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Abstract

Background

Data on infectious encephalitis in immunodeficient (ID) individuals are scarce. This population may present with atypical clinical symptoms, be infected by uncommon pathogens and develop poor outcomes.

Aim

We aimed to describe the epidemiology of infectious encephalitis among HIV-negative ID patients.

Methods

Patients from the ENCEIF (Etude Nationale de Cohorte des Encéphalites Infectieuses en France) prospective cohort meeting criteria for infectious encephalitis between January 2016 and December 2019 were included. We compared clinical presentation, magnetic resonance imaging (MRI) results, biological results, infection causes and outcome of ID patients with immunocompetent (IC) patients using Pearson’s chi-squared test and Student’s t-test. We carried out logistic regression to assess the role of immunodeficiency as risk factor for poor outcome.

Results

ID patients (n = 58) were older (mean 72 vs 59 years), had higher prevalence of diabetes (26% vs 12%), pre-existing neurological disorders (12% vs 5%) and higher case-fatality rate (23.6% vs 5.6%) compared to IC patients (n = 436). Varicella zoster virus was the primary cause of encephalitis in ID patients (this aetiology was more frequent in ID (25.9%) than in IC patients (11.5%)), with herpes simplex virus second (22.4% in ID patients vs 27.3% in IC patients). Immunodeficiency was an independent risk factor for death or major sequelae (odds ratio: 3.41, 95%CI: 1.70–6.85).

Conclusions

Varicella zoster virus is the most frequent cause of infectious encephalitis in ID patients. Immunodeficiency is a major risk factor for poor outcome. ID encephalitis patients should benefit from stringent investigation of cause and early empiric treatment.

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/content/10.2807/1560-7917.ES.2024.29.6.2300046
2024-02-08
2024-11-29
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2024.29.6.2300046
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References

  1. George BP, Schneider EB, Venkatesan A. Encephalitis hospitalization rates and inpatient mortality in the United States, 2000-2010. PLoS One. 2014;9(9):e104169.  https://doi.org/10.1371/journal.pone.0104169  PMID: 25192177 
  2. Mailles A, De Broucker T, Costanzo P, Martinez-Almoyna L, Vaillant V, Stahl JP, Steering Committee and Investigators Group. Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France. Clin Infect Dis. 2012;54(10):1455-64.  https://doi.org/10.1093/cid/cis226  PMID: 22460967 
  3. Venkatesan A. Epidemiology and outcomes of acute encephalitis. Curr Opin Neurol. 2015;28(3):277-82.  https://doi.org/10.1097/WCO.0000000000000199  PMID: 25887770 
  4. Mailles A, Stahl JP, Steering Committee and Investigators Group. Infectious encephalitis in france in 2007: a national prospective study. Clin Infect Dis. 2009;49(12):1838-47.  https://doi.org/10.1086/648419  PMID: 19929384 
  5. Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10(12):835-44.  https://doi.org/10.1016/S1473-3099(10)70222-X  PMID: 20952256 
  6. Castro I, Ruiz J, Tasias M, Montero M, Salavert M. Central nervous system infections in immunocompromised patients. Rev Esp Quimioter. 2018;31(Suppl 1) Suppl 1;56-61. PMID: 30209926 
  7. Mailles A, Argemi X, Biron C, Fillatre P, De Broucker T, Buzelé R, et al. Changing profile of encephalitis: Results of a 4-year study in France. Infect Dis Now. 2021. PMID: 34896660 
  8. Le Maréchal M, Mailles A, Seigneurin A, Tattevin P, Stahl JP, Épaulard O, et al. A Prospective Cohort Study to Identify Clinical, Biological, and Imaging Features That Predict the Etiology of Acute Encephalitis. Clin Infect Dis. 2021;73(2):264-70.  https://doi.org/10.1093/cid/ciaa598  PMID: 32433723 
  9. Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013;57(8):1114-28.  https://doi.org/10.1093/cid/cit458  PMID: 23861361 
  10. Stahl JP, Azouvi P, Bruneel F, De Broucker T, Duval X, Fantin B, et al. Guidelines on the management of infectious encephalitis in adults. Med Mal Infect. 2017;47(3):179-94.  https://doi.org/10.1016/j.medmal.2017.01.005  PMID: 28412044 
  11. McMillan T, Wilson L, Ponsford J, Levin H, Teasdale G, Bond M. The Glasgow Outcome Scale - 40 years of application and refinement. Nat Rev Neurol. 2016;12(8):477-85.  https://doi.org/10.1038/nrneurol.2016.89  PMID: 27418377 
  12. Hosmer DW, Hosmer T, Le Cessie S, Lemeshow S. A comparison of goodness-of-fit tests for the logistic regression model. Stat Med. 1997;16(9):965-80.  https://doi.org/10.1002/(SICI)1097-0258(19970515)16:9<965::AID-SIM509>3.0.CO;2-O  PMID: 9160492 
  13. Chemaly RF, Hill JA, Voigt S, Peggs KS. In vitro comparison of currently available and investigational antiviral agents against pathogenic human double-stranded DNA viruses: A systematic literature review. Antiviral Res. 2019;163:50-8.  https://doi.org/10.1016/j.antiviral.2019.01.008  PMID: 30677427 
  14. Ryan L, Heed A, Foster J, Valappil M, Schmid ML, Duncan CJA. Acute kidney injury (AKI) associated with intravenous aciclovir in adults: Incidence and risk factors in clinical practice. Int J Infect Dis. 2018;74:97-9.  https://doi.org/10.1016/j.ijid.2018.07.002  PMID: 30048817 
  15. Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008;47(3):303-27.  https://doi.org/10.1086/589747  PMID: 18582201 
  16. Bertrand A, Leclercq D, Martinez-Almoyna L, Girard N, Stahl JP, De-Broucker T. MR imaging of adult acute infectious encephalitis. Med Mal Infect. 2017;47(3):195-205.  https://doi.org/10.1016/j.medmal.2017.01.002  PMID: 28268128 
  17. Le Bot A, Ballerie A, Pronier C, Bénézit F, Reizine F, Tas M, et al. Characteristics and outcome of varicella-zoster virus central nervous system infections in adults. Eur J Clin Microbiol Infect Dis. 2021;40(11):2437-42.  https://doi.org/10.1007/s10096-021-04245-y  PMID: 33907935 
  18. Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, et al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology. 2008;70(11):853-60.  https://doi.org/10.1212/01.wnl.0000304747.38502.e8  PMID: 18332343 
  19. Seeley WW, Marty FM, Holmes TM, Upchurch K, Soiffer RJ, Antin JH, et al. Post-transplant acute limbic encephalitis: clinical features and relationship to HHV6. Neurology. 2007;69(2):156-65.  https://doi.org/10.1212/01.wnl.0000265591.10200.d7  PMID: 17620548 
  20. Hartman EA, Huang D. Update on PML: lessons from the HIV uninfected and new insights in pathogenesis and treatment. Curr HIV/AIDS Rep. 2008;5(3):112-9.  https://doi.org/10.1007/s11904-008-0018-0  PMID: 18627659 
  21. Song T, Rao Z, Tan Q, Qiu Y, Liu J, Huang Z, et al. Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation: Report of 2 Cases and Literature Review. Medicine (Baltimore). 2016;95(14):e3173.  https://doi.org/10.1097/MD.0000000000003173  PMID: 27057842 
  22. Kyritsis AP, Markoula S, Alexiou G, Asimakopoulos A, Jabbour P, Fotopoulos A, et al. Diagnosis and treatment of limbic encephalitis in the cancer patient. Future Oncol. 2020;16(22):1647-55.  https://doi.org/10.2217/fon-2020-0080  PMID: 32511017 
  23. Kunchok A, Aksamit AJ Jr, Davis JM 3rd, Kantarci OH, Keegan BM, Pittock SJ, et al. Association Between Tumor Necrosis Factor Inhibitor Exposure and Inflammatory Central Nervous System Events. JAMA Neurol. 2020;77(8):937-46.  https://doi.org/10.1001/jamaneurol.2020.1162  PMID: 32421186 
  24. Larkin J, Chmielowski B, Lao CD, Hodi FS, Sharfman W, Weber J, et al. Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis. Oncologist. 2017;22(6):709-18.  https://doi.org/10.1634/theoncologist.2016-0487  PMID: 28495807 
  25. Saylor D, Thakur K, Venkatesan A. Acute encephalitis in the immunocompromised individual. Curr Opin Infect Dis. 2015;28(4):330-6.  https://doi.org/10.1097/QCO.0000000000000175  PMID: 26098507 
  26. Tan IL, McArthur JC, Venkatesan A, Nath A. Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology. 2012;79(21):2125-32.  https://doi.org/10.1212/WNL.0b013e3182752ceb  PMID: 23136265 
  27. Andrei G, Topalis D, Fiten P, McGuigan C, Balzarini J, Opdenakker G, et al. In vitro-selected drug-resistant varicella-zoster virus mutants in the thymidine kinase and DNA polymerase genes yield novel phenotype-genotype associations and highlight differences between antiherpesvirus drugs. J Virol. 2012;86(5):2641-52.  https://doi.org/10.1128/JVI.06620-11  PMID: 22190713 
  28. Stránská R, Schuurman R, Nienhuis E, Goedegebuure IW, Polman M, Weel JF, et al. Survey of acyclovir-resistant herpes simplex virus in the Netherlands: prevalence and characterization. J Clin Virol. 2005;32(1):7-18.  https://doi.org/10.1016/j.jcv.2004.04.002  PMID: 15572000 
  29. Gaudot C. [Prevention of Listeria infections]. Bull Acad Natl Med. 2000;184(2):287-93, discussion 294. PMID: 10989538 
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