The specificity of the ZstatFlu test is reported to be between 95% and 100%.4 However, when performed in this community family practice office by a laboratory technician trained by the test’s manufacturer, the specificity was only 85%. Many of the false-positive test results were coded as “weakly positive,” suggesting that the end point for positivity was somewhat unclear or that the laboratory technician was influenced by the patient’s symptoms. The specificity improved in the second year, suggesting an improvement in technique. We submit that this is an example of the discrepancy between test characteristics determined under “ideal” circumstances and test characteristics in actual practice settings. Another explanation is that patients with weakly positive ZstatFlu test results actually had influenza that would have been documented had serology been used as the gold standard instead of culture.
Limitations
A weakness of our study is the proportion of patients with flu-like symptoms from whom culture results were not available. Flu season actually began earlier than January during the 1998-1999 season and extended beyond January with the 1999-2000 season, but cultures were not available during a portion of these time periods. Although patients with cough were more likely to be cultured, this potential bias should not have affected our conclusions, since cough was not associated with culture result.
Two other diagnostic concerns are the lack of serologic tests and the known tendency of cultures to be more reliable early in the illness. Serology would probably have identified some additional influenza cases. This would have resulted in higher pretest probabilities of influenza. It is unclear how it would have affected the other analyses. Since there was no association between duration of symptoms and culture result in 2 of the 3 epidemics and in the combined analysis, we do not believe that waning sensitivity of flu cultures was a significant factor in this population. In the third epidemic it seems more likely that flu patients felt worse (eg, had more myalgias) and therefore came in earlier than that cultures became negative in those who delayed seeing the physician. Additionally, the study had insufficient power to detect a statistically significant difference between the diagnostic value of the ZstatFlu alone, and the combination of the WBC count and the ZstatFlu test.
It should be noted that patients were enrolled during an outbreak of influenza. In fact, the practice involved was one of the first in the state to recognize the onset of the epidemic because they were involved in this study. The conclusions reached about diagnostic strategies can only be generalized to similar epidemic situations.
Conclusions
Since influenza is associated with considerable morbidity and mortality, especially in high-risk populations, and given the brief window of opportunity (less than 48 hours) to treat patients with the flu with the newer agents, early and accurate diagnosis may be important in at least some cases. The use of screening WBC counts or rapid antigen tests could improve patient care during influenza epidemics. A cost-effectiveness analysis is needed to more fully elucidate this issue.
Acknowledgments
We would like to acknowledge the financial support of ZymeTx Corporation for supplying the ZstatFlu reagents, training, and influenza cultures at no cost. The support received from ZymeTx Corporation was unrestricted, and the company had no influence on our decision to analyze the results in the manner that we did or on the contents of this manuscript. We also want to thank Lavonne Glover for her expert assistance and patience in the preparation of the manuscript.