 |
|
Clinical Signs and Symptoms Predicting Influenza Infection
Arnold S. Monto, MD;
Stefan Gravenstein, MD;
Michael Elliott, MD;
Michael Colopy, PhD;
Jo Schweinle, MD
Arch Intern Med. 2000;160:3243-3247.
ABSTRACT
| |
Background New antiviral drugs are available for the treatment of influenza type A and type B infections. In clinical practice, antiviral use has rarely been guided by antecedent laboratory diagnosis. Defined clinical predictors of an influenza infection can help guide timely therapy and avoid unnecessary antibiotic use.
Objective To examine which clinical signs and symptoms are most predictive of influenza infection in patients with influenzalike illness using a large data set derived from clinical trials of zanamivir.
Methods This analysis is a retrospective, pooled analysis of baseline signs and symptoms from phase 2 and 3 clinical trial participants. It was conducted in mainly unvaccinated (mean age, 35 years) adults and adolescents who had influenzalike illness, defined as having fever or feverishness plus at least 2 of the following influenzalike symptoms: headache, myalgia, cough, or sore throat who underwent laboratory testing for influenza. Clinical signs and symptoms were evaluated in statistical models to identify those best predicting laboratory confirmation of influenza.
Results Of 3744 subjects enrolled with baseline influenzalike symptoms, and included in this analysis, 2470 (66%) were confirmed to have influenza. Individuals with influenza were more likely to have cough (93% vs 80%), fever (68% vs 40%), cough and fever together (64% vs 33%), and/or nasal congestion (91% vs 81%) than those without influenza. The best multivariate predictors of influenza infections were cough and fever with a positive predictive value of 79% (P<.001). The positive predictive value rose with the increase in the temperature at the time of recruitment.
Conclusion When influenza is circulating within the community, patients with an influenzalike illness who have both cough and fever within 48 hours of symptom onset are likely to have influenza and the administration of influenza antiviral therapy may be appropriate to consider.
INTRODUCTION
INFLUENZA VIRUS infection is a major public health problem, occurring, typically, in the Northern Hemisphere, between the months of December and April. Epidemics of influenza are characterized by an increased morbidity and mortality in the community and result in increased absenteeism from school and work.1-6 The classic influenza syndrome is sudden in onset and is characterized by fever, headache, cough, sore throat, myalgia, nasal congestion, weakness, and loss of appetite.3-8
Vaccines, the most cost-effective primary prevention for influenza, are effective and readily available but have their limitations.9-10 Two antiviral agents with similar activity, amantadine hydrochloride and rimantadine hydrochloride, have been available many years for prophylaxis and treatment of influenza.3, 10-13 However, both of these agents are active only against influenza type A and not influenza type B, and resistance of influenza A viruses to these drugs can be a problem.14-15 Zanamivir and oseltamivir, new, recently approved antiviral agents, are inhibitors of the influenza virus enzyme neuraminidase and are active against influenza type A and type B.3, 11-12,16 When administered early in the course of infection, both reduce the time to alleviation of clinical symptoms in individuals infected with influenza.3, 11-12
To be maximally effective against influenza, antiviral therapy must be initiated as soon as possible after symptom onset, and clearly cannot await traditional laboratory diagnosis.11-12,17-18 This analysis examined which clinical signs and symptoms are most predictive of influenza infection in patients with influenzalike illness using a large data set derived from clinical trials of zanamivir. Knowledge of the most predictive symptoms of influenza could be used by physicians to diagnose influenza more accurately and to begin an appropriate course of treatment in time to be of most benefit to the patient.
PATIENTS AND METHODS
STUDIES AND DESIGN
Eight double-blind, placebo-controlled studies involving 231 study centers in North America, Europe, and the Southern Hemisphere were included in this analysis (Table 1). These studies were phase 2 and 3 clinical trials designed to evaluate the use of the antiviral agent zanamivir vs placebo for the treatment of influenza type A and type B viral infections and were conducted during the fall and/or winter of 1994 through 1998.
|
|
|
|
Table 1. Study Features and Clinical Characteristics of the 8 Multicenter, Phase 2 and 3 Studies Evaluating the Safety and Efficacy of the Antiviral Zanamivir for the Treatment of Influenza Type A and Type B Infections
|
|
|
Data regarding patients' signs and symptoms, collected at baseline (ie, prior to any treatment), were pooled across the 8 studies. All available study data were included in the analysis to minimize the potential for bias.
PATIENTS
To be eligible, study participants were required to have fever (body temperature  37.8°C or 37.2°C for patients 65 years old in NAIA/B3002 [the protocol report number]) or a symptom of feverishness, plus at least 2 of the following influenzalike symptoms: headache, myalgia, cough, or sore throat. Feverishness was defined as the patient's subjective symptom of feeling like they had a fever or chill. Specific influenzalike symptoms required for patient enrollment into each study are also summarized by study in Table 1.
A requirement for a study site to begin patient enrollment was the identification of at least 2 individuals with culture-confirmed influenza within a 7-day period prior to enrollment, who resided in the geographic region around the site. Geographic region was defined as the area within a 50-mile radius of the study location. This requirement was to improve the probability that influenza was actually present in the geographic region of the study.
DATA COLLECTION AND ANALYSIS
The following baseline signs or symptoms were analyzed as potential predictors of influenza infection: fever, feverishness, cough, headache, sore throat, myalgia, nasal congestion, weakness, and loss of appetite. Although the symptoms were collected using a 4-point severity scale, for this analysis they were analyzed as either absent or present. A diagnosis of influenza was defined either as a positive culture for influenza virus or as a 4-fold or greater increase in influenza antibody titer in convalescent vs acute serum samples as determined by hemagglutination inhibition. In some studies, influenza infection could also or alternatively be confirmed by polymerase chain reaction (NAIA/B3002 [the protocol report number]) or by immunofluorescence.19-20
Univariate and multivariate analyses were conducted to compare clinical signs and symptoms with the diagnosis of influenza. Demographic factors such as age, sex, high-risk populations (defined as having chronic respiratory disease, cardiovascular disease, or more advanced age [ie, 65 years old]), and hours from symptom onset to collection of the diagnostic specimen were also incorporated into the analysis. A stepwise logistic regression analysis was performed to determine which baseline symptoms and patient characteristics best predict influenza infection. The stepwise procedure selected the best explanatory variable into the model first, then selected the second best explanatory variable, and so forth. The stepwise procedure stopped selecting additional variables when they did not reach statistical significance at the  = .05 level, given the other variables already in the model. The stepwise logistic regression model was tested for goodness of fit to determine the most parsimonious model. Odds ratios and their 95% confidence intervals were calculated for each variable in the logistic regression model. Measures of positive predictive value (PPV), negative predictive value, sensitivity, and specificity were calculated to also identify the best predictors of an influenza infection. Positive predictive values were compared for individual symptoms, as well as combinations of symptoms (SAS Statistical Analysis Software, version 6.12; SAS Institute Inc, Cary, NC).
RESULTS
A total of 3744 clinical trial participants with influenzalike symptoms were enrolled during the fall and/or winter of 1994 through 1998. Demographic information of study participants, the percentage who had been vaccinated against influenza, and the percentage with a positive diagnosis of influenza, are given in Table 2. Approximately two thirds of the patients recruited to this study were identified as being infected with influenza virus.
|
|
|
|
Table 2. Baseline Characteristics of Pooled Participants
|
|
|
Among individuals with influenza, the most frequently reported symptoms were weakness (94%), myalgia (94%), cough (93%), and nasal congestion (91%) (Table 3). Among those individuals without influenza, weakness (94%) and myalgia (94%) were also commonly reported. Individuals with influenza were more likely than those without influenza to have baseline cough (93% vs 80%), fever (68% vs 40%), and cough and fever together (64% vs 33%).
|
|
|
|
Table 3. Proportion of Pooled Participants With Baseline Symptoms
|
|
|
As listed in Table 4, the stepwise logistic regression selected 9 baseline symptoms and characteristics into the model, with fever (odds ratio = 3.26; P<.001) and cough (odds ratio = 2.85; P<.001) as the 2 best explanatory variables. Headache, myalgia, and high-risk status were poor explanatory variables (P>.05) and were not selected into the model. Feverishness was not included since fever (body temperature 37.8°C) was already in the model. Both older age and onset over 36 hours from recruitment predicted positive influenza status. This may relate to the greater likelihood that such individuals would be seen by a physician for management of their symptoms. Sore throat negatively predicted the presence of influenza.
|
|
|
|
Table 4. Stepwise Logistic Regression Analysis of Predictors of Influenza Infection
|
|
|
The ability to use these findings to identify which patients are most likely to have influenza was examined in a sensitivity analysis (Table 5). Of particular interest is the PPV proportion of those with a symptom who are confirmed positive for influenza. The PPV for baseline fever and cough was 79%, with sensitivity and specificity values of 64% and 67%, respectively. The PPV for baseline cough and fever was even higher (PPV = 85%) in the subset of patients with time from onset between 36 and 48 hours; in those recruited closer to illness onset, the PPV was still 77%. Adding other symptoms did not improve the PPV substantially. However, as shown in Figure 1, the probability of a patient having confirmed influenza increased with increasing baseline temperature and was consistently greater in patients with a cough than in patients without a cough. The proportion of patients who were confirmed positive for influenza exceeded 80% when their temperature was above 38°C.
|
|
|
|
Table 5. Multivariate Predictors of Influenza Infection With Sensitivity and Specificity Analyses*
|
|
|
|
|
|
|
Percentage of patients with a positive influenza test result by baseline cough and temperature score.
|
|
|
COMMENTS
Acute respiratory illnesses are the leading cause of medical visits for outpatients of all ages. The precise origins for these illnesses are rarely identified.8 This is largely because for most respiratory viral diseases, establishment of the specific viral cause is neither necessary (ie, does not direct therapy) and thus is not cost-effective. The situation is different for influenza virus infection, for which specific antiviral therapy has been available for many years. The introduction of the new neuraminidase inhibitors has made the need to be able to recognize influenza illness much more important.3, 10-12
This analysis determined if there are clinical signs and symptoms that might help the clinician discriminate influenza infection from illness due to other respiratory viruses. The most common presenting symptoms among individuals with influenza in this cohort were feverishness (feeling of fever or chills), cough, myalgia, and weakness, consistent with previous publications.4-8,21 In this population, the PPV of cough and fever was 79%, compared with the 69% reliability of "practitioner intuition" as recently described.7 The PPV rose even further as the height or degree of fever at recruitment increased. Thus, during periods when influenza virus is known to be present within a community, a high index of suspicion for influenza is warranted in patients who are seen with acute onset of cough and fever (body temperature 37.8°C).
Our results corroborate those of Monto and Ohmit,21 who reported that in individuals with influenzalike illness, the 2 best predictors of a laboratory-confirmed diagnosis of influenza are cough and fever, both for type A (H3N2) and type B viruses. The current results, analyzed from a much greater number of patients, show that cough and fever are better predictors of influenza infection than either symptom alone. Most isolates in the current analysis were type A(H3N2) viruses but based on the previous study, there is no reason to think that the situation with type B will be different. In contrast, Carrat et al22 examined 610 patients, of whom only 168 (28%) were positive for influenza, mainly type A viruses. They found that fever and, for type A(H3N2) viruses, cough predicted influenza infection, but the PPV was not high with a variety of case definitions. The difference in conclusions may reflect the very different settings of the 2 studies, one derived from a surveillance program in which general practitioners were asked to collect a fixed number of specimens, and ours, derived from a clinical trial in which only patients with a predefined influenzalike illness were considered in the presence of circulating influenza. In any event, in 3 different studies, fever and cough have independently been found to predict influenza infection.
The clinical studies analyzed herein were performed in geographic regions where influenza was known to be present. Knowledge of the prevalence of influenza virus in the community can optimize the practicability of making the clinical diagnosis of influenza. First, there is the expected relationship between the PPV and the prevalence of a condition. Also, when influenza virus is prevalent, the incidence of illness due to other respiratory viruses tends to decrease, and because of this, the PPV of clinical signs and symptoms increases.4 Although physicians are often informally aware of the arrival of influenza virus in the community, their knowledge could be increased with the help of better surveillance and rapid confirmation of infection. A problem arises at the start of an epidemic, when information is scanty and the PPV might be lower. Physicians might collect diagnostic specimens from patients who are seen at the start of the epidemic, not as much to direct therapy for these patients as to gather information about the local prevalence of the virus. These surveillance techniques, in combination with the symptoms of cough and fever, could improve the accuracy of physicians in making a clinical diagnosis of influenza.
There are limitations to the application of this information in everyday practice. Young children were not included nor were significant numbers of older individuals. It is known that in elderly persons, living in the community and especially in nursing homes, outbreaks of agents such as respiratory syncytial virus can sometimes mimic those of influenza, so that identifications on the circulating viruses should be done in a small number of those affected to confirm the cause.23-24 In the present analysis, fever or feverishness (a feeling of fever or chills) was an enrollment criterion for participation in these study protocols. In everyday practice, a diagnosis of influenza may be missed in individuals who do not have fever at the time of their office visit or clinical presentation. Furthermore, this analysis cannot consider altered (reduced) symptom presentation that may occur with antecedent vaccination (reducing or altering sensitivity and specificity of fever, cough, and other symptoms of influenza), since most participants were unvaccinated. Due to the selection of a patient population with defined symptoms of influenzalike illness such as fever, we may have overestimated the PPV that would actually be observed among practicing physicians in the community. The prevalence of laboratory-confirmed influenza infection in our study population of individuals with defined influenzalike illnesses was 66%; Cate4 reported that at least 50% of throat swab specimens from patients with respiratory illness yielded influenza virus during a typical epidemic. However, these investigators suggest that this percentage might increase if specimens were collected only during the first few days of the disease.4 Thus, if it is clear that influenza is prevalent within a practitioner's practice area, the PPV of all symptoms would increase and the threshold for intervention should be lowered.
Thus, the results of this study suggest that cough and fever are good predictors of infection among patients with an influenzalike illness when influenza is present within the community. To maximize their ability to diagnose and treat influenza, clinicians should work with community health officials and among themselves to keep apprised of influenza in the community. Education, better surveillance methods, an appropriate index of suspicion, and early treatment can reduce the time to alleviation of symptoms for patients suffering from influenza infection.
AUTHOR INFORMATION
Accepted for publication June 14, 2000.
These studies were funded by Glaxo Wellcome Inc, Research Triangle Park, NC.
We thank Chandra Louise at Glaxo Wellcome Inc, and Don Smith at MediTech Media, Atlanta, Ga, for assistance in preparing the manuscript.
Presented in part as an abstract at the 1999 Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, Calif, September 26, 1999.
Corresponding author: Arnold S. Monto, MD, University of Michigan, 3080 SPH-1, 109 Observatory St, Ann Arbor, MI 48109-2029 (e-mail: asmonto{at}umich.ed).
From the Department of Epidemiology, University of Michigan, Ann Arbor (Dr Monto); Center for Geriatrics and Gerontology, East Virginia Medical School, Norfolk (Dr Gravenstein); and Infectious Diseases and Hepatitis, Glaxo Wellcome Inc, Research Triangle Park, NC (Drs Elliott, Colopy, and Schweinle). Dr Monto has received honoraria and research support from Glaxo Wellcome Inc and Hoffmann-LaRoche Inc. Dr Gravenstein is a consultant to Glaxo Wellcome Inc and Hoffmann-LaRoche Inc and has received research support from Glaxo Wellcome Inc. Drs Elliott, Colopy, and Schweinle are employees of Glaxo Wellcome Inc and may hold Glaxo Wellcome stock or stock options.
REFERENCES
| |
1. Schoenbaum SC. Economic impact of influenza: the individual's perspective. Am J Med. 1987;82:26-30.
ISI
| PUBMED
2. Monto AS. Influenza: quantifying morbidity and mortality. Am J Med. 1987;82:20-25.
3. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections: The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Lancet. 1998;352:1877-1881. [published erratum appears in Lancet. 1999;353:504].
ISI
| PUBMED
4. Cate TR. Clinical manifestations and consequences of influenza. Am J Med. 1987;82:15-19.
5. Monto AS, Ohmit SE, Margulies JR, Talsma A. Medical practice-based influenza surveillance: viral prevalence and assessment of morbidity. Am J Epidemiol. 1995;141:502-1506.
FREE FULL TEXT
6. Monto AS. Studies of the community and family: acute respiratory illness and infection. Epidemiol Rev. 1994;16:351-373.
FREE FULL TEXT
7. Carrat F, Tachet A, Housset B, Valleron AJ, Rouzioux C. Influenza and influenza-like illness in general practice: drawing lessons for surveillance from a pilot study in Paris, France. Br J Gen Pract. 1997;47:217-220.
ISI
| PUBMED
8. Long CE, Hall CB, Cunningham CK, et al. Influenza surveillance in community-dwelling elderly compared with children. Arch Fam Med. 1997;6:459-465.
ABSTRACT
9. Glezen WP. Influenza control—unfinished business. JAMA. 1999;281:944-945.
FREE FULL TEXT
10. Mossad SB. Underused options for preventing and treating influenza. Cleve Clin J Med. 1999;66:19-23.
ISI
| PUBMED
11. Hayden FG, Treanor JJ, Betts RF, Lobo M, Esinhart JD, Hussey EK. Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza. JAMA. 1996;275:295-299.
ABSTRACT
12. Hayden FG, Osterhaus AD, Treanor JJ, et al for the GG167 Influenza Study Group. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. N Engl J Med. 1997;337:874-880.
FREE FULL TEXT
13. Dolin R, Reichman RC, Madore HP, Maynard R, Linton PN, Webber-Jones J. A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. N Engl J Med. 1982;307:580-584.
ABSTRACT
14. Hayden FG, Hay AJ. Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine. Curr Top Microbiol Immunol. 1992;176:119-130.
ISI
| PUBMED
15. Mast EE, Harmon MW, Gravenstein S, et al. Emergence and possible transmission of amantadine-resistant viruses during nursing home outbreaks of influenza A (H3N2). Am J Epidemiol. 1991;134:988-997.
FREE FULL TEXT
16. Hayden FG, Treanor JJ, Fritz RS, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA. 1999;282:1240-1246.
FREE FULL TEXT
17. Sintchenko V, Dwyer DE. The diagnosis and management of influenza: an update. Aust Fam Physician. 1999;28:313-7.
PUBMED
18. Piedra PA. Influenza virus pneumonia: pathogenesis, treatment, and prevention. Semin Respir Infect. 1995;10:216-223.
PUBMED
19. Claas EC, van Milaan AJ, Sprenger MJ, et al. Prospective application of reverse transcriptase polymerase chain reaction for diagnosing influenza infections in respiratory samples from a children's hospital. J Clin Microbiol. 1993;31:2218-2221.
FREE FULL TEXT
20. Grandien M, Pettersson CA, Gardner PS, Linde A, Stanton A. Rapid viral diagnosis of acute respiratory infections: comparison of enzyme-linked immunosorbent assay and the immunofluorescence technique for detection of viral antigens in nasopharyngeal secretions. J Clin Microbiol. 1985;22:757-760.
FREE FULL TEXT
21. Monto AS, Ohmit SE. The evolving epidemiology of influenza infection and disease. In: Brown LE, Hampson AW, Webster RG, eds. Options for the Control of Influenza III. Amsterdam, the Netherlands: Elsevier Science BV; 1996:45-49.
22. Carrat F, Tachet A, Rouzioux C, Housset B, Valleron AJ. Evaluation of clinical case definitions of influenza: detailed investigation of patients during the 1995-1996 epidemic in France. Clin Infect Dis. 1999;28:283-290.
ISI
| PUBMED
23. Nicholson KG, Kent J, Hammersley V, Cancio E. Acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden. BMJ. 1997;315:1060-1064.
FREE FULL TEXT
24. Wald TG, Miller BA, Shult P, Drinka P, Langer L, Gravenstein S. Can respiratory syncytial virus and influenza A be distinguished clinically in institutionalized older persons? J Am Geriatr Soc. 1995;43:170-174.
ISI
| PUBMED
25. A Double-blind, Randomised, Placebo-Controlled, Parallel-Group, Multicentre Study to Investigate the Efficacy and Safety of Inhaled Plus Intranasal Zanamivir in the Treatment of Influenza A and B Viral Infections. Greenford, England: Glaxo Wellcome Research & Development; 1998. Study NAIB2007.
26. Monto AS, Fleming DM, Henry D, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza A and B virus infections. J Infect Dis. 1999;180:254-261.
FULL TEXT
|
ISI
| PUBMED
27. Lalezari J, Klien T, Stapleton J, Elliott M, Flack N, Keene O. The efficacy and safety of inhaled zanamivir in the treatment of influenza in otherwise healthy and `high risk' individuals in North America [abstract]. J Antimicrob Chemother. 1999;44:42.
28. Makela MJ, Pauksens K, Rostila T, et al. Clinical efficacy and safety of the orally inhaled neuraminidase inhibitor zanamivir in the treatment of influenza: a randomized, double-blind, placebo-controlled European study. J Infect. 2000;40:42-48.
FULL TEXT
|
ISI
| PUBMED
RELATED LETTER
Clinical Signs and Symptoms Predicting Influenza Infection
Eelko Hak, Karl G. M. Moons, Theo J. M. Verheij, Arno W. Hoes, Arnold S. Monto, Stefan Gravenstein, Michael Elliott, Michael Colopy, and Jo Schweinle
Arch Intern Med. 2001;161(10):1351-1352.
EXTRACT
| FULL TEXT
RELATED ARTICLE
Archives of Internal Medicine Reader's Choice: Continuing Medical Education
Arch Intern Med. 2000;160(21):3332-3333.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Acute Febrile Respiratory Illness in the ICU: Reducing Disease Transmission
Sandrock and Stollenwerk
Chest 2008;133:1221-1231.
ABSTRACT
| FULL TEXT
Emerging Pathogens: Challenges and Successes of Molecular Diagnostics
Dong et al.
J. Mol. Diagn. 2008;10:185-197.
ABSTRACT
| FULL TEXT
Acute respiratory infections and winter pressures on hospital admissions in England and Wales 1990-2005
Elliot et al.
J Public Health (Oxf) 2008;30:91-98.
ABSTRACT
| FULL TEXT
Pathogen-directed Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Martinez
Proc Am Thorac Soc 2007;4:647-658.
ABSTRACT
| FULL TEXT
Pandemic flu: clinical management of patients with an influenza-like illness during an influenza pandemic
Lim
Thorax 2007;62:1-46.
FULL TEXT
Prevention of Antigenically Drifted Influenza by Inactivated and Live Attenuated Vaccines
Ohmit et al.
NEJM 2006;355:2513-2522.
ABSTRACT
| FULL TEXT
Acute Bronchitis
Wenzel and Fowler
NEJM 2006;355:2125-2130.
FULL TEXT
Effectiveness of half-dose versus full-dose influenza vaccine in health care workers.
Kramer et al.
Am J Health Syst Pharm 2006;63:2111-2115.
ABSTRACT
| FULL TEXT
Recommendations for the management of cough in adults
Morice et al.
Thorax 2006;61:i1-i24.
FULL TEXT
Risk and predictors of fatigue after infectious mononucleosis in a large primary-care cohort
Petersen et al.
QJM 2006;99:49-55.
ABSTRACT
| FULL TEXT
Chronic Cough Due to Acute Bronchitis: ACCP Evidence-Based Clinical Practice Guidelines
Braman
Chest 2006;129:95S-103S.
ABSTRACT
| FULL TEXT
Reduction of Inappropriate Hospital Admissions of Children With Influenza-Like Illness Through the Implementation of Specific Guidelines: A Case-Controlled Study
De Marco et al.
Pediatrics 2005;116:e506-e511.
ABSTRACT
| FULL TEXT
Neuraminidase inhibitors for influenza.
Moscona
NEJM 2005;353:1363-1373.
FULL TEXT
Does This Patient Have Influenza?
Call et al.
JAMA 2005;293:987-997.
ABSTRACT
| FULL TEXT
Clinical Predictors of Influenza in Children
Friedman and Attia
Arch Pediatr Adolesc Med 2004;158:391-394.
ABSTRACT
| FULL TEXT
A Systematic Review of the History and Physical Examination to Diagnose Influenza
Ebell et al.
J Am Board Fam Med 2004;17:1-5.
ABSTRACT
| FULL TEXT
Accuracy of Screening for Inhalational Anthrax after a Bioterrorist Attack
Hupert et al.
ANN INTERN MED 2003;139:337-345.
ABSTRACT
| FULL TEXT
Comparison of the Directigen Flu A+B Test, the QuickVue Influenza Test, and Clinical Case Definition to Viral Culture and Reverse Transcription-PCR for Rapid Diagnosis of Influenza Virus Infection
Ruest et al.
J. Clin. Microbiol. 2003;41:3487-3493.
ABSTRACT
| FULL TEXT
{blacktriangledown}Oseltamivir for influenza
DTB 2002;40:89-91.
ABSTRACT
| FULL TEXT
Influenza Burden of Illness: Estimates From a National Prospective Survey of Household Contacts in France
Carrat et al.
Arch Intern Med 2002;162:1842-1848.
ABSTRACT
| FULL TEXT
Evaluation of the Directigen FluA+B Test for Rapid Diagnosis of Influenza Virus Type A and B Infections
Chan et al.
J. Clin. Microbiol. 2002;40:1675-1680.
ABSTRACT
| FULL TEXT
Role of Picornaviruses in Flu-Like Illnesses of Adults Enrolled in an Oseltamivir Treatment Study Who Had No Evidence of Influenza Virus Infection
Boivin et al.
J. Clin. Microbiol. 2002;40:330-334.
ABSTRACT
| FULL TEXT
Considerations for Distinguishing Influenza-like Illness From Inhalational Anthrax
JAMA 2001;286:2537-2539.
FULL TEXT
Influenza Vaccination for Healthy Young Adults
Ahmed et al.
NEJM 2001;345:1543-1547.
FULL TEXT
Diagnosis of Influenza in the Community: Relationship of Clinical Diagnosis to Confirmed Virological, Serologic, or Molecular Detection of Influenza
Zambon et al.
Arch Intern Med 2001;161:2116-2122.
ABSTRACT
| FULL TEXT
Clinical Signs and Symptoms Predicting Influenza Infection
Hak et al.
Arch Intern Med 2001;161:1351-1352.
FULL TEXT
Clinical Predictors of Influenza Infection
JWatch General 2000;2000:5-5.
FULL TEXT
|
