Our study highlights the difficulty of diagnosing influenza in hospitalized adults 50 years of age or older by using routine hospital laboratory studies (rapid antigen testing and viral culture) and clinical syndrome–based definitions. In older hospitalized adults, the sensitivity of the research rapid antigen test was 19.2%, and the sensitivity of viral culture was 34.6%. Thus, most adults with influenza were not identified by use of these methods. The specificity of the clinical presentation of influenza-like illness was 40.6%, yielding positive predictive values that were too low for optimal clinical decision making.
It has been reported that older adults infected with influenza are less likely to have the virus recovered from culture, even in the setting of an epidemic, possibly because of decreased shedding or delay in presentation.3, 4
Because there is an interval of 2–5 days before a diagnosis of influenza by culture can be made, this method is not very useful for determining initial treatment or for making decisions about isolating hospitalized adults. New culture techniques, such as the shell-vial technique, decrease the time to diagnosis but have also shown a sensitivity similar to that of conventional techniques.13
Although direct fluorescent antibody assays are used in some hospitals, they are not used routinely in our clinical laboratory, and thus we did not evaluate their performance. Other studies have demonstrated direct fluorescent antibody testing to be more sensitive than rapid antigen testing but less sensitive than viral culture or RT-PCR.14
Because of the results of earlier studies, it is likely that the sensitivity of direct fluorescent antibody testing would be suboptimal in older adults.
Currently, many clinicians rely on rapid antigen testing to diagnose influenza infection and to make decisions about isolating patients. However, we have demonstrated the poor sensitivity (19.2%) of this method in hospitalized older adults. Although our reported sensitivity for rapid antigen testing is somewhat lower than that reported by Walsh et al15
(43%), it is very similar to the sensitivities reported by Steininger et al6
(8%–22% for adults 80 years of age or older).
Physician diagnosis of influenza is another method used to identify influenza. Diagnosis of influenza-like illness has better sensitivity for identifying influenza than does rapid antigen testing or culture, but it lacks specificity because the symptoms of influenza are similar to those of other viral respiratory illnesses and because of the fact that fever may not be a reliable symptom in older adults. In a prospective study by Neuzil et al,16
fever had a sensitivity of only 26% in older adults. Similarly, a study in the Netherlands found fever in only 34% of adults 60 years of age or older.17
In addition, Babcock et al18
reported a poor sensitivity (43%) of influenza-like illness symptoms in adults (approximately half of whom were 65 years of age or older) when obtained by chart review rather than when reported by patient.
None of the diagnostic tests discussed here (except RT-PCR) can be used to quickly determine the exact influenza A subtype. This determination has become increasingly important, because the Centers for Disease Control and Prevention has issued warnings about antiviral resistance based on influenza A subtype. In the fall of 2008, there were 24 of 25 H1N1 isolates that were found to be resistant to oseltamivir, whereas all 5 H3N2 isolates were resistant to adamantanes.19
This determination is even more important in the context of the novel H1N1 2009 influenza virus. To date, the novel H1N1 strain is generally susceptible to oseltamivir.
In our study, quantification of the viral load introduces a novel aspect to earlier studies of influenza diagnosis in older adults and allowed us to explore differences between diagnostic tests. Recently, Lee et al20
showed that higher viral loads were associated with more severe disease. Our study was not powered to evaluate severity based on viral load but was able to show that lower viral loads were associated with negative rapid antigen test results and negative culture results. Although it is unknown whether influenza virus detected by use of RT-PCR remains viable and transmissible or whether the viral load influences transmission, our studies do have important infection control ramifications. It is recommended practice to place patients with suspected or known influenza under droplet precautions to prevent healthcare-associated transmission of influenza virus; however, a negative rapid antigen test result is often used as an indicator that the patient can be removed from isolation. The data presented in the present study suggest that, in older adults, a negative antigen test result does not provide assurance that a patient is uninfected with influenza.
Our study shows the limitations of currently used tools for diagnosing influenza in hospitalized older adults. However, with the use of RT-PCR, influenza and its complications can be more easily identified. The introduction of RT-PCR into hospital clinical laboratories would increase the recognition of disease due to influenza in older adults, aid in appropriate isolation methods, and assure the appropriate use of antiviral therapy.