Table 2.

Characteristics of Included Studies

Study and YearPopulation and Season(s)NInfluenza Prevalence, %CountryReference StandardComment
DIF=direct immunofluorescence; ED = emergency department; ELISA = enzyme-linked immunosorbent assay; ILI = influenza-like illness; NPV = negative predictive value; PCR = polymerase chain reaction; RSV = respiratory syncytial virus; RTI = respiratory tract infection.
Govaert et al,13 1998Average-risk, unvaccinated primary care patients older than 60 y with ILI during 1991–1992 flu season1,838 (logistic regression); 1,791 (heuristics)6.6NetherlandsIncrease in antibody titerAny symptoms reported during study period were included; part of randomized trial of vaccination.
Carrat et al,23 1999Primary care patients older than 1 y with ILI, RTI syndrome, and/or fever >38°C without signs of other infections during 1995–1996 flu season60026FranceDIF and ELISA; if disagreement, further testing with PCR and cultureSeparate models created for H1N1 and H3N2 subtypes, and for all influenza.
Monto et al,11 2000Adolescent or older with fever and ≥2 other symptoms (headache, myalgia, cough, or sore throat) during fall or winter of 1994–19983,74466North America, Europe, southern hemisphereCulture or increase in antibody titer (in some studies PCR or immunofluorescence)High prevalence of influenza. Data from 6 randomized trials of zanamivir vs placebo.
Boivin et al,12 2000Patients with ILI (fever ≥37.8°C and ≥2 other symptoms) seeking care at an outpatient clinic during 1998–1999 flu season10079CanadaPCR and culture–
van Elden et al,10 2001Primary care patients with fever (≥38°C), ≥1 constitutional symptom (malaise, headache, myalgia, chills), and ≥1 respiratory symptom (coryza, sneeze, cough, sore throat, hoarseness) seeking care within 48 hr of onset during 1997–1998 flu season8151NetherlandsPCR and cultureOnly PCR results were used for model development.
Zambon et al,19 2001Persons aged 12 y or older seen within 48 hr of onset of ILI as part of a multicenter international clinical trial of an influenza drug1,03377 (any test positive);
 67 (all 3 tests positive)Europe, North AmericaPCR, culture, or increase in antibody titerReference standard was abnormal finding on all 3 tests.
Walsh et al,21 2002Inpatients older than age 65 y or with underlying cardiopulmonary conditions with a respiratory diagnosis during 1999–2000 flu season33218United StatesCulture, rapid antigen test, increase in antibody titer, or PCRA model with 2 variables (temperature >38°C and absence of dyspnea) reportedly did not discriminate well; results not reported by authors.
Friedman and Attia,20 2004Children (0–17 y) seen in the ED with suspected ILI (fever and coryza, cough, headache, sore throat, or muscle aches) during 2002 flu season12835United StatesCulture–
Senn et al,7 2005Persons with ILI seeking care at an outpatient clinic during 1999–2000 flu season20152SwitzerlandCultureCutoff for logistic model presumably probability of influenza >50%.
Stein et al,8 2005Consecutive adults with RTI in past 3 wk with cough, sinus pain, congestion/ rhinorrhea, sore throat, or fever seen in the ED during 2002 flu season25821United StatesPCRValidated previously developed fever and cough rule.11
Ohmit and Monto,24 2006Study 1 (zanamivir): children aged 5–12 y with fever and duration of illness <36 hr during flu season
 Study 2 (oseltamivir): children aged 1–12 y with fever and cough or nasal symptoms, and duration <48 hr during flu seasonStudy 1: 468
 Study 2 (1–4 y): 255
 Study 2 (5–12 y): 221Study 1: 74
 Study 2: 67United StatesCulture and/or 4-fold increase in antibody titer (or PCR in zanamivir trial only)Validated previously developed fever and cough rule.11 RSV infection excluded. Unable to calculate sensitivity, specificity, NPV from data for fever and cough rule.
van den Dool et al,22 2008Adult inpatients in the general medicine, pulmonology, and infectious disease wards of a tertiary care hospital during 2006–2007 flu season2648.7NetherlandsPCRIncluded all patients regardless of symptoms; validated previously developed fever and cough rule.11