DIAGNOSIS

Persons with suspected or confirmed 2009 H1N1 influenza who require hospitalization should be given priority for 2009 H1N1 testing. Others may be eligible for priority testing as determined by state and local health departments. When considering the diagnosis, physicians should keep in mind that atypical presentations occur in infants and in elderly and immunocompromised persons. In addition to the CDC’s published guidance on specimen collection, processing, and testing, state and local health department recommendations should be followed.

A nasopharyngeal or oropharyngeal swab, nasal aspirate, or combined nasopharyngeal and oropharyngeal swab should be used for sampling. Swabs should be made of inert materials, such as synthetic tips and aluminum or plastic shafts. Endotracheal aspirates or bronchoalveolar lavage should be obtained from intubated patients. Samples should be transported in 1 to 3 mL of viral transport media, cooled with ice or refrigerated, and stored at 4°C for no longer than 4 days. Shipped specimens should be transported on wet ice or cold packs and clearly labeled with the information requested by the appropriate state public health laboratory.

Real-time reverse transcriptase polymerase chain reaction is recommended for confirmation of cases of 2009 H1N1 infection. With RT-PCR, 2009 H1N1 will test positive for influenza A and negative for seasonal H1 or H3. Strong reactivity for influenza A (cycle threshold value <30) is indicative of 2009 H1N1. Although not approved by the Food and Drug Administration (FDA) for this indication, RT-PCR assays can be performed by public health laboratories in the United States. However, clinicians should bear in mind the limitations of this testing. In the review of medical records of 32 Spanish patients requiring intensive care described previously, 4 (13%) tested negative for 2009 H1N1 at admission to the intensive care unit.

Commercially available rapid influenza diagnostic tests (RIDTs) detect influenza viral nucleoprotein antigen and can provide results within 30 minutes. Although some RIDTs can distinguish between influenza A and B viruses, no FDA-approved RIDT can discriminate among viral subtypes (H1 from H3). The sensitivity of RIDTs for detecting 2009 H1N1 has varied from 10% to 70% and is directly related to the amount of virus in the specimen and inversely related to the threshold cycle value of the test. Thus, negative findings on a test do not “rule out” infection with the 2009 H1N1 virus; when clinical suspicion remains high despite negative test findings, the clinician should empirically treat high-risk patients and institute appropriate infection control measures. Positive results on an RIDT test for influenza type A likely mean that influenza A is present but do not distinguish among 2009 H1N1, seasonal influenza A, and influenza A of animal origin. Thus, for definitive diagnosis of 2009 H1N1 infection, only viral culture or RT-PCR can be used.

TREATMENT

To date, with few exceptions, the 2009 H1N1 virus remains susceptible to NA inhibitors (oseltamivir and zanamivir) and resistant to the adamantanes (amantadine and rimantadine). Antiviral treatment is recommended for all hospitalized patients with confirmed, probable, or suspected 2009 H1N1 infection and patients at high risk of complications. Because low-risk persons with uncomplicated febrile illness are unlikely to derive substantial benefit from antiviral therapy, treatment is not recommended for these patients. Treatment benefit is greatest if antiviral medications are started within 48 hours of illness onset; however, studies have suggested that hospitalized patients benefit from treatment initiation even later. Treatment dosages and duration are the same as for seasonal influenza.

Because infants are at high risk of influenza-related complications and limited safety data are favorable, the FDA issued an Emergency Use Authorization approving the use of oseltamivir for treatment and prophylaxis in pediatric patients younger than 1 year (Table 4).

Postexposure chemoprophylaxis with oral oseltamivir or inhaled zanamivir can be considered for high-risk persons, health care workers, public health workers, or first responders who have, within the past 48 hours, been in close contact with a case of confirmed, probable, or suspected 2009 H1N1 during the infectious period. Although the infectious period starts 1 day before and can extend at least 7 to 10 days after illness onset, for purposes of postexposure prophylaxis the infectious period is considered to begin 1 day before symptoms and to end 24 hours after resolution of fever. The prophylactic course should extend for 10 days from the most recent contact with the infectious person. The patient should be informed that influenza can be acquired despite prophylaxis and to seek medical attention if influenza-like symptoms develop. Alternatively, clinicians can consider forgoing postexposure prophylaxis in appropriate patients reliable enough to seek immediate care if symptoms develop.

Preexposure prophylaxis with oseltamivir or zanamivir should generally be considered for high-risk persons with frequent exposures (health care workers, public health workers, or first responders) to 2009 H1N1 after consultation with local public health authorities. For this indication, the antiviral agent should be given during the potential exposure and continued for 10 days after the last known If an outbreak in a nursing home or long-term care facility were to occur, chemoprophylaxis with oseltamivir or zanamivir should be administered to all healthy residents and continued for a minimum of 7 days after illness onset in the last patient or 2 weeks, whichever comes later. This strategy also applies for use in other closed settings, such as correctional facilities; however, it does not apply to settings where lower-risk populations congregate, such as schools and workplaces.

Special treatment considerations exist for pregnant women because of their high risk of complications from both seasonal and 2009 H1N1 influenza. They should receive oseltamivir or zanamivir for 5 days, and the drug should ideally be initiated within 48 hours of illness onset. Although both of these agents are pregnancy category C (controlled human studies are unavailable), pregnancy should not be considered a contraindication to their use. Pregnant women in contact with a confirmed, probable, or suspected case of infection with the 2009 H1N1 virus should receive 10 days of prophylactic therapy with zanamivir or oseltamivir. Because of its limited systemic absorption, inhaled zanamivir may be the preferred prophylactic agent in these women who do not otherwise have contraindications for its use.

All patients should be counseled regarding potential adverse effects and reactions from these antiviral agents. Oseltamivir can cause nausea and vomiting that can be alleviated if taken with food. Transient neuropsychiatric events, such as self-injury and delirium, have been reported from postmarketing surveillance studies of oseltamivir. Zanamivir is licensed only for persons without underlying respiratory (especially asthma) or cardiac disease. Cases of respiratory deterioration and allergic reactions (including angioedema) have been reported from postmarketing surveillance of zanamivir.

Clinicians should be aware that use of peramivir, an intravenous NA inhibitor, has been authorized by the FDA under an Emergency Use Authorization. Although still being evaluated in phase 3 trials, limited data regarding its safety and efficacy are available (Fact Sheet for Health Care Providers). Its use is restricted to hospitalized patients who are not responding to either oral or inhaled antiviral therapy or to those for whom oral or inhaled therapy is not expected to be effective. The standard dose is 600 mg intravenously once daily for 5 to 10 days. Although no children have received the drug in clinical trials, its use in children has been permitted under emergency investigational new drug procedures. Peramivir has not been administered to pregnant women or nursing mothers in clinical trials. Adverse effects have included nausea, vomiting, diarrhea, and neutropenia.