Accepted Manuscript Title: Viral infections of the central nervous system in elderly patients: a retrospective study Author: Saverio G. Parisi Monica Basso Claudia Del Vecchio Samantha Andreis Elisa Franchin Federico Dal Bello Silvana Pagni Maria Angela Biasolo Riccardo Manganelli Luisa Barzon Giorgio Palu` PII: DOI: Reference:
S1201-9712(16)00013-8 http://dx.doi.org/doi:10.1016/j.ijid.2016.01.012 IJID 2522
To appear in:
International Journal of Infectious Diseases
Received date: Revised date: Accepted date:
18-12-2015 18-1-2016 20-1-2016
Please cite this article as: Parisi SG, Basso M, Del Vecchio C, Andreis S, Franchin E, Dal Bello F, Pagni S, Biasolo MA, Manganelli R, Barzon L, Palu` G, Viral infections of the central nervous system in elderly patients: a retrospective study, International Journal of Infectious Diseases (2016), http://dx.doi.org/10.1016/j.ijid.2016.01.012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Highlights A positive result was more frequent in patients older than 80 years. EV is the second most frequent virus detected.
Ac ce
pt
ed
M
an
us
cr
ip t
Patients older than 80 years had more frequently VZV detected in CSF.
1 Page 1 of 9
Viral infections of the central nervous system in elderly patients: a retrospective study
Saverio G. Parisi ab *, Monica Basso ab, Claudia Del Vecchio ab, Samantha Andreisa, Elisa Franchin ab
, Federico Dal Bello ab, Silvana Pagni ab, Maria Angela Biasolo ab, Riccardo Manganelli ab, Luisa
ip t
Barzon ab, Giorgio Palù ab.
Department of Molecular Medicine, University of Padova, Via Gabelli 63, 35100 Padova, Italy
b
Microbiology and Virology Unit, Padova Hospital, Via Nicolò Giustiniani 2, 35100 Padova, Italy
an
us
cr
a
Corresponding Author:
Department of Molecular Medicine,
M
Saverio G. Parisi, MD
ed
University of Padova, Padova, Italy,
Phone 00390498272344
Ac ce
Fax 00390498272355
pt
Via Gabelli 63, 35100 Padova, Italy
[email protected]
2 Page 2 of 9
Abstract Objectives: Very few data exists regarding viral meningitis and encephalitis in elderly patients (>65 years old). Methods: This study investigated the detection of herpes simplex virus (HSV), varicella zoster
ip t
virus (VZV), human herpes virus-6 (HHV-6), human herpes virus-7 (HHV-7), human herpes virus 8 (HHV-8), cytomegalovirus (CMV), Epstein Barr virus (EBV), enterovirus (EV), adenovirus
cr
(HAdV), human parechoviruses (HPeVs) and tick-borne encephalitis virus (TBEV) through Real
us
Time-PCR (RT-PCR) in patients > 65 years who had cerebrospinal fluid (CSF) tested for a suspected CNS infection.
an
Results: A total of 2868 RT-PCR were performed on 502 cerebrospinal fluid samples. Overall, 65 positive RT-PCR were detected: 23 for HSV (35.4% of positives), 15 for EV (23.1% of positives),
M
14 for EBV (21.5 of positives), 12 for VZV (18.5 of positives) and 1 CMV (1.5 of positives). A positive RT-PCR in CSF was detected in 24 (17.4%) patients aged more than 80 years and in 35
ed
(9.6%) patients aged less than 80 years (p=0.02): VZV was more frequently detected in the oldest subjects (5.9% versus 1.6%, p=0.03).
pt
Conclusions: HSV was the most common viral etiology identified in the study with VZV infection
elderly
Ac ce
being recognized more frequently in those patients above the age of 80 years.
Key words
Varicella zoster virus cerebrospinal fluid
3 Page 3 of 9
1.Introduction Elderly patients (age above 65 years) have worse outcomes in community acquired meningitis and encephalitis, but these patients are underrepresented in clinical reports and a very few data are available in patients ≥ 80 years old.1-3
ip t
This retrospective study investigated the detection of herpes simplex virus (HSV), Varicella zoster virus (VZV), human herpes virus-6 (HHV-6), human herpes virus-7 (HHV-7), human herpes virus
cr
8 (HHV-8), Cytomegalovirus (CMV), Epstein Barr virus (EBV), Enterovirus (EV), adenovirus
us
(HAdV), Human parechoviruses (HPeVs) and tick-borne encephalitis virus (TBEV) through molecular techniques in patients aged more 65 years who had cerebrospinal fluid (CSF) tested in
M
an
routine clinical practice for a suspected CNS infection.
2.Methods
ed
All the CSFs tested for EV and/or HSV from August 1 2012 to May 31 2015 were included. The study was approved by the Ethical Committee for Clinical Experimentation, Padova Province
pt
(50443/08-21-15). The Real Time-PCRs (RT-PCRs) included in the diagnostic panel were at the
Ac ce
discretion of the treating physician and they were performed using the protocols currently applied at the Microbiology and Virology Unit of the Padova Hospital. The age was evaluated as a binary variable: 65 to 79 years versus age ≥ 80 years. The number of tests performed was described as median and 95% confidence interval (CI): Mann-Whitney, chisquared test (with Yates' correction when appropriate) and Fisher exact test were applied as appropriate. The limit of significance for all analyses was established at p 80 years): total 65 positive RT-PCR. They were evaluated both as absolute value and as percentage respect to the number of test performed for the specific virus. In bold the significant value. Patients aged Patients aged p Total 65-79 years > 80 years HSV positive n (%) 16 (4.5) 7 (5.1) 0.77 23 (4.6) EV positive, n (%) 8 (3.1) 7 (7.7) 0.06 15 (4.3) EBV positive, n (%) 8 (3.3) 6 (7.3) 0.12 14 (4.3) VZV positive, n (%) 5 (1.6) 7 (5.9) 12 (2.8) 0.03 CMV positive, n (%) 0 1 (1.1) 0.09 1 (0.3) HPeVs positive, n (%) 0 0 0 TBEV positive, n (%) 0 0 0 HAdV positive, n (%) 0 0 0 HHV-6 positive, n (%) 0 0 0 HHV-7 positive, n (%) 0 0 0 HHV-8 positive, n (%) 0 0 0 HHV-7 tested from January 2013 CSF: cerebrospinal fluid RT-PCR: Real Time polymerase chain reaction HSV: herpes simplex virus; VZV: varicella zoster virus; CMV: cytomegalovirus; EV: enterovirus; HPeVs: Human parechoviruses; EBV: Epstein Barr virus; TBEV: tick-borne encephalitis; HAdV: human adenovirus; HHV-6: human herpes virus-6; HHV-7: human herpes virus-7; HHV-8: human herpes virus-8
7 Page 7 of 9
Acknowledgments
This work was supported by MURST ex 60% 2015 (to M.B.). SGP designed and coordinated the study, supervised the laboratory experiments, collected the data, interpreted the findings, and wrote the paper;
ip t
MB, performed the statistical analysis and write the paper;
cr
CDV performed the laboratory experiments EF performed the laboratory experiments;
us
SA performed the laboratory experiments, helped to interpret the findings
an
FDB performed the laboratory experiments SP performed the laboratory experiments
M
MAB helped to interpret the findings RM helped to interpret the findings
ed
LB helped to interpret the findings
Ac ce
pt
GP helped to interpret the findings and write the paper
Conflict of interest
Conflicts of interest: none
8 Page 8 of 9
References
1. Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis: causes,
ip t
management, and predictors of outcome. Neurology 2015;84:359-66. 2. Wang AY, Machicado JD, Khoury NT, Wootton SH, Salazar L, Hasbun R. Community-
cr
acquired meningitis in older adults: clinical features, etiology, and prognostic factors. J Am Geriatr Soc 2014;62:2064-70.
us
3. de Ory F, Avellón A, Echevarría JE, Sánchez-Seco MP, Trallero G, Cabrerizo M et al. S.
an
Viral infections of the central nervous system in Spain: a prospective study. J Med Virol 2013;85:554-62.
M
4. Kleines M, Scheithauer S, Schiefer J, Häusler M. Clinical application of viral cerebrospinal fluid PCR testing for diagnosis of central nervous system disorders: a retrospective 11-year
ed
experience. Diagn Microbiol Infect Dis 2014;80:207-15. 5. Volle R, Bailly JL, Mirand A, Pereira B, Marque-Juillet S, Chambon M et al. Variations in
pt
cerebrospinal fluid viral loads among enterovirus genotypes in patients hospitalized with
Ac ce
laboratory-confirmed meningitis due to enterovirus. J Infect Dis 2014;210:576-84. 6. Miranda C M, Torres T JP, Larrañaga L C, Acuña L G. Meningomyelitis associated with infection by human herpes virus 7: report of two cases. Rev Med Chil. 2011;139:1588-91. 7. Zambito Marsala S, Pistacchi M, Gioulis M, Mel R, Marchini C, Francavilla E. Neurological complications of tick borne encephalitis: the experience of 89 patients studied and literature review. Neurol Sci. 2014;35:15-21.
9 Page 9 of 9
