands Chile Colombia Costa Rica Cuba Curacao Dominica Dominican Republic Ecuador El Salvador Falkland Islands French Guiana Grenada Guadaloupe Guatemala Guyana Haiti Honduras Jamaica Martinique Mexico Nicaragua Panama Paraguay Peru Saint Kitts & Nevus Saint Lucia Saint Martin Saint Vincent & Grenadines Sint Eustatius Suriname Trinidad & Tobago Turks & Caicos Islands United States Uruguay Venezuela	Andorra Austria Armenia Azerbaijan Belgium Bosnia/Herzegovina Bulgaria Croatia Czech Republic Denmark Estonia Finland France Germany Greece Hungary Iceland Italy Ireland Isle of Man Jersey Latvia Lithuania Luxembourg Malta Macedonia Moldova Monaco Montenegro Netherlands Norway Poland Portugal Romania Russia Serbia Spain Slovakia Slovenia Sweden Switzerland Ukraine United Kingdom	Algeria Angola Botswana Burundi Cameroon Cape Verde Chad Congo Cote d'Ivoire Djibouti Ethiopia Gabon Ghana Kenya Lesotho Libya Malawi Mali Mozambique Mauritania Mauritius Morocco Namibia Niger Nigeria Rawanda Reunion Island Sao Tome/Principe Senegal Seychelles Somalia South Africa Sudan Swaziland Tanzania Tunisia Uganda Zambia Zimbabwe	Afghanistan Bahrain Cyprus Egypt Iran Iraq Israel Jordan Kuwait Lebanon Oman Palestine Saudi Arabia Syria Turkey United Arab Emirates West Bank/Gaza Strip Yemen	American Somoa Australia Bangladesh Brunei Darussalam Bhutan Cambodia China Cook Island Fiji French Polynesia Guam India Indonesia Japan Kazakhstan Kiribati Korea, Democratic People's Republic of Korea, Republic of Laos Madagascar Malaysia Maldives Marshall Islands Micronesia Mongolia Myanmar Nauru Nepal New Caledonia New Zealand Pakistan Palau Papua New Guinea Philippines Samoa Singapore Solomon Islands Sri Lanka Thailand Timor-Leste Tonga Tuvalu Vanuatu Vietnam Wallis & Futuna

CDC Case Definitions for Novel H1N1 Influenza Virus Infection

The CDC case definitions for confirmed and probable cases (published June 1, 2009) are as follows (see References: CDC 2009: Interim guidance on case definitions to be used for investigations of swine influenza A [H1N1] cases).

Confirmed case: A confirmed case of novel H1N1 infection is defined as a person with an acute febrile respiratory illness with laboratory confirmed infection by one or more of the following tests:

Real-time reverse-transcription polymerase chain reaction (RT-PCR)
Viral culture

Probable case: A probable case of novel H1N1 infection is defined as a person with ILI (ie, an illness with a fever and a cough or sore throat) who is positive for influenza A, but negative for H1 and H3 by RT-PCR.

Clinical Information

Preexisting immunity to the novel H1N1 strain

According to the CDC, vaccination with recent (2005 to 2009) seasonal influenza vaccines is unlikely to provide protection or pre-existing immunity against the novel influenza A H1N1 virus (see References: CDC 2009: Serum cross-reactive antibody response to a novel influenza A [H1N1] virus after vaccination with seasonal influenza vaccine).

Children in the United States appear to be largely serologically naive to the novel influenza A H1N1 virus. Conversely, adults may have some degree of preexisting immunity, especially those 60 years of age or older. It is possible that some adults in this age-group may have had previous exposure (through either prior infection or remote vaccination) to an influenza A H1N1 virus that is genetically and antigenically more closely related to the novel influenza A H1N1 virus than are contemporary seasonal H1N1 strains (see References: CDC 2009: Serum cross-reactive antibody response to a novel influenza A [H1N1] virus after vaccination with seasonal influenza vaccine).

Transmission

Available data indicate that the novel H1N1 virus is transmitted in ways similar to other influenza viruses, including large-particle respiratory droplet transmission (eg, when an infected person coughs or sneezes near a susceptible person); transmission via aerosols may also be important.
Two recent studies of novel H1N1 transmission in ferrets found somewhat conflicting results:

A study from the Netherlands showed that the virus was readily transmitted between ferrets, primarily through aerosols, and that the virus replicated deep in the lungs (see References: Munster 2009).
A study from the CDC and the Massachusetts Institute of Technology found that the virus was transmitted via direct contact and by respiratory droplets, but that transmission was not highly efficient between infected and uninfected ferrets (see References: Maines 2009).

Monitoring the reproduction ratio estimate (ie, average number of secondary cases per primary case) for the novel H1N1 virus is a way to determine the potential overall magnitude of spread. A recent report suggests that the reproduction ratio was less than 2.2 to 3.1 in Mexico, depending on the generation interval (which estimates the average time between infection in a primary case and its secondary cases) (see References: Boelle 2009). The reproduction ratio for The potential for ocular, conjunctival, or gastrointestinal infection is unknown; therefore, all respiratory secretions and bodily fluids (including diarrheal stool) of novel H1N1 influenza cases should be considered potentially infectious. For more information on transmission, see the section Infection Control Considerations below.

Incubation period

The estimated incubation period is unknown and could range from 1 to 7 days, although the incubation period for most cases will likely range from 1 to 4 days.

Infectious period

The duration of shedding for the novel H1N1 virus is unknown; therefore, until data are available, the estimated duration of viral shedding is based on seasonal influenza virus infection.

Infected persons are assumed to be shedding virus from the day prior to illness onset until resolution of symptoms. Persons with novel H1N1 infection should be considered potentially contagious for up to 7 days following illness onset.
Persons who continue to be ill longer than 7 days after illness onset should be considered potentially contagious until symptoms have resolved.
Children (especially younger children) and immunosuppressed or immunocompromised persons might be contagious for longer periods.

Clinical findings

From April 15 through May 5, 642 confirmedcases of novel H1N1 infection were identified in the United States (see References: Novel Swine-Origin Influenza A [H1N1] Virus Investigation Team). In patients for whom clinical information was available, the most common presentingsymptoms were fever (371 of 394 [94%]), cough (365 of 397 [92%]), and sorethroat (242 of 367 [66%]). Diarrhea was present in 82 of 323 patients (25%) and vomiting in 74 of 295 patients (25%).Of the 399 patients for whom hospitalization status was known,36 (9%) required hospitalization. Two patients died; one was a 23-month-old child and one was a pregnant 33-year-old woman.

In a report from the WHO dated May 22, 2009, key clinical features of laboratory-confirmed cases for which data are available include the following (see References: WHO 2009: Human infection with new influenza A [H1N1] virus: clinical observations from Mexico and other affected countries, May 2009):

Most patients appear to have uncomplicated, typical influenza-like illness and recover spontaneously. The most commonly reported symptoms include cough, fever, sore throat, malaise, and headache. Fever has been absent in some patients.
Almost one half of cases in the United States requiring hospitalization as well as 21 (46%) of 45 fatal cases in Mexico for which data are available involved underlying conditions, including pregnancy, asthma, other lung diseases, diabetes, morbid obesity, autoimmune disorders and associated immunosuppressive therapies, neurologic disorders, and cardiovascular disease.
Among 20 pregnant women with H1N1 in the United States, three required hospitalization and one of these died.
Among 45 fatal cases in Mexico, 54% of patients were previously healthy and most were 20 to 59 years of age. The median time from symptom onset to death was 10 days (range, 2 to 33 days). The clinical course for fatal cases in Mexico has been characterized by:

Severe pneumonia with multifocal infiltrates (including nodular alveolar and, less frequently, basilar opacities) on chest x-ray (bacterial coinfections were documented in three fatal cases)
Rapid progression to acute respiratory distress syndrome (ARDS) and renal or multiorgan failure (24% of fatal cases)

Another study from Mexico found a significant increase in the rate of severe pneumonia between March 24 and April 29, 2009 (during the time of peak novel H1N1 influenza activity), with a shift in the age distribution to a younger segment of the population. The age-group 5 to 59 represented 87% of deaths from severe pneumonia compared to approximately 17% on average during other influenza epidemic periods (see References: Chowell 2009). A case series of 18 patients with pneumonia caused by H1N1 influenza who were hospitalized in the Mexico City area during March and April 2009 reported that 12 patients required mechanical ventilation and seven died (see References: Perez-Padilla 2009); most patients were previously healthy adults. These findings clearly demonstrate that novel H1N1 can cause severe disease and death in otherwise healthy persons.

A report issued in August 2009 analyzed data on 574 fatal cases worldwide (see References: Vaillant 2009). The authors found that the mean and median age in fatal cases was 37 and 51% of patients were between 20 and 49 years old. The overall case-fatality rate was 0.4% (although this rate may be falsely high, since the denominator [ie, total number of known cases] is likely underestimated). Approximately one half of the patients had an underlying medical condition; obesity and diabetes were most commonly identified.

Groups at high risk for complications

According to the CDC, at this time, the same age and risk groups who are at higher risk for seasonal influenza complications should also be considered at higher risk for novel H1N1 influenza complications. These include the following groups:

Pregnant women
Children less than 5 years old
Persons aged 65 or older (the risk of infection in this group appears to be lower than for other age-groups, but once people of this age become ill they are at increased risk of complications)
Children and adolescents (age 6 months to 18 years) who are receiving long-term aspirin therapy and who might be at risk for experiencing Reye syndrome after influenza virus infection
Adults and children who have chronic pulmonary, cardiovascular, hepatic, hematological, neurologic, neuromuscular, or metabolic disorders
Adults and children who have immunosuppression (including immunosuppression caused by medications or by HIV)
Residents of nursing homes and other chronic-care facilities

Clinical guidance for management of certain high-risk patients can be found on the CDC Swine Flu H1N1 Guidance Web page.

Pandemic Perspective

Pandemic Phases

As noted above, on June 11, 2009, the WHO declared the start of an influenza pandemic for the novel H1N1 virus. The various phases that a pandemic will likely go through are outlined in the following table (see References: WHO: Current WHO phase of pandemic alert).

WHO Pandemic Phases
Phase	Description
Phase 1	No viruses circulating among animals have been reported to cause infections in humans.
Phase 2	An animal influenza virus circulating among domesticated or wild animals is known to have caused infection in humans, and is therefore considered a potential pandemic threat.
Phase 3	An animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks. Limited human-to-human transmission may occur under some circumstances, for example, when there is close contact between an infected person and an unprotected caregiver. However, limited transmission under such restricted circumstances does not indicate that the virus has gained the level of transmissibility among humans necessary to cause a pandemic.
Phase 4	This phase is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause “community-level outbreaks.” The ability to cause sustained disease outbreaks in a community marks a significant upwards shift in the risk for a pandemic. Any country that suspects or has verified such an event should urgently consult with WHO so that the situation can be jointly assessed and a decision made by the affected country if implementation of a rapid pandemic containment operation is warranted. Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion.
Phase 5	This phase 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.
Phase 6	This pandemic phase is characterized by community-level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in phase 5. Designation of this phase will indicate that a global pandemic is under way.
Post-Peak Period	During the post-peak period, pandemic disease levels in most countries with adequate surveillance will have dropped below peak observed levels. The post-peak period signifies that pandemic activity appears to be decreasing; however, it is uncertain if additional waves will occur, and countries will need to be prepared for a second wave. Previous pandemics have been characterized by waves of activity spread over months. Once the level of disease activity drops, a critical communications task will be to balance this information with the possibility of another wave. Pandemic waves can be separated by months, and an immediate “at-ease” signal may be premature.
Post-pandemic period	In the post-pandemic period, influenza disease activity will have returned to levels normally seen for seasonal influenza. It is expected that the pandemic virus will behave as a seasonal influenza A virus. At this stage, it is important to maintain surveillance and update pandemic preparedness and response plans accordingly. An intensive phase of recovery and evaluation may be required.

Historic Considerations

Scientists and public health officials have long been concerned that a reassorted influenza A virus could emerge in pigs and become a pandemic strain.

Pigs can be infected with influenza A viruses from avian, human, or swine origin; therefore, pigs have been considered a "mixing vessel" for new viruses that can occur as a result of reassortment between viruses of diverse origins (see References: Webster 1992). Triple reassorted viruses (containing genetic material from human, avian, and swine strains) have been transmitted from pigs to humans (see References: Newman 2008), and the current H1N1 strain appears to be a reassorted virus.
Because this novel H1N1 virus is of swine origin, it is substantially different from human influenza A H1N1 viruses; therefore, a large proportion of the population might be susceptible to infection and the seasonal influenza vaccine H1N1 strain likely will not provide protection (see References: CDC 2009: Swine influenza A [H1N1] infection in two children—Southern California, March-April 2009). These features enhance the pandemic potential of the new strain.

Of interest, the 1918 pandemic began with a relatively mild "herald" wave in the spring of 1918. During that time, outbreaks were reported in Europe and in the United States (particularly in military training camps for new recruits headed to the war in Europe) (see References: Reid 2001, Glezen 1996).This first wave was followed by two additional waves in the fall and winter of 1918-19 that were much more severe (see References: Taubenberger 2006). The second, highly virulent, wave spread rapidly around the world in the fall of 1918; it took only 2 months for the pandemic to circle the globe at that time.

Of the three pandemics that occurred in the 1900s, two involved reassorted viruses, but none were reassortants with swine viruses.

Recent genetic sequencing of the 1918 H1N1 strain indicates that the strain was of avian origin and that the strain did not reassort with a human strain, but rather gradually adapted to humans until it could be efficiently transmitted person to person (see References: Taubenberger 2005). Current evidence indicates that the 1918 virus was an avian-like virus derived in toto from an unknown source (see References: Taubenberger 2006).
The 1957-58 pandemic, referred to as the "Asian flu," was caused by an H2N2 strain and originated in China. The pandemic strain acquired three genes from the avian influenza gene pool in wild ducks by genetic reassortment and obtained five other genes from the then-circulating human strain.
The 1968-69 pandemic, referred to as the "Hong Kong flu," was caused by an H3N2 strain. The strain acquired two genes from the duck reservoir by reassortment and kept six genes from the virus circulating at the time in humans.

Laboratory Testing for the Novel H1N1 Virus in Humans

Duration of viral shedding

The estimated duration of viral shedding is based on seasonal influenza virus infection. Infected persons are assumed to be shedding virus and potentially infectious from the day prior to illness onset until resolution of fever. Infected persons should be assumed to be contagious up to 7 days from illness onset. Some persons who are infected might potentially shed virus and be contagious for longer periods (eg, young infants, and immunosuppressed or immunocompromised persons).

Screening for the Novel H1N1 Infection

The CDC recommends the following for H1N1 testing (see References: CDC 2009: Interim guidance for clinicians on identifying and caring for patients with swine-origin influenza A [H1N1 virus infection):

Clinicians should test persons for the novel influenza H1N1 virus if they have an acute febrile respiratory illness or sepsis-like syndrome. Certain groups may have atypical presentations including infants, elderly and persons with compromised immune systems.
Priority for testing includes persons who: (1) require hospitalization or (2) are at high risk for severe disease.
Not all people with suspected novel influenza H1N1 infection need to have the diagnosis confirmed, especially if the person resides in an affected area or if the illness is mild.
Recommendations on whom to test may differ by state or community. Clinicians should be aware of local guidance on testing and should use their clinical judgment in addition to this guidance for deciding when to test for the novel influenza A H1N1 virus.
Clinicians should contact their state public health department if they test a person for novel influenza A H1N1 infection to obtain information on what clinical and epidemiological data to collect and specimen shipment protocols in their state.

Specimen Collection

All suspected cases of novel H1N1 infection should have upper respiratory specimens collected to test for the virus (see References: CDC 2009: Interim guidance on specimen collection and processing for patients with suspected swine influenza A (H1N1) virus infection).

Preferred respiratory specimens

The following should be collected as soon as possible after illness onset: nasopharyngeal swab/aspirate or nasal wash/aspirate. If these specimens cannot be collected, a nasal swab or oropharyngeal swab is acceptable.
For patients who are intubated, an endotracheal aspirate should also be collected. Bronchoalveolar lavage (BAL) and sputum specimens are also acceptable.
Specimens should be placed into sterile viral transport media (VTM) and immediately placed on ice or cold packs or at 4°C (refrigerator) for transport to the laboratory.

Swabs

Ideally, swab specimens should be collected using swabs with a synthetic tip (eg, polyester or Dacron) and an aluminum or plastic shaft. Swabs with cotton tips and wooden shafts are not recommended. Specimens collected with swabs made of calcium alginate are not acceptable.
The swab specimen collection vials should contain 1 to 3 mL of VTM (eg, containing protein stabilizer, antibiotics to discourage bacterial and fungal growth, and buffer solution).

Storing clinical specimens

All respiratory specimens should be kept at 4°C for no longer than 4 days.

Shipping clinical specimens

Clinical specimens should be shipped on wet ice or cold packs in appropriate packaging.
All specimens should be labeled clearly and include information requested by the appropriate state public health laboratory.
Suspect case specimens shipped from the state public health laboratory to the CDC should include all information required for seasonal influenza surveillance isolate or specimen submission.

Real-Time RT PCR Testing

Currently, the novel H1N1 virus will test positive for influenza A and negative for H1 and H3 by real-time RT-PCR. If reactivity of real-time RT-PCR for influenza A is strong (eg, Ct <30), it is more suggestive of a novel influenza A virus.
Confirmation of novel H1N1 virus is available by real-time RT-PCR at state public health laboratories.

Rapid Influenza Diagnostic Tests

Background

Rapid influenza diagnostic tests (RIDTs) detect influenza viral nucleoprotein antigen; these tests can provide results within 30 minutes or less. Commercially available RIDTs can perform one of the following functions:

Detect and distinguish between influenza A and B viruses
Detect both influenza A and B but not distinguish between influenza A and B viruses
Detect only influenza A viruses

None of the RIDTs currently approved by the US Food and Drug Administration (FDA) can distinguish between influenza A virus subtypes, and RIDTs cannot provide any information about antiviral drug susceptibility. For detection of seasonal influenza A virus infection in respiratory specimens, RIDTs have low to moderate sensitivity compared with viral culture or RT-PCR. The sensitivities of RIDTs to detect influenza B viruses are lower than for detection of influenza A viruses. The sensitivities of RIDTs appear to be higher for specimens collected from children than specimens collected from adults.

The CDC has recently developed guidance on the use and interpretation of rapid tests for diagnosis of H1N1 influenza (see References: CDC 2009: Interim guidance for the detection of novel influenza A virus using rapid influenza diagnostic tests).

Reliability and interpretation of rapid influenza test results

The reliability of rapid influenza diagnostic tests depends largely on the conditions under which they are used, and is entirely based on the experience with seasonal influenza.
For detection of seasonal influenza virus infection, sensitivities of rapid diagnostic tests are approximately 50% to 70% when compared with viral culture or RT-PCR, and specificities of rapid diagnostic tests for influenza are approximately 90% to 95%.
A recent analysis of rapid-test results (using the QuickVueInfluenza A+B test) among military service personnel and their dependents showed that the sensitivity of the rapid test for novel H1N1 influenza virus detection (using RT-PCR as the standard) was 51% with a 95% confidence interval [CI] of 35 to 67 (see References: Faix 2009). The sensitivity of the test for seasonal H1N1 was 63% and for seasonal H3N2 31%, and the specificity of the test for each of the three viruses was 99%.
False-positive (and true-negative) results are more likely to occur when influenza is uncommon in the community, which is generally at the beginning and end of an outbreak.
False-negative (and true-positive) results are more likely to occur when influenza is common in the community, which is typically at the height of an outbreak.
Test sensitivity may vary depending on collection timing. Respiratory specimens for testing should be collected in the first 4 to 5 days of illness when viral shedding is greatest.
Given these limitations, the decision of whether or not to test patients with rapid influenza diagnostic tests should be based on the patient's presenting symptoms, whether or not cases of novel H1N1 infection have been confirmed in the area, and the patient's risk for severe disease or other complications.
How to interpret a positive test result:

A patient testing positive for influenza B by a rapid diagnostic test likely has been infected with seasonal influenza B virus that is continuing to circulate or is a false-positive result. Such a patient is unlikely to have a novel H1N1 infection.
There are several possibilities when a patient tests positive for influenza A by rapid antigen test:

The patient might have novel H1N1 virus infection.
The patient might have seasonal influenza A virus infection.
The result might be a false-positive.

Follow-up actions for patients who test positive for influenza A on a rapid test depend on the local situation, and clinicians should follow guidance from their state or local health departments.

In areas with many new confirmed cases of novel H1N1 infection and where community spread of H1N1 is occurring, patients who test positive can be treated empirically with antiviral medications if clinically indicated without further testing.
In areas with no or few confirmed cases of novel H1N1 infection, a nasopharyngeal swab/aspirate or nasal aspirate should be collected and sent to the state public health laboratory for RT-PCR to determine if the patient has novel H1N1 infection, seasonal influenza A virus infection, or a false-positive result.

Follow-up actions for patients who test negative for influenza A on a rapid test also depend on the local situation, and clinicians should follow guidance from their state or local health departments.

Novel H1N1 infection cannot be excluded when a patient tests negative for influenza A by rapid antigen test.
If the patient has an epidemiologic link to a confirmed case (ie, close contact with a confirmed case), or has either traveled to or resides in a community where there are one or more confirmed novel H1N1 cases, further testing and treatment should be based on clinical suspicion, severity of illness, and risk for complications.
If there is no epidemiologic link and the patient has mild illness, further testing and treatment are not recommended.

Immunofluorescence (DFA or IFA)

These tests can distinguish between influenza A and B viruses.
A patient with a positive test for influenza A by immunofluorescence may meet criteria for a probable case.
Immunofluorescence depends on the quality of a clinical specimen and operator skills, and has unknown sensitivity and specificity to detect human infection with the novel H1N1 virus in clinical specimens. Therefore, a negative immunofluorescence could be a false-negative and should not be assumed a final diagnostic test for novel H1N1 infection.

Viral Culture

Isolation of the novel H1N1 virus is diagnostic of infection, but may not yield timely results for clinical management.
A negative viral culture does not exclude infection with the novel H1N1 virus.

Submission of Tissue Specimens for Pathologic Evaluation for the Novel H1N1 Virus

Collection of tissue specimens

The CDC has released guidance on collection of tissue specimens (see References: CDC 2009: Guidelines for the submission of tissue specimens for the pathologic evaluation of influenza virus infections). According to the CDC, the preferred specimens include fresh-frozen and wet-fixed tissue specimens representing extensive samples from pulmonary sites in addition to specimens from other organs showing pathology. Appropriate specimens include:

Central (hilar) lung with segmental bronchi, right and left primary bronchi, trachea (proximal and distal)
Representative pulmonary parenchyma from right and left lung
For patients with suspected myocarditis, encephalitis, or rhabdomyalysis, myocardium (right and left ventricle), central nervous system (cerebral cortex, basal ganglia, pons, medulla, and cerebellum), and skeletal muscle, respectively
Any other organ showing significant gross or microscopic pathology

Submission of specimens

Wet tissue: Multiple 1- x 2-cm pieces of tissue from sites listed above in 10% neutral buffered formalin are submitted.
Fresh-frozen tissue: Single piece of tissue as listed above are sent separately on dry ice.
Paraffin-embedded tissue blocks: Blocks can be submitted in addition to wet–fixed and fresh-frozen and are the preferred specimens to submit in cases where tissues have been in formalin for a significant time. Prolonged fixation (>2 weeks) may interfere with some immunohistochemical and molecular diagnostic assays.
Shipping details: Information on shipping can be found in the CDC guidance, "Guidelines for the submission of tissue specimens for the pathologic evaluation of influenza virus infections" (see References).

Required supporting documentation

A brief clinical history
Copy of the preliminary or final pathology report including, if available, digital photos of gross specimens
Copy of any pertinent laboratory reports (including rapid antigen, culture, and PCR test results)
The full name, title, complete mailing address, e-mail address, phone and fax numbers of the submitter

Laboratory Biosafety

Guidance on laboratory biosafety is available from the CDC (see References: CDC 2009: Interim biosafety guidance for all individuals working with clinical specimens or isolates from patients with suspected novel influenza A H1N1 virus infection).

Rapid tests

The appropriate personal protective equipment (PPE) for most rapid testing includes:

Laboratory coat
Gloves
Eye protection
Facemask (surgical, dental, medical procedure, isolation, or laser masks)

For other rapid tests involving more complex test methods that might include steps that could generate aerosols (eg, vortexing), additional respiratory protection (such as an N-95 respirator) is needed.

Clinical laboratory testing (laboratory diagnostic work)

Diagnostic laboratory work on clinical samples from patients who are suspected cases of novel influenza A H1N1 virus infection should be conducted in a biosafety level 2 (BSL-2) laboratory. All sample manipulations with the potential for creating an aerosol should be done inside a biosafety cabinet (BSC) that is certified annually. PPE should include:

Gloves
Laboratory coat
Eye protection

Viral isolation

Growth of the virus in cell culture or embryonated eggs should be performed in a BSL-2 laboratory with BSL-3 practices. All viral manipulations should be done inside a BSC that is certified annually. PPE may include the following, based on a site-specific risk assessment:

Respiratory protection—fit-tested N-95 respirator or higher level of protection.
Shoe covers
Closed-front gown
Double gloves
Eye protection
Laboratory waste

All waste-disposal procedures should be followed as outlined in an institution's facility standard laboratory operating procedures. Steam autoclaving is the preferred method for all decontamination processes. Alternative methods may be considered based on applicable local, state, and federal regulations as well as on a site-specific risk assessment.

Appropriate disinfectants

Several chemical disinfectants, including chlorine, alcohols, peroxygen, detergents, iodophors, quaternary ammonium, and phenolic compounds, are effective against human influenza viruses if used at the correct concentration for the appropriate contact time as specified in the manufacturer's recommendations.

Work surfaces and equipment should be decontaminated as soon as possible after specimens are processed. Studies have shown that influenza viruses can survive on environmental surfaces and can infect a person for up to 2 to 8 hours after being deposited on an environmental surface.

Occupational health

Personnel who have had an occupational exposure to clinical material or live virus from a confirmed case of novel influenza A H1N1 should immediately report to their supervisor. Antiviral chemoprophylaxis is available and should be considered.

Personnel should self-monitor for fever and other symptoms such as cough, sore throat, runny or stuffy nose, body aches, headache, chills, and fatigue. Any ILI should be reported to the lab supervisor immediately.

Community Mitigation Measures

Home Isolation of Cases

The CDC recommends that people with ILI (fever with either cough or sore throat) remain at home until at least 24 hours after they are free of fever (100°F [37.8°C]) or signs of fever without the use of fever-reducing medications (see References: CDC 2009: CDC recommendations for the amount of time persons with influenza-like illness should be away from others.) (This recommendation does not apply to healthcare settings where the exclusion period should be continued for 7 days from symptom onset or until the resolution of symptoms, whichever is longer.)

Epidemiologic data indicate that most people with the 2009 H1N1 influenza virus who were not hospitalized had a fever that lasted 2 to 4 days; this would require an exclusion period of 3 to 5 days in most cases. Those with more severe illness are likely to have a fever for a longer period of time.
CDC recommends this exclusion period regardless of whether or not antiviral medications are used.
Decisions about extending the exclusion period should be made at the community level, in conjunction with local and state health officials.
More stringent guidelines and longer periods of exclusion—for example, until complete resolution of all symptoms—may be considered for people returning to a setting where large numbers of high-risk people may be exposed, such as a camp for children with asthma or a child-care facility for children younger than 5 years old.

Recommendations for Large Public Gatherings

The CDC has provided the following recommendations for large public gatherings (defined as an assembly or grouping of many people in one place where crowding is likely to occur, including indoor and outdoor gatherings) (see References: Interim CDC guidance for public gatherings in response to human infections with novel influenza A [H1N1]). The recommendations are as follows (Note: the recommendations have been adapted from the CDC Web site to be consistent with the more recent recommendations on home isolation, which are outlined above):

Persons with ILI should be advised to stay home for at least 24 hours after they are free of fever.
Persons who are at high risk of complications from novel influenza A H1N1 infection (for example, persons with certain chronic medical conditions, children less than 5 years, persons 65 or older, and pregnant women) should consider their risk of exposure to novel influenza if they attend public gatherings in communities where novel influenza A virus is circulating. Persons who are at risk of complications from influenza should consider staying away from public gatherings.
All persons should be reminded to use appropriate respiratory and hand hygiene precautions.
Based on currently available information, for non-healthcare settings where frequent exposures to persons with novel influenza A H1N1 are unlikely, masks and respirators are not recommended.

Recommendations for Specific Settings

The CDC has issued a variety of interim guidance documents for specific settings, including day-care programs, schools, colleges, universities, residential summer camps, homeless and emergency shelters, correctional and detention facilities, workplaces and businesses, cruise ships, and others; these can be found on the CDC Web site (see References: CDC 2009: H1N1 flu clinical and public health guidance).

Use of Face Masks and Respirators

Facemasks:

Unless otherwise specified, the term "facemasks" refers to disposable facemasks cleared by the FDA for use as medical devices. This includes masks labeled as surgical, dental, medical procedure, isolation, or laser.
Facemasks help stop droplets from being spread by the person wearing them. They also keep splashes or sprays from reaching the mouth and nose of the person wearing the mask. They are not designed to protect against breathing in small-particle aerosols that may contain viruses.
Facemasks should be used once and then thrown away in the trash.

Respirators:

Unless otherwise specified, "respirator" refers to an N95 or higher filtering face piece respirator certified by the CDC/National Institute for Occupational Safety and Health (NIOSH).
A respirator is designed to protect the person wearing the respirator against breathing in small-particle aerosols that may contain viruses.
When respiratory protection is required in an occupational setting, respirators must be used in the context of a comprehensive respiratory protection program as required under OSHA's Respiratory Protection standard (29 CFR 1910.134). This includes fit testing, medical evaluation, and training of the worker. When required in the occupational setting, tight-fitting respirators cannot be used by people with facial hair that interferes with the face seal.

Current recommendations from the CDC regarding use of respirators and face masks are outlined in the tables below (see References: CDC 2009: Interim recommendations for facemask and respirator use to reduce novel influenza A (H1N1) virus transmission.

CDC Interim Recommendations for Facemask and Respirator Use for Home, Community, and Occupational Settings for Non-Ill Persons to Prevent Infection with Novel H1N1
Setting	Persons not at increased risk of severe illness from influenza (Non-high risk persons)	Persons at increased risk of severe illness from influenza (High-Risk Persons) ³
Community
No novel H1N1 in community	Facemask/respirator not recommended	Facemask/respirator not recommended
Novel H1N1 in community: not crowded setting	Facemask/respirator not recommended	Facemask/respirator not recommended
Novel H1N1 in community: crowded setting	Facemask/respirator not recommended	Avoid setting. If unavoidable, consider facemask or respirator
Home
Caregiver to person with influenza-like illness	Facemask/respirator not recommended	Avoid being caregiver. If unavoidable, use facemask or respirator
Other household members in home	Facemask/respirator not recommended	Facemask/respirator not recommended
Occupational (non-healthcare)
No novel H1N1 in community	Facemask/respirator not recommended	Facemask/respirator not recommended
Novel H1N1 in community	Facemask/respirator not recommended but could be considered under certain circumstances	Facemask/respirator not recommended but could be considered under certain circumstances
Occupational (healthcare)
Caring for persons with known, probable or suspected novel H1N1 or influenza-like illness	Respirator	Consider temporary reassignment. Respirator

CDC Interim Recommendations For Facemask Use For Persons Ill With Confirmed, Probable, Or Suspected Novel Influenza A (H1N1)1 To Prevent Transmission Of Novel H1N1
Setting	Recommendation
Home (when sharing common spaces with other household members)	Facemask preferred, if available and tolerable, or tissue to cover cough/sneeze
Health care settings (when outside of patient room)	Facemask, if tolerable
Non-healthcare setting	Facemask preferred, if available and tolerable, or tissue to cover cough/sneeze
Breast-feeding	Facemask preferred, if available and tolerable, or tissue to cover cough/sneeze

Recommendations for Use of Influenza A H1N1 2009 Monovalent Vaccine

Target Groups

H1N1 vaccine is expected to be available during the fall of 2009. The Advisory Committee on Immunization Practices (ACIP) released US guidance on the use of monovalent H1N1 vaccine on August 21, 2009 (see References: ACIP 2009). The ACIP recommends that vaccination efforts should focus initially on persons in five target groups whose members are at higher risk for influenza or influenza-related complications, are likely to come in contact with influenza viruses as part of their occupation and could transmit influenza viruses to others in medical care settings, or are close contacts of infants younger than 6 months of age (who are too young to be vaccinated). In the event that vaccine availability is unable to meet initial demand, priority should be given to a subset of the five target groups. These groups are as follows:

Pregnant women
Persons who live with or provide care for infants younger than 6 months (eg, parents, siblings, and day-care providers)
Healthcare and emergency medical services personnel
Persons aged 6 months to 24 years
Persons aged 25 to 64 years who have medical conditions that put them at higher risk for influenza-related complications

These five target groups comprise an estimated 159 million persons in the United States. This estimate does not accurately account for persons who might be included in more than one category (eg, a healthcare worker with a high-risk condition).

Subset of Target Groups During Limited Vaccine Availability

If the supply of the vaccine initially available is not adequate to meet demand for vaccination among the five target groups listed above, ACIP recommends that the following subset of the initial target groups receive priority for vaccination until vaccine availability increases (order of target groups does not indicate priority):

Pregnant women
Persons who live with or provide care for infants younger than 6 months
Healthcare and emergency medical services personnel who have direct contact with patients or infectious material
Children aged 6 months to 4 years
Children and adolescents aged 5 to18 years who have medical conditions that put them at higher risk for influenza-related complications

This subset of the five target groups comprises approximately 42 million persons in the United States. Vaccination programs and providers should give priority to this subset only if vaccine availability is too limited to initiate vaccination for all persons in the five initial target groups.

Expanding Vaccination Efforts Beyond Initial Target Groups

Decisions about expanding vaccination to include additional populations beyond the five initial target groups should be made at the local level because vaccine availability and demand might vary considerably by area.

Once vaccination programs and providers are meeting the demand for vaccine among the persons in the five initial target groups, vaccination should be expanded to all persons aged 25 to 64 years.
Current studies indicate the risk for infection among persons aged 65 and older is less than the risk for persons in younger age-groups. Expanding vaccination recommendations to include adults 65 and older is recommended only after assessment of vaccine availability and demand at the local level. Once demand for vaccine among younger age-groups is being met, vaccination should be expanded to all persons 65 and older. This recommendation might need to be reassessed as new epidemiologic, immunologic, or clinical trial data warrant and in the context of global need for vaccine.

Additional Recommendations

The number of doses of vaccine required for immunization against novel influenza A H1N1 has not been established. Because vaccine availability is expected to increase over time, vaccine should not be held in reserve for patients who already have received one dose but might require a second dose.
Simultaneous administration of inactivated vaccines against seasonal and novel influenza A H1N1 viruses is permissible if different anatomic sites are used. However, simultaneous administration of live, attenuated vaccines against seasonal and novel influenza A H1N1 virus is not recommended.
All persons currently recommended for seasonal influenza vaccine, including those 65 and older, should receive the seasonal vaccine as soon as it is available.

Use of Antiviral Agents

To date,most isolates of the novel H1N1 virus generally have been susceptible to neuraminidase inhibitors, although several isolates have been found to be resistant.

The CDC has released guidelines for use of antiviral agents to treat novel H1N1 infection cases and for prophylaxis (pre-exposure or post-exposure) (see References: CDC 2009: Interim guidance on antiviral recommendations for patients with confirmed or suspected swine influenza A H1N1 virus infection and close contacts). Key points from those guidelines (as of April 28, 2009) are as follows:

Treatment of Confirmed, Probable, and Suspected Cases

Antiviral treatment should be considered for confirmed, probable, and suspected cases of novel H1N1 infection, with priority given to hospitalized patients and patients at higher risk for influenza complications.
Antiviral treatment with zanamivir or oseltamivir should be initiated as soon as possible after the onset of symptoms. Evidence for benefits from treatment in studies of seasonal influenza is strongest when treatment is started within 48 hours after illness onset. However, some studies of treatment of seasonal influenza have indicated benefit, including reductions in mortality or duration of hospitalization, even for patients whose treatment was started more than 48 hours after illness onset.
Recommended duration of treatment is 5 days.

Antiviral Chemoprophylaxis

For antiviral chemoprophylaxis of novel H1N1 infection, either oseltamivir or zanamivir is recommended.
Duration of antiviral chemoprophylaxis post-exposure is 10 days after the last known exposure to an ill confirmed case of novel H1N1 infection.
For pre-exposure protection, chemoprophylaxis should be given during the potential exposure period and continued for 10 days after the last known exposure to an ill confirmed case of novel H1N1 infection.
Antiviral chemoprophylaxis (pre-exposure or post-exposure) with either oseltamivir or zanamivir is recommended for the following individuals:

Household close contacts who are at high risk for complications of influenza (eg, persons with certain chronic medical conditions, persons 65 or older, children younger than 5 years old, and pregnant women) of a confirmed or probable case
Healthcare workers or public health workers who were not using appropriate personal protective equipment during close contact with an ill confirmed, probable, or suspect case of novel H1N1 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:

Household close contacts who are at high risk for complications of influenza (eg, persons with certain chronic medical conditions, persons 65 years or older, children younger than 5 years old, and pregnant women) of a suspected case
Children attending school or daycare who are at high risk for complications of influenza (eg, children with certain chronic medical conditions) and who had close contact (face-to-face) with a confirmed, probable, or suspected case
Healthcare workers who are at high risk for complications of influenza (eg, persons with certain chronic medical conditions, persons 65 or older, and pregnant women) who are working in an area of the healthcare facility that contains patients with confirmed cases of novel H1N1 infection or who are caring for patients who have any acute febrile respiratory illness
Travelers to Mexico who are at high risk for complications of influenza (eg, persons with certain chronic medical conditions, persons 65 or older, children younger than 5 years old, and pregnant women) (Note: A travel warning is currently in effect indicating that nonessential travel to Mexico should be avoided.)
First responders who are at high risk for complications of influenza (eg, persons with certain chronic medical conditions, persons 65 or older, children younger than 5 years old, and pregnant women) and who are working in areas with confirmed cases of novel H1N1 infection

Oseltamivir and Zanamivir Prescribing Information
Agent, group		Treatment	Chemoprophylaxis
Oseltamivir
Adults		75-mg capsule twice per day for 5 days	75-mg capsule once per day
Children (age >12 mo), weight	<15 kg	60 mg per day divided into 2 doses	30 mg once per day
	15-23 kg	90 mg per day divided into 2 doses	30 mg once per day
	24-40 kg	120 mg per day divided into 2 doses	60 mg once per day
	>40	150 mg per day divided into 2 doses	75 mg once per day
Zanamivir
Adults		Two 5-mg inhalations (10 mg total) twice per day	Two 5-mg inhalations (10 mg total) once per day
Children		Two 5-mg inhalations (10 mg total) twice per day (age, 7 years or older)	Two 5-mg inhalations (10 mg total) once per day (age, 5 years or older)

Children Under 1 Year of Age

Children <1 year of age are at high risk for complications from seasonal human influenza virus infections. At this time, public health officials do not know whether infants are at higher risk for complications associated with novel H1N1 infection compared with older children and adults.
Limited safety data on the use of oseltamivir (or zanamivir) are available for children <1 year of age, and oseltamivir is not licensed for use in children <1 year of age. Available data suggest, however, that severe adverse events are rare.
Because infants typically have high rates of morbidity and mortality from influenza, infants with novel H1N1 infections may benefit from treatment using oseltamivir.
Oseltamivir use for children <1 year of age was recently approved by the US Food and Drug Administration (FDA) under an Emergency Use Authorization (EUA), and dosing for these children is age-based.
Dosing for children <1 year old can be found in two documents currently available from the CDC: "Interim guidance on antiviral recommendations for patients with confirmed or suspected swine influenza A (H1N1) virus infection and close contacts" and "Interim guidance for clinicians on the prevention and treatment of swine-origin influenza virus infection in young children."

Pregnant Women

Oseltamivir and zanamivir are all "Pregnancy Category C" medications, indicating that no clinical studies have been conducted to assess their safety for pregnant women.
Because of the unknown effects of oseltamivir and zanamivir on pregnant women and their fetuses, these drugs 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 such women.
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.
Additional information regarding care of pregnant women can be found in the CDC guidance, "Interim guidance—pregnant women and swine influenza: considerations for clinicians."

Infection Control Considerations

Modes of Transmission for Influenza Viruses

The CDC has developed infection control guidance for the care of patients who have suspected or confirmed novel H1N1 infection (see References: CDC 2009: Interim guidance for infection control for care of patients with confirmed or suspected swine-origin influenza A [H1N1] virus infection in a healthcare setting).

Recommendations on infection control practices are based on available data regarding the modes of transmission of influenza viruses in general. Influenza viruses potentially can be transmitted through droplet, contact, and airborne modes. Although existing data are limited regarding the contribution of each mode of transmission, a recent review concluded that influenza virus transmission occurs at close range rather than over long distances (see References: Brankston 2007). Information on the modes of transmission for influenza viruses are outlined below.

Droplet transmission

Influenza viruses are predominantly transmitted by large droplets (ie, >5 mcm).
Droplets are expelled by coughing and sneezing and generally travel through the air no more than 3 feet from the infected person.
Transmission via large droplets requires close contact between the source and recipient persons, permitting droplets, which do not remain suspended in the air, to come into direct contact with oral, nasal, or ocular mucosa.
Special air handling and ventilation systems are not required to prevent droplet transmission.

Direct and indirect contact transmission

Direct contact transmission involves skin-to-skin contact (such as hand-to-hand) between an infected person and a susceptible person.
The proportion of influenza virus transmission caused by direct or indirect contact remains unknown; however, transmission by these routes can occur.
Influenza viruses can live for 24 to 48 hours on nonporous environmental surfaces and less than 12 hours on porous surfaces (see References: Bean 1982), indicating that transmission can occur when hands that touch contaminated surfaces subsequently come into contact with oral, ocular, or nasal mucosa. Fomite transmission appears to be rare.

Airborne transmission

Airborne transmission of influenza viruses (ie, transmission via droplet nuclei [<5 mcm], which remain suspended in the air and have the potential to travel farther than several feet) has been suggested in several reports, although evidence to conclusively support airborne transmission of influenza virus is limited (see References: Bridges 2003).
Available data suggest that airborne transmission does not play a major role in the spread of influenza viruses (see References: Brankston 2007). However, airborne transmission of influenza viruses may occur, at least over short distances (see References: Tellier 2006), and further study is needed to determine the importance of this mode of transmission in healthcare or other settings.
Aerosol-generating procedures (eg, intubation, bronchoscopy, nebulizer treatments) theoretically could promote dissemination of droplet nuclei from infected patients, although this has not been studied for influenza.
There is no evidence to date that droplet nuclei containing influenza viruses can travel through ventilation systems or across long distances, such as can occur with tuberculosis and certain other viral agents.

Recommended Isolation Precautions to Prevent Transmission of the Novel H1N1 Virus

Healthcare workers are at risk of acquiring novel H1N1 infection (see References: CDC 2009: Novel influenza A (H1N1) virus infections among health-care personnel).

Information from the CDC guidance on infection control and isolation precautions is outlined below (see References: CDC 2009: Interim guidance for infection control for care of patients with confirmed or suspected swine influenza A (H1N1) virus infection in a healthcare setting).

Patient placement and transport

Any patients who are confirmed, probable, or suspected cases of novel H1N1 infection and present for care at a healthcare facility should be placed directly into individual rooms with the door kept closed.
Procedures that are likely to generate aerosols (eg, bronchoscopy, elective intubation, suctioning, administering nebulized medications) should be done in a location with negative pressure air handling whenever feasible. 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. Facilities should monitor and document the proper negative-pressure function of AIIRs, including those in operating rooms, intensive care units, emergency departments, and procedure rooms.
Procedures for transport of patients in isolation precautions should be followed. Facilities should also ensure that plans are in place to communicate information about suspected cases that are transferred to other departments in the facility (eg, radiology, laboratory) and other facilities. The ill person should wear a surgical mask to contain secretions when outside of the patient room, and should be encouraged to perform hand hygiene frequently and follow respiratory hygiene/cough etiquette practices.

Limitation of healthcare personnel entering the isolation room

Healthcare personnel entering the room of a patient in isolation should be limited to those performing direct patient care.

Isolation precautions

Standard and Contact Precautions plus eye protection should be used for all patient-care activities for patients being evaluated or in isolation for novel H1N1 infection (ie, including all healthcare personnel who enter the patient's room).
Adherence to hand hygiene should be maintained by washing with soap and water or using alcohol-based hand sanitizer immediately after removing gloves and other equipment and after any contact with respiratory secretions. Nonsterile gloves and gowns along with eye protection should be donned upon room entry.
All healthcare personnel who enter the rooms of patients in isolation for novel H1N1 infection should wear a fit-tested disposable N-95 respirator or equivalent (eg, powered air purifying respirator). Respiratory protection should be donned upon room entry. (Note: This recommendation differs from current infection control guidance for seasonal influenza, which recommends that healthcare personnel wear surgical masks for patient care. The rationale for the use of respiratory protection is that a more conservative approach is needed until more is known about the specific transmission characteristics of this new virus.)

Management of visitors

Visitors to patients in isolation for novel H1N1 infection should be limited to persons who are necessary for the patient's emotional well-being and care.
Visitors who have been in contact with the patient before and during hospitalization are a possible source of novel H1N1 virus. Therefore, visits should be scheduled and controlled to allow for appropriate screening for acute respiratory illness before entering the hospital and appropriate instruction on use of personal protective equipment and other precautions (eg, hand hygiene, limiting surfaces touched) while in the patient's room. Visitors also should be instructed to limit their movement within the facility.
Visitors may be offered a gown, gloves, eye protection, and respiratory protection (ie, N-95 respirator) and should be instructed by healthcare personnel on their use before visitors enter the patient's room.

Duration of precautions

Isolation precautions should be continued for 7 days from symptom onset or until the resolution of symptoms, whichever is longer.
Persons with novel H1N1 virus infection should be considered potentially contagious from 1 day before to 7 days following illness onset. Persons who continue to be ill longer than 7 days after illness onset should be considered potentially contagious until symptoms have resolved. Children, especially younger children, might be contagious for longer periods.

Surveillance of Healthcare Personnel

In communities where novel H1N1 virus transmission is occurring, healthcare personnel should be monitored daily for signs and symptoms of febrile respiratory illness. Healthcare personnel who develop these symptoms should be instructed not to report to work, or if at work, should cease patient care activities and notify their supervisor and infection control personnel.
In communities without novel H1N1 virus transmission, healthcare personnel working in areas of a facility where there are patients being assessed or isolated for swine influenza infection should be monitored daily for signs and symptoms of febrile respiratory infection. This would include healthcare personnel exposed to patients in an outpatient setting or the emergency department. Healthcare personnel who develop these symptoms should be instructed not to report to work, or if at work, should cease patient care activities and notify their supervisor and infection control personnel.
Healthcare personnel who do not have a febrile respiratory illness may continue to work. Asymptomatic healthcare personnel who have had an unprotected exposure to novel H1N1 virus also may continue to work if they are started on antiviral prophylaxis.

Management of Ill Healthcare Personnel

Healthcare personnel should not report to work if they have a febrile respiratory illness. In communities where swine influenza virus transmission is occurring, healthcare personnel who develop a febrile respiratory illness should be excluded from work for 7 days or until symptoms have resolved, whichever is longer.
In communities without swine influenza virus transmission, healthcare personnel who develop a febrile respiratory illness and have been working in areas of the hospital where swine influenza patients are present, should be excluded from work for 7 days or until symptoms have resolved, whichever is longer.
In communities where swine influenza virus transmission is not occurring, healthcare personnel who develop febrile respiratory illness and have not been in areas of the facility where swine influenza patients are present should follow facility guidelines on returning to work.

Issues Related to Postmortem Care, Including Autopsies

Guidance from the CDC includes the following recommendations (see References: CDC 2009: Post-mortem care and safe autopsy procedures for novel H1N1 influenza):

Transport of deceased persons

Transport of deceased persons does not require any additional precautions when bodies have been secured in a transport bag. Hand hygiene should be performed after completing transport.
Standard Precautions should be used when handling deceased persons and when preparing bodies for autopsy or transfer to mortuary services, including appropriate use of personal protective equipment (PPE) (gowns, gloves, masks, and/or eye protection). After PPE is removed, hand hygiene should be performed.

Family contact with the deceased in healthcare settings

For deceased persons with confirmed, probable, or suspected novel influenza A H1N1, contact with the body in healthcare settings should be limited to close family members.
Direct contact with the body is discouraged; however, necessary contact may occur as long as hands are washed immediately with soap and water.

Autopsy procedures

In general, Standard Precautions as well as safety procedures consistent with those for any autopsy procedure should be used for human remains infected with novel influenza virus.
Additional respiratory protection is needed during an autopsy procedure that generates aerosols (eg, use of an oscillating saw).
The number of personnel participating in postmortem examinations should be minimized.

Personal protective equipment

Standard autopsy PPE should be worn, including a scrub suit worn under an impervious gown or apron, eye protection (eg, goggles, face shield), double surgical gloves with an interposed layer of cut-proof synthetic mesh gloves, surgical mask or respirator, and shoe covers.
N-95 or N-100 disposable particulate respirators or a powered air-purifying respirator (PAPR) should be worn if aerosols might be generated. Autopsy personnel who cannot wear a disposable particulate respirator because of facial hair or other fit limitations should wear a loose-fitting (eg, helmeted or hooded) PAPR.
PPE should be removed before leaving the autopsy suite and disposed of in accordance with facility policies and procedures.

Engineering controls

Whenever possible, autopsies on human remains infected with novel influenza A H1N1 should be performed in autopsy settings that have an adequate air-handling system. This includes:

A minimum of 6 (old construction) to 12 (new construction) air changes per hour (ACH)
Negative pressure relative to adjacent areas as per recommendations for airborne infection isolation rooms (AIIRs)
Direct exhaust of air to the outside or passed through a HEPA filter if air is recirculated

Exhaust systems around the autopsy table should direct air (and aerosols) away from healthcare workers performing the procedure (eg, exhaust downward). For autopsies, local airflow control (eg, laminar flow systems) can be used to direct aerosols away from personnel; however, this safety feature does not eliminate the need for appropriate PPE.
Containment devices should be used whenever possible. Biosafety cabinets should be used for the handling and examination of smaller specimens. When available, vacuum shrouds should be used for oscillating saws to contain aerosols and reduce the volume released into the ambient air environment.
Protective outer garments should be removed when leaving the immediate autopsy area and discarded in appropriate laundry or waste receptacles, either in an antechamber to the autopsy suite or immediately inside the entrance if an antechamber is unavailable.

Stewardship of Personal Protective Equipment and Antivirals

Facilities should implement plans to ensure appropriate allocation of personal protective equipment, including N-95 respirators, and antivirals.

Environmental Infection Control

Routine cleaning and disinfection strategies used during influenza seasons can be applied to the environmental management of swine influenza. Management of laundry, utensils and medical waste should also be performed in accordance with procedures followed for seasonal influenza.

Facility Access Control

Facilities should have signage at entry points instructing patients and visitors about hospital policies, including the need to notify staff immediately if they have signs and symptoms of febrile respiratory illness. Facilities in communities where swine influenza transmission is occurring should limit points of entry to the facility.

Administration of the Current 2008-2009 Seasonal Influenza Vaccine

It is not anticipated that the seasonal influenza vaccine will provide protection against novel H1N1 infection. However, in some parts of the country, seasonal influenza viruses are still circulating. Influenza vaccination is effective against these seasonal viruses and should continue to be given to unvaccinated patients in areas where seasonal influenza cases are still occurring.

Food Safety Issues

According to the WHO, the Food and Animal Health Organization (FAO) of the United Nations, and the World Organization for Animal Health (OIE), influenza viruses are not known to be transmissible to people through eating processed pork or other food products derived from pigs (see References: WHO 2009: Joint FAO/WHO/OIE statement on influenza A [H1N1] and the safety of pork). The United States Department of Agriculture has echoed this statement (see References: USDA)

Heat treatments commonly used in cooking meat (eg, 70°C/160°F core temperature) will readily inactivate any viruses potentially present in raw meat products.
Pork and pork products, handled in accordance with good hygienic practices recommended by the WHO, Codex Alimentarius Commission, and the OIE, will not be a source of infection
Authorities and consumers should ensure that meat from sick pigs or pigs found dead are not processed or used for human consumption under any circumstances.

References

ACIP. Use of influenza A (H1N1) 2009 monovalent vaccine [Full text]

Adiego SB, Omenaca TM, Martinez CS, et al. Human cases of swine influenza A (H1N1), Aragon, Spain, November 2008. Eurosurveill 2009 Feb 19;14(7):19120 [Full text]

American Veterinary Medical Association (AVMA). Backgrounder: Swine influenza. Feb 14, 2007 [Web page]

Australian Government Department of Agriculture, Fisheries, and Forestry. Pandemic H1N1 2009 [Web page]

Bean B, Moore BM, Sterner B, et al. Survival of influenza viruses on environmental surfaces. J Infect Dis 1982 Jul;146(1):47-51 [Abstract]

Beveridge WI. Influenza: the last great plague: an unfinished story of discovery. New York, NY: Prodist, 1978

Boelle PY, P Bernillon P, Desenclos J C. A preliminary estimation of the reproduction ratio for new influenza A (H1N1) from the outbreak in Mexico, March–April 2009. Euro Surveill 2009 May 14;14(19):1-4 [Full text]

Brankston G, Gitterman L, Hirji Z, et al. Transmission of influenza A in human beings. Lancet Infect Dis 2007 Apr;7(4):257-65 [Abstract]

Bridges CB, Kuehnert MJ, Hall CB. Transmission of influenza: implications for control in healthcare settings. Clin Infect Dis 2003 Oct 15;37(8):1094-1101 [Full text]

CDC. CDC protocol of real time RT PCR for swine influenza A (H1N1). April 30, 2009 [Full text]

CDC. CDC recommendations for the amount of time persons with influenza-like illness should be away from others. Aug 5, 2009 [Full text]

CDC. Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings 2007 [Full text]

CDC. Guidelines for the submission of tissue specimens for the pathologic evaluation of influenza virus infections. 2009 [Full text]

CDC. H1N1 flu situation updates [Web page]

CDC. H1N1 flu clinical and public health guidance [Web page]

CDC. Interim biosafety guidance for all individuals working with clinical specimens or isolates from patients with suspected novel influenza A H1N1 virus infection. May 13, 2009 [Full text]

CDC. Interim CDC guidance for institutions of higher education and post-secondary educational institutions in response to human infections with novel influenza A [H1N1] virus. May 11, 2009 [Full text]

CDC. Interim CDC guidance for nonpharmaceutical community mitigation in response to human infections with swine influenza (H1N1) virus. 2009 [Full text]

CDC. Interim CDC guidance for public gatherings in response to human infections with novel influenza A (H1N1). May 10, 2009 [Full text]

CDC. Interim guidance for clinicians on identifying and caring for patients with swine-origin influenza A (H1N1) virus infection. Last updated May 5, 2009 [Full text]

CDC. Interim guidance for clinicians on the prevention and treatment of swine-origin influenza virus infection in young children. 2009 [Full text]

CDC. Interim guidance for infection control for care of patients with confirmed or suspected swine influenza A (H1N1) virus infection in a healthcare setting. 2009 [Full text]

CDC. Interim guidance for swine influenza A (H1N1): taking care of a sick person in your home. [Full text]

CDC. Interim guidance for the detection of novel influenza A virus using rapid influenza diagnostic tests. Aug 10, 2009 [Full text]

CDC. Interim guidance—HIV-infected adults and adolescents: considerations for clinicians regarding swine-origin influenza A (H1N1) virus. 2009 [Full text]

CDC. Interim guidance on antiviral recommendations for patients with confirmed or suspected swine influenza A (H1N1) virus infection and close contacts. 2009 [Full text]

CDC. Interim guidance on case definitions to be used for investigations of swine influenza A (H1N1) cases. 2009 [Full text]

CDC. Interim guidance on specimen collection, processing, and testing for patients with suspected swine-origin influenza A (H1N1) virus infection. 2009 [Full text]

CDC. Interim guidance—pregnant women and swine influenza: considerations for clinicians. 2009 [Full text]

CDC. Interim recommendations for facemask and respirator use to reduce novel influenza A (H1N1) virus transmission. Aug 5, 2009 [Full text]

CDC. Novel influenza A (H1N1) virus infections among health-care personnel—United States, April-May 2009. MMWR 2009 Jun 19;58(23):641-5 [Full text]

CDC. Novel influenza A (H1N1) virus infections in three Pregnant Women—United States, April—May 2009 [Full text]

CDC. Outbreak of swine-origin influenza A (H1N1) virus infection—Mexico, March-April 2009. MMWR 2009 Apr 30;58(Dispatch):1-3 [Full text]

CDC. Post-mortem care and safe autopsy procedures for novel H1N1 influenza. 2009 [Full text]

CDC. Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR 2009 May 22;58(19):521-4 [Full text]

CDC. Swine influenza A (H1N1) infection in two children—southern California, March-April 2009. MMWR 2009 Apr 21;58(Dispatch):1-3 [Full text]

CDC. Swine influenza A (H1N1) virus biosafety guidelines for laboratory workers. 2009 [Full text]

CDC. Update on school (K-12) dismissal and childcare facilities: interim CDC guidance in response to human infections with the 2009 influenza A H1N1 virus. 2009 [Full text]

CDC. Update: Swine influenza A (H1N1) infections—California and Texas. MMWR April 24 2009;58(Dispatch):1-3 [Full text]

CDC. Use of rapid influenza diagnostic tests for patients with influenza-like illness during the novel H1N1 influenza virus (swine flu) outbreak. 2009 [Full text]

CFIA. An Alberta swine herd investigated for H1N1 flu virus. 2009 [Press release]

CFIA. Management of pandemic H1N1 in swine herds. 2009 [Web page]

Gani R, Hughes H, Fleming D, et al. Potential impact of antiviral drug use during influenza pandemic. Emerg Infect Dis 2009;11(9):1355-62 [Full text]

FAO. H1N1 flu in turkeys may spread: poultry connection strengthens global H1N1 pandemic. Aug 27, 2009 [Press release]

Faix DJ, Sherman SS, Waterman, SH. Rapid-test sensitivity for novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009 (published online Jun 29) [Full text]

Garten RJ, Davis CT, Russell CA, et al. Antigenic and genetic characteristics of swine-origin 2009 A (H1N1) influenza viruses circulating in humans. Science 2009 May 22; early online publication [Abstract]

Gaydos JC, Top FH, Hodder AR, et al. Swine influenza A outbreak, Fort Dix, New Jersey, 1976. Emerg Infect Dis 2006;12(1):23-28 [Full text]

Chowell D, Bertozzi S, Arantxa Colchero M, et al. Severe respiratory disease concurrent with the circulation of H1N1 influenza. N Engl J Med 2009 (published online Jun 29) [Full text]

Glezen WP. Emerging infections: pandemic influenza. Epidemiol Rev 1996;18(1):64-76 [Full text]

Khan K. Spread of a novel influenza A (H1N1) virus via global airline transportation. N Engl J Med 2009 (published online Jun 29) [Full text]

Lekcharoensuk P, Lager KM, Vemulapalli R, et al. Novel swine influenza virus subtype H3N1, United States. Emerg Infect Dis 2006 May 12(5):787-94 [Full text]

Maines TR, Jayaraman A, Belser J, et al. Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science 2009 Jul 2; early online edition [Abstract]

Munster VJ, de Wit E, van den Brand JM, et al. Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets Science 2009 Jul 2; early online edition [Abstract]

Myers KP, Olsen CW, Gray GC. Cases of swine influenza in humans: a review of the literature. Clin Infect Dis 2007;44:1084–8 [Abstract]

Nava GM, Attene-RamosMS, Ang JK, et al. Origins of the new influenza A(H1N1) virus; time to take action. Eurosurveillance 2009 June 4;14(22) [Full text]

Newman AP, Reisdorf E, Beinemann J, et al. Human case of swine influenza A (H1N1) triple reassortant virus infection, Wisconsin. Emerg Infect Dis 2008;14(9):1470-2 [Full text]

Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009 May 7 (Epub ahead of print) [Full text]

Olsen CW. The emergence of novel swine influenza viruses in North America. Virus Res. 2002;85:199–210 [Abstract]

OIE. Immediate notification report: A/H1N1 influenza. Jun 25, 2009 [Full text]

Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 2009 (published online Jun 29) [Full text]

Reid AH, Taubenberger JK, Fanning TG. The 1918 Spanish influenza: integrating history and biology. Microbes Infect 2001 Jan:3(1):81-7 [Abstract]

Schonberger LB, Bregman DJ, Sullivan-Bolyai JZ, et al. Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States, 1976--1977. Am J Epidemiol 1979 Aug;110(2):105-23 [Abstract]

Sencer DJ, Millar JD. Reflections on the 1976 Swine Flu Vaccination Program. Emerg Infect Dis 2006 Jan;12(1):20-33 [Full text]

Shinde V, Bridges CB, Uyeki TM, et al. Triple-reassortant swine influenza A (H1) in humans in the United States, 2005–2009. 2009 May 7 (Epub ahead of print) [Full text]

Taubenberger JK, Reid AH, Lourens RM, et al. Characterization of the 1918 influenza virus polymerase genes. (Letter) Nature 2005;437(7060):889-93 [Full text]

Taunbenberger JK, Morens DM. 1918 influenza: the mother of all pandemics. Emerg Infect Dis 2006 Jan;12(1):15-22 [Full text]

Tellier R. Review of aerosol transmission of influenza A virus. Emerg Infect Dis 2006 Nov;12(11) [Full text]

Van Reeth K, Nicoll A. A human case of swine influenza virus infection in Europe—implications for human health and research. Euro Surveill 2009 Feb 19;14(7) pii: 19124 [Full text]

Vaillant L, La Ruche G, Tarantola A, et al. Epidemiology of fatal cases associated with pandemic H1N1 influenza 2009. (Rapid Communications) Eurosurveill 2009 Aug 20;14(33):pii=19309 [Full text]

Webster RG, Bean WJ, Gorman OT, et al. Evolution and ecology of influenza A viruses. Microbiol Rev Mar 1992;56(1):152-79 [Full text]

WHO. Current WHO phase of pandemic alert [Web page]

WHO. Influenza A (H1N1): frequently asked questions. 2009 [Full text]

WHO. Instructions on how to obtain CDC real time RT-PCR kits for detection of influenza A (H1N1). May 2, 2009 [Full text]

WHO. Joint FAO/WHO/OIE statement on influenza A (H1N1) and the safety of pork. Apr 30, 2009 [Full text]

WHO. Pandemic (H1N1) 2009 briefing note 3 (revised). Jul 16, 2009 [Full text]

WHO. Situation updates—influenza A(H1N1) [Web page—click on most recent]

WHO. Status of candidate vaccine virus development for the current influenza A (H1N1) virus. May 8, 2009 [Full text]

WHO. Timeline of influenza A (H1N1) cases. Updated frequently [Web page]

WHO. WHO global influenza preparedness plan: the role of WHO and recommendations for national measures before and during pandemics. Apr 2005 [Full text]

WHO. Human infection with new influenza A (H1N1) virus: clinical observations from Mexico and other affected countries, May 2009. Weekly Epidemiological Record 2009;84(21):185–9 [Full text]

WHO. WHO guidelines for the collection of human specimens for laboratory diagnosis of avian influenza infection. Jan 12, 2005 [Full text]

WHO. WHO guidelines for the storage and transport of human and animal specimens for laboratory diagnosis of suspected avian influenza A infection. Jan 12, 2005 [Full text]

WHO. WHO laboratory biosafety guidelines for handling specimens suspected of containing avian influenza A virus. Jan 12, 2005 [Full text]

Zimmer SM, Burke DS. Historical perspective—emergence of influenza A (H1N1) viruses. N Engl J Med 2009 Jul 16;361(3):279-85 [Full text]


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