George Theocharis,1, MD, Evridiki K. Vouloumanou,2, MD, Petros I. Rafailidis,2,3, MD, MRCP UK, MSc, Matthew E. Falagas,2,3,4, MD, MSc, DSc
1. SOS Doctors, Athens, Greece
2. Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece
3. Department of Medicine, Henry Dunant Hospital, Athens, Greece
4. Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA
Corresponding author: Matthew E. Falagas, MD, MSc, DSc
Alfa Institute of Biomedical Sciences (AIBS),
9 Neapoleos Street, 151 23 Marousi, Athens, Greece
Tel: +30 (694) 611-0000,
Fax: +30 (210) 683-9605
E-mail: [email protected]
Short title: Direct test for seasonal influenza in outpatients.
Conflict of interest: None
Word counts: abstract:, text:
Number of tables: 3
Number of figures: 0
Number of references: 25
Influenza is an important clinical entity with significant morbidity and mortality. The use of a rapid direct test during seasonal influenza and during the currents A/H1N1 pandemic may aid considerably in the early detection of influenza cases and consequently enable a proper treatment.
To present our experience regarding the use of a rapid diagnostic test for seasonal influenza A and B.
We systematically collected and analyzed our data on the use of a rapid diagnostic test for seasonal influenza A and B in patients with specific respiratory symptoms that sought medical services from a network of doctors that performs house-call visits in the area of Attica, Greece.
The visiting physicians prescribed significantly more anti-influenza agents (oseltamivir) to patients that were tested for influenza, compared to the patients that were not tested. Moreover, significantly more anti-influenza agents, but significantly fewer antibiotics were prescribed to patients that had a positive test result for Influenza A or B, compared to patients that had a negative test result. No difference was found regarding the number of hospitalizations in any of the performed comparisons.
The use of a rapid diagnostic test for seasonal influenza A and B in patients with specific respiratory symptoms that sought medical services from a specific network of doctors that performs house-call visits in the area of Attica, Greece encourages the targeted use of anti-influenza treatment, as well as in a reduction of unnecessary antibiotic treatment in patients with a positive test for influenza.
influenza, diagnostic test, antiviral treatment, oseltamivir, swine flu
Influenza is an important clinical entity with significant morbidity and mortality.1-3 Influenza is also a significant burden in the community as it is associated with both increased direct medical costs from excess hospitalizations, drug prescriptions, and outpatient visits,4,5 as well as indirect costs from work or school absenteeism and reduced production capacity.6,7
The clinical symptoms of influenza tend to overlap with the symptoms of other respiratory, mainly viral infections, in pediatric and adult populations.8-10 This makes the clinical diagnosis of influenza problematic. As a result, a rapid test that enables the early recognition of patients with influenza has many advantages, including the prevention of unnecessary antibiotic prescriptions, hospitalizations, and influenza transmission, and also the economic burden of influenza. In addition, early diagnosis of influenza may enable a proper use of antiviral agents. Literature provides evidence of the use of rapid direct tests for detection of influenza in patients with respiratory symptoms in various settings, mainly in pediatric populations.11-18
In the current A/H1N1 pandemic, the use of a rapid direct test may aid considerably in the early detection of influenza cases and consequently enable a proper treatment. In this study we aimed to systematically collect and analyze our data on the use of a rapid diagnostic test for seasonal influenza A and B in patients with specific respiratory symptoms that sought medical services from a network of doctors that performs house-call visits in the area of Attica, Greece.
Eligible patients for inclusion in this study were patients of all ages that sought medical services from the SOS doctors in Attica, Greece during the time period from 01/01/2009 to 30/05/2009. Eligible patients were the patients that complained for respiratory/influenza-like symptoms such as fever >38oC, cough, sore throat, nasal discharge, muscles aches, headache, or fatigue at the discretion of the physician.
Specimens’ collection and testing procedure
A nasal swab was obtained during the house-call visit from the visiting physician from the eligible patients. The test used was the “Influ A&B Uni-Strip – Dry Swabs (C-1512)” test, which is manufactured by Coris BioConcept (http://www.corisbio.com). Specifically, this test is an acute-phase screening test that allows detection of both Influenza A and B in liquid swabs as it consists of two sides sensitized with a monoclonal antibody specific for influenza A and B, respectively. Directly after sampling the nasal swab was dipped in 15 droplet or in 500 μL of DS buffer. The Influ A&B Uni-Strip test was then dipped directly into this solution. After 15 minutes of incubation the results were read on wet strips.
Interpretation of the test results
For each of the two sides of the device, if 1 line (upper) appeared, the test was considered as negative, if 2 lines appeared; the test was considered as positive. If no line appeared, the test was considered as invalid and the sample wad retested.
To the introduction of the rapid test for influenza as an additional diagnostic tool that enables the differentiation of patients with influenza from those who don’t have influenza, and consequently aids in clinical decision making, the SOS doctors (pathologists, in particular) responded as follows: a) a group of doctors decided to use the test systematically (Group A), b) a group of doctors used the test occasionally (in less than 15% of the respective house-calls) (Group B) and c) a group of doctors didn’t use the test at all (Group C). The visiting physician was aware of the results of the influenza test performed during each house-call visit. The decision regarding the patient’s treatment was left at the discretion of the visiting physician. Specifically, the treatment options were: treatment with anti-influenza agents, antibiotic treatment, symptomatic therapy or the appropriate combinations. The follow up of the patients included in the study was performed through a phone communication with the patient.
Data collection and analysis
We prospectively collected, during the evaluated period, data regarding the patient’s name, age (years), location and cause of the call, the visiting doctor’s name, the result of the influenza test (positive/negative; influenza A/B in case of a positive result), the treatment prescribed (antibiotic/antiviral/symptomatic/other or combinations), immediate hospitalization (at the same day with the house-call visit), as well as time to defervescence (days after treatment’s institution/visit).
regarding the number of anti-influenza agents and antibiotics prescribed, as well as the number of hospitalizations between the patients who were tested for influenza and those who were not tested for influenza were performed. The respective comparisons between the subgroups of patients with a positive and those with a negative influenza test were also performed. All comparisons were performed with the use of the OpenEpi software.19
During the study period the network of SOS doctors performed a total of 16.335 house-call visits. The cause for 3412 (20.8%) of these 16.335 calls was a complain for respiratory/influenza-like symptoms. Eight hundred and twenty three (24.1%) of these 3412 house-call visits were performed from doctors constituting Group A, 1181 (34.6%) house-call visits were performed from doctors constituting Group B, and the remaining 1408 (41.2%) house-call visits were performed from doctors constituting Group C (data are presented in Table 1.)
One hundred ninety seven patients (5.7%) of the 3412 patients seen with respiratory/influenza-like symptoms seen in the respective 3412 house-call visits were tested with the direct influenza test. Data regarding the number of patients tested per group of doctors are presented in Table 1. In addition, specific data regarding the demographic characteristics, diagnosis, treatment prescribed, time to defervescence, and immediate hospitalizations for all the evaluated patients are presented in Table 2.
The main finding of our study is that the use of a rapid direct diagnostic test for seasonal Influenza A and B from a network of doctors performing house-call visits in the area of Attica, Greece resulted in more prescriptions for anti-influenza agents (oseltamivir) to patients to whom the test was performed in comparison to patients to whom the test was not performed. Similarly, more anti-influenza agents but fewer antibiotics were prescribed to patients that had a positive influenza test in comparison to those that had a negative test. No difference was found regarding the number of immediate hospitalizations was found in both of the performed comparisons.
The accuracy of rapid direct diagnostic tests to detect seasonal influenza has already been evaluated in several studies that referred mainly to pediatric populations. The reported specificities were relatively high in comparison with the reference standard tests, whereas the reported sensitivities varied considerably.15,20-22 Additionally, a considerable number of studies have also evaluated the impact of the use of a rapid influenza test on physicians’ decision making, and patients’ management. Specifically, according to these studies the use of the rapid influenza test in patients with influenza-like illness resulted in decreased further diagnostic tests and examinations, and consequently decreased medical associated costs.11-14,23 Moreover, the use of a rapid influenza test decreased the number of antibiotic prescriptions.12,14 Similarly, in our study, the number of antibiotics prescribed to patients with a positive test for influenza was significantly lower compared to those prescribed to patients with a negative test for influenza. In this era of alarmingly increasing antibiotic resistance rates, the reduction of unnecessary antibiotic treatment (such as in patients with viral infections) is an issue of major importance in terms of both personal and public health perspectives.
In our study, the number of anti-influenza agents prescribed to patients that were tested for influenza was higher compared to those that were not tested. Similarly, the number of anti-influenza agents prescribed to patients that had a positive test either for Influenza A, or B was significantly higher compared to those that had a negative test for influenza. These findings imply that the use of a rapid test and the awareness of a positive test for influenza resulted in a targeted prescription of anti-influenza agents to patients with influenza-like symptoms in this specific clinical setting.
The use of a rapid direct influenza test enables a timely and proper use of antiviral treatment, and simultaneously a reduction of unnecessary antibiotic treatment. Yet, one may consider that the use of rapid influenza test might potentially lead to overperscription of antivirals. This may result in the emergence of viral strains that are resistant to the available antiviral agents.24 Specifically, regarding the seasonal influenza during the evaluated period (winter 2009) in European countries, a considerably high rate of A/H1N1 viral strains (98%) resistant to oseltamivir was detected.25 The above considerations become even more important in the current A/H1N1 pandemic where the emergence of A/H1N1 strains resistant to oseltamivir may narrow our armamentarium against this virus. However, the use of rapid direct test could potentially be a useful tool for the detection of swine flu cases that will enable the proper antiviral treatment as well as the detection of swine flu outbreaks in specific clinical settings. Even though the specific test used in our study is capable of detecting A/H1N1 swine flu cases (http://www.corisbio.com), no swine flu case was detected in our study population. Notably, the 1st swine flu case in was reported at May 18, 2009; the evaluated period of our study was from 01/01/2009 to 30/05/2009.
In conclusion, our experience with the use of a rapid diagnostic test for seasonal influenza A and B in patients with specific respiratory symptoms that sought medical services from a specific network of doctors that performs house-call visits in the area of Attica, Greece indicates that the use of the rapid influenza test resulted in a targeted use of anti-influenza agents, as well as in a reduction of unnecessary antibiotic treatment in patients that had a positive test for influenza. In this regard, a rapid direct diagnostic test could be a useful tool during seasonal influenza and the current A/H1N1 pandemic.
1. Dushoff J, Plotkin JB, Viboud C, Earn DJ, Simonsen L. Mortality due to influenza in the United States--an annualized regression approach using multiple-cause mortality data. Am J Epidemiol 2006;163:181-7.
2. Reichert TA, Simonsen L, Sharma A, Pardo SA, Fedson DS, Miller MA. Influenza and the winter increase in mortality in the United States, 1959-1999. Am J Epidemiol 2004;160:492-502.
3. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003;289:179-86.
4. Assink MD, Kiewiet JP, Rozenbaum MH, et al. Excess drug prescriptions during influenza and RSV seasons in the Netherlands: Potential implications for extended influenza vaccination. Vaccine 2008.
5. Neuzil KM, Mellen BG, Wright PF, Mitchel EF, Jr., Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000;342:225-31.
6. Keech M, Beardsworth P. The impact of influenza on working days lost: a review of the literature. Pharmacoeconomics 2008;26:911-24.
7. Neuzil KM, Hohlbein C, Zhu Y. Illness among schoolchildren during influenza season: effect on school absenteeism, parental absenteeism from work, and secondary illness in families. Arch Pediatr Adolesc Med 2002;156:986-91.
8. Bellei N, Carraro E, Perosa A, Watanabe A, Arruda E, Granato C. Acute respiratory infection and influenza-like illness viral etiologies in Brazilian adults. J Med Virol 2008;80:1824-7.
9. Call SA, Vollenweider MA, Hornung CA, Simel DL, McKinney WP. Does this patient have influenza? JAMA 2005;293:987-97.
10. Simoes EA. Overlap between respiratory syncytial virus infection and influenza. Lancet 2001;358:1382-3.
11. Abanses JC, Dowd MD, Simon SD, Sharma V. Impact of rapid influenza testing at triage on management of febrile infants and young children. Pediatr Emerg Care 2006;22:145-9.
12. Benito-Fernandez J, Vazquez-Ronco MA, Morteruel-Aizkuren E, Mintegui-Raso S, Sanchez-Etxaniz J, Fernandez-Landaluce A. Impact of rapid viral testing for influenza A and B viruses on management of febrile infants without signs of focal infection. Pediatr Infect Dis J 2006;25:1153-7.
13. Bonner AB, Monroe KW, Talley LI, Klasner AE, Kimberlin DW. Impact of the rapid diagnosis of influenza on physician decision-making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial. Pediatrics 2003;112:363-7.
14. Esposito S, Marchisio P, Morelli P, Crovari P, Principi N. Effect of a rapid influenza diagnosis. Arch Dis Child 2003;88:525-6.
15. Grijalva CG, Poehling KA, Edwards KM, et al. Accuracy and interpretation of rapid influenza tests in children. Pediatrics 2007;119:e6-11.
16. Poehling KA, Zhu Y, Tang YW, Edwards K. Accuracy and impact of a point-of-care rapid influenza test in young children with respiratory illnesses. Arch Pediatr Adolesc Med 2006;160:713-8.
17. Rodriguez WJ, Schwartz RH, Thorne MM. Evaluation of diagnostic tests for influenza in a pediatric practice. Pediatr Infect Dis J 2002;21:193-6.
18. Rothberg MB, Fisher D, Kelly B, Rose DN. Management of influenza symptoms in healthy children: cost-effectiveness of rapid testing and antiviral therapy. Arch Pediatr Adolesc Med 2005;159:1055-62.
19. Dean A, Sullivan K, Soe M. OpenEpi: Open Source Epidemiologic Statistics for Public Health, Version 2.2.1. Updated 2008/04/06 [cited 2008/09/18]; Available from: www.OpenEpi.com.
20. Agoritsas K, Mack K, Bonsu BK, Goodman D, Salamon D, Marcon MJ. Evaluation of the Quidel QuickVue test for detection of influenza A and B viruses in the pediatric emergency medicine setting by use of three specimen collection methods. J Clin Microbiol 2006;44:2638-41.
21. Uyeki TM. Influenza diagnosis and treatment in children: a review of studies on clinically useful tests and antiviral treatment for influenza. Pediatr Infect Dis J 2003;22:164-77.
22. Uyeki TM, Prasad R, Vukotich C, et al. Low sensitivity of rapid diagnostic test for influenza. Clin Infect Dis 2009;48:e89-92.
23. Poehling KA, Griffin MR, Dittus RS, et al. Bedside diagnosis of influenzavirus infections in hospitalized children. Pediatrics 2002;110:83-8.
24. Weinstock DM, Zuccotti G. The evolution of influenza resistance and treatment. JAMA 2009;301:1066-9.