OBJECTIVE: Our goal was to determine the utility of clinical clues, white blood cell (WBC) and differential counts, and a rapid antigen test for differentiating influenza from coexistent infectious diseases during influenza epidemics.
STUDY DESIGN: Data were collected during 3 consecutive influenza outbreaks over a 2-year period. The information collected included date of onset, symptoms, vaccine status, WBC and differential counts, ZstatFlu test (ZymeTx, Oklahoma City, Ok), and influenza culture. Using culture positivity as the criterion for influenza diagnosis, we compared cases with noncases on each variable independently and by logistic regression.
POPULATION: We included consecutive patients presenting to a family practice office with fever, cough, sore throat, myalgia, and/or headache during flu season.
OUTCOMES MEASURED: The outcomes were sensitivity, specificity, and other measures of test accuracy.
RESULTS: Culture-positive cases could not be reliably distinguished from those that were culture negative using symptoms or vaccination status. Both WBC count and ZstatFlu results discriminated fairly well, and their combination did somewhat better. Differential counts were not helpful. WBC counts above 8000 were associated with a low probability of influenza. The sensitivity and specificity of the ZstatFlu were 65% and 83%, respectively.
CONCLUSIONS: Our data suggest that symptoms and vaccine status do not reliably identify patients with influenza. Use of WBC counts and the ZstatFlu test can be helpful. The sequence, combination, and criteria for use of these tests depend on tradeoffs between undertreatment of influenza cases and the overtreatment of noninfluenza cases, and the cost and benefit projections for individual patients.
Influenza affects between 20% and 30% of the United States population annually. Three fourths of the infected individuals develop an acute respiratory illness, and one third of these seek medical attention. In a typical year, more than 20,000 to 40,000 Americans die, and more than 100,000 are hospitalized because of complications related to influenza.1 Immunizations usually provide between 70% and 90% protection, yet many people at high risk do not receive the vaccine. An effective method for quickly differentiating patients with influenza from those with other respiratory illnesses might be helpful, since 2 new medications (the zanamivir inhaler and oseltamivir tablets) that are active against both influenza A and B are now available. Two other medications, amantadine and rimantidine, are active against influenza A only.2,3 In the past, physicians have relied on symptoms alone or in conjunction with a manual or automated white blood cell (WBC) count with a differential count to assist them in making the diagnosis of influenza. However, several researchers have found that symptoms and signs have relatively poor predictive value during influenza outbreaks.4-6 A recent pooled analysis of 3744 subjects involved in clinical trials of the antiviral agent zanamivir found that patients with influenza were somewhat more likely to have fever (68% vs 40%), cough (93% vs 80%), and nasal congestion (91% vs 81%) than patients with other infections.7
ZstatFlu is an office test for the diagnosis of both influenza A and B. It detects neuraminidase, an enzyme found on the influenza virus. In the presence of the virus, chromagen is cleaved off a synthetic neuraminidase substrate. A positive test results in a blue color change. The ZstatFlu test is 1 of 4 approved tests on the market for rapid diagnosis of influenza. Three of the 4 detect both influenza A and B8 To determine the most effective and efficient approach to the office diagnosis of influenza, we collected and analyzed clinical and laboratory data from patients seen in a family practice office setting during 2 consecutive influenza seasons.
Methods
Patients
We included consecutive patients presenting to a private family practice clinic that had 4 physicians and 1 physician assistant in a suburban setting in Oklahoma between January and March 1999 and November 1999 and January 2000 with fever, cough, sore throat, myalgia, and/or headache. No patients were systematically excluded. Consenting patients received a WBC and differential count, a rapid flu test (ZstatFlu), and an influenza culture by oropharynageal swab. Some patients consented to some but not all of these tests. Cultures were unavailable during a portion of each study period. Viral serologies were not done.
Procedure
Patients were triaged by the office nurse, who asked when they had become ill and whether they had experienced any of the following signs or symptoms: fever higher than 101°F (38.5 °C), cough, sore throat, headache, or myalgia. They were also asked if they had received that year’s flu vaccine. A WBC and differential count was performed by a laboratory technician in the clinic using a Cell-Dyn 1700 machine (Abbott Laboratories; Abbott Park, Ill). The ZstatFlu test was performed by the same laboratory technician using the method described by the manufacturer. An oropharyngeal swab for influenza culture was also obtained. The swabs were placed in viral culture medium and refrigerated. They were picked up once daily and transported to one of 2 laboratories (at ZymeTx or the Oklahoma State Department of Health) and plated that day. All participating patients gave informed consent. The protocol was approved by the Research Consultants Review Committee, Austin, Texas, and by the Institutional Review Committee at the University of Oklahoma Health Sciences Center.