INTRODUCTION — In late March and early April 2009, an outbreak of H1N1 influenza A virus infection was detected in Mexico, with subsequent cases observed in many other countries, including the United States [1,2]. On June 11, 2009, the World Health Organization raised its pandemic alert level to the highest level, phase 6, indicating widespread community transmission on at least two continents [3]. (See "Epidemiology, clinical manifestations, and diagnosis of pandemic H1N1 influenza ('swine influenza')", section on '2009 pandemic'.)

The pandemic that began in March 2009 was caused by an H1N1 influenza A virus that represents a quadruple reassortment of two swine strains, one human strain, and one avian strain of influenza. (See "Epidemiology, clinical manifestations, and diagnosis of pandemic H1N1 influenza ('swine influenza')", section on 'Genetic and antigenic characterization'.)

The prevention of pandemic H1N1 influenza A virus infection will be reviewed here. The epidemiology, clinical manifestations, diagnosis, and treatment of pandemic H1N1 influenza A virus, and the treatment and prevention of seasonal and avian (H5N1) influenza virus infections are discussed separately. (See "Epidemiology, clinical manifestations, and diagnosis of pandemic H1N1 influenza ('swine influenza')" and "Treatment of pandemic H1N1 influenza ('swine influenza')" and "Treatment of seasonal influenza in adults" and "Antiviral drugs for the prevention and treatment of influenza in children" and "Prevention of seasonal influenza in adults" and "Treatment and prevention of avian influenza".)

DEFINITIONS

Case definitions — The following case definitions have been provided by the United States Centers for Disease Control and Prevention [4]:

• Influenza-like illness (ILI) is defined as fever (temperature of 100ºF [37.8ºC] or greater) with cough or sore throat in the absence of a known cause other than influenza.
• A confirmed case of pandemic H1N1 influenza A is defined as an individual with an ILI with laboratory-confirmed H1N1 influenza A virus detected by real-time reverse transcriptase (rRT)-PCR or culture.
• Pandemic H1N1 influenza A may be suspected in an individual who does not meet the definition of confirmed pandemic H1N1 influenza A, but has an ILI and an epidemiologic link.

High risk groups — High risk groups for the development of complications of pandemic H1N1 influenza A are thought to be similar to those defined for seasonal influenza.

High risk groups include [5-11]:

• Children younger than 5 years of age, but especially those younger than 2
• Individuals 65 years of age or older

• - Although individuals ≥65 years of age who become infected with H1N1 influenza virus are thought to be at increased risk for influenza complications, this age group appears to be at lower risk of becoming infected with H1N1 influenza compared with younger persons, presumably because of immunity (antibodies) from previous exposure to related virus strains. Thus, the United States Centers for Disease Control and Prevention recommends that members of this age group who do not have other high-risk conditions be at low priority for vaccination with the H1N1 influenza vaccination. (See 'Preexisting antibodies' below and 'Target groups' below and "Epidemiology, clinical manifestations, and diagnosis of pandemic H1N1 influenza ('swine influenza')", section on High risk adults.)

• Individuals younger than 19 years of age who are receiving long-term aspirin therapy and who therefore might be at risk for Reye syndrome after influenza virus infection
• Pregnant women and women up to two weeks postpartum (including those who have had pregnancy loss)
• Individuals with chronic medical conditions requiring ongoing medical care, including:

• - Chronic pulmonary disease, including asthma (particularly if systemic glucocorticoids have been required during the past year)
• - Cardiovascular disease, except isolated hypertension
• - Active malignancy
• - Chronic renal insufficiency
• - Chronic liver disease
• - Diabetes mellitus
• - Hemoglobinopathies such as sickle cell disease
• - Immunosuppression, including HIV infection (particularly if CD4 <200 cells/microL), organ or hematopoietic stem cell transplantation, inflammatory disorders treated with immunosuppressants
• - Certain rheumatologic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, antiphospholipid syndrome, systemic sclerosis/scleroderma, spondyloarthropathies, Sjogren's syndrome, polymyositis/dermatomyositis, vasculitis (eg, giant cell arteritis), necrotizing arteritis, sarcoidosis, and polyarteritis nodosa [12]
• - Individuals who have any condition that can compromise handling of respiratory secretions (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, neuromuscular disorders, cerebral palsy, metabolic conditions)
• - Children with an underlying metabolic disorder, such as medium-chain acyl-CoA dehydrogenase deficiency, who are unable to tolerate prolonged fasting

Obesity has not been recognized as a risk factor for severe seasonal influenza, but cases of severe pandemic H1N1 influenza A, including pneumonia and acute respiratory distress syndrome, have been reported in obese individuals without known underlying conditions [13-15].

A disproportionately high percentage of the indigenous populations of Australia, New Zealand, and Canada have been affected by severe pandemic H1N1 influenza infection. (See "Epidemiology, clinical manifestations, and diagnosis of pandemic H1N1 influenza ('swine influenza')", section on 'Range of complications'.)

Although there are no data regarding the risk for severe or complicated influenza among asplenic individuals, influenza is a risk factor for secondary bacterial infections that can cause severe disease among such patients. (See "Prevention of seasonal influenza in adults", section on 'Definition of high risk' and "Antiviral drugs for the prevention and treatment of influenza in children".)

In the United States, 40 percent of children and 20 percent of adults requiring hospitalization for pandemic H1N1 influenza have had no known risk factors for severe disease [16].

Close contacts — Close contacts are defined by the United States Centers for Disease Control and Prevention as the following [5]:

• Having cared for or lived with a person who is a confirmed or suspected case of pandemic H1N1 influenza A
• Having been in a setting where there was a high likelihood of contact with respiratory droplets and/or bodily fluids of a confirmed or suspected case of pandemic H1N1 influenza A
• Having had close contact (kissing, embracing, sharing eating or drinking utensils, physical examination, or any other contact likely to result in exposure to respiratory droplets) with a confirmed or suspected case of pandemic H1N1 influenza A
• In a healthcare setting, being within 6 feet of a confirmed or suspected case of pandemic H1N1 influenza A or entering into a small enclosed airspace of such an individual, such as a typical patient room [17]

Close contact does not typically include such activities as walking by an infected individual or sitting across from a symptomatic patient in a waiting room.

ANTIVIRAL PROPHYLAXIS — While awaiting further data, we suggest following the United States Centers for Disease Control and Prevention guidelines in deciding who should or should not receive antiviral prophylaxis of pandemic H1N1 influenza A virus infection [10,18]. See the CDC's website for updated recommendations (http://www.cdc.gov/h1n1flu/). Clinicians in other countries should consult with their ministries of health and/or the World Health Organization for specific recommendations.

Adults — The indications for post-exposure antiviral prophylaxis are based upon close contact with a patient who is a confirmed or suspected case of pandemic H1N1 influenza A infection [18]. (See 'Close contacts' above.)

The United States Centers for Disease Control and Prevention states that post-exposure antiviral prophylaxis can be considered for [18]:

• Individuals who are at high risk for complications of influenza (eg, individuals with certain chronic medical conditions, ≥65 years of age, pregnant women) who have had close contact with a confirmed or suspected case.
• Health care workers, public health workers, or first responders who were not using appropriate personal protective equipment during close contact with a confirmed or suspected patient during that person's infectious period.

Prophylaxis is generally NOT recommended if >48 hours have elapsed since the last contact with an infectious individual.

An alternative to post-exposure prophylaxis for individuals who meet the criteria outlined above is to counsel them about the early signs and symptoms of influenza and to advise them to contact their healthcare provider for evaluation and potential early treatment if they become symptomatic. Early recognition and treatment of influenza infection is preferred to prophylaxis for vaccinated individuals following a possible exposure [18].

Post-exposure prophylaxis should NOT be used [18]:

• In healthy children or adults based upon potential exposures in the community, school, camp, or other settings.
• When contact occurred before or after, but not during, the ill individual's infectious period. (See 'Home isolation' below.)

Certain individuals who have ongoing occupational risk for exposure (eg, healthcare workers, public health workers, first responders), and who are also at increased risk of influenza complications, should follow guidelines for personal protective equipment stringently or consider temporary reassignment in order to reduce the need for post-exposure prophylaxis [18].

Choice of agent — The vast majority of strains of pandemic H1N1 influenza A virus circulating in 2009 appear sensitive in vitro to the neuraminidase inhibitors, oseltamivir and zanamivir, but all strains tested have been resistant to amantadine and rimantadine. Zanamivir is relatively contraindicated in individuals with asthma or chronic obstructive pulmonary disease. (See "Treatment of pandemic H1N1 influenza ('swine influenza')", section on 'ANTIVIRAL THERAPY'.)

When antiviral prophylaxis is indicated, either oseltamivir or zanamivir should be used [18]. The dosing of antivirals for pandemic H1N1 influenza A infection is the same as for seasonal influenza (table 1). Since oseltamivir is primarily excreted by the kidneys, dosing must be modified for renal insufficiency. Zanamivir inhalation powder should not be reconstituted in any liquid formulation and is not recommended for use in nebulizers or mechanical ventilators [19]. (See "Prevention of seasonal influenza in adults" and "Pharmacology of antiviral drugs for influenza".)

A notable difference between pandemic and seasonal strains of H1N1 influenza A is the resistance pattern to oseltamivir. The low rate of oseltamivir resistance among pandemic H1N1 influenza A strains to date contrasts with the extremely high rate among seasonal H1N1 influenza A strains. This is discussed in detail separately. (See "Treatment of seasonal influenza in adults", section on 'Neuraminidase inhibitor resistance'.)

Pregnancy and postpartum — The United States Centers for Disease Control and Prevention states that antiviral chemoprophylaxis can be considered in pregnant women and women who are up to two weeks postpartum (including following pregnancy loss) who are close contacts of individuals with suspected or confirmed pandemic H1N1 influenza A infection [6]. Early treatment is an alternative to prophylaxis for some pregnant and postpartum women who have been exposed to an individual with possible influenza infection.

Zanamivir is probably the drug of choice for prophylaxis given its limited systemic absorption (table 1). Oseltamivir is an alternative agent for women with a relative contraindication to zanamivir, such as asthma or chronic obstructive pulmonary disease.

Oseltamivir and zanamivir are Pregnancy Category C drugs, reflecting that clinical studies have not been done to assess the safety of their use during pregnancy [5]. No adverse events have been shown to be caused by oseltamivir or zanamivir among women who received these agents during pregnancy or among infants who were exposed while in utero. (See "Pharmacology of antiviral drugs for influenza", section on 'Pregnancy'.)

Long-term care facilities — No outbreaks of pandemic H1N1 influenza A virus have been identified in nursing homes or other long-term care facilities [5]. If such an outbreak occurs, ill patients should be treated with oseltamivir or zanamivir, and prophylaxis with oseltamivir or zanamivir should be initiated as soon as possible to all non-ill residents. Prophylaxis should be continued for a minimum of 2 weeks AND until approximately 7 days after illness onset of the last patient. (See "Prevention of seasonal influenza in adults".)

Children — The United States Centers for Disease Control and Prevention states that post-exposure antiviral prophylaxis can be considered for close contacts who are at high risk for complications of influenza (eg, individuals with certain chronic medical conditions, those <5 years of age) of a confirmed or suspected case [18]. Early evaluation and treatment is an alternative to prophylaxis following a suspected exposure to an individual with influenza infection [20]. (See 'Close contacts' above.)

Antiviral prophylaxis should generally NOT be used in healthy children and adolescents following exposures in community, school, camp, or other settings [20].

Oseltamivir or zanamivir are recommended for prophylaxis of pandemic H1N1 influenza A [18,20]. Although oseltamivir is approved in children ≥1 year of age for seasonal influenza, the US Food and Drug Administration has issued an emergency use authorization for clinicians to use oseltamivir during the current pandemic when indicated in infants under one year of age [20,21]. Because of a lack of safety data, prophylaxis of asymptomatic infants under 3 months of age is not recommended unless the situation is judged to be critical [20]. (See "Treatment of pandemic H1N1 influenza ('swine influenza')", section on 'Children'.)

Zanamivir is approved for the prevention of influenza in children ≥5 years of age, but is relatively contraindicated in individuals with asthma.

Postmarketing reports have identified rare, but serious neuropsychiatric events in children with influenza who are taking oseltamivir. (See "Antiviral drugs for the prevention and treatment of influenza in children", section on 'Rare adverse effects'.)

Pediatric dosing — The dosing of antivirals for pandemic H1N1 influenza A prophylaxis is the same as for seasonal influenza (table 2) [18,20]. The dosing of oseltamivir for infants <1 year of age depends upon the age of the infant:

• Age <3 months — Not recommended except in critical situations.
• Age 3 to 5 months — 20 mg once daily
• Age 6 to 11 months — 25 mg once daily

Some experts prefer weight-based dosing of oseltamivir for infants under one year of age, as follows:

• Age <9 months — 3 mg/kg per dose once daily
• Age ≥9 months — 3.5 mg/kg per dose once daily

When the commercially-available oseltamivir oral suspension is not available, oseltamivir 75 mg capsules can be compounded into a suspension at many retail pharmacies [18]. It is important to note that the commercially-available oseltamivir oral suspension concentration is 12 mg/mL, whereas the compounded suspension concentration is 15 mg/mL. Thus, the concentration of the oral suspension should always be specified.

When dispensing the oral suspension of oseltamivir to children <1 year of age, providers and pharmacists must take care to provide a dosing device that matches the units of measure on the prescription [22,23]. Health care providers should write doses in mg if the dosing dispenser with the drug is in mg [23]. As an alternative, the oral dosing dispenser that is provided in the package (which has markings for 30 mg, 45 mg, and 60 mg) can be removed and pharmacists or health care personnel should provide an oral syringe that can accurately measure the prescribed milliliter (mL) dose [18,22]. The caregiver should also be counseled regarding proper administration.

Zanamivir inhalation powder should not be reconstituted in any liquid formulation and is not recommended for use in nebulizers or mechanical ventilators [19].

Duration — Antiviral prophylaxis should be continued for 10 days after the last known exposure to an individual with confirmed pandemic H1N1 influenza A [18,20].

VACCINATION

Pandemic H1N1 influenza vaccination — The United States Centers for Disease Control and Prevention distributed pandemic H1N1 influenza A seed stocks to vaccine manufacturers in late May 2009 for use in a vaccine [24,25]. The first preparations of pandemic H1N1 influenza vaccine became available in the United States in early October, although it will take time for adequate supplies to be produced and distributed.

Both non-adjuvanted and adjuvanted formulations of the pandemic H1N1 influenza vaccine are being evaluated, although only non-adjuvanted vaccines have been approved for use in the United States [26].

Seasonal influenza vaccines are discussed in detail separately. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza vaccination in children".)

Since no vaccine is 100 percent effective, individuals who have been vaccinated against pandemic H1N1 influenza A who have signs and/or symptoms of influenza infection and have indications for treatment should be treated [18]. (See "Treatment of pandemic H1N1 influenza ('swine influenza')", section on 'Indications'.)

Vaccination against pandemic H1N1 influenza A is not expected to provide protection against seasonal strains of influenza, and vaccination against seasonal influenza is not expected to provide protection against pandemic H1N1 influenza A infection [18].

Although the efficacy of vaccination against pandemic H1N1 influenza A has not been proven, a study that modeled the effectiveness and cost-effectiveness of vaccination suggested that vaccinating 40 percent of the population of a large US city (population 8.3 million) with a vaccine that is 75 percent effective in November 2009 would avert 1468 deaths, gain 49,422 quality-adjusted life-years, and save $302 million [27]. In another analysis by the same researchers, the combination of vaccination with expanded availability of antiviral prophylaxis was also found to be effective and cost-effective [28].

Immunogenicity — Trials of both nonadjuvanted and adjuvanted pandemic influenza vaccines are being conducted, and preliminary results have been reported. Randomized trials have shown that a single dose of pandemic H1N1 vaccine is immunogenic against pandemic H1N1 influenza virus in a substantial percentage of healthy older children, healthy adults, and pregnant women, but in a smaller percentage of children ≤9 years of age and adults ≥61 years of age. A summary of findings follows:

• In one trial, an inactivated vaccine was administered twice (21 days apart) to approximately 2200 healthy individuals aged 3 to 77 years [29]. Vaccinees received either placebo or vaccine (7.5, 15, or 30 mcg) with or without alum adjuvant. Among the individuals who received the 15 mcg dose of nonadjuvanted vaccine, a hemagglutination-inhibition (HI) titer of ≥1:40 was achieved by day 21 in 75 percent of individuals aged 3 to 11 years, in 97 percent of those aged 12 to 60 years, and in 79 percent of those ≥61 years. By day 35, an HI titer ≥1:40 was observed in 98 percent of those aged 3 to 11 years, in 100 percent of those aged 12 to 17 years, in 97 percent of those aged 18 to 60 years, and in 93 percent of those ≥61 years. The nonadjuvanted vaccine resulted in both greater immunogenicity and a lower incidence of local reactions compared with the adjuvanted vaccine.
• In another trial of a nonadjuvanted inactivated vaccine, 240 healthy adults between 18 and 64 years of age were randomly assigned to receive either 15 or 30 mcg of pandemic H1N1 hemagglutinin antigen intramuscularly [30]. By 21 days following vaccination, HI titers ≥1:40 were observed in 97 percent of individuals who received the 15 mcg dose and 93 percent of those who received the 30 mcg dose. No deaths or serious adverse events were reported. The most common adverse effects were injection site tenderness or pain (in 46 percent) and systemic symptoms such as headache (in 45 percent).
• In the interim analysis of a trial in which 100 adults between 18 and 50 years of age received one or two doses of 7.5 mcg of MF59-adjuvanted H1N1 hemagglutinin antigen vaccine, 80 percent of the 25 individuals who received a single dose had HI titers ≥1:40 at 21 days following vaccination [31]. Among the individuals who received two doses of vaccine (three groups of 25 subjects received either: both doses on day 0, one on day 0 and one on day 7, or one on day 0 and one on day 14), 92 to 96 percent had HI titers ≥1:40 at 21 days following the first dose. The most common adverse events were pain at the injection site (in 70 percent) and muscle aches (in 42 percent). Data from the same trial comparing nonadjuvanted and adjuvanted formulations are pending.
• Preliminary results from a small trial assessing the immunogenicty of a nonadjuvanted inactivated pandemic H1N1 influenza vaccine in pregnant women during the second or third trimester have demonstrated that a single dose elicited a strong immune response in the majority of women; 23 of 25 women (92 percent) who received a single 15 mcg dose generated an immune response that is likely to be protective compared with 24 of 25 women (96 percent) who received a single 30 mcg dose [32].
• Preliminary results from a trial evaluating the immunogenicity of a nonadjuvanted inactivated pandemic H1N1 influenza vaccine in children have shown that a single 15 mcg dose induced a strong immune response in 76 percent in children aged 10 to 17 years, but was less likely to induce robust responses in younger children (36 percent of 3 to 9 year olds, 25 percent of 6 to 35 month olds) [33]. Eight to 10 days following a second dose of 15 mcg of vaccine, 94 percent of children aged 3 to 9 years had a robust immune response; 100 percent of children aged 6 to 35 months had a robust immune response following the second dose [34]. The immune responses in children who received two 15 mcg doses were similar to those among children who received two 30 mcg doses.

Preexisting antibodies — Recent seasonal influenza vaccines have not included antigens from the pandemic H1N1 influenza A virus that emerged in the spring of 2009. Nor does the recently approved 2009 to 2010 influenza vaccine contain antigens from the pandemic virus.

A study of cross-reactive antibody responses to pandemic H1N1 influenza A in the sera of individuals who were vaccinated with seasonal influenza vaccines between 2005 and 2009 showed that prior vaccination is unlikely to elicit a protective antibody response against this strain [35,36]. However, 39 of 115 (34 percent) of individuals born before 1950 had preexisting microneutralization titers ≥80 against pandemic H1N1 influenza, whereas only 4 of 107 (4 percent) of individuals born after 1980 had titers ≥40 [36]. Microneutralization titers ≥80 to 160 in adults and ≥40 in children often correlate with at least a 50 percent decrease in risk for influenza infection or disease, but whether these titers offer partial protection against pandemic H1N1 influenza A virus infection or disease is unclear. (See "Seasonal influenza vaccination in adults".)

In contrast to the lack of protective antibodies conferred by the seasonal influenza vaccine observed in the studies above [35,36], a case-control study that included 60 patients with laboratory-confirmed pandemic H1N1 influenza A infection and 180 controls in Mexico City from March to May 2009 showed that the seasonal influenza vaccine may confer some protection against pandemic H1N1 influenza A infection [37]. Individuals who had received the 2008-2009 seasonal influenza vaccine were less likely to develop pandemic H1N1 influenza A infection (adjusted odds ratio 0.27, 95% CI 0.11 to 0.66). Furthermore, none of the eight vaccinated patients who became infected with pandemic H1N1 influenza died.

Target groups — The recommended target groups for pandemic H1N1 influenza vaccination differ from those for seasonal influenza; the target groups for seasonal influenza vaccination are discussed in detail separately. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza vaccination in children".)

The US CDC's Advisory Committee on Immunization Practices has recommended the following order for administration of the pandemic H1N1 influenza vaccine, starting with the highest priority groups [38]:

• Pregnant women
• Household contacts and caregivers of children younger than 6 months of age (eg, parents, siblings, and daycare providers)
• Healthcare and emergency medical services personnel
• Individuals from 6 months through 24 years of age
• Individuals from 25 through 64 years of age with health conditions associated with increased risk of influenza complications (see 'High risk groups' above)

Healthcare personnel include all individuals working in a healthcare setting who may be exposed to patients with influenza or to infectious materials, such as body substances, contaminated medical supplies and equipment, or contaminated environmental surfaces.

If the vaccine supply is limited, the following groups should receive priority for vaccination:

• Pregnant women
• Household contacts and caregivers of children younger than 6 months of age (eg, parents, siblings, and daycare providers)
• 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 to 18 years who have medical conditions that put them at increased risk of complications (see 'High risk groups' above)

Once these groups have been vaccinated, all individuals between the ages of 25 and 64 years should be vaccinated, followed by individuals 65 years and older. Decisions about expansion of vaccination campaigns beyond the initial target groups should be made at the local level, based on vaccine availability.

For the pandemic H1N1 influenza A vaccine, the appropriate formulation (live attenuated intranasal vaccine versus inactivated vaccine), precautions, and contraindications are similar to those for the seasonal influenza vaccine. The live attenuated intranasal vaccine is only approved in individuals from 2 to 49 years of age and is contraindicated in pregnant women, those with underlying medical conditions that confer a higher risk for influenza complications, and children less than 5 years old with one or more episodes of wheezing in the past year [26]. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza vaccination in children".)

Egg allergy is a relative contraindication to both the live attenuated intranasal and the inactivated formulation of the pandemic H1N1 influenza vaccine. Patients with egg allergy should consult their physician and review the risks and benefits of vaccination. (See "Influenza vaccination in individuals with egg allergy".)

Dosing schedule — In the United States, it is recommended that children aged six months to nine years receive two doses of the vaccine, separated by approximately four weeks; individuals ≥10 years of age should receive one dose [26].

In individuals who require more than one dose of the H1N1 influenza A vaccine, vaccine should not be held in reserve for high-priority patients who have received only one dose of vaccine since vaccine availability is expected to increase over time; lower priority patients should be vaccinated once high-priority patients have received one dose of vaccine [38].

The seasonal and pandemic influenza vaccines are being produced as separate preparations. The US CDC's Advisory Committee on Immunization Practices states that inactivated vaccines against seasonal and pandemic H1N1 influenza viruses may be administered simultaneously if different anatomic sites are used [38]. In a trial in which adults >60 years of age received inactivated vaccines against seasonal and pandemic H1N1 influenza viruses concurrently in separate arms, both vaccines induced strong antibody responses [39].

In contrast to recommendations for the administration of inactivated vaccines, simultaneous administration of live attenuated vaccines against seasonal and pandemic H1N1 influenza viruses is not recommended. For individuals with indications for both of the live attenuated influenza vaccines (against seasonal and pandemic H1N1 influenza viruses), the minimum recommended interval between the vaccines is 14 days, and ideally at least 28 days [40]. If the live attenuated formulations of the seasonal and pandemic H1N1 influenza vaccines are given <14 days apart, the vaccine more recently administered should be readminstered at least 14 days, and ideally 28 days, after the first vaccine.

The World Health Organization (WHO) and the European Union's drug regulatory agency have developed recommendations for the dosing of pandemic H1N1 influenza vaccines. The WHO recommends a single dose of vaccine not only for individuals ≥10 years of age, but also for younger children in order to provide some protection to as many children as possible [41]. In contrast, the European Medicines Agency is recommending two doses of vaccine, even for older children and adults [42].

Safety — A major concern with the use of a novel vaccine for pandemic H1N1 influenza A is safety, particularly given the limited time available to perform clinical trials prior to the fall influenza season in the northern hemisphere.

In 1976, approximately 45 million people in the United States were immunized against an influenza virus of swine origin, but the program was discontinued prematurely, in part due to an increased incidence of Guillain-Barre syndrome among vaccinees [43]. Between 409,000 to 970,000 individuals would need to be vaccinated in order to detect a risk similar to the risk associated with the 1976 influenza vaccine. Although the mechanism for Guillain-Barre syndrome has not been elucidated, the fact that no increased risk has been observed with subsequent influenza vaccines is reassuring. (See "Pathogenesis of Guillain-Barré syndrome in adults", section on 'Influenza vaccination'.)

Pregnant women often have concerns about the safety of vaccines for their fetuses. In a small trial of an inactivated pandemic H1N1 influenza vaccine in pregnant women, it was well tolerated and no safety concerns arose [32]. Furthermore, no studies have shown an increased risk of either maternal complications or adverse fetal outcomes associated with inactivated influenza vaccines; in addition, there is no evidence that vaccines that contain thimerosal are harmful to the children of women who received thimerosal-containing vaccines during pregnancy [44]. The single dose vials of the inactivated vaccine do not contain thimerosal [45]. (See "Autism and chronic disease: Little evidence for thimerosal as a contributing factor".)

Since the pandemic H1N1 influenza A vaccine is similar in design to the the seasonal influenza vaccine, adverse effects are expected to be similar to those seen following seasonal influenza vaccination. (See "Seasonal influenza vaccination in adults", section on 'Adverse reactions'.)

Detailed information about the various vaccine formulations can be found on the website of the US Food and Drug Association: http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Post-MarketActivities/LotReleases/ucm181956.htm.

Pneumococcal vaccination — During influenza outbreaks, pneumococcal vaccination may be helpful in preventing secondary bacterial infections among those infected with influenza. Pneumococcal vaccination is recommended only for those who meet the criteria outlined by the United States Advisory Committee on Immunization Practices [46]. (See "Pneumococcal vaccination in adults" and "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children".)

INFECTION CONTROL IN HEALTHCARE SETTINGS — Recommendations regarding infection control measures for pandemic H1N1 influenza A infection in healthcare settings have been provided by the United States Centers for Disease Control and Prevention [17].

Healthcare facilities should develop and review written pandemic influenza preparedness plans and should use the following hierarchy of controls to prevent influenza virus transmission, starting with the highest priority items: elimination of potential exposures, engineering controls, administrative controls, and use of personal protective equipment [17].

The following measures should be undertaken to prevent the spread of influenza viruses in healthcare settings [17]:

• Administer the pandemic H1N1 and seasonal influenza vaccines to healthcare workers and emergency medical services personnel (see 'Pandemic H1N1 influenza vaccination' above.
• Enforce respiratory hygiene and cough etiquette
• Establish facility access control measures and triage procedures
• Manage visitor access and movement within the facility
• Follow facility procedures for transport and movement of patients who are on isolation precautions
• Limit the number of healthcare personnel entering an isolation room
• Apply isolation precautions

A detailed discussion of these measures can be found on the CDC's website (http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm).

Efficacy of face masks and N95 respirators — The effectiveness of face masks and N95 respirators in preventing transmission of pandemic H1N1 influenza A is not known [47]. However, in a randomized trial in which 446 nurses in hospital settings were randomly assigned to use either face masks or fit-tested N95 respirators when caring for patients with febrile respiratory illness during influenza season, face masks were non-inferior to N95 respirators for the prevention of seasonal influenza; laboratory-confirmed influenza infection occurred in 24 percent of individuals who used face masks and 23 percent of individuals who used N95 respirators [48].

Face masks do not seal tightly to the face and are used to prevent large droplets from coming into contact with the user's mouth or nose. N95 respirators fit tightly and filter out small particles. The optimal use of N95 respirators requires fit testing, training, and medical clearance. N95 respirators are not recommended for children or individuals with facial hair.

Isolation precautions — The CDC recommends the following isolation precautions for healthcare personnel who have close contact with patients with suspected or confirmed pandemic H1N1 influenza A infection; close contact is defined as being within six feet of the patient or entering a small enclosed airspace shared with the patient, such as a typical patient room [17]:

• Standard precautions — Gloves should be used for any contact with potentially infectious material, followed by hand hygiene immediately after glove removal. Gowns and eye protection should be used for any activity that might generate splashes of respiratory secretions or other infectious material.
• Respiratory protection — The CDC and the Institute of Medicine recommend the use of fit-tested N95 respirators for healthcare personnel in close contact with patients with suspected or confirmed pandemic H1N1 influenza A infection [17,49,50]. However, some facilities are experiencing shortages of N95 respirators. Additionally, some hospitals and state health departments have issued recommendations that differ from the CDC's with regard to the mode of respiratory protection.

The CDC recommends that the following measures be taken to reduce the numbers of respirators used and to prioritize their use for the highest risk situations [17]:

• - Reduce the number of healthcare workers who come into contact with patients with influenza-like illness, using the preparedness plan described above.
• - Use alternative respiratory protection equipment, such as reusable elastomeric tight-fitting respirators and powered air-purifying respirators, when available.
• - Prepare a plan for prioritized respirator use so that in the event of a significant shortage, healthcare workers at the highest risk for exposure (eg, those performing aerosol-generating procedures) will have access to respirators that are at least as protective as N95 respirators. When facilities are in prioritized use mode, N95 respirator use may be temporarily discontinued for workers at lower risk of exposure and/or lower risk of influenza complications; in such situations, face masks should be used as an alternative to N95 respirators.

Facilities should maintain a sufficient reserve of N95 (or equivalent) respirators to meet the needs of workers performing aerosol-generating procedures and for caring for patients with other conditions that require respiratory precautions, such as tuberculosis.

• Hand hygiene — Frequent hand hygiene should be performed, including before and after every patient contact, contact with respiratory secretions, and before putting on and after taking off personal protective equipment.

Further details regarding prioritized respiratory use and other issues related to isolation precautions can be found on the CDC's website (http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm ).

Aerosol-generating procedures — Aerosol-generating procedures include endotracheal intubation and extubation, bronchoscopy, cardiopulmonary resuscitation, collection of clinical specimens, open suctioning of airways, and autopsies [17]. Although nebulizer treatments, acquisition of nasopharyngeal samples, and use of high-flow oxygen might create infectious aerosols, less is known about the risk of these procedures. In addition to the use of N95 (or equivalent) respirators in healthcare workers performing aerosol-generating procedures, additional measures should be taken such as conducting such procedures in an airborne infection isolation room when feasible and limiting the number of healthcare personnel present during the procedure.

A detailed discussion of these measures can be found on the CDC's website (http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm ).

Duration of precautions — In hospitalized patients with suspected or confirmed pandemic H1N1 influenza A infection, isolation precautions should generally be continued for seven days after illness onset or until 24 hours after resolution of fever and respiratory symptoms, whichever is longer while the individual remains hospitalized [17]. The recommended duration of isolation precautions is longer for hospitalized patients compared with outpatients since the duration of shedding is likely to be longer among those requiring hospital admission.

Isolation precautions may be continued for a longer duration in patients who might shed influenza virus for a longer period, such as young children and severely immunocompromised individuals. If private rooms are limited, they should be prioritized among patients who are earlier in the course of illness. Patients should be discharged from the hospital based on their clinical status, and should not be kept in the hospital based on the duration of isolation.

Monitoring of healthcare workers — Occupational health departments should establish procedures for tracking absences; reviewing job tasks and identifying workers at increased risk for complications; assuring that workers have access to medical consultation via telephone, including access to early treatment; and promptly identifying workers with possible influenza infection [17].

Healthcare workers who develop a fever and respiratory symptoms should [17]:

• Not report to work, or if at work, should promptly notify their supervisor and infection control personnel or the occupational health department
• Not return to work for at least 24 hours after fever has resolved without the use of fever-reducing medicines.
• Consider temporary reassignment or exclusion from work for seven days or until resolution of symptoms, whichever is longer, for employees who work with severely immunocompromised patients. Clinical judgment should be used for employees with only cough as a symptom, since cough after influenza may be prolonged and may not indicate viral shedding. Personnel who are recovering may resume caring for severely immunocompromised patients sooner if real-time reverse transcriptase PCR for pandemic H1N1 influenza A is negative.
• Practice frequent hand hygiene, respiratory hygiene, and cough etiquette after returning to work.

Healthcare workers who develop acute respiratory symptoms without fever should be:

• Allowed to continue or return to work unless they work with severely immunocompromised patients. Personnel who work with severely immunocompromised patients should be temporarily reassigned or excluded from work for seven days from symptom onset or until the resolution of symptoms, whichever is longer. Clinical judgment should be used for employees with only cough as a symptom, since cough after influenza may be prolonged and may not indicate viral shedding. Personnel who are recovering may resume caring for severely immunocompromised patients sooner if real-time reverse transcriptase PCR for pandemic H1N1 influenza A is negative.
• Reminded of the importance of frequent hand hygiene, respiratory hygiene, and cough etiquette.

Healthcare workers with an influenza-like illness who are at increased risk for influenza complications should consult with their healthcare provider in order to receive early treatment. (See "Treatment of pandemic H1N1 influenza ('swine influenza')".)

Other recommendations can be found on the CDC's website (http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm ).

The remainder of this card is discussed separately.