Diagnostic Challenges Are Anticipated in Pandemic Flu

VAIL, COLO. — Recent anecdotal reports suggest that the diagnosis of 2009 influenza A(H1N1) should not be ruled out by a negative upper respiratory tract specimen in a patient with pneumonia.

There have been two patients at Albany (N.Y.) Medical Center and one in Denver who were hospitalized with severe lower respiratory tract infections whose nasopharyngeal swabs were negative for influenza A by rapid tests—but who had endotracheal aspirates positive for the 2009 H1N1 virus by culture and polymerase chain reaction (PCR).

“That's something to watch for. It would be consistent with findings in animal models showing the virus replicates very well in the lower respiratory tract,” said Dr. Adriana Weinberg, who reported on the cases at a conference on pediatric infectious diseases sponsored by the Children's Hospital, Denver.

“As the pandemic evolves, perhaps we may see more cases with florid infection in the lower respiratory tract and not so much virus in the upper respiratory tract,” said Dr. Weinberg, professor of medicine, pediatrics, and pathology and medical director of the clinical virology laboratory at the University of Colorado Hospital, Aurora.

At present, the preferred specimens for making the diagnosis of 2009 H1N1 are the same as for seasonal influenza: nasopharyngeal aspirates or swabs in adults and nasal washings in children. Yet negative results on upper respiratory tract specimens do not necessarily rule out 2009 H1N1 in patients with lower respiratory tract infections.

“In these patients, you may want to proceed with obtaining an induced sputum, an endotracheal aspirate, or a bronchoalveolar lavage specimen to rule out the pandemic strain,” Dr. Weinberg said.

Most diagnostic tests for seasonal influenza A or A plus B also will pick up the pandemic H1N1 strain. A caveat is that the rapid tests, which in general are not terribly sensitive for the diagnosis of seasonal influenza viruses, appear to be even less sensitive for 2009 H1N1.

“A positive rapid test indicates you may be dealing with the pandemic strain, but a negative test does not rule out pandemic influenza. However, culture and PCR are extremely sensitive for this strain,” she continued.

The Centers for Disease Control and Prevention acted quickly in preparing tools for the diagnosis of 2009 H1N1. Regular PCR and culture cannot differentiate between seasonal influenza A and the 2009 H1N1 strain. But just 2 weeks after the first U.S. case of 2009 H1N1 disease was diagnosed in April, the CDC began sending out to sentinel laboratories PCR kits that are highly specific for the virus. Less than 2 months later, the kits were on-site at 233 U.S. laboratories, including all state health department laboratories.

Physicians can expect to see a lot of patients with a prominent gastrointestinal presentation of 2009 H1N1. Animal studies suggest that the pandemic strain replicates much better in the GI tract than do seasonal influenza viruses. That has been borne out in the first 400 U.S. cases of 2009 H1N1: More than 90% presented with fever and cough, and two-thirds had a sore throat—all typical of seasonal influenza—but in addition, 25% presented with diarrhea and 25% had vomiting.