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Treatment and prevention of swine H1N1 influenza

Author Anna R Thorner, MD

Section Editor Martin S Hirsch, MD

Deputy Editor Barbara H McGovern, MD

Last literature review for version 17.1: enero 1, 2009  |  This topic last updated: junio 30, 2009

INTRODUCTION — Swine influenza viruses usually infect pigs, but occasionally can cross species barriers to infect humans. In the past, cases of person-to-person transmission have been reported but have been confined to small outbreaks [1,2].

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 [2,3]. 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 [4].

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

DEFINITIONS

Case definitions — Definitions are changing as we learn more about this virus and the syndromes it causes. Cases in the United States are confirmed by diagnostic testing at the Centers for Disease Control and Prevention [5-7]. (See "Epidemiology, clinical manifestations, and diagnosis of swine H1N1 influenza A", section on Diagnosis).

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 [7].

The following case definitions have been provided by the United States Centers for Disease Control and Prevention [7]:

A confirmed case of H1N1 influenza A is defined as an individual with an ILI with laboratory-confirmed H1N1 influenza A virus detection by real-time reverse transcriptase (RT)-PCR or culture.

A probable case of H1N1 influenza A is defined as an individual with an ILI who is positive for influenza A, but negative for H1 and H3 by RT-PCR

H1N1 influenza A may be suspected in an individual who does not meet the definitions of confirmed or probable H1N1 influenza A, but has an ILI and an epidemiologic link (eg, likely exposure to a confirmed or probable case within the past seven days). Full case definitions can be found at the CDC's website (http://www.cdc.gov/swineflu/).

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

High risk groups include [5,8-12]:

Children younger than 5 years of age (particularly those less than 2 years of age)

Individuals 65 years of age or older

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

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      - 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

Children with poor nutritional and fluid intake because of prolonged vomiting and diarrhea

Residents of nursing homes and other chronic care facilities

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 "Antiviral drugs for the prevention of influenza in adults", section on Definition of high risk, and see "Antiviral drugs for the prevention and treatment of influenza in children").

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, probable, or suspected case of 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, probable, or suspected case of 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, probable, or suspected case of H1N1 influenza A

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.

MEDICAL CARE FOR SUSPECTED CASES — Not all individuals with suspected H1N1 influenza A infection need to be seen by a health care provider or treated [9,13]. Patients with severe illness and those at high risk of complications from influenza should contact their health care provider or seek medical care. (See "High risk groups" above).

ANTIVIRAL THERAPY — The vast majority of strains of swine 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 [5,14,15]. However, there are no reported studies yet on the clinical benefits of antiviral therapy.

In June 2009, a single isolate of H1N1 influenza virus that was resistant to oseltamivir was detected in a patient in Denmark who was receiving a low dose of oseltamivir for prophylaxis following exposure to an individual with influenza [25]. The isolate appeared to be sensitive to zanamivir, and the individual was switched to this drug and recovered without complications; transmission of the virus to others was not detected.

The United States Centers for Disease Control and Prevention (CDC) has released guidelines for the use of antivirals for patients with confirmed or suspected H1N1 influenza A virus infection and close contacts [5]. Our recommendations reflect those of the CDC. Guidelines may change as more information becomes available. 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.

Therapy should be started as soon as possible, since evidence of benefit is strongest for seasonal influenza when treatment is started within 48 hours of illness onset [5,12]. Some studies of hospitalized patients have demonstrated benefit even when therapy for seasonal influenza is started >48 hours after onset of illness. In patients who are more than mildly ill, we would initiate therapy even past 48 hours of symptoms [5]. (See "Antiviral drugs for the treatment of influenza in adults" and see "Antiviral drugs for the prevention and treatment of influenza in children").

Adults — We recommend antiviral therapy for [5]:

All hospitalized patients with confirmed, probable, or suspected H1N1 influenza A virus infection (see "Case definitions" above) and

Patients at increased risk for complications (see "High risk groups" above).

During the current pandemic, patients with mild illness do not need to be tested or treated unless they have risk factors for complications [5,13]. However, the decision of whether to initiate antiviral therapy for each patient should be based upon the clinician's judgment and on what is known about the benefits of therapy for seasonal influenza. (See "Medical care for suspected cases" above and see "Antiviral drugs for the treatment of influenza in adults").

In areas with limited antiviral availability, local public health officials might provide additional guidance regarding their prioritization [5].

Choice of antiviral — For patients requiring treatment, we recommend either zanamivir or oseltamivir [5]. Zanamivir is contraindicated in patients with asthma or chronic obstructive pulmonary disease. (See "Pharmacology of antiviral drugs for influenza").

During this pandemic, in patients suspected to have influenza but who have no epidemiologic link to swine H1N1 influenza A, we recommend treatment with a neuraminidase inhibitor. However, in locations where oseltamivir-resistant seasonal

influenza A (H1N1) virus is still circulating, we suggest that the neuraminidase inhibitor be zanamivir rather than oseltamivir. In such a setting, for patients who are unable to take zanamivir, we suggest the addition of an adamantane (rimantadine or amantadine) to oseltamivir [5]. (See "Antiviral drugs for the treatment of influenza in adults").

The dosing of antivirals for the treatment of swine H1N1 influenza A infection in adults is the same as for seasonal influenza (show table 1). (See "Antiviral drugs for the treatment of influenza in adults" and see "Pharmacology of antiviral drugs for influenza").

Antiviral therapy should be continued for five days, as with seasonal influenza [5].

Pregnancy — Seasonal and pandemic strains of influenza cause more severe disease and an increased rate of mortality among pregnant women [8]. Cases of severe swine H1N1 influenza A have been reported in pregnant women, including a fatal case in a woman with psoriasis and mild asthma who was diagnosed at 35 weeks' gestation [16]. (See "Epidemiology, clinical manifestations, and diagnosis of swine H1N1 influenza A").

Oseltamivir, zanamivir, amantadine, and rimantadine are Pregnancy Category C drugs, reflecting that clinical studies have not been done to assess the safety of their use during pregnancy [5]. Both amantadine and rimantadine have been found to be teratogenic and embryotoxic when given at high doses in animal studies. 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).

Pregnant women who meet current case definitions for confirmed, probable, or suspected H1N1 influenza A infection should receive antiviral therapy with either oseltamivir or zanamivir, since the potential benefit outweighs the theoretical risk to the fetus [8]. (See "Choice of antiviral" above).

Children — Oseltamivir is approved in the United States for the treatment of influenza A and B viral infections in individuals ≥1 year of age. Zanamivir is approved for the treatment of influenza A and B viral infections in individuals ≥7 years of age. However, the US Food and Drug Administration has issued an emergency use authorization for clinicians to use oseltamivir or zanamivir in younger children, when indicated, during the current pandemic [12]. Limited safety data on oseltamivir treatment in infants <1 year of age suggest that severe adverse reactions are rare [5].

We recommend antiviral therapy for [5]:

All hospitalized patients with confirmed, probable, or suspected H1N1 influenza A virus infection (see "Case definitions" above) and

Patients at higher risk of complications. In addition to patients with underlying illnesses, all children younger than 5 years of age, particularly those less than 2

years of age, are at increased risk for complications of influenza. (See "High risk groups" above).

During the current pandemic, patients with mild illness do not need to be tested or treated unless they have risk factors for complications [13]. However, the decision of whether to initiate antiviral therapy in each patient should be based upon the clinician's judgment and on what is known about the benefits of therapy for seasonal influenza. (See "Medical care for suspected cases" above).

For children <1 year of age, oseltamivir is the recommended antiviral [12]. Therapy should be started as soon as possible.

The dosing of antivirals for swine H1N1 influenza A infection in children is the same as that for seasonal influenza (show table 2). Treatment should be continued for five days. (See "Antiviral drugs for the prevention and treatment of influenza in children" and see "Pharmacology of antiviral drugs for influenza").

For infants younger than 1 year of age, the oseltamivir dose depends upon the age of the infant:

Age <3 months — 12 mg twice daily Age 3 to 5 months — 20 mg twice daily Age 6 to 11 months — 25 mg twice daily

Antiviral therapy should be continued for five days, as with seasonal influenza [12].

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 events).

Children who may have influenza infection should not take aspirin or aspirin-containing products, such as bismuth subsalicyclate (PeptoBismol), due to the increased risk of Reye syndrome [5].

ANTIBACTERIAL THERAPY — Patients with H1N1 influenza A who develop pneumonia should be treated empirically for community-acquired pneumonia (CAP) [9]. In hospitalized patients with severe CAP requiring intensive care unit admission who also have either necrotizing/cavitary infiltrates or empyema, methicillin-resistant Staphylococcus aureus (MRSA) infection should be suspected and treated in addition to other potential causes. (See "Treatment of community-acquired pneumonia in adults who require hospitalization" and see "Inpatient treatment of pneumonia in children").

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 H1N1 influenza A virus infection [5,12]. 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.

Indications in adults — The indications for post-exposure antiviral prophylaxis are based upon close contact with a patient who is a confirmed, probable, or suspected case of H1N1 influenza A infection [5]. (See "Close contacts" above).

The United States Centers for Disease Control and Prevention states that post-exposure antiviral prophylaxis can be considered for [5]:

Close contacts who are at high risk for complications of influenza (eg, individuals with certain chronic medical conditions, ≥65 years of age, pregnant women) of a confirmed, probable, 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, probable, or suspected patient during that person's infectious period.

Pre-exposure antiviral prophylaxis should only be used in limited situations, and in consultation with local medical or public health authorities [5]. Certain individuals who have ongoing occupational risk for exposure (eg, healthcare workers, public health workers, first responders) who are also at increased risk of influenza complications should follow guidelines for personal protective equipment stringently or consider temporary reassignment.

Choice of agent — When antiviral prophylaxis is indicated, either oseltamivir or zanamivir should be used [5]. The dosing of antivirals for swine H1N1 influenza A infection is the same as for seasonal influenza in adults (show table 1). (See "Antiviral drugs for the prevention of influenza in adults" and see "Pharmacology of antiviral drugs for influenza").

Indications during pregnancy — Pregnant women who are close contacts of individuals with suspected, probable, or confirmed cases should receive antiviral prophylaxis with zanamivir or oseltamivir [8]. (See "Pregnancy" above).

Indications in long-term care facilities — No outbreaks of the current 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 "Antiviral drugs for the prevention of influenza in adults").

Indications in children — The US Food and Drug Administration has issued an emergency use authorization for clinicians to use oseltamivir or zanamivir during the current pandemic when indicated in children younger than the ages for which they have been approved [12]. (See "Children" above).

Antiviral prophylaxis with oseltamivir or zanamivir is recommended for the following children [12]:

The United States Centers for Disease Control and Prevention states that post-exposure antiviral prophylaxis can be considered for [5]:

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, probable, or suspected case. (See "Close contacts" above).

Oseltamivir or zanamivir are recommended for prophylaxis of H1N1 influenza A in children ≥1 year of age when indicated [12]. Oseltamivir can also be used for prophylaxis in infants <1 year of age, but should not be used in infants <3 months of age unless the patient is critically ill.

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 events).

Pediatric dosing — The dosing of antivirals for swine H1N1 influenza A prophylaxis is the same as for seasonal influenza (show table 2). The dosing of oseltamivir for infants <1 year of age depends upon the age of the infant:

Age <3 months — Not recommended unless the patient is critically ill. Age 3 to 5 months — 20 mg once daily Age 6 to 11 months — 25 mg once daily

Duration of prophylaxis — Antiviral prophylaxis should be continued for 10 days after the last known exposure to an individual with confirmed H1N1 influenza A [5,12]. In individuals who receive pre-exposure prophylaxis, the antiviral drug should be given during the potential exposure period and continued for 10 days after the last known exposure to a patient with confirmed H1N1 influenza A.

Post-exposure prophylaxis should be considered for contact during the infectious period (one day before until seven days after the case's onset of illness) [5]. If the contact occurred more than seven days earlier, prophylaxis is not necessary.

VACCINATION — The United States Centers for Disease Control and Prevention distributed H1N1 influenza A seed stocks to vaccine manufacturers in late May 2009 for use in a vaccine, which will take several months to produce [17,18].

Recent seasonal influenza vaccines have not included antigens from the H1N1 influenza A virus that emerged in the spring of 2009. A study of cross-reactive antibody responses to swine 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 [19]. However, 33 percent of

individuals over age 60 had microneutralization titers ≥160 compared with 6 percent of individuals aged 18 to 40, and 9 percent of individuals aged 18 to 64. Microneutralization titers ≥160 often correlate with at least a 50 percent decrease in risk for influenza infection or disease, but whether these titers offer partial protection against H1N1 influenza A virus infection or disease is unclear. (See "Influenza vaccination in adults").

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 [20]. (See "Pneumococcal vaccination in adults" and see "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children").

INFECTION CONTROL — In regions with known cases of H1N1 influenza A, all patients with an acute febrile respiratory illness (a measured temperature of 100ºF or higher and recent onset of at least one of the following: rhinorrhea, nasal congestion, sore throat, or cough) should be managed using the following infection control guidelines [21]. The same precautions should be taken with patients with an acute febrile respiratory illness in a region in which cases have not been identified, but who have had contact within the previous seven days with an individual with confirmed, probable, or suspected H1N1 influenza A virus or who have traveled to a region with confirmed cases within the previous seven days.

As the pandemic evolves, the ability to use epidemiologic links may be lost. Updated recommendations can be found on the CDC website (http://www.cdc.gov/h1n1flu/).

Initial management — Healthcare facilities should establish mechanisms for prompt screening of patients for respiratory illness and isolation of symptomatic patients [21]. Respiratory hygiene and cough etiquette should be adhered to strictly at the first point of contact with a potentially infected person. Screening of patients should be done in a location with negative pressure air handling, whenever possible.

Patients with suspected or confirmed H1N1 influenza A virus infection should be placed directly into single patient rooms with the door kept closed [21]. Air from the patient's room can be vented directly outside or can be recirculated after high-efficiency particulate (HEPA) filtration.

Precautions — Standard and contact precautions plus eye protection should be used and continued for seven days after the onset of illness or until symptoms have resolved, whichever is longer [21]. In addition, all healthcare workers should wear fit-tested N95 respirators while providing routine care. Clinicians providing care or collecting clinical specimens from suspected or confirmed cases of H1N1 influenza A should wear disposable non-sterile gloves, gowns, and eye protection. Stringent hand hygiene should be adhered to, involving washing hands with soap and water or with an alcohol-based hand sanitizer immediately after removing gloves and other personal protective equipment and after any contact with respiratory secretions.

Personnel involved in aerosol-generating activities (endotracheal intubation, nebulizer treatment, bronchoscopy, cardiopulmonary resuscitation, collection of clinical specimens) should wear a fit-tested N95 respirator. An airborne infection isolation room with negative pressure air handling with 6 to 12 air changes per hour can be used, if available.

The patient should wear a surgical mask if he or she needs to leave the room, should wash hands frequently, and follow respiratory hygiene practices.

Monitoring of healthcare workers — Healthcare workers (HCWs) should be monitored daily for signs and symptoms of an acute febrile respiratory illness [21]. If a HCW develops such findings, he or she should not report to work or, if already at work, should cease patient care activities and notify his or her supervisor and infection control personnel.

In communities in which H1N1 influenza A is present, HCWs with a febrile respiratory illness should be excluded from work for seven days or until symptoms have resolved, whichever is longer. HCWs with a febrile respiratory illness who are in a community without H1N1 influenza A transmission and who have not been caring for patients with H1N1 influenza A should follow the guidelines of their institution regarding returning to work.

Asymptomatic HCWs who have had unprotected exposure to H1N1 influenza A may continue to work if they are started on antiviral prophylaxis. (See "Indications in adults" above).

Visitors — Visits should be limited to individuals who are necessary for the patient's care and emotional well-being [21]. Visitors should be screened for acute respiratory illness before entering the hospital, since they may be sources of infection. Visitors should be offered a gown, gloves, eye protection, and an N95 respirator and should be instructed on how to use them. They should also be instructed about hand hygiene and limiting surfaces touched, as well as about limiting their movement within the healthcare facility.

Further information about infection control recommendations can be found on the website of the CDC (http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm).

SOCIAL DISTANCING MEASURES — The United States Centers for Disease Control and Prevention recommends several measures for preventing the spread of H1N1 influenza A virus, including home isolation of ill individuals and the use of face masks or respirators when there is risk of transmission [22,23].

Individuals who are at high risk of complications (eg, those with chronic medical conditions, children <5 years of age, pregnant women) should consider their risk of exposure to H1N1 influenza A if they attend public gatherings in areas where it is known to be circulating [23]. In communities in which several cases have been reported, those at high risk of complications should consider avoiding public gatherings. (See "High risk groups" above).

Face masks and respirators — The effectiveness of face masks and N95 respirators in preventing transmission of H1N1 influenza A is not known [23]. 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.

Use of a face mask or N95 respirator is NOT recommended for individuals who are not at increased risk for influenza complications in the community, even when H1N1 influenza A is known to be circulating [23]. Use of a face mask or N95 respirator should be considered only under certain circumstances in community settings [23,24].

When crowded settings or close contact with others cannot be avoided in areas where transmission of H1N1 influenza A has been confirmed, the following measures should be taken:

      - Close contact with individuals who might be ill and being in crowded settings should be avoided whenever possible.

      - Individuals at increased risk for influenza complications should consider wearing a face mask or N95 respirator if avoidance of a crowded setting is not possible. (See "High risk groups" above).

For occupational exposures in non-healthcare settings, face masks or N95 respirators are generally not recommended, but the following measures should be taken for work activities that involve contact with individuals with an (ILI, fever with cough or sore throat):

      -  Workers should try to maintain a distance of ≥6 feet from the person with an ILI.

      -  Interactions with individuals with an ILI should be as brief as possible.

      - The ill person should be asked to follow good cough etiquette and hand hygiene and to wear a face mask, if available. (See "High risk groups" above).

      - Workers at increased risk for influenza complications should avoid individuals with an ILI (eg, temporary reassignment).

      - Workers who are unable to avoid individuals with an ILI may consider wearing a face mask or N95 respirator.

The use of face masks and N95 respirators in healthcare settings and for caregivers of ill individuals at home are discussed separately. (See "Infection control" above and see "Household contacts" below).

Home isolation — Individuals with an influenza-like illness (ILI, fever with cough or sore throat) should self-isolate in their home for seven days after the onset of illness or for at least 24 hours after symptoms have resolved, whichever is longer [22-24]. Infected children may be contagious for longer than seven days. (See "Epidemiology, clinical manifestations, and diagnosis of swine H1N1 influenza A", section on Shedding).

Those who plan to seek medical care should contact their health care providers to report their illness before seeking care. Patients who are severely ill (respiratory distress) should seek medical attention immediately.

Ill persons who must go into the community (eg, to seek medical care) should wear a face mask [23,24]. (See "Face masks and respirators" above).

Those in home isolation and their household members should be given infection control instructions, including frequent handwashing with soap and water or use of alcohol-based hand gels when soap and water are not available and hands are not visibly dirty.

An individual with an ILI should stay in a separate room from others with the door kept closed; a separate bathroom should be used if possible [24]. The bathroom should be cleaned daily with disinfectant. The ill person should wear a face mask when he or she is within 6 feet of household members and when it is necessary to be in common areas near other individuals [24].

Additional recommendations regarding home isolation can be found at: http://www.cdc.gov/h1n1flu/guidance_homecare.htm.

Household contacts — Household contacts who are well should minimize contact in the community, designate a single household member as the ill person's caregiver, and remain home at the earliest sign of illness should it develop [22,24]. Pregnant women should avoid caring for the ill person.

Use of a face mask or N95 respirator is NOT recommended for the routine care of individuals who are not at increased risk for influenza complications in the community or at home, even when caring for an individual with an influenza-like illness (fever with cough or sore throat) [23]. However, use of a face mask or N95 respirator should be considered by individuals who are at increased risk for influenza complications and who are required to be the caregiver of an infected individual. (See "High risk groups" above).

N95 respirators should be used by caretakers during administration of respiratory treatments (eg, using a nebulizer or inhaler) [24]. (See "Face masks and respirators" above).

BREASTFEEDING — The United States Centers for Disease Control and Prevention recommends that lactating women with H1N1 influenza A infection continue to breastfeed since the passive transfer of antibodies against the virus can protect the infant; this is particularly important for infants less than 6 months of age [8]. Women with an influenza-like illness (fever with cough or sore throat) should wear a face mask during breastfeeding;

if a face mask is unavailable or intolerable, a tissue should be used to cover the face when coughing and sneezing [23].

If maternal illness prevents breastfeeding, the infant's mother should pump, if possible, so that the infant can still receive breastmilk. The risk of H1N1 influenza A virus transmission via breastmilk is unknown, although reports of viremia with seasonal influenza are rare. Antiviral treatment or prophylaxis of the mother is not a contraindication to breastfeeding.

Infants who are ill with H1N1 influenza A should continue to breastfeed [8].

TRAVEL ADVISORIES — For updated information about travel advisories, see the United States Centers for Disease Control and Prevention website (http://www.cdc.gov/travel/) and/or the World Health Organization website (http://www.who.int/csr/disease/swineflu/en/index.html).

SUMMARY AND RECOMMENDATIONS — In late March and early April 2009, an outbreak of swine H1N1 influenza A virus infection was detected in Mexico, with subsequent cases observed in many other countries including the United States. (See "Introduction" above).

Case definitions of H1N1 influenza A

Case definitions of suspected, probable, and confirmed H1N1 influenza A virus infection are based on symptoms, signs, and epidemiologic information. (See "Case definitions" above).

Treatment — The vast majority of strains of swine 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. No clinical studies have confirmed benefit of therapy, however. (See "Antiviral therapy" above).

Not all individuals with suspected H1N1 influenza A infection need to be seen by a health care provider or treated. Patients with severe illness and those at high risk of complications from influenza should contact their health care provider or seek medical care. (See "Medical care for suspected cases" above).

We recommend antiviral therapy (with zanamivir or oseltamivir) for all hospitalized patients with confirmed, probable, or suspected H1N1 influenza A virus infection and for patients at increased risk for complications (Grade 1B). During the current pandemic, patients with mild illness do not need to be tested or treated unless they have risk factors for complications. (See "Adults" above).

In locations where oseltamivir-resistant seasonal influenza A (H1N1) virus is still circulating, zanamivir is the preferred antiviral. Patients who are unable to take zanamivir in such a setting can be given the combination of an adamantane (rimantadine or amantadine) with oseltamivir. (See "Choice of agent" above).

Treatment should be initiated as soon as possible. In patients who are more than mildly ill, we would initiate therapy even past 48 hours of symptoms. (See "Antiviral therapy" above).

The duration of therapy is five days. (See "Antiviral therapy" above).

Recommendations for the treatment of pregnant women and infants are discussed above. (See "Pregnancy" above and see "Children" above).

Prophylaxis — No clinical studies have confirmed benefit of prophylaxis for H1N1 influenza A virus infection.

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 prophylaxis (Grade 2C). (See "Antiviral prophylaxis" above).

For patients in whom prophylaxis for H1N1 influenza A virus infection is indicated, we recommend either oseltamivir or zanamivir (Grade 1B). Antiviral prophylaxis should be continued for a total of 10 days following the last known exposure to a confirmed case. (See "Antiviral prophylaxis" above).

Recommendations for the prophylaxis of pregnant women and infants are discussed above. (See "Indications during pregnancy" above and see "Indications in children" above).

Infection control and social distancing measures

Stringent infection control practices and social distancing measures should be implemented in order to reduce transmission of H1N1 influenza A. (See "Infection control" above and see "Social distancing measures" above).

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5. United States Centers for Disease Control and Prevention. Interim guidance on antiviral recommendations for patients with novel influenza A (H1N1) virus infection and their close contacts. http://www.cdc.gov/h1n1flu/recommendations.htm (Accessed May 7, 2009).

6. United States Centers for Disease Control and Prevention. Interim guidance on specimen collection, processing, and testing for patients with suspected swine-origin influenza A (H1N1) virus infection. http://www.cdc.gov/h1n1flu/specimencollection.htm (Accessed May 12, 2009).

7. United States Centers for Disease Control and Prevention. Interim guidance on case definitions to be used for investigations of novel influenza A (H1N1) cases. http://www.cdc.gov/h1n1flu/casedef.htm (Accessed June 2, 2009).

8. United States Centers for Disease Control and Prevention. Pregnant women and novel influenza A (H1N1): considerations for clinicians. http://www.cdc.gov/h1n1flu/clinician_pregnant.htm (Accessed May 10, 2009).

9. United States Centers for Disease Control and Prevention. Interim guidance for clinicians on identifying and caring for patientswith swine-origin influenza A (H1N1) virus infection http://www.cdc.gov/swineflu/identifyingpatients.htm (Accessed May 5, 2009).

10. United States Centers for Disease Control and Prevention. Interim guidance — HIV-infected adults and adolescents: Considerations for clinicians regarding novel influenza A (H1N1) virus. http://www.cdc.gov/h1n1flu/guidance_HIV.htm (Accessed June 9, 2009).

11. United States Centers for Disease Control and Prevention. H1N1 flu and patients with cardiovascular disease (heart disease and stroke): Interim guidance and considerations for health care providers and for state and local public health agencies. http://www.cdc.gov/h1n1flu/guidance/cardiovascular.htm (Accessed May 3, 2009).

12. United States Centers for Disease Control and Prevention. Interim guidance for clinicians on the prevention and treatment of novel influenza A (H1N1) influenza virus Infection in infants and young children. http://www.cdc.gov/h1n1flu/childrentreatment.htm (Accessed May 10, 2009).

13. The Commonwealth of Massachusetts Department of Public Health. Interim guidance on testing and antiviral treatment for influenza H1N1. http://www.mass.gov/Eeohhs2/docs/dph/cdc/flu/swine_interim_guidance_testing_and_antiviral_treatment.pdf (Accessed May 5, 2009).

14. World Health Organization. Influenza-like illness in the United States and Mexico, 24 April 2009. http://www.who.int/csr/don/2009_04_24/en/index.html (Accessed April 27, 2009).

15. Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR Morb Mortal Wkly Rep 2009; 58:433.

16. Novel influenza A (H1N1) virus infections in three pregnant women - United States, April-May 2009. MMWR Morb Mortal Wkly Rep 2009; 58:497.

17. World Health Organization. Vaccines for the new influenza A(H1N1), 2 May 2009. http://www.who.int/csr/disease/swineflu/frequently_asked_questions/vaccine_preparedness/en/index.html (Accessed May 6, 2009).

18. United States Centers for Disease Control and Prevention. CDC Telebriefing on Investigation of Human Cases of H1N1 Flu, May 28, 2009. http://www.cdc.gov/media/transcripts/2009/t090528.htm (Accessed June 2, 2009).

19. Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR Morb Mortal Wkly Rep 2009; 58:521.

20. United States Centers for Disease Control and Prevention. Interim guidance for use of 23-valent pneumococcal polysaccharide vaccine during novel influenza A (H1N1) outbreak. http://www.cdc.gov/h1n1flu/guidance/ppsv_h1n1.htm (Accessed June 11, 2009).

21. United States Centers for Disease Control and Prevention. Interim guidance for infection control for care of patients with confirmed or suspected novel influenza A (H1N1) virus infection in a healthcare setting. http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm (Accessed May 14, 2009).

22. United States Centers for Disease Control and Prevention. Interim CDC guidance for nonpharmaceutical community mitigation in response to human infections with swine influenza (H1N1) virus. http://www.cdc.gov/swineflu/mitigation.htm (Accessed April 27, 2009).

23. United States Centers for Disease Control and Prevention. Interim Recommendations for Facemask and Respirator Use to Reduce Novel Influenza A (H1N1) Virus Transmission. http://www.cdc.gov/h1n1flu/masks.htm (Accessed May 28, 2009).

24. United States Centers for Disease Control and Prevention. Interim guidance for H1N1 Flu (Swine Flu): Taking care of a sick person in your home. http://www.cdc.gov/h1n1flu/guidance_homecare.htm (Accessed May 14, 2009).

25. The New York Times. Drug-resistant flu strain turns up in Denmark but doesn’t last long. http://www.nytimes.com/2009/06/30/health/30glob.html?_r=1&emc=eta1 (Accessed June 30, 2009).