Thursday, November 05, 2009

Influenza update

Recent coverage of influenza in the professional media has consisted of a dizzying flurry of disjointed sound bites. I have set out to put together the essentials here.

We continue to struggle to find an appropriate name for the pandemic strain. The latest is “2009 H1N1” (formerly novel influenza A H1N1, to be distinguished from any ordinary seasonal H1N1 strains).

Who should receive antiviral treatment? This Medscape Medical News piece summarizes the latest revision (October 16) of the CDC recommendations. In short, the treatment is recommended for individuals with suspected influenza considered to be at high risk. This will include 70% of hospitalized patients. From the news piece:

High-risk groups include children younger than 2 years, adults 65 years or older, and pregnant women and those up to 2 weeks after delivery or miscarriage. In addition, persons at high-risk include those with immunosuppression; disorders compromising respiratory tract function or handling of respiratory secretions or increasing risk for aspiration; or chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematologic (including sickle cell disease), or metabolic diseases (including diabetes mellitus).

Severity of illness may trump host factors in clinical decision making (my emphasis):

Treatment or prophylaxis with antiviral medications is not necessary for most healthy individuals with an illness consistent with uncomplicated influenza or for those who appear to be recovering from influenza. Severe symptoms, including evidence of lower respiratory tract infection or clinical deterioration, in persons of any age or previous health status presenting with suspected influenza should mandate prompt empiric antiviral therapy.

And, because so many hospitalized patients fall under the high risk definition:

All persons hospitalized for suspected or confirmed influenza should be treated with oseltamivir or zanamivir.

The above principles apply to both treatment and prophylaxis.

What about the IV preparation?

Peramivir, an IV neuraminidase inhibitor, although lacking full approval, has been made available under an FDA emergency use authorization for hospitalized patients with proven or suspected pandemic flu in whom oral or inhalation therapy is not feasible or appropriate according to their criteria. Usage criteria, procedures for obtaining the drug and full prescribing information are contained in this FDA fact sheet.

How reliable is point of care testing? According to the Medscape news piece the sensitivity for pandemic flu is poor, ranging from 10-70%.

When influenza is diagnosed, either by point of care testing or clinical assessment, what's the likelihood it's pandemic flu as opposed to ordinary flu? From the Medscape news piece:

"As of October 3, 2009, 99% of circulating influenza viruses in the United States were 2009 H1N1 influenza (previously referred to as novel influenza A [H1N1])," the guidelines authors write.

So, it appears, if your point of care test is positive for influenza A it's almost certainly pandemic. If your diagnosis is on clinical grounds alone it's less certain, as many other respiratory pathogens prevail during flu season. (But many cases will need to be diagnosed and treated on clinical grounds given the relatively poor sensitivity of point of care testing).

Since initial diagnosis must often be clinical, what is the case definition which would trigger appropriate isolation procedures and antiviral treatment of high risk patients? Strangely, the CDC has taken down their link to the case definitions page. This Medscape article by John G. Bartlett, MD has the information:

The CDC defines cases as influenza-like illness (ILI) if there is fever of ≥100° F (37.8° C) plus cough and/or sore throat in the absence of a known cause other than influenza.

That last phrase is important. In my career I’ve seen a case of gram negative sepsis and diabetic foot infection (yeah, somebody didn’t look down there) diagnosed as influenza. Raised public awareness and the advice to patients to stay home if symptoms are mild will, I’m sure, lead to cases of sepsis attributed to the flu, and with bad outcomes. As pointed out in the Medscape article, more cases of pandemic flu seem to have GI symptoms than cases of seasonal flu.

Since the sensitivity of commonly used rapid tests for influenza is low, what is the definitive test? The recommended definitive test is the real-time reverse transcriptase PCR (rRT-PCR).

Which patients should be tested with rRT-PCR? Here the recommendations are inconsistent. The CDC recommends such testing in:

Hospitalized patients with suspected influenza

Patients for whom a diagnosis of influenza will inform decisions regarding clinical care, infection control, or management of close contacts.

Patients who died of an acute illness in which influenza was suspected.

However, other recommendations, such as those contained in this Medscape article, seem more vague, and recommend testing for anyone with an acute febrile respiratory infection or sepsis syndrome. It’s difficult, for me anyway, to know how to reconcile these testing recommendations, so I’ll tend to err on the side of over testing. All patients with pneumonia, all COPD exacerbations with fever and all respiratory and undifferentiated sepsis syndromes might be included for definitive testing, isolation and treatment. That seems like a pretty broad net. Testing recommendations and procedures might vary from state to state, and one should follow local health department procedures. The infection control nurses in your hospital should be able to provide guidance.

Since flu is believed to be transmitted by large droplets, propelled no more than six feet, are N-95 masks really necessary? Although the CDC has gone along with the recommendation of the Institute of Medicine that N-95 masks be used, the data are not convincing that they are better than surgical masks. Studies have been inconsistent. The latest, published in JAMA, reached this conclusion:

Among nurses in Ontario tertiary care hospitals, use of a surgical mask compared with an N95 respirator resulted in noninferior rates of laboratory-confirmed influenza.

I’m gonna be team player and use the N-95.

Much more clinically useful information is available in John Bartlett’s “Just the Facts” series of articles in Medscape’s alert center.

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