TREATMENT AND PREVENTION H1N1

The treatment and prevention of swine H1N1 influenza A virus infection will be reviewed here. The epidemiology, clinical manifestations, and diagnosis of swine H1N1 influenza A virus infection, and seasonal and avian (H5N1) influenza virus infections are discussed separately. (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” and other topic reviews).

CASE DEFINITIONS — Definitions are changing as we learn more about this virus and the syndromes it causes. Updated definitions can be found at the CDC’s website (http://www.cdc.gov/swineflu/). Cases in the United States are confirmed by diagnostic testing at the Centers for Disease Control and Prevention [1,5]. (See “Epidemiology, clinical manifestations, and diagnosis of swine H1N1 influenza A”, section on Diagnosis).

The following case definitions have been provided by the United States Centers for Disease and Prevention and are current as of April 29, 2009 [1,5,6]:

  • A confirmed case of swine H1N1 influenza A is defined as an individual with an acute febrile respiratory illness (a measured temperature of 37.8ºC [100.4ºF] and recent onset of at least one of the following: rhinorrhea, nasal congestion, sore throat, or cough) with laboratory-confirmed swine H1N1 influenza A virus detection by real-time reverse transcriptase (RT)-PCR or culture.
  • A probable case of swine H1N1 influenza A is defined as an individual with an acute febrile respiratory illness who is positive for influenza A, but negative for H1 and H3 by RT-PCR
  • A suspected case of swine H1N1 influenza A is defined as an individual with an acute febrile respiratory illness who:

      – Develops symptoms within seven days of close contact with a person who is a confirmed case of swine H1N1 influenza A virus infection or

      – Develops symptoms within seven days of travel to a community either within the United States or internationally where there are one or more confirmed swine H1N1 influenza A cases or

      – Resides in a community where there are one or more confirmed swine H1N1 influenza A cases (see “Epidemiology, clinical manifestations, and diagnosis of swine H1N1 influenza A”, section on Epidemiology)

DEFINITION OF HIGH RISK — High risk groups for the development of complications of swine H1N1 influenza A are thought to be similar to those defined for seasonal influenza. (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”).

ANTIVIRAL THERAPY — The strain of swine H1N1 influenza A virus circulating in Mexico and other countries in the spring of 2009 appears sensitive to oseltamivir and zanamivir in vitro, but resistant to amantadine and rimantadine [1,7]. However, there are no reported studies yet on the clinical benefits of antiviral therapy.

The United States Centers for Disease Control and Prevention (CDC) has released guidelines for the use of antivirals for patients with confirmed or suspected swine H1N1 influenza A virus infection and close contacts [1]. 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/swineflu/). 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 [8]. Some studies have demonstrated benefit even when therapy for seasonal influenza is started >48 hours after onset of illness. While awaiting further information, we would initiate treatment in ill patients even past 48 to 72 hours of symptoms. (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 empiric antiviral therapy for any ill person with confirmed, probable, or suspected swine H1N1 influenza A virus infection. (See “Case definitions” aboveSee “Case definitions” above) [1]. For such patients, we recommend either zanamivir or oseltamivir. Zanamivir is CONTRAINDICATED in patients with asthma or chronic obstructive pulmonary disease. (See “Pharmacology of antiviral drugs for influenza”).

The highest priority should be given to treating hospitalized patients and those at increased risk for complications. (See “Definition of high risk” above).

During this outbreak, in patients suspected to have influenza but who have no epidemiologic link to swine H1N1 influenza A, we recommend treatment with a neuraminidase inhibitor. In locations where oseltamivir-resistant seasonal influenza A (H1N1) virus is still circulating, we suggest that the neuraminidase inhibitor be zanamavir rather than oseltamivir. In such a setting, for patients who are unable to take zanamivir, we recommend the addition of an adamantane (rimantadine or amantadine) to oseltamivir [1]. (See “Antiviral drugs for the treatment of influenza in adults” and see “Antiviral drugs for the prevention and treatment of influenza in children”).

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 [1].

Pregnancy — Seasonal and pandemic strains of influenza cause more severe disease and an increased rate of mortality among pregnant women [9]. (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 [1]. Both amantadine and rimantadine have been found to be teratogenic and embryotoxic when given at high doses in animal studies. No adverse effects have been reported among women who received oseltamivir or zanamivir 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 swine H1N1 influenza A infection should receive antiviral therapy with either oseltamivir or zanamivir [9].

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 outbreak [8].

We recommend antiviral treatment with oseltamivir or zanamivir in children with confirmed, probable, or suspected swine H1N1 influenza A infection [8]. For children <1 year of age, oseltamivir is the recommended antiviral. 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❤ 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 [8].

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 [1].

ANTIBACTERIAL THERAPY — Patients with swine H1N1 influenza A who develop pneumonia should be treated empirically for community-acquired pneumonia (CAP) [10]. 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 swine H1N1 influenza A virus infection [1,8]. See the CDC’s website for updated recommendations (http://www.cdc.gov/swineflu/). Clinicians in other countries should consult with their ministries of health and/or the World Health Organization for specific recommendations.

Indications in adults — Antiviral prophylaxis is recommended by the United States Centers for Disease Control and Prevention (CDC) for [1]:

  • Health care workers or public health workers who were not using appropriate personal protective equipment during close contact with an ill confirmed, probable, or suspected patient during that person’s infectious period.

The CDC states that antiviral prophylaxis can be considered for:

  • Household 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 suspected case.
  • School children or daycare attendees who are at high risk for complications of influenza (children with certain chronic medical conditions) and who had face-to-face contact with a confirmed, probable, or suspected case.
  • Health care workers who are at high risk for complications of influenza who are working in an area of the healthcare facility that has patients with confirmed swine H1N1 influenza A cases, or who are caring for patients with any acute febrile respiratory illness.
  • Travelers to Mexico who are at high risk for complications of influenza.
  • First responders who are at high risk for complications of influenza and who are working in areas with confirmed cases.

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 [9].

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 outbreak when indicated in children younger than the ages for which they have been approved [8]. (See “Children” above).

Antiviral prophylaxis with oseltamivir or zanamivir is recommended for the following children [8]:

  • School children or daycare attendees who are at high risk of influenza complications (children <5 years of age, certain chronic conditions) who had close contact (face-to-face) with a confirmed, probable, or suspected case.

Oseltamivir or zanamivir are recommended for prophylaxis of swine H1N1 influenza A in children ≥1 year of age when indicated [8]. Oseltamivir can also be used for prophylaxis in infants <1 year of age, but should not be used in infants❤ 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 for infants <1 year of age depends upon the age of the infant:

  • Age❤ months — Not recommended unless the patient is critically ill.
  • Age 3 to 5 months — 20 mg once daily
  • 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 swine H1N1 influenza A [1,8]. 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 swine 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). If the contact occurred more than seven days earlier, prophylaxis is not necessary.

VACCINATION — The United States Centers for Disease Control and Prevention are growing swine H1N1 influenza A seed stocks for use in a vaccine, which will take several months to produce [11,12].

The 2008 to 2009 seasonal influenza vaccine does not include antigens from the swine H1N1 influenza A virus that emerged in the spring of 2009. It is not known whether some cross-protection will be afforded by H1N1 strains present in the existing vaccine. (See “Influenza vaccination in adults”).

INFECTION CONTROL — Respiratory hygiene and cough etiquette should be adhered to strictly at the first point of contact with a potentially infected person [13]. Healthcare facilities should establish mechanisms for prompt screening of patients for respiratory illness and segregation of symptomatic patients.

In regions with known cases of swine H1N1 influenza A, all patients with an acute febrile respiratory illness (a measured temperature of 37.8ºC [100.4ºF] and recent onset of at least one of the following: rhinorrhea, nasal congestion, sore throat, or cough) should be managed using these infection control guidelines. 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 swine H1N1 influenza A virus or who have traveled to a region with confirmed cases within the previous seven days.

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

Patients with suspected or confirmed swine H1N1 influenza A virus infection should be placed directly into single patient rooms with the door should be kept closed [13]. An airborne infection isolation room with negative pressure air handling with 6 to 12 air changes per hour can be used, if available. Air from the patient’s room can be vented directly outside or can be recirculated after high-efficiency particulate (HEPA) filtration. A procedure room with negative air pressure handling should be used for bronchoscopy, intubation, or suctioning.

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. In addition, all healthcare workers should wear N95 respirators. Clinicians providing care or collecting clinical specimens from suspected or confirmed cases of swine 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. In addition, until further clarification of the transmission pattern of this virus, all clinicians should wear a fit-tested N95 respirator while providing routine care.

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.

Healthcare workers should be monitored daily for signs and symptoms of an acute febrile respiratory illness. If a healthcare worker 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.

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

SOCIAL DISTANCING MEASURES — The United States Centers for Disease Control and Prevention recommends the following measures for preventing the spread of swine H1N1 influenza A virus [14]:

  • Home isolation of cases — Individuals with an influenza-like illness (fever with either cough or sore throat) should self-isolate in their home for seven days after the onset of illness or at least 24 hours after symptoms have resolved, whichever is longer.

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. Those who do not have a face mask should use a handkerchief or tissues to cover any coughing.

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.

The ill person should wear a face mask when he or she is within 6 feet of household members.

  • 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.
  • School and childcare closings — Schools and childcare facilities should strongly consider closing if there is a confirmed or suspected case that is epidemiologically linked to a confirmed case.
  • Other social distancing measures — Large gatherings linked to settings or institutions with laboratory-confirmed cases should be cancelled (eg, an event linked to a school with cases).

Individuals with underlying medical conditions who are at high risk of complications of influenza may choose to avoid large gatherings. (See “Antiviral drugs for the treatment of influenza in adults”, section on Definition of high risk).

SURVEILLANCE — For updated information about cases of swine H1N1 influenza A virus infection worldwide, see the website of the World Health Organization: http://www.who.int/csr/disease/swineflu/en/index.html.

For surveillance of cases in the United States, see the Centers for Disease Control and Prevention website: http://www.cdc.gov/swineflu.

TRAVEL ADVISORIES — For updated information about travel advisories, see the United States Centers for Disease Control and Prevention website (http://wwwn.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 several other countries including the United States. The 2008 to 2009 seasonal influenza vaccine does not include antigens from the strain of influenza virus that emerged in the spring of 2009. It is not known whether some cross-protection will be afforded by H1N1 antigens from strains present in the existing vaccine. (See “Introduction” above and see “Vaccination” above).

Case definitions

Treatment — The strain of swine H1N1 influenza A virus circulating in the spring of 2009 is sensitive to zanamivir and oseltamivir in vitro, but resistant to amantadine and rimantadine. No clinical studies have confirmed benefit of therapy, however.

  • In patients who are ill with confirmed, probable, or suspected swine H1N1 influenza A virus infection, we recommend treatment with either zanamivir or oseltamivir (Grade 1B). Treatment should be initiated as soon as possible. While awaiting further information, we would initiate treatment in ill patients even past 48 to 72 hours of symptoms. (See “Antiviral therapy” above).
  • During this outbreak, in patients suspected to have influenza but who have no epidemiologic link to swine H1N1 influenza A, we recommend treatment with a neuraminidase inhibitor (Grade 1A). In locations where oseltamivir-resistant seasonal influenza A (H1N1) virus is still circulating, we suggest that the neuraminidase inhibitor be zanamavir rather than oseltamivir (Grade 2B). In such a setting, for patients who are unable to take zanamivir, we recommend the addition of rimantadine or amantadine to oseltamivir (Grade 1B). (See “Antiviral therapy” above).

Prophylaxis — No clinical studies have confirmed benefit of prophylaxis for swine 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).

Infection control and social distancing measures

 

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REFERENCES
  1. United States Centers for Disease Control and Prevention. Interim Guidance on Antiviral Recommendations for Patients with Confirmed or Suspected Swine Influenza A (H1N1) Virus Infection and Close Contacts. http://www.cdc.gov/swineflu/recommendations.htm (Accessed April 29, 2009).
  2. Myers, KP, Olsen, CW, Gray, GC. Cases of swine influenza in humans: a review of the literature. Clin Infect Dis 2007; 44:1084.
  3. World Health Organization. Swine influenza – update 3, 27 April 2009. http://www.who.int/csr/don/2009_04_27/en/index.html (Accessed April 27, 2009).
  4. The New York Times. Mexico Limits Many Activities as Flu Alerts Are Increased. http://www.nytimes.com/2009/05/01/health/01flu.html?_r=1 & hp (Accessed April 30, 2009).
  5. United States Centers for Disease Control and Prevention. Interim Guidance on Specimen Collection and Processing for Patients with Suspected Swine Influenza A (H1N1) Virus Infection. http://www.cdc.gov/swineflu/specimencollection.htm. (Accessed April 28, 2009).
  6. United States Centers for Disease Control and Prevention. Interim Guidance on Case Definitions to be Used For Investigations of Swine Influenza A (H1N1) Cases. http://www.cdc.gov/swineflu/casedef_swineflu.htm (Accessed April 29, 2009).
  7. 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).
  8. United States Centers for Disease Control and Prevention. Interim Guidance for Clinicians on the Prevention and Treatment of Swine-Origin Influenza Virus Infection in Young Children, April 28, 2009. http://www.cdc.gov/swineflu/childrentreatment.htm (Accessed April 29, 2009).
  9. United States Centers for Disease Control and Prevention. Interim Guidance — Pregnant Women and Swine Influenza: Considerations for Clinicians, April 28, 2009. http://www.cdc.gov/swineflu/clinician_pregnant.htm (Accessed April 29, 2009).
  10. United States Centers for Disease Control and Prevention. Interim Guidance for Clinicians on Identifying and Caring for Patients with Swine-origin Influenza A (H1N1) Virus Infection http://www.cdc.gov/swineflu/identifyingpatients.htm (Accessed April 29, 2009).
  11. Time. How Fast Could a Swine Flu Vaccine Be Produced? http://www.time.com/time/health/article/0,8599,1894625,00.html?iid=tsmodule (Accessed April 29, 2009).
  12. Medscape Medical News. HHS Secretary Sebelius Says Swine Flu Vaccine Proceeding Quickly. http://www.medscape.com/viewarticle/702093 (Accessed April 29, 2009).
  13. United States Centers for Disease Control and Prevention. Interim Guidance for Infection Control for Care of Patients with Confirmed or Suspected Swine Influenza A (H1N1) Virus Infection in a Healthcare Setting. http://www.cdc.gov/swineflu/guidelines_infection_control.htm. (Accessed April 29, 2009).
  14. 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).

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