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Burden of herpes simplex virus encephalitis in the United States

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Abstract

Herpes simplex virus encephalitis (HSVE) is a disease of public health concern, but its burden on the healthcare of United States has not been adequately assessed recently. We aimed to define the incidence, complications and outcomes of HSVE in the recent decade by analyzing data from a nationally representative database. Healthcare Cost and Utilization Project databases were utilized to identify patients with primary discharge diagnosis of HSVE. Annual hospitalization rate was estimated and several preselected inpatient complications were identified. Regression analyses were used to identify mortality predictors. Key epidemiological factors were compared with those from other countries. Total 4871 patients of HSVE were included in our study. The annual hospitalization rate was 10.3 ± 2.2 cases/million in neonates, 2.4 ± 0.3 cases/million in children and 6.4 ± 0.4 cases/million in adults. Median age was 57 years and male:female incidence ratio was 1:1. Rates of some central nervous system complications were seizures (38.4%), status epilepticus (5.5%), acute respiratory failure (20.1%), ischemic stroke (5.6%) and intracranial hemorrhage (2.7%), all of which were significantly associated with mortality. In-hospital mortality in neonates, children and adults were 6.9, 1.2 and 7.7%, respectively. HSVE still remains a potentially lethal infectious disease with high morbidity and mortality. Most recent epidemiological data in this study may help understanding this public health disease, and the patient outcome data may have prognostic significance.

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References

  1. Glaser C, Honarmand S, Anderson L et al (2006) Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis 43:1565–1577

    Article  CAS  PubMed  Google Scholar 

  2. George BP, Schneider EB, Venkatesan A (2014) Encephalitis hospitalization rates and inpatient mortality in the United States, 2000–2010. PLoS One 9:e104169

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA (2012) The frequency of autoimmune N-methyl-d-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 2012:cir1038

    Google Scholar 

  4. Lai M, Hughes EG, Peng X et al (2009) AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 65:424–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lancaster E, Lai M, Peng X et al (2010) Antibodies to the GABA B receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol 9:67–76

    Article  CAS  PubMed  Google Scholar 

  6. Dalmau J, Gleichman AJ, Hughes EG et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lai M, Huijbers MG, Lancaster E et al (2010) Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 9:776–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mailles A, Stahl J-P (2009) Infectious encephalitis in France in 2007: a national prospective study. Clin Infect Dis 49:1838–1847

    Article  PubMed  Google Scholar 

  9. Singh TD, Fugate JE, Rabinstein AA (2015) The spectrum of acute encephalitis. Causes, management, and predictors of outcome. Neurology 84:359–366

    Article  CAS  PubMed  Google Scholar 

  10. Whitley RJ, Soong S-J, Dolin R, Galasso GJ, Ch’ien LT, Alford CA (1977) Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis: National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study. N Engl J Med 297:289–294

    Article  CAS  PubMed  Google Scholar 

  11. Erdem H, Cag Y, Ozturk-Engin D et al (2015) Results of a multinational study suggest the need for rapid diagnosis and early antiviral treatment at the onset of herpetic meningoencephalitis. Antimicrob Agents Chemother 59:3084–3089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sköldenberg B, Alestig K, Burman L et al (1984) Acyclovir versus vidarabine in herpes simplex encephalitis: randomised multicentre study in consecutive Swedish patients. Lancet 324:707–711

    Article  Google Scholar 

  13. Dodson MG, Kerman RH, Lange CF, Stefani SS, O’Leary JA (1977) T and B cells in pregnancy. Obstet Gynecol 49:299–300

    CAS  PubMed  Google Scholar 

  14. Riancho J, Delgado-Alvarado M, Sedano MJ, Polo JM, Berciano J (2013) Herpes simplex encephalitis: clinical presentation, neurological sequelae and new prognostic factors. Ten years of experience. Neurol Sci 34:1879–1881

    Article  PubMed  Google Scholar 

  15. Jouan Y, Grammatico-Guillon L, Espitalier F, Cazals X, François P, Guillon A (2015) Long-term outcome of severe herpes simplex encephalitis: a population-based observational study. Crit Care 19:1–9

    Article  Google Scholar 

  16. Jain P, Jain A, Kumar A et al (2014) Epidemiology and etiology of acute encephalitis syndrome in North India. Jpn J Infect Dis 67:197–203

    Article  PubMed  Google Scholar 

  17. Sheybani F, Arabikhan H, Naderi H (2013) Herpes simplex encephalitis (HSE) and its outcome in the patients who were admitted to a tertiary care hospital in Mashhad, Iran, over a 10-year period. J Clin Diagn Res 7:1626

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Dagsdóttir HM, Sigurðardóttir B, Gottfreðsson M et al (2014) Herpes simplex encephalitis in Iceland 1987–2011. SpringerPlus 1:1–7

    Google Scholar 

  19. Sili U, Kaya A, Mert A, Group HES (2014) Herpes simplex virus encephalitis: clinical manifestations, diagnosis and outcome in 106 adult patients. J Clin Virol 60:112–118

    Article  Google Scholar 

  20. HCUP Overview (2016) Healthcare Cost and Utilization Project (HCUP). https://www.hcup-us.ahrq.gov/overview.jsp. Accessed 25 May 2016

  21. Hjalmarsson A, Blomqvist P, Sköldenberg B (2007) Herpes simplex encephalitis in Sweden, 1990–2001: incidence, morbidity, and mortality. Clin Infect Dis 45:875–880

    Article  PubMed  Google Scholar 

  22. Barbadoro P, Marigliano A, Ricciardi A, D’Errico M, Prospero E (2012) Trend of hospital utilization for encephalitis. Epidemiol Infect 140:753–764

    Article  CAS  PubMed  Google Scholar 

  23. Population, total; The World Bank. http://data.worldbank.org/indicator/SP.POP.TOTL. Accessed 25 May 2016

  24. International Data Base; United States Census Bureau. https://www.census.gov/population/international/data/idb/informationGateway.php. Accessed 25 May 2016

  25. Adams H, Miller D (1973) Herpes simplex encephalitis: a clinical and pathological analysis of twenty-two cases. Postgrad Med J 49:393

    Article  PubMed Central  Google Scholar 

  26. Kennedy P, Adams J, Graham D, Clement G (1988) A clinico-pathological study of herpes simplex encephalitis. Neuropathol Appl Neurobiol 14:395–415

    Article  CAS  PubMed  Google Scholar 

  27. Raschilas F, Wolff M, Delatour F et al (2002) Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis 35:254–260

    Article  PubMed  Google Scholar 

  28. McGrath N, Anderson N, Croxson M, Powell K (1997) Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J Neurol Neurosurg Psychiatry 63:321–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Granerod J, Ambrose HE, Davies NW et al (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10:835–844

    Article  PubMed  Google Scholar 

  30. Rodríguez-Sainz A, Escalza-Cortina I, Guio-Carrión L et al (2013) Intracerebral hematoma complicating herpes simplex encephalitis. Clin Neurol Neurosurg 115:2041–2045

    Article  PubMed  Google Scholar 

  31. Zis P et al (2016) Herpes simplex virus type 2 encephalitis as a cause of ischemic stroke: case report and systematic review of the literature. J Stroke Cerebrovasc Dis 25(2):335–339

    Article  PubMed  Google Scholar 

  32. Sas AM et al (2009) Herpes simplex virus type-1 encephalitis and occipital ischemic stroke. Pediatr Neurol 41(4):294–296

    Article  PubMed  Google Scholar 

  33. Burón Mediavilla F, Rodríguez Borregan J, Miñambres E et al (2005) Encefalitis herpética en adultos: 23 casos. Anales de medicina interna 2005:473–477 (SciELO Espana)

    Google Scholar 

  34. Puchhammer-Stöckl E, Popow-Kraupp T, Heinz FX, Mandl CW, Kunz C (1990) Establishment of PCR for the early diagnosis of herpes simplex encephalitis. J Med Virol 32:77–82

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI, 48202, USA

    S. Modi, Abhimanyu Mahajan, D. Dharaiya, P. Varelas & P. Mitsias

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  1. S. Modi
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  2. Abhimanyu Mahajan
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  3. D. Dharaiya
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  4. P. Varelas
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  5. P. Mitsias
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Correspondence to Abhimanyu Mahajan.

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The authors of this manuscript report no conflict of interest.

Ethical standards

This study used de-identified patient databases. Therefore, this study did not require IRB review in accordance with the Code of Federal Regulations, 45 CFR 46.

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The authors do not report any external source of funding.

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Modi, S., Mahajan, A., Dharaiya, D. et al. Burden of herpes simplex virus encephalitis in the United States. J Neurol 264, 1204–1208 (2017). https://doi.org/10.1007/s00415-017-8516-x

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  • DOI: https://doi.org/10.1007/s00415-017-8516-x

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