hpg/nov 06 Folie 1

A Tick Bite

between

the First and Second TBE Vaccination

Hp. Gnehm, Aarau

hpg/nov 06 Folie 2

Adolescent girl G., 15 years

• Hospital admission July 02 2006

• History: headache the day before admission, on day of hospital admission increasing, piercing, fluctuating.

Fever up to 38,5° C.

Immunizations complete incl. MMR and Hep. B, FSME vaccine doses on May 29 and June 28 2006

Tick bite in endemicity area around June 17 2006

hpg/nov 06 Folie 3

• Personal history:

Twin A born at term, SGA. Twin B, boy, in good health.

At 8 years: recurrent episodes of fever,

clinical presentation and work up negative.

CBC, CRP, ESR normal, IgG, IgA, IgM and IgG-

subclasses normal,

immunization antibodies against T,D,HiB pos.

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• Hospital admission on July 02 2006:

38,8° C, well oriented, adequate reactions, weary, neck stiffness, photophobia, GCS 14-15, circulatory and respiratory systems unremarkable, no neurological signs

• CSF: 215 cells/mm3: 26 mono, 189 poly

tot. protein 0.47 g/l, glucose 3.37mmol/l, lactate 2.26 mmol/l

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• Course:

Transfer after 2 days to ICU (July 04 2006): drowsiness, coma, generalized convulsions,

CCT: signs of generalized brain edema

2 CCTon July 06: increasing brain edema, loss of differenciation of gray and white matter, whitecerebellum sign

Death July 06 2006

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week 22 23 24 25 26 27

FSMEvaccine

1st dose 2nd dose

tick bite hospital

Time table: G. , girl 15 years old

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CT July 04 CT July 06, 04 am CT July 06, 06 am

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• CSF: HSV PCR neg., enterovirus PCR neg., bacterial cultures negative

Borreliosis and FSME IgM and IgG neg.

• Serum: WBC and diff., ESR, CRP normal,

FSME ELISA titer within 4 days: IgM from 41 VE to 62 VE (Virotech-Einh.)

IgG from 28 VE to 34 VE

all other serologies negative

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• Brain autopsy:

Inspection: massive brain edema, signs of herniation

Histology: severe lymphocytic meningoencephalitis

(no signs of ADEM)

Cortex Brain stem

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Further investigations:Klin. Institut für Virologie, Universität Wien:

FSME Virus July 2 July 6

Neutralizing ab 1 : 20 1 : 320

ELISA IgGVIE units

2660 220‘000

ELISA IgM VIE units

„grenzwertig“ > 1000

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Further investigations:Klin. Institut für Virologie, Universität Wien:

FSME RNA PCR July 2 July 7 (brain autopsy)

CSF neg -

Brain stem - pos

Cortex - pos

Cerebellum - pos

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Further investigations:Klin. Institut für Neurologie, Universität Wien:

Immunhistology (cerebellum and brain stem):

FSME viral anigen-antibodies:

positive in the nucleus dentatus

Tests negative for HSV, VZV, CMV, measles, toxoplasmosis

Immunphenotype:

CD68, CD3, OPD4 CD8 immunrecactive T cells

CD20, CD79A positive B cells

Classical, multifocal polioencephalitis, compatible with FSME

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• Diagnosis meningoencephalitis:

history, clinical presentation and course, brainhistology

• Etiology:FSME serology (NT ab, IgM and IgG),

RNA PCR for FSME (wild type) in brain tissue,

immunhistochemistry

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Summary of Prof. Stephan Aberle, Wien:

„Die klinischen Angaben, die Histo, die serologischen Befunde und das PCR Ergebnis sprechen für eine gesicherte Infektion mit FSME bei der Patientin … Die vorliegende Sequenzanalyse spricht für Infektion mit WT Virus.“

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FSME Endemiegebiete 2006

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FSME S

ticho

rte

imAar

gau

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B BAG OFSP UFSP SFOPHFSME___________________________________________________

0

50

100

150

200

250

300

1984 1988 1992 1996 2000 2004

n

Fälle mit neurologischen SymptomenTotalFälle <6 Jahre

Schätzung31.12.2006:n = 270

Zeckenenzephalitis (FSME) 1984 – 2006 (22.8.06)Meldungen der Laboratorien und Ärzte (n=1719)

hpg/nov 06 Folie 18

Impfprophylaxe nach Exposition

Frühsommer-Meningoenzephalitis (FSME) PEP– passiv:

nicht für Kinder/Jugendliche < 14 J– aktiv:

nur möglich bei schon Teilimmunisierten, falls:letzte Impfung mindestens 14 Tage zurückliegt &Zeckenstich weniger als 48h zurückliegt

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• Pathogenesis:– immune competent adolescent girl

– impact of second FSME immunization?

– second FSME immunization administered later thanrecommended post-exposure immunization (PEP)

– no similar case known (Baxter data file)

FSME Immun 0.5ml 19 mio doses SAE 0.99/100‘000 FSME Immun 0.25ml 5 mio doses SAE 1.19/100‘000