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ScienceDirect www.sciencedirect.com Médecine et maladies infectieuses 44 (2014) 123–127
Short communication
Contribution of systematic RT-PCR screening for influenza during the epidemic season Intérêt du dépistage systématique de grippe en période épidémique par RT-PCR M. Martinot a,∗,1,2,4 , R. Heller b,c,3,4 , A. Martin a,2,4 , E. Sagot a,2,4 , L. Souply b,c,3,4 , A. Mothes a,2,4 , M. Mohseni-Zadeh a,2,4 , D. de Briel b,c,3,4 a
Service de médecine E, hôpital Pasteur, 39, avenue de la Liberté, 68000 Colmar, France b Service d’hygiène hospitalière, hôpital Pasteur, 68000 Colmar, France c Service de microbiologie, hôpital Pasteur, 68000 Colmar, France
Received 13 September 2013; received in revised form 11 December 2013; accepted 28 January 2014 Available online 4 March 2014
Abstract Objective. – We assessed the systematic RT-PCR screening of patients admitted to an infectious diseases department (IDD), during the 2012–2013 influenza outbreak. Methodology. – Patients admitted with cough and fever underwent a nasopharyngeal smear for RT-PCR screening. Results. – Ninety-eight patients were admitted in the IDD, from January 1st to February 22nd, 46 were screened; 11 male and 6 female patients (17.3%, mean age of 68 years) were positive. The diagnoses made in the emergency department, before RT-PCR screening, were most frequently lung infection and sepsis, but influenza in only 4 cases. The diagnosis of influenza led to stopping antibiotics (n = 4), initiating curative (n = 4) and preventive (n = 4) treatments with oseltamivir, and isolating patients to prevent a hospital outbreak. Conclusion. – Systematic RT-PCR screening allows a rapid therapeutic management and the prevention of hospital epidemic through appropriate isolation measures. © 2014 Elsevier Masson SAS. All rights reserved. Keywords: Influenza; Screening; PCR
Résumé Objectif. – Nous avons évalué l’intérêt d’un dépistage systématique par RT-PCR à l’admission dans une unité d’infectiologie. Méthodologie. – Toute personne admise au service avec toux et fièvre bénéficiait d’un frottis rhinopharyngé pour RT-PCR. Résultats. – En 2 mois, 98 admissions ont été réalisées en service d’infectiologie, 46 patients ont bénéficié d’un dépistage avec 17 résultats positifs (17,3 %) chez 11 hommes et 6 femmes d’âge moyen 68 ans. Les diagnostics issus du service d’urgence avant RT-PCR comportaient la mention d’infections pulmonaires ou sepsis (grippe dans seulement 4 cas). Le diagnostic de grippe a permis des arrêts d’antibiothérapie (n = 4), la mise en place de traitements curatifs (n = 4) et préventifs par oseltamivir (n = 4), un isolement des patients et ainsi la prévention d’épidémie hospitalière. Conclusion. – Le dépistage systématique par RT-PCR autorise une prise en charge thérapeutique rapide des patients et la prévention d’épidémie hospitalière notamment par le biais de mesures d’isolement adaptées. © 2014 Elsevier Masson SAS. Tous droits réservés. Mots clés : Grippe ; Dépistage ; PCR
∗ 1 2 3 4
Corresponding author. E-mail address: [email protected] (M. Martinot). M. Martinot wrote the study protocol, coordinated its implementation, and wrote the article. M. Martinot, M. Mohseni Zadeh, A. Mothes, A. Martin, and E. Sagot managed the study inclusions. R. Heller, L. Souply, and D. de Briel performed the study’s biological analyses. All the authors participated in the validation and proofreading of the article.
0399-077X/$ – see front matter © 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.medmal.2014.01.011
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M. Martinot et al. / Médecine et maladies infectieuses 44 (2014) 123–127
1. Objective Influenza is a contagious viral disease affecting 5 to 10% of the world population, complicated by a significant morbidity and mortality and responsible for outbreaks in healthcare departments [1]. The prevention relies first on vaccination of populations at risk and healthcare personnel, the vaccinal coverage remains insufficient and strategies for the screening of hospitalized patients allowing droplet isolation and adapted treatments should improve the management of this disease in healthcare units [1]. We assessed the systematic RT-PCR screening of patients admitted to an infectious diseases department (IDD), during the 2012–2013 influenza outbreak.
with influenza by RT-PCR; antibiotherapy was stopped early (in the 24 hours following admission) in 4 cases. Antibiotherapy was maintained for the 10 other patients because of pulmonary bacterial superinfection (5 patients), an associated infection (4 patients including 1 with sinusitis, 2 urinary tract infections, and 1 with enterococcal septicemia); antibiotherapy was stopped for 1 patient at 48 hours. A curative treatment by oseltamivir was initiated for 4 patients for patients with a delay after onset inferior to 48 hours. Four patients not diagnosed with influenza before RTPCR were initially hospitalized in double-bedrooms, creating 4 contact patients for whom a preventive oseltamivir treatment was initiated. Isolation and/or cohorting of patients presenting with influenza diagnosed by RT-PCR was performed. No secondary case was diagnosed during the study period.
2. Patients and method 4. Discussion Patients admitted to the IDD presenting with cough and fever were screened for influenza. Fever was documented by anamnestic data or on axillary temperature >38 ◦ C. A nurse performed the nasopharyngeal smear (swab and Virocult® transport medium). The smears collected in the morning were processed on the same day, those collected in the afternoon the morning after. RT-PCR was not available on Sundays, so smears collected on Saturday afternoon or Sundays were analyzed on Monday morning. The analysis included extraction of nucleic acids made by the auto mated “NucliSenseasyMAG® by Biomérieux, and the RT-PCR amplification on the same day same with duplex detection by TaqMan® hydrolysis probes of genes encoding the matrix proteins M of influenza A and B viruses (kit Influenza A/B r-gene® by Argene). This technique used a Cell control r-gene® warranting the quality of the sample by preventing false negatives (pauci-cellular samples). 3. Results Ninety-eight patients were admitted to the IDD (a 16-bed unit) from January 1st, 2013 to February 22nd, 2013. Fifty-one patients presented with respiratory symptoms and fever but only 46 patients underwent the screening with 17 positive results (36.9% of patients tested and 17.3% of admissions) (Fig. 1). Eleven male and 6 female patients presented with influenza (mean age of 68 years, range 25 to 90 years of age), 15 cases of influenza A and 2 of influenza B. The diagnoses made in the emergency department (ED) for the 17 patients, before RTPCR screening, were most frequently lung infection (sepsis from a pulmonary focus, pneumonia, or exacerbation of chronic bronchitis, 6 patients), influenza syndrome (4 patients), sepsis (2 patients), headaches (1 patient), lumbalgia (1 patient), fall (1 patient), infective endocarditis (1 patient), alteration of the global health status with gastroenteritis and dehydration (1 patient) (Table 1). The vaccinal status for influenza was vaccinated (4 patients), not vaccinated (8 patients), unknown (5 patients). RT-PCR results for patients with influenzas were obtained on the day of admission in 6 cases, the morning after in 8 cases, and within 48 hours in 3 cases, with a median delay before results of 1 day (interquartile range 0–1 day). Fourteen patients were treated with antibiotics when they were diagnosed
The epidemic threshold was reached during 11 weeks during the 2012–2013 influenza outbreak (end of December to beginning of March) with a peak at the end of January and beginning of February, and a higher incidence than in the 2 previous seasons: 10.2 million consultations compared to 3.5 in 2011–2012, and 6.7 in 2010–2011 [2]. This high epidemic was not unusual. All age ranges were concerned. This outbreak featured co-circulation of 3 types and subtypes (B, A H1N1, and A H3N2; type B was predominant). Unexpectedly, our patients were infected most frequently by type A viruses. All patient with respiratory signs of the infectious origin are supposed to be put in droplet isolation [3], but these recommendations are difficult to implement because of the frequency of these symptoms, because of the unit set-ups (numerous small double-bed rooms, etc.) especially during influenza outbreaks. A targeted screening for influenza in the hospital seems to be necessary because of an insufficient vaccinal coverage both for patients [4] and for healthcare personnel [5]. The American recommendations are to systematically screen all hospitalized patients presenting with influenza symptoms, using RT-PCR if possible [6]. This allows for early treatment but also for the prevention of secondary cases and of outbreaks in healthcare units. RT-PCR is the recommended method because commercial rapid diagnostic tests for influenza lack sensitivity (40 to 90%) [6]. Screening by RT PCR is more expensive (the cost of the “Influenza A/B r-gene® kit reagent for our institution was 395 D “Hors Taxe” for 60 tests, for 50 patient, tests to which was added 209 D for cell control “Cell control r-gene® for 100 tests); it is more complex and slower than commercial rapid diagnostic test for influenza but it is significantly more sensitive. We were able to implement daily screening during the epidemic period 6 days a week, with a median delay for results of 1 day (interquartile range 0–1 day), allowing for a quick therapeutic adjustment (initiating oseltamivir, stopping antibiotherapy) and an early implementation of adapted isolation measures. Four patients only were given oseltamivir as curative treatment, since we had restricted indications for patients with a delay after onset inferior to 48 hours; conversely the American recommendations allow treatment of patients hospitalized for more than 48 hours, independently of the presence of severity signs [6]. The contribution of a curative
Table 1 Main clinical and laboratory data for 17 patients presenting with influenza. Principales données cliniques et biologiques des 17 patients grippés. Patients
Cause of the admission
History
T in ◦ C CRP (mg/l) PCT (ng/l)
Final diagnosis
Antibiotics
Stop
Oseltamivir
M, 80 years of age
Sepsis
Post-AHT cardiopathy, AFCA, ECOBP, colon cancer
Superinfected influenza A EBPCO
Amox–clavac
D1
No
7
M, 81 years of age
Sepsis from a pulmonary focus
Dementia, DMT2, prostatic adenocarcinoma, ECOBP
D8
Yes
2
Dehydration gastroenteritis
Crohn’s disease ileostomy
No
–
No
6
F, 84 years of age
Headaches, inflammatory syndrome
DMT2, HTA, dementia
Superinfected influenza A to Haemophilus EBPCO Influenza A Dehydration Influenza A Maxillary sinusitis
Amox–clavac
F, 44 years of age
Amox–clavac
D5
No
8
F, 63 years of age
Sepsis
DMT2, HTA, ischemic cardiopathy
Superinfected influenza A
Amox–clavac
D5
No
6
M, 71 years of age
EBPCO, dyspnea
HTA, ECOBP
Superinfected influenza A
Amox–clavac
D6
No
10
M, 76 years of age
Endocarditis, fever, rash
Influenza A Toxidermia
Amox–clavac
D0
No
4
M, 68 years of age
Influenza A Enterococcal prostatitis Superinfected influenza A Escherichia coli UTI Influenza A Clostridium difficile colitis
Teicoplanin
D21
No
9
Ceftriaxone then cefixim Amox–clavac Metronidazole
D14
Yes
12
F, 90 years of age
Acute community acquired pneumonia Sepsis from a pulmonary and urinary tract focus Aspiration pneumonia
HTA, AFCA, ischemic cardiopathy, LLC, valvular prosthesis AFCA, ECOBP, ischemic cardiopathy, DMT2 DMT2, HTA, dementia
39 CRP: 75 PCT: 0.15 40 CRP: 137 PCT: 0.2 Home CRP: 2 Home CRP: 183 PCT: 0.17 38.5 CRP: 183 PCT: 0.6 Home CRP: 163 PCT: 0.17 38.5 CRP: 32
D1D10
No
9
M, 86 years of age
Influenza
DMT2, vesical adenocarcinoma
Influenza A
Amox–clavac
D1
No
4
M, 25 years of age
Lumbalgia
–
Influenza A
Ceftriaxone
D2
No
3
F, 63 years of age
Dyspnea, influenza
HTA, ischemic cardiopathy
Influenza A
No
–
No
4
M, 39 years of age
Fall and head trauma
multi-operated cholesteatoma
Cefotaxime
D3
No
8
M, 35 years of age
Influenza
–
Influenza B Meningeal hemorrhage Petrous bone fracture Influenza A
No
–
Yes
1
M, 78 years of age
Sepsis from a pulmonary focus
D20
No
19
Influenza, EBPCO
Influenza B Enterococcal septicemia Angiocholitis Superinfected influenza A
Teicoplanine
M, 90 years of age
Caroli disease with biliary and digestive derivation, angiocholitis ECOBP, dementia, ischemic cardiopathy
Amox–clavac
D5
Yes
15
HTA, dementia
39.2 CRP: 127 PCT: 0.35 38.2 CRP: 116 PCT: 1.78 38 CRP: 40 PCT: 0.28
125
T: temperature; M: male; F: female; ECOBP: exacerbation of chronic obstructive bronchopneumonia; AHT: arterial hypertension; DMT2: diabetes mellitus type 2; CLL: chronic lymphoid leukemia; home: fever at home; amox–clavac: amoxicillin–clavulanic acid; DS: duration of hospital stay in days; UTI: urinary tract infection.
M. Martinot et al. / Médecine et maladies infectieuses 44 (2014) 123–127
F, 90 years of age
Home CRP: 53 39 CRP: 69 38 CRP: 127 PCT: 5.61 38.2 CRP: 43 39 CRP: 144 PCT: 0.28 Home CRP: 2 38.2 CRP: 67
DS
126
M. Martinot et al. / Médecine et maladies infectieuses 44 (2014) 123–127
98 paents hospitalized
Respiratory signs and fever
YES
NO
No screening Screening by
5 paents not screened n=47
rhino-pharyngeal swab and RT-PCR n=46
17 posive results
29 negave results
15 for influenza A 2 for influenza B
Fig. 1. Screening strategy for flu among hospitalized patients. Stratégie de dépistage de grippe des patients hospitalisés.
treatment with neuraminidase inhibitors remains controversial [7]. Furthermore, preventive treatment, presumed to be more effective [7], of contact patients in hospitals or even outside of hospitals may be initiated. Many patients transferred from the emergency department were not identified as presenting with influenza, a common case because of atypical clinical presentations, especially in the geriatric patients, or because of associated superinfections [8]. It was important to be ready to use screening in healthcare departments during the epidemic period because of the low vaccinal coverage and the partial effectiveness of this vaccination [1,4,9,10]. There are currently no French guidelines recommending the systematic screening for influenza in healthcare departments outside of outbreaks [8]. Using RT-PCR for a systematic screening for influenza during the epidemic has a cost/effectiveness ratio, which is difficult to assess but which may seem positive for some authors [11], especially for aged patients. Its use in more limited hospital settings allows managing a smaller number of patients, often aged and presenting with many chronic diseases, for whom the cost/effectiveness ratio was more favorable. Our study has several limitations due to the method used and the results: small number of patients included, small number
of curative treatments with oseltamivir and with a disputable effectiveness, reduced number of antibiotherapy interruptions because of suspected bacterial superinfections or of associated infections, delay before obtaining RT-PCR result still too long, and finally 10% of patients with cough and fever who were not screened. But it allowed determining how frequently patients not identified as presenting with influenza were hospitalized during the epidemic period; and it highlighted the contribution of rapid screening for the implementation of droplet isolation, and preventive treatment of contact cases so as to prevent outbreaks in healthcare departments. The RT-PCR tests are highly sensitive but the delay before results, its availability, and cost should be improved. Other tests, not available in our institution, could be used for the screening: Multiplex PCR has for advantage to allow screening for several pathogenic agents, or molecular testing for a single pathogen made by an automated device, especially for hospitals without any molecular biology unit. Using sensitive tests (PCR), which can be performed rapidly with results that come back in the hours following patient admission, seems to be necessary for a strategy of hospital outbreak prevention.
M. Martinot et al. / Médecine et maladies infectieuses 44 (2014) 123–127
5. Conclusion Influenza was diagnosed in 17.3% of patients admitted to our unit during the epidemic period. The diagnosis is often not made because of terrain, of a sometimes atypical clinical presentation, and of possible superinfections. During the epidemic period, RTPCR, more sensitive than commercial rapid diagnostic tests for influenza, is a reliable method for the diagnosis of influenza, ensuring a better management, and allowing prevention of outbreaks in healthcare departments, especially by implementing droplet isolation rapidly. Disclosure of interest
[5]
[6]
[7]
[8]
The authors declare that they have no conflicts of interest concerning this article. [9]
References [1] Sydnor ER, Perl TM. Hospital epidemiology and infection control in acutecare settings. Clin Microbiol Rev 2011;24(1):141–73. [2] GROG. Bilan de la saison grippale 2012/2013. Bulletin GROG 2013 [accédé le 10 décembre 2013] http://www.grog.org/cgi-files/ db.cgi?action=bulletin grog [3] Société franc¸aise d’hygiène hospitalière. Recommandations nationales. Prévention de la transmission croisée par voie respiratoire : air ou gouttelettes. Recommandations pour la pratique clinique. Hygienes 2013;21(1):1–53. [4] Privileggio L, Falchi A, Grisoni ML, Souty C, Turbelin C, Fonteneau L, et al. Rates of immunization against pandemic and seasonal influenza in persons at high risk of severe influenza illness: a cross-sectional study
[10]
[11]
127
among patients of the French Sentinelles general practitioners. BMC Public Health 2013;13:246. Guthmann JPAD. Vaccination chez les soignants des établissements de soins, France. Couverture vaccinale, connaissances et perception des vaccinations, rapport final. Saint-Maurice: Institut de veille sanitaire; 2011 http://www.invs.sante.fr Harper SA, Bradley JS, Englund JA, File TM, Gravenstein S, Hayden FG, et al. Seasonal influenza in adults and children – diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48(8):1003–32. Michiels B, Van Puyenbroeck K, Verhoeven V, Vermeire E, Coenen S. The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews. PLoS One 2013;8(4):e60348. Haut Conseil de la santé publique. Conduite à tenir devant une ou plusieurs infections respiratoires aiguës dans les collectivités de personnes âgées; 2012 [accédé le 10 décembre 2013] http://www.hcsp.fr/Explore.cgi/ avisrapportsdomaine?clefr=288 Falchi A, Souty C, Grisoni ML, Mosnier A, Hanslik T, Daviaud I, et al. Field seasonal influenza vaccine effectiveness: evaluation of the screening method using different sources of data during the 2010/2011 French influenza season. Hum Vaccin Immunother 2013;9(11): 2453–9. Kissling E, Valenciano M, Larrauri A, Oroszi B, Cohen JM, Nunes B, et al. Low and decreasing vaccine effectiveness against influenza A(H3) in 2011/12 among vaccination target groups in Europe: results from the I-MOVE multicentre case-control study. Euro Surveill 2013;18(5) [PII: 20390. Available online: http://www.eurosurveillance.org/ViewArticle. aspx?ArticleId=20390]. Lee BY, McGlone SM, Bailey RR, Wiringa AE, Zimmer SM, Smith KJ, et al. To test or to treat? An analysis of influenza testing and antiviral treatment strategies using economic computer modeling. PLoS One 2010;5(6):e11284.
ScienceDirect www.sciencedirect.com Médecine et maladies infectieuses 44 (2014) 123–127
Short communication
Contribution of systematic RT-PCR screening for influenza during the epidemic season Intérêt du dépistage systématique de grippe en période épidémique par RT-PCR M. Martinot a,∗,1,2,4 , R. Heller b,c,3,4 , A. Martin a,2,4 , E. Sagot a,2,4 , L. Souply b,c,3,4 , A. Mothes a,2,4 , M. Mohseni-Zadeh a,2,4 , D. de Briel b,c,3,4 a
Service de médecine E, hôpital Pasteur, 39, avenue de la Liberté, 68000 Colmar, France b Service d’hygiène hospitalière, hôpital Pasteur, 68000 Colmar, France c Service de microbiologie, hôpital Pasteur, 68000 Colmar, France
Received 13 September 2013; received in revised form 11 December 2013; accepted 28 January 2014 Available online 4 March 2014
Abstract Objective. – We assessed the systematic RT-PCR screening of patients admitted to an infectious diseases department (IDD), during the 2012–2013 influenza outbreak. Methodology. – Patients admitted with cough and fever underwent a nasopharyngeal smear for RT-PCR screening. Results. – Ninety-eight patients were admitted in the IDD, from January 1st to February 22nd, 46 were screened; 11 male and 6 female patients (17.3%, mean age of 68 years) were positive. The diagnoses made in the emergency department, before RT-PCR screening, were most frequently lung infection and sepsis, but influenza in only 4 cases. The diagnosis of influenza led to stopping antibiotics (n = 4), initiating curative (n = 4) and preventive (n = 4) treatments with oseltamivir, and isolating patients to prevent a hospital outbreak. Conclusion. – Systematic RT-PCR screening allows a rapid therapeutic management and the prevention of hospital epidemic through appropriate isolation measures. © 2014 Elsevier Masson SAS. All rights reserved. Keywords: Influenza; Screening; PCR
Résumé Objectif. – Nous avons évalué l’intérêt d’un dépistage systématique par RT-PCR à l’admission dans une unité d’infectiologie. Méthodologie. – Toute personne admise au service avec toux et fièvre bénéficiait d’un frottis rhinopharyngé pour RT-PCR. Résultats. – En 2 mois, 98 admissions ont été réalisées en service d’infectiologie, 46 patients ont bénéficié d’un dépistage avec 17 résultats positifs (17,3 %) chez 11 hommes et 6 femmes d’âge moyen 68 ans. Les diagnostics issus du service d’urgence avant RT-PCR comportaient la mention d’infections pulmonaires ou sepsis (grippe dans seulement 4 cas). Le diagnostic de grippe a permis des arrêts d’antibiothérapie (n = 4), la mise en place de traitements curatifs (n = 4) et préventifs par oseltamivir (n = 4), un isolement des patients et ainsi la prévention d’épidémie hospitalière. Conclusion. – Le dépistage systématique par RT-PCR autorise une prise en charge thérapeutique rapide des patients et la prévention d’épidémie hospitalière notamment par le biais de mesures d’isolement adaptées. © 2014 Elsevier Masson SAS. Tous droits réservés. Mots clés : Grippe ; Dépistage ; PCR
∗ 1 2 3 4
Corresponding author. E-mail address: [email protected] (M. Martinot). M. Martinot wrote the study protocol, coordinated its implementation, and wrote the article. M. Martinot, M. Mohseni Zadeh, A. Mothes, A. Martin, and E. Sagot managed the study inclusions. R. Heller, L. Souply, and D. de Briel performed the study’s biological analyses. All the authors participated in the validation and proofreading of the article.
0399-077X/$ – see front matter © 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.medmal.2014.01.011
124
M. Martinot et al. / Médecine et maladies infectieuses 44 (2014) 123–127
1. Objective Influenza is a contagious viral disease affecting 5 to 10% of the world population, complicated by a significant morbidity and mortality and responsible for outbreaks in healthcare departments [1]. The prevention relies first on vaccination of populations at risk and healthcare personnel, the vaccinal coverage remains insufficient and strategies for the screening of hospitalized patients allowing droplet isolation and adapted treatments should improve the management of this disease in healthcare units [1]. We assessed the systematic RT-PCR screening of patients admitted to an infectious diseases department (IDD), during the 2012–2013 influenza outbreak.
with influenza by RT-PCR; antibiotherapy was stopped early (in the 24 hours following admission) in 4 cases. Antibiotherapy was maintained for the 10 other patients because of pulmonary bacterial superinfection (5 patients), an associated infection (4 patients including 1 with sinusitis, 2 urinary tract infections, and 1 with enterococcal septicemia); antibiotherapy was stopped for 1 patient at 48 hours. A curative treatment by oseltamivir was initiated for 4 patients for patients with a delay after onset inferior to 48 hours. Four patients not diagnosed with influenza before RTPCR were initially hospitalized in double-bedrooms, creating 4 contact patients for whom a preventive oseltamivir treatment was initiated. Isolation and/or cohorting of patients presenting with influenza diagnosed by RT-PCR was performed. No secondary case was diagnosed during the study period.
2. Patients and method 4. Discussion Patients admitted to the IDD presenting with cough and fever were screened for influenza. Fever was documented by anamnestic data or on axillary temperature >38 ◦ C. A nurse performed the nasopharyngeal smear (swab and Virocult® transport medium). The smears collected in the morning were processed on the same day, those collected in the afternoon the morning after. RT-PCR was not available on Sundays, so smears collected on Saturday afternoon or Sundays were analyzed on Monday morning. The analysis included extraction of nucleic acids made by the auto mated “NucliSenseasyMAG® by Biomérieux, and the RT-PCR amplification on the same day same with duplex detection by TaqMan® hydrolysis probes of genes encoding the matrix proteins M of influenza A and B viruses (kit Influenza A/B r-gene® by Argene). This technique used a Cell control r-gene® warranting the quality of the sample by preventing false negatives (pauci-cellular samples). 3. Results Ninety-eight patients were admitted to the IDD (a 16-bed unit) from January 1st, 2013 to February 22nd, 2013. Fifty-one patients presented with respiratory symptoms and fever but only 46 patients underwent the screening with 17 positive results (36.9% of patients tested and 17.3% of admissions) (Fig. 1). Eleven male and 6 female patients presented with influenza (mean age of 68 years, range 25 to 90 years of age), 15 cases of influenza A and 2 of influenza B. The diagnoses made in the emergency department (ED) for the 17 patients, before RTPCR screening, were most frequently lung infection (sepsis from a pulmonary focus, pneumonia, or exacerbation of chronic bronchitis, 6 patients), influenza syndrome (4 patients), sepsis (2 patients), headaches (1 patient), lumbalgia (1 patient), fall (1 patient), infective endocarditis (1 patient), alteration of the global health status with gastroenteritis and dehydration (1 patient) (Table 1). The vaccinal status for influenza was vaccinated (4 patients), not vaccinated (8 patients), unknown (5 patients). RT-PCR results for patients with influenzas were obtained on the day of admission in 6 cases, the morning after in 8 cases, and within 48 hours in 3 cases, with a median delay before results of 1 day (interquartile range 0–1 day). Fourteen patients were treated with antibiotics when they were diagnosed
The epidemic threshold was reached during 11 weeks during the 2012–2013 influenza outbreak (end of December to beginning of March) with a peak at the end of January and beginning of February, and a higher incidence than in the 2 previous seasons: 10.2 million consultations compared to 3.5 in 2011–2012, and 6.7 in 2010–2011 [2]. This high epidemic was not unusual. All age ranges were concerned. This outbreak featured co-circulation of 3 types and subtypes (B, A H1N1, and A H3N2; type B was predominant). Unexpectedly, our patients were infected most frequently by type A viruses. All patient with respiratory signs of the infectious origin are supposed to be put in droplet isolation [3], but these recommendations are difficult to implement because of the frequency of these symptoms, because of the unit set-ups (numerous small double-bed rooms, etc.) especially during influenza outbreaks. A targeted screening for influenza in the hospital seems to be necessary because of an insufficient vaccinal coverage both for patients [4] and for healthcare personnel [5]. The American recommendations are to systematically screen all hospitalized patients presenting with influenza symptoms, using RT-PCR if possible [6]. This allows for early treatment but also for the prevention of secondary cases and of outbreaks in healthcare units. RT-PCR is the recommended method because commercial rapid diagnostic tests for influenza lack sensitivity (40 to 90%) [6]. Screening by RT PCR is more expensive (the cost of the “Influenza A/B r-gene® kit reagent for our institution was 395 D “Hors Taxe” for 60 tests, for 50 patient, tests to which was added 209 D for cell control “Cell control r-gene® for 100 tests); it is more complex and slower than commercial rapid diagnostic test for influenza but it is significantly more sensitive. We were able to implement daily screening during the epidemic period 6 days a week, with a median delay for results of 1 day (interquartile range 0–1 day), allowing for a quick therapeutic adjustment (initiating oseltamivir, stopping antibiotherapy) and an early implementation of adapted isolation measures. Four patients only were given oseltamivir as curative treatment, since we had restricted indications for patients with a delay after onset inferior to 48 hours; conversely the American recommendations allow treatment of patients hospitalized for more than 48 hours, independently of the presence of severity signs [6]. The contribution of a curative
Table 1 Main clinical and laboratory data for 17 patients presenting with influenza. Principales données cliniques et biologiques des 17 patients grippés. Patients
Cause of the admission
History
T in ◦ C CRP (mg/l) PCT (ng/l)
Final diagnosis
Antibiotics
Stop
Oseltamivir
M, 80 years of age
Sepsis
Post-AHT cardiopathy, AFCA, ECOBP, colon cancer
Superinfected influenza A EBPCO
Amox–clavac
D1
No
7
M, 81 years of age
Sepsis from a pulmonary focus
Dementia, DMT2, prostatic adenocarcinoma, ECOBP
D8
Yes
2
Dehydration gastroenteritis
Crohn’s disease ileostomy
No
–
No
6
F, 84 years of age
Headaches, inflammatory syndrome
DMT2, HTA, dementia
Superinfected influenza A to Haemophilus EBPCO Influenza A Dehydration Influenza A Maxillary sinusitis
Amox–clavac
F, 44 years of age
Amox–clavac
D5
No
8
F, 63 years of age
Sepsis
DMT2, HTA, ischemic cardiopathy
Superinfected influenza A
Amox–clavac
D5
No
6
M, 71 years of age
EBPCO, dyspnea
HTA, ECOBP
Superinfected influenza A
Amox–clavac
D6
No
10
M, 76 years of age
Endocarditis, fever, rash
Influenza A Toxidermia
Amox–clavac
D0
No
4
M, 68 years of age
Influenza A Enterococcal prostatitis Superinfected influenza A Escherichia coli UTI Influenza A Clostridium difficile colitis
Teicoplanin
D21
No
9
Ceftriaxone then cefixim Amox–clavac Metronidazole
D14
Yes
12
F, 90 years of age
Acute community acquired pneumonia Sepsis from a pulmonary and urinary tract focus Aspiration pneumonia
HTA, AFCA, ischemic cardiopathy, LLC, valvular prosthesis AFCA, ECOBP, ischemic cardiopathy, DMT2 DMT2, HTA, dementia
39 CRP: 75 PCT: 0.15 40 CRP: 137 PCT: 0.2 Home CRP: 2 Home CRP: 183 PCT: 0.17 38.5 CRP: 183 PCT: 0.6 Home CRP: 163 PCT: 0.17 38.5 CRP: 32
D1D10
No
9
M, 86 years of age
Influenza
DMT2, vesical adenocarcinoma
Influenza A
Amox–clavac
D1
No
4
M, 25 years of age
Lumbalgia
–
Influenza A
Ceftriaxone
D2
No
3
F, 63 years of age
Dyspnea, influenza
HTA, ischemic cardiopathy
Influenza A
No
–
No
4
M, 39 years of age
Fall and head trauma
multi-operated cholesteatoma
Cefotaxime
D3
No
8
M, 35 years of age
Influenza
–
Influenza B Meningeal hemorrhage Petrous bone fracture Influenza A
No
–
Yes
1
M, 78 years of age
Sepsis from a pulmonary focus
D20
No
19
Influenza, EBPCO
Influenza B Enterococcal septicemia Angiocholitis Superinfected influenza A
Teicoplanine
M, 90 years of age
Caroli disease with biliary and digestive derivation, angiocholitis ECOBP, dementia, ischemic cardiopathy
Amox–clavac
D5
Yes
15
HTA, dementia
39.2 CRP: 127 PCT: 0.35 38.2 CRP: 116 PCT: 1.78 38 CRP: 40 PCT: 0.28
125
T: temperature; M: male; F: female; ECOBP: exacerbation of chronic obstructive bronchopneumonia; AHT: arterial hypertension; DMT2: diabetes mellitus type 2; CLL: chronic lymphoid leukemia; home: fever at home; amox–clavac: amoxicillin–clavulanic acid; DS: duration of hospital stay in days; UTI: urinary tract infection.
M. Martinot et al. / Médecine et maladies infectieuses 44 (2014) 123–127
F, 90 years of age
Home CRP: 53 39 CRP: 69 38 CRP: 127 PCT: 5.61 38.2 CRP: 43 39 CRP: 144 PCT: 0.28 Home CRP: 2 38.2 CRP: 67
DS
126
M. Martinot et al. / Médecine et maladies infectieuses 44 (2014) 123–127
98 paents hospitalized
Respiratory signs and fever
YES
NO
No screening Screening by
5 paents not screened n=47
rhino-pharyngeal swab and RT-PCR n=46
17 posive results
29 negave results
15 for influenza A 2 for influenza B
Fig. 1. Screening strategy for flu among hospitalized patients. Stratégie de dépistage de grippe des patients hospitalisés.
treatment with neuraminidase inhibitors remains controversial [7]. Furthermore, preventive treatment, presumed to be more effective [7], of contact patients in hospitals or even outside of hospitals may be initiated. Many patients transferred from the emergency department were not identified as presenting with influenza, a common case because of atypical clinical presentations, especially in the geriatric patients, or because of associated superinfections [8]. It was important to be ready to use screening in healthcare departments during the epidemic period because of the low vaccinal coverage and the partial effectiveness of this vaccination [1,4,9,10]. There are currently no French guidelines recommending the systematic screening for influenza in healthcare departments outside of outbreaks [8]. Using RT-PCR for a systematic screening for influenza during the epidemic has a cost/effectiveness ratio, which is difficult to assess but which may seem positive for some authors [11], especially for aged patients. Its use in more limited hospital settings allows managing a smaller number of patients, often aged and presenting with many chronic diseases, for whom the cost/effectiveness ratio was more favorable. Our study has several limitations due to the method used and the results: small number of patients included, small number
of curative treatments with oseltamivir and with a disputable effectiveness, reduced number of antibiotherapy interruptions because of suspected bacterial superinfections or of associated infections, delay before obtaining RT-PCR result still too long, and finally 10% of patients with cough and fever who were not screened. But it allowed determining how frequently patients not identified as presenting with influenza were hospitalized during the epidemic period; and it highlighted the contribution of rapid screening for the implementation of droplet isolation, and preventive treatment of contact cases so as to prevent outbreaks in healthcare departments. The RT-PCR tests are highly sensitive but the delay before results, its availability, and cost should be improved. Other tests, not available in our institution, could be used for the screening: Multiplex PCR has for advantage to allow screening for several pathogenic agents, or molecular testing for a single pathogen made by an automated device, especially for hospitals without any molecular biology unit. Using sensitive tests (PCR), which can be performed rapidly with results that come back in the hours following patient admission, seems to be necessary for a strategy of hospital outbreak prevention.
M. Martinot et al. / Médecine et maladies infectieuses 44 (2014) 123–127
5. Conclusion Influenza was diagnosed in 17.3% of patients admitted to our unit during the epidemic period. The diagnosis is often not made because of terrain, of a sometimes atypical clinical presentation, and of possible superinfections. During the epidemic period, RTPCR, more sensitive than commercial rapid diagnostic tests for influenza, is a reliable method for the diagnosis of influenza, ensuring a better management, and allowing prevention of outbreaks in healthcare departments, especially by implementing droplet isolation rapidly. Disclosure of interest
[5]
[6]
[7]
[8]
The authors declare that they have no conflicts of interest concerning this article. [9]
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