BACKGROUND: Arthropod-borne viral encephalitis of diverse origins shows similar clinical symptoms, histopathology and magnetic resonance imaging, indicating that the patho mechanisms may be similar. There is no specific therapy to date. However, vaccination remains the best prophylaxis against a selected few. Regardless of these shortcomings, there are an increasing number of case reports that successfully treat arboviral encephalitis with high doses of intravenous immunoglobulins. DISCUSSION: To our knowledge, high dose intravenous immunoglobulin has not been tested systematically for treating severe cases of tick-borne encephalitis. Antibody-dependent enhancement has been suspected, but not proven, in several juvenile cases of tick-borne encephalitis. Although antibody-dependent enhancement during secondary infection with dengue virus has been documented, no adverse effects were noticed in a controlled study of high dose intravenous immunoglobulin therapy for dengue-associated thrombocytopenia. The inflammation-dampening therapeutic effects of generic high dose intravenous immunoglobulins may override the antibody-dependent enhancement effects that are potentially induced by cross-reactive antibodies or by virus-specific antibodies at sub-neutralizing levels. SUMMARY: Analogous to the increasing number of case reports on the successful treatment of other arboviral encephalitides with high dose intravenous immunoglobulins, we postulate whether it may be possible to also treat severe cases of tick-borne encephalitis with high dose intravenous immunoglobulins as early in the course of the disease as possible.

Academy of Sciences of the Czech Republic Biology Centre Institute of Parasitology Branisovska 31 CZ 37005 Ceske Budejovice Czech Republic

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Dobler G, Gniel D, Petermann R, Pfeffer M. Epidemiology and distribution of tick-borne encephalitis. Wien Med Wochenschr. 2012;162:230–238. doi: 10.1007/s10354-012-0100-5. PubMed DOI

Heinz FX, Stiasny K. Flaviviruses and flavivirus vaccines. Vaccine. 2012;30:4301–4306. doi: 10.1016/j.vaccine.2011.09.114. PubMed DOI

Suss J. Tick-borne encephalitis 2010: epidemiology, risk areas, and virus strains in Europe and Asia-an overview. Ticks Tick Borne Dis. 2011;2:2–15. doi: 10.1016/j.ttbdis.2010.10.007. PubMed DOI

Haglund M, Gunther G. Tick-borne encephalitis–pathogenesis, clinical course and long-term follow-up. Vaccine. 2003;21(Suppl 1):S11–S18. PubMed

Rostasy K. Tick-borne encephalitis in children. Wien Med Wochenschr. 2012;162:244–247. doi: 10.1007/s10354-012-0101-4. PubMed DOI

Kluger G, Schottler A, Waldvogel K, Nadal D, Hinrichs W, Wundisch GF. et al.Tick borne encephalitis despite specific immunoglobulin prophylaxis. Lancet. 1995;346:1502. PubMed

Waldvogel K, Bossart W, Huisman T, Boltshauser E, Nadal D. Severe tick-borne encephalitis following passive immunization. Eur J Pediatr. 1996;155:775–779. doi: 10.1007/BF02002905. PubMed DOI

Schottler A, Kluger G, Laub MC. Frühsommermeningoenzephalitis - Schwere Verlaufsformen bei Kindern nach passiver immunisierung. Pädiat Prax. 1997;52:429–437. PubMed

Ozherelkov SV, Kalinina ES, Kozhevnikova TN, Sanin AV, Timofeeva TI, Timofeev AV. et al.Experimental study of the phenomenon of antibody dependent tick-borne encephalitis virus infectivity enhancement in vitro. Zh Mikrobiol Epidemiol Immunobiol. 2008;6:39–43. PubMed

Kreil TR, Eibl MM. Pre- and post exposure protection by passive immunoglobulin but no enhancement of infection with a Flavivirus in a mouse model. J Virol. 1997;71:2921–2927. PubMed PMC

Gunther G, Haglund M, Lindquist L, Skoldenberg B, Forsgren M. Intrathecal production of neopterin and beta 2 microglobulin in tick-borne encephalitis (TBE) compared to meningoencephalitis of other etiology. Scand J Infect Dis. 1996;28:131–138. doi: 10.3109/00365549609049063. PubMed DOI

Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994–98: a prospective study of 656 patients. Brain. 1999;122:2067–2078. doi: 10.1093/brain/122.11.2067. PubMed DOI

Alkadhi H, Kollias SS. MRI in tick-borne encephalitis. Neuroradiology. 2000;42:753–755. doi: 10.1007/s002340000396. PubMed DOI

Lorenzl S, Pfister HW, Padovan C, Yousry T. MRI abnormalities in tick-borne encephalitis. Lancet. 1996;347:698–699. doi: 10.1016/S0140-6736(96)91256-8. PubMed DOI

Ruzek D, Salat J, Palus M, Gritsun TS, Gould EA, Dykova I. et al.CD8+ T-cells mediate immunopathology in tick-borne encephalitis. Virology. 2009;384:1–6. doi: 10.1016/j.virol.2008.11.023. PubMed DOI

Semenov BF, Khozinsky VV, Vargin VV. The damaging action of cellular immunity in Flavivirus infections of mice. Med Biol. 1975;53:331–336. PubMed

Sitati EM, Diamond MS. CD4+ T-cell responses are required for clearance of West Nile virus from the central nervous system. J Virol. 2006;80:12060–12069. doi: 10.1128/JVI.01650-06. PubMed DOI PMC

Shrestha B, Diamond MS. Role of CD8+ T cells in control of West Nile virus infection. J Virol. 2004;78:8312–8321. doi: 10.1128/JVI.78.15.8312-8321.2004. PubMed DOI PMC

Ruzek D, Gritsun TS, Forrester NL, Gould EA, Kopecky J, Golovchenko M. et al.Mutations in the NS2B and NS3 genes affect mouse neuroinvasiveness of a Western European field strain of tick-borne encephalitis virus. Virology. 2008;374:249–255. doi: 10.1016/j.virol.2008.01.010. PubMed DOI

Atrasheuskaya AV, Fredeking TM, Ignatyev GM. Changes in immune parameters and their correction in human cases of tick-borne encephalitis. Clin Exp Immunol. 2003;131:148–154. doi: 10.1046/j.1365-2249.2003.02050.x. PubMed DOI PMC

Stangel M, Pul R. Basic principles of intravenous immunoglobulin (IVIg) treatment. J Neurol. 2006;253(Suppl 5):V18–V24. PubMed

Niller HH. Myelodysplastic syndrome (MDS) as a late stage of subclinical hemophagocytic lymphohistiocytosis (HLH): a putative role for Leptospira infection. A hypothesis. Acta Microbiol Immunol Hung. 2010;57:181–189. doi: 10.1556/AMicr.57.2010.3.3. PubMed DOI

Taneichi H, Miyawaki T. High-dose intravenous immunoglobulin treatment. Nihon Rinsho. 2011;69:515–519. PubMed

Kedar R, Shoenfeld Y, Amital H. In: Autoimmune diseases. Khamashta MA, Ramos-Casals M, editor. London: Springer; 2011. The role of intravenous immunoglobulins in the management of acute complex autoimmune conditions; pp. 359–374.

Shoji H, Murakami T, Murai I, Kida H, Sato Y, Kojima K. et al.A follow-up study by CT and MRI in 3 cases of Japanese encephalitis. Neuroradiology. 1990;32:215–219. doi: 10.1007/BF00589115. PubMed DOI

Kleiter I, Jilg W, Bogdahn U, Steinbrecher A. Delayed humoral immunity in a patient with severe tick-borne encephalitis after complete active vaccination. Infection. 2007;35:26–29. doi: 10.1007/s15010-006-6614-2. PubMed DOI

Rabel PO, Planitzer CB, Farcet MR, Kreil TR. Tick-borne encephalitis virus-neutralizing antibodies in different immunoglobulin preparations. Clin Vaccine Immunol. 2012;19:623–625. doi: 10.1128/CVI.05705-11. PubMed DOI PMC

Caramello P, Canta F, Balbiano R, Lipani F, Ariaudo S, De Agostini M. et al.Role of intravenous immunoglobulin administration in Japanese encephalitis. Clin Infect Dis. 2006;43:1620–1621. doi: 10.1086/509644. PubMed DOI

Caramello P, Canta F, Balbiano R, Lipani F, Ariaudo S, De Agostini M. et al.A case of imported JE acquired during short travel in Vietnam. Are current recommendations about vaccination broader? J Travel Med. 2007;14:346–348. doi: 10.1111/j.1708-8305.2007.00140.x. PubMed DOI

Shioya A, Ishii A, Oda A, Ohkoshi N, Takasaki T, Tamaoka A. A case of Japanese encephalitis associated with Parkinsonism and lesions in the thalamus and substantia nigra on magnetic resonance imaging. J Mov Disord Disab. 2010;20:9–14.

Dimaano EM, Saito M, Honda S, Miranda EA, Alonzo MT, Valerio MD. et al.Lack of efficacy of high-dose intravenous immunoglobulin treatment of severe thrombocytopenia in patients with secondary dengue virus infection. Am J Trop Med Hyg. 2007;77:1135–1138. PubMed

Rajapakse S. Intravenous immunoglobulins in the treatment of dengue illness. Trans R Soc Trop Med Hyg. 2009;103:867–870. doi: 10.1016/j.trstmh.2008.12.011. PubMed DOI

Petersen LR, Roehrig JT. West Nile virus: a re-emerging global pathogen. Emerg Infect Dis. 2001;7:611–614. PubMed PMC

Makhoul B, Braun E, Herskovitz M, Ramadan R, Hadad S, Norberto K. Hyperimmune gammaglobulin for the treatment of West Nile virus encephalitis. Isr Med Assoc J. 2009;11:151–153. PubMed

Walid MS, Mahmoud FA. Successful treatment with intravenous immunoglobulin of acute flaccid paralysis caused by west nile virus. Perm J. 2009;13:43–46. PubMed PMC

Shimoni Z, Niven MJ, Pitlick S, Bulvik S. Treatment of West Nile virus encephalitis with intravenous immunoglobulin. Emerg Infect Dis. 2001;7:759. PubMed PMC

Hamdan A, Green P, Mendelson E, Kramer MR, Pitlik S, Weinberger M. Possible benefit of intravenous immunoglobulin therapy in a lung transplant recipient with West Nile virus encephalitis. Transpl Infect Dis. 2002;4:160–162. doi: 10.1034/j.1399-3062.2002.01014.x. PubMed DOI

Haley M, Retter AS, Fowler D, Gea-Banacloche J, O'Grady NP. The role for intravenous immunoglobulin in the treatment of West Nile virus encephalitis. Clin Infect Dis. 2003;37:e88–e90. doi: 10.1086/377172. PubMed DOI

Saquib R, Randall H, Chandrakantan A, Spak CW, Barri YM. West Nile virus encephalitis in a renal transplant recipient: the role of intravenous immunoglobulin. Am J Kidney Dis. 2008;52:e19–e21. doi: 10.1053/j.ajkd.2008.03.042. PubMed DOI

Gergely L, Fazakas J, Mandli T, Gerlei Z, Varga M, Toronyi E. et al.Vesetranszplantált beteg West Nile vírus okozta központi idegrendszeri megbetegedése: elso eset Magyarországon. Aneszteziológia és Intenzív Terápia. 2009;39:132–136.

Rhee C, Eaton EF, Concepcion W, Blackburn BG. West Nile virus encephalitis acquired via liver transplantation and clinical response to intravenous immunoglobulin: case report and review of the literature. Transpl Infect Dis. 2011;13:312–317. doi: 10.1111/j.1399-3062.2010.00595.x. PubMed DOI

Smudla A, Gerlei Z, Gergely L, Varga M, Toronyi E, Doros A. et al.West Nile virus encephalitis in kidney transplanted patient, first case in Hungary: Case report. Intervent Med Appl Sci. 2011;3:80–83. doi: 10.1556/IMAS.3.2011.2.8. DOI

Ben Nathan D, Gershoni-Yahalom O, Samina I, Khinich Y, Nur I, Laub O. et al.Using high titer West Nile intravenous immunoglobulin from selected Israeli donors for treatment of West Nile virus infection. BMC Infect Dis. 2009;9:18. doi: 10.1186/1471-2334-9-18. PubMed DOI PMC

Golomb MR, Durand ML, Schaefer PW, McDonald CT, Maia M, Schwamm LH. A case of immunotherapy-responsive eastern equine encephalitis with diffusion-weighted imaging. Neurology. 2001;56:420–421. doi: 10.1212/WNL.56.3.420. PubMed DOI

Chusri S, Siripaitoon P, Hirunpat S, Silpapojakul K. Case reports of neuro-Chikungunya in southern Thailand. AmJTrop Med Hyg. 2011;85:386–389. doi: 10.4269/ajtmh.2011.10-0725. PubMed DOI PMC

Sakurai T, Kimura A, Tanaka Y, Hozumi I, Ogura S, Inuzuka T. Case of adult influenza type a virus-associated encephalopathy successfully treated with primary multidisciplinary treatments. Rinsho Shinkeigaku. 2007;47:639–643. PubMed

Iwanaga N, Nakamura S, Tanaka A, Fukuda Y, Imamura Y, Miyazaki T. et al.An adult case of influenza-associated encephalitis successfully treated with high dose intravenous immunoglobulins. Kansenshogaku Zasshi. 2012;86:295–299. doi: 10.11150/kansenshogakuzasshi.86.295. PubMed DOI

Yoshidome Y, Hayashi S, Maruyama Y. A case of brainstem encephalitis caused by herpes simplex virus type 1 with possible infection via trigeminal nerve. Rinsho Shinkeigaku. 2005;45:293–297. PubMed

Moschovi MA, Katsibardi K, Theodoridou M, Michos AG, Tsakris A, Spanakis N. et al.Enteroviral infections in children with malignant disease: a 5-year study in a single institution. J Infect. 2007;54:387–392. doi: 10.1016/j.jinf.2006.07.002. PubMed DOI

Cheng MF, Chen BC, Huang TS, Hsieh KS, Chen SN, Liu YC. Clinical application of reverse-transcription polymerase chain reaction and intravenous immunoglobulin for enterovirus encephalitis. Jpn J Infect Dis. 2008;61:18–24. PubMed

Sonneville R, Klein I, de Broucker T, Wolff M. Post-infectious encephalitis in adults: diagnosis and management. J Infect. 2009;58:321–328. doi: 10.1016/j.jinf.2009.02.011. PubMed DOI PMC

Pohl D, Tenembaum S. Treatment of acute disseminated encephalomyelitis. Curr Treat Options Neurol. 2012;14:264–275. doi: 10.1007/s11940-012-0170-0. PubMed DOI

Nishikawa M, Ichiyama T, Hayashi T, Ouchi K, Furukawa S. Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. Pediatr Neurol. 1999;21:583–586. doi: 10.1016/S0887-8994(99)00042-9. PubMed DOI

Ferenczi E, Ban E, Abraham A, Kaposi T, Petranyi G, Berencsi G. et al.Severe tick-borne encephalitis in a patient previously infected by West Nile virus. Scand J Infect Dis. 2008;40:759–761. doi: 10.1080/00365540801995386. PubMed DOI

Khozinsky VV, Semenov BF. Experimental basis of a protocol for the pathogenetic immunotherapy of tick-borne encephalitis. Vopr Virusol. 1982;27:692–696. PubMed

History of Arbovirus Research in the Czech Republic