Influenza 2010–2011: Lessons from the 2009 pandemic

SEASONAL INFLUENZA: USUALLY ACUTE AND SELF-LIMITED

Most seasonal influenza infections are acute and self-limited. Risk factors for complications or severe illness include age 2 years or younger, age 65 years or older, pregnancy, and chronic medical conditions.^5,30,34

Secondary bacterial infections occur at a rate similar to that during the pandemic.^4,19 The prevalence of bacterial superinfection is about 5% to 15%, depending on the virus, the local prevalence of bacterial pathogens, and the tests used to diagnose the infections.

Hospitalization rates in the United States average 0.052% but range from 0.0115% for ages 5 to 49 to 0.773% for ages 85 and older. ³⁵ Death rates range from year to year from 0.0014% to 0.0167%.² Indications for hospital admission include viral pneumonia, bacterial pneumonia, and exacerbation of underlying medical conditions, especially asthma or chronic obstructive pulmonary disease. Exacerbation of underlying lung disease appears to be a more common indication for admission in patients with seasonal infection than with pandemic infection.^5,30–34

CLINICAL DIAGNOSIS OF INFLUENZA IS UNRELIABLE

Clinical diagnosis of influenza is unreliable, particularly in patients requiring hospitalization. ³⁶ The wide clinical spectrum of influenza infection overlaps with those of other common respiratory viral or bacterial infections. In hospitalized patients, the diagnosis is further confounded by underlying conditions, immunosuppression, and extrapulmonary complications.

Thus, up to half of cases may go unrecognized. ^31,33,36 Clinicians should consider influenza as a potential cause of or contributor to any hospitalization whenever influenza is circulating in the community (ie, during seasonal peaks or pandemics).

Diagnostic tests

Several diagnostic assays are commonly used.^37,38

Rapid antigen tests generally have low sensitivity, in the range of 50% to 60%, particularly for the 2009 A (H1N1) virus. Therefore, a negative test result does not exclude infection and should be interpreted with caution. Newer technologies are being developed that may improve the diagnostic yield of these assays.^4,37–39

Immunofluorescence antigen tests, when performed on nasopharyngeal aspirates or on flocked swabs, are very sensitive for seasonal influenza. However, their sensitivity is lower for 2009 H1N1 influenza.⁴⁰

In general, the sensitivity of antigen assays depends on where the specimen is collected (nose, throat, or lower respiratory tract—eg, tracheal aspirates, bronchoalveolar lavage), the collection method (conventional vs flocked swabs, nasopharyngeal aspirate and wash, bronchoalveolar lavage), the assay type, the virus, and the viral burden at the time of testing (the longer the time, the lower the viral load).^40,41

Viral culture is 100% specific and more sensitive than antigen assays, but it takes 2 to 3 days to run, limiting its usefulness in guiding patient management.

Polymerase chain reaction (PCR) is highly sensitive and specific and, where available, is now the test of choice.⁴⁰ In addition, it can be performed on a wide range of specimens, and subtype-specific PCR assays may provide immediate information on virus subtypes, which may have therapeutic implications. Expanded assays can detect a wider range of pathogens, such as respiratory syncytial virus, although these assays are typically used in selected patients, such as those requiring intensive care or those who are immunocompromised.

Consider sampling the lower airway

In patients with 2009 H1N1 viral pneumonia, up to 19% may have had negative upper respiratory tract samples but detectable virus in the lower airways. Therefore, obtaining a lower respiratory tract specimen for testing should be considered, whenever possible, in cases of suspected influenza pneumonia.^4,42,43

Similarly, when monitoring clearance of the virus in cases of influenza pneumonia, clinicians should remember that the upper respiratory tract may become negative earlier than the lower airways. Active viral replication may continue in the lungs despite apparent clearance in the upper airways.^29,43,44

Relapsed disease and viral replication have been documented when antiviral drugs are discontinued early, even when upper tract shedding is no longer measurable.^29,45,46 Nonetheless, no study has compared the risk of transmission in patients who remain PCR- or culture-positive for a prolonged time. In theory, those who are culture-positive could transmit infection. Clinicians should consult with local infection-control clinicians to determine the duration of isolation for individual patients.

DRUG THERAPY FOR INFLUENZA INFECTION

Antiviral drugs that are active against influenza are:

• The neuraminidase inhibitors oseltamivir (Tamiflu), zanamivir (Relenza), and peramivir (commercially available only in Japan and South Korea)⁴⁷
• The adamantanes amantadine (Symmetrel) and rimantadine (Flumadine)⁴⁸
• Ribavirin (Rebetol).⁴⁹

The neuraminidase inhibitors and adamantanes are generally well tolerated. These classes of drugs have been reviewed extensively elsewhere.^47,48 The oral agents may be challenging to administer to patients who cannot swallow and in those with critical illness or gastrointestinal dysfunction. Some studies have shown reasonable absorption of oseltamivir given by nasogastric tube in critically ill patients.⁵⁰

Inhaled zanamivir, taken via a proprietary “Diskhaler” device, requires the patient to inspire deeply and may induce bronchospasm, which could be problematic in those with underlying airway diseases such as chronic obstructive pulmonary disease or asthma.⁴⁷ Nebulization of the commercially available preparation has been reported to cause ventilator dysfunction and even death, so this should not be done.⁵¹