Treatment is largely supportive and consists of bedrest, increased fluid consumption, cough suppressants, and antipyretics and analgesics (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) for fever and myalgias. Severe cases may require intravenous hydration and other supportive measures. Antiviral agents may also be considered for treatment or prophylaxis (see Medication).
Patients should be encouraged to stay home if they become ill, to avoid close contact with people who are sick, to wash their hands often, and to avoid touching their eyes, nose, and mouth. The CDC recommends the following actions when human infection with H1N1 influenza (swine flu) is confirmed in a community[22] :
Laboratory testing has found the H1N1 influenza A (swine flu) virus susceptible to the prescription antiviral drugs oseltamivir and zanamivir, and the CDC has issued interim guidance for the use of these drugs to treat and prevent infection with swine influenza viruses.[27, 28] As part of its preparation for the emergency, the US Department of Homeland Security is releasing 25% of stockpiled antiviral agents (ie, oseltamivir [Tamiflu], zanamivir [Relenza]).
The usual vaccine for influenza administered at the beginning of the flu season is not effective for this viral strain. Also, other antiviral agents (eg, amantadine, rimantadine) are not recommended because of recent resistance to other influenza strains documented over the past several years.
Basic supportive care (ie, hydration, analgesics, cough suppressants) should be prescribed. Empiric antiviral treatment should be considered for confirmed, probable, or suspected cases of H1N1 influenza. Treatment of hospitalized patients and patients at higher risk for influenza complications should be prioritized.
WHO guidelines
WHO guidelines recommend treating serious cases immediately.[29] The guidelines represent an international panel of experts who reviewed all available studies regarding antiviral agents (with emphasis on oseltamivir and zanamivir). Evidence indicates that oseltamivir, when properly prescribed, significantly decreases risk of pneumonia (a leading cause of death for both pandemic and seasonal influenza) and the need for hospitalization.
In the 2009 H1N1 pandemic, oseltamivir-resistant strains were observed in a small number of patients. Most oseltamivir resistance occurred in severely immunocompromised patients with prior exposure to oseltamivir.[30]
For patients who initially present with severe illness or whose condition begins to deteriorate, initiate oseltamivir as soon as possible. For patients with severe or deteriorating illness, treatment should be provided even if started later. Where oseltamivir is unavailable or cannot be used for any reason, zanamivir may be given. This recommendation applies to all patient groups, including pregnant women, and all age groups, including young children and infants.
For patients with underlying medical conditions that increase the risk of more severe disease, WHO recommends treatment with either oseltamivir or zanamivir. These patients should also receive treatment as soon as possible after symptom onset, without waiting for the results of laboratory tests. Pregnant women are included among groups at increased risk, and WHO recommends that pregnant women receive antiviral treatment as soon as possible after symptom onset.
At the same time, the presence of underlying medical conditions will not reliably predict all or even most cases of severe illness. Worldwide, around 40% of severe cases are now occurring in previously healthy children and adults, usually younger than 50 years. Some of these patients experience a sudden and very rapid deterioration in their clinical condition, usually on day 5 or 6 following the onset of symptoms.
Clinical deterioration is characterized by primary viral pneumonia, which destroys the lung tissue and does not respond to antibiotics, and the failure of multiple organs, including the heart, kidneys, and liver. These patients require management in intensive care units using therapies in addition to antivirals.
Peramivir, an investigational, intravenous neuraminidase inhibitor in Phase 3 clinical trials, has been used successfully in adults and children under an emergency investigational new drug program in the United States. It was well tolerated and associated with recovery in the majority of patients hospitalized with severe H1N1 infection.[31]
Initiate antiviral agents within 48 hours
Prompt initiation of antiviral agents within 48 hours of symptom onset is imperative for providing treatment efficacy against influenza virus. In studies of seasonal influenza, evidence for benefits of treatment is strongest when treatment is started within 48 hours of illness onset. However, some studies of treatment of seasonal influenza have indicated benefit, including reductions in mortality or duration of hospitalization, even in patients in whom treatment was started more than 48 hours after illness onset. The recommended duration of treatment is 5 days.[27, 28]
Prophylaxis with antiviral agents should also be considered in the following individuals (pre-exposure or postexposure):
Close household contacts of a confirmed or suspected case who are at high risk for complications (eg, chronic medical conditions, persons >65 y or < 5 y, pregnant women)
School children at high risk for complications who have been in close contact with a confirmed or suspected case
Travelers to Mexico who are at high risk for complications (eg, chronic medical conditions, persons >65 y or < 5 y, pregnant women)
Health care providers or public health workers who were not using appropriate personal protective equipment during close contact with a confirmed or suspected case
In September 2009, the CDC updated recommendations concerning the use of antiviral medications for prevention because of reported oseltamivir resistance; antivirals should not be used for postexposure chemoprophylaxis in healthy children or adults to manage outbreaks in the community, school, camp, or other settings.
[32] Reserve antiviral chemoprophylaxis for persons at higher risk for influenza-related complications who have had contact with someone likely to have been infected with influenza.
Pre-exposure prophylaxis can be considered in the following persons:
Any health care provider who is at high risk for complications (eg, persons with chronic medical conditions, adults >65 y, pregnant women)
Individuals not considered to be at high risk but who are nonetheless traveling to Mexico, first responders, or border workers who are working in areas with confirmed cases
Oseltamivir ring prophylaxis can be considered for outbreaks of pandemic H1N1 influenza A, especially among closed populations such as military personnel; ring prophylaxis involved the use of oseltamivir 75 mg once daily to members of the same military unit where contact opportunities were substantial.
[33]
Pediatric considerations
Aspirin or aspirin-containing products (eg, bismuth subsalicylate [Pepto Bismol]) should not be included in the treatment of confirmed or suspected viral infection in persons aged 18 years or younger because of the risk of Reye syndrome. For relief of fever, other antipyretic medications (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) are recommended.
Pregnant women
Oseltamivir and zanamivir are "Pregnancy Category C" medications, indicating that no clinical studies have been conducted to assess the safety of these medications in pregnant women.
Because of the unknown effects of influenza antiviral drugs on pregnant women and their fetuses, oseltamivir or zanamivir should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus; the manufacturers' package inserts should be consulted. However, no adverse effects have been reported among women who received oseltamivir or zanamivir during pregnancy or among infants born to women who have received oseltamivir or zanamivir.
Prompt use of antiviral drugs during the 2009 H1N1 influenza pandemic improved survival among severely ill pregnant women. The CDC examined reports of severe flu (resulting in death or ICU admission) in 347 pregnant women during the pandemic, including 272 who were admitted to the ICU and survived and 75 who died. Severely ill postpartum women (n=15), including 9 who died, also were reported.
Of the 307 pregnant women for whom information regarding the presence of underlying medical conditions was available, half had underlying conditions such as asthma, diabetes, or hypertension. Among those who died, 86.1% received antiviral treatment with oseltamivir or zanamivir, compared with 94.8% of survivors. Time to initiate treatment from symptom onset was significantly different for women who died, compared with those who survived (P < .01). Only 4 women (7%) of those who died received an antiviral within 2 days of symptom onset, compared with 41% of survivors.
This analysis reaffirms the importance of prevention (ie, vaccination of pregnant women regardless of trimester) and prompt treatment with a neuraminidase inhibitor (ie, within 2 d of symptom onset) if influenza occurs during pregnancy.[34]
Pregnancy should not be considered a contraindication to oseltamivir or zanamivir use. Because zanamivir is an inhaled medication and has less systemic absorption, some experts prefer zanamivir over oseltamivir for use in pregnant women, when feasible.[27, 35] Others recommend that, because pregnant women may have a decreased ability to inhale zanamivir, they should be given oseltamivir.
Antiviral Agent
Class Summary
Drugs indicated for treatment of H1N1 influenza A virus include neuraminidase inhibitors (ie, oseltamivir and zanamivir).
Oseltamivir and zanamivir inhibit neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, these agents decrease the release of viruses from infected cells and, thus, viral spread.
These antivirals are effective in the treatment of influenza A or B and must be administered within 48 hours of symptom onset to provide optimal treatment. The sooner the drug is administered after symptom onset, the better the likelihood of a good outcome. However, some studies of treatment of seasonal influenza have indicated benefit, including reductions in mortality or duration of hospitalization even for patients whose treatment was started more than 48 hours after illness onset.[27] Antivirals reduce the length of illness by an average of 1.5 days. (In a subgroup of high-risk patients, illness was reduced by 2.5 d.) In addition, the severity of symptoms is also reduced.
On October 23, 2009, the FDA announced emergency-use authorization of the investigational intravenous neuraminidase inhibitor, peramivir. In an observational study of 31 patients, intravenous peramivir was administered to patients with progressive H1N1 pneumonia despite treatment with oseltamivir.[31] Peramivir was well-tolerated, and the 56-day survival rate was 59%. Further studies are necessary to evaluate the effectiveness of peramivir. To request peramivir, see the information at the CDC's H1N1 website or call (800) CDC-INFO (232-4636).
Oseltamivir (Tamiflu)
Inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, decreases release of viruses from infected cells and thus viral spread. Effective to treat influenza A or B. Start within 40 h of symptom onset. Available as 30-mg, 45-mg, and 75-mg oral capsules and as a powder for suspension that contains 12 mg/mL after reconstitution.
Zanamivir (Relenza)
Inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. Effective against both influenza A and B. Inhaled through Diskhaler oral inhalation device. Circular foil discs containing 5-mg blisters of drug are inserted into supplied inhalation device.
Individuals with asthma or other respiratory conditions that may decrease ability to inhale the drug should be given oseltamivir (eg, asthma, pregnancy). Severe respiratory failure caused by H1N1 influenza has been reported in the southern hemisphere during July and August 2009; therefore, in severely ill patients, the ability to inhale zanamivir may be impaired.
Peramivir (investigational)
Investigational neuraminidase inhibitor. Emergency-use authorization issued by US FDA for use of peramivir in hospitalized adult and pediatric patients with suspected or laboratory-confirmed 2009 H1N1 influenza unresponsive to oseltamivir or zanamivir, unable to take PO or inhaled drugs (or delivery route not dependable or feasible), or other circumstances determined by clinician. To request peramivir, see information at www.cdc.gov/h1n1flu/eua or call (800) CDC-INFO (232-4636).
Vaccine
Class Summary
Several manufacturers are supplying the H1N1 vaccine. The vaccine is available as an IM injection and as an intranasal product. A systematic review and meta-analysis has reported on the immunogenicity and safety of the 2009 influenza A (H1N1) vaccine. No death or case report of Guillain-Barre was reported and the vaccine, with or without adjuvant, appeared to be generally seroprotective after one dose among those aged older than 36 months.[36]
H1N1 Influenza A Vaccine (H1N1)
Available as monovalent, inactivated influenza A virus vaccine (H1N1) for IM injection. Indicated for active immunization against influenza caused by pandemic (H1N1) 2009 virus. Stimulates active immunity to influenza virus infection by inducing production of specific antibodies.
H1N1 Influenza A Vaccine, Intranasal (H1N1)
Available as monovalent live virus vaccine for intranasal administration. Indicated for active immunization against influenza caused by pandemic (H1N1) 2009 virus. Stimulates active immunity to influenza virus infection by inducing production of specific antibodies.
Deterrence/Prevention
Vaccination campaign
The 2009 influenza A (H1N1) monovalent vaccine is in production and is expected to be released in mid October. The immunization series consists of 2 doses for children younger than 10 years, consisting of an initial dose and a booster to be administered several weeks later. Adults and children 10 years and older will receive a single dose. Target populations recommended to receive the 2009 H1N1 vaccine include pregnant women, household contacts and caregivers of children younger than 6 months, healthcare and emergency medical services personnel, children aged 6 months to 18 years, young adults aged 19-24 years, and persons aged 25 through 64 years with conditions associated with higher risk of medical complications from influenza.[37, 38]
A separate seasonal influenza vaccine was needed for the 2009/2010 influenza season. Now H1N1 is a component of the 2011/2012 influenza vaccine.
A 2011 CDC analysis reaffirms the importance of vaccinating pregnant women regardless of trimester and prompt treatment with a neuraminidase inhibitor (ie, within 2 d of symptom onset) if influenza occurs during pregnancy.[34]
There are only a limited number of studies that describe the safety of giving influenza vaccine to pregnant women. A 2012 study in Denmark found no evidence of an increased risk of fetal death associated with exposure to an adjuvanted pandemic A/H1N1 2009 influenza vaccine during pregnancy.[39]
Community precautions
The CDC recommends the following actions when human infection with H1N1 influenza (swine flu) is confirmed in a community[22] :
Household contacts who are not ill
- Remain home at the earliest sign of illness.
- Minimize contact in the community to the extent possible.
- Designate a single household family member as caregiver for the patient to minimize interactions with asymptomatic persons.
School dismissal and childcare facility closure
- Strong consideration should be given to close schools upon a confirmed case of H1N1 flu or a suspected case epidemiologically linked to a confirmed case.
- Decisions regarding broader school dismissal within these communities should be left to local authorities, taking into account the extent of influenzalike illness within the community.
- Cancelation of all school or childcare related gatherings should also be announced.
- Encourage parents and students to avoid congregating outside of the school if school is canceled.
- Duration of schools and childcare facilities closings should be evaluated on an ongoing basis depending on epidemiological findings.
- Consultation with local or state health departments is essential for guidance concerning when to reopen schools. If no additional confirmed or suspected cases are identified among students (or school-based personnel) for a period of 7 days, schools may consider reopening.
- Schools and childcare facilities in unaffected areas should begin preparation for possible school closure.
Social distancing
- Large gatherings linked to settings or institutions with laboratory-confirmed cases should be canceled (eg, sporting events or concerts linked to a school with cases); other large gatherings in the community may not need to be canceled at this time.
- Additional social distancing measures are currently not recommended.
- Persons with underlying medical conditions who are at high risk for complications of influenza should consider avoiding large gatherings.
Preventive measures for health care personnel
The CDC has issued interim recommendations for controlling the spread of H1N1 influenza in health care settings.[40] Recommended measures for care of patients with suspected or confirmed H1N1 influenza include the following:
Place patients in a single-patient room with the door kept closed. An airborne-infection isolation room with negative-pressure air handling can be used, if available. Air can be exhausted directly outside or can be recirculated after filtration by a high efficiency particulate air (HEPA) filter.
Suctioning, bronchoscopy, or intubation should be performed in a procedure room with negative-pressure air handling.
Patients should wear a surgical mask when outside their room.
Encourage patients to wash their hands frequently and to follow respiratory hygiene practices. Cups and other utensils used by the ill person should be washed with soap and water before use by other persons.
Routine cleaning and disinfection strategies used during influenza seasons can be applied.
Standard, droplet, and contact precautions should be used for all patient care activities and maintained for 7 days after illness onset or until symptoms have resolved.
Health care personnel should wash their hands with soap and water or use hand sanitizer immediately after removing gloves and other equipment and after any contact with respiratory secretions.
Personnel providing care to or collecting clinical specimens from patients should wear disposable nonsterile gloves, gowns, and eye protection (eg, goggles) to prevent conjunctival exposure.
As per previous recommendations regarding mask and respirator use during influenza pandemics, personnel engaged in aerosol-generating activities (eg, collection of clinical specimens, endotracheal intubation, nebulizer treatment, bronchoscopy) and/or resuscitation involving emergency intubation or cardiac pulmonary resuscitation should wear a fit-tested disposable N95 respirator.
Pending clarification of transmission patterns for the 2009 H1N1 influenza A (swine flu) virus, personnel providing direct patient care for suspected or confirmed cases should wear a fit-tested disposable N95 respirator when entering the patient's room.
2009 H1N1 vaccine efficacy and adverse effects
Zhu et al (2009) assessed the safety and immunogenicity of the 2009 H1N1 vaccine in a randomized clinical trial in populations ranging in age from 3-77 years. In the study, 2200 individuals received one dose, 2103 (95.6%) of whom received a second dose or placebo. A single 15-mcg dose of hemagglutinin antigen without alum adjuvant induced a typically protective immune response in most participants aged 12-60 years. Severe adverse effects were not observed. Mild injection-site reactions were reported in up to 16% of individuals.[41]
Communication from the US FDA Commissioner, Margaret Hamburg, summarized safety data after 11.3 million doses of intranasal and 34.9 million doses of injectable vaccine were distributed. Analysis of 3783 reports of adverse events was reported to the vaccine adverse event reporting system (VAERS) through November 24, 2009, based on 438,376 people vaccinated. The vast majority (94%) of adverse events described were classified as nonserious (eg, soreness at site of injection). No cases of Guillain-Barré syndrome have been reported. As of December 30, 2009, nearly 100 million doses of H1N1 vaccine had been distributed.[42]
Prognosis
A review of medical records from the 2009 US pandemic found hospitalized patients with pandemic H1N1 and pneumonia were at risk for severe outcomes including ARDS, sepsis, and death. However, patients often received delayed antiviral treatment (>2 days after illness onset). Patients with H1N1 and pneumonia should receive early and aggressive treatment with antibiotics and influenza antiviral agents.[43]
In a multicenter study in Britain consisting of over 1,500 patients, independent predictors of severe outcome included age 55-64 years, certain chronic lung diseases, underlying neurological disease, obesity, delayed admission (≥5 days after illness onset), pneumonia, and others.[44]
Patient Education
Patients should be referred to the eMedicine Health article Swine Flu.