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HHV6 & HHV7. Dr Kate Ward UCLH. 3.3.24. SEIZURES. 13% (21/160) c. 1 O HHV-6 Median age 14 months 2 children hospitalised for seizures. NEJM 331 (1994) 432. HHV-6 & -7 ANTIBODIES IN BRITISH CHILDREN. Ward. J Clin Virol (2005) 183-193.
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HHV6 & HHV7 Dr Kate Ward UCLH
SEIZURES 13% (21/160) c. 1O HHV-6 Median age 14 months 2 children hospitalised for seizures NEJM 331 (1994) 432
HHV-6 & -7 ANTIBODIES IN BRITISH CHILDREN Ward. J Clin Virol (2005) 183-193
1O HUMAN HERPESVIRUSES-6 & -7 (HHV-6/-7) INFECTIONSMAY BEIMPORTANT CAUSES OF ENCEPHALITIS IN 1ST 3 YEARS BRITISH ISLES-WIDE SURVEY STARTED OCT 1998USING THE NETWORK OF THE BRITISH PAEDIATRIC SURVEILLANCE UNIT (BPSU) 3.4.23
ENCEPHALITIS IN FIRST 3 YEARS – THE STUDYDesign: Prospective thro’out UK & Republic of IrelandPopulation: Children aged 2-35 months 3.4.25
ENCEPHALITIS IN FIRST 3 YEARS – THE STUDYCase ascertainment: BPSU via telephoning reportingReporting definition: Suspected encephalitis &/or severe convulsions c fever Follow up of cases: Regardless of aetiologyLaboratory analysis: HHV-6 & -7 at UCL Other infections at local labs 3.4.27
HHV-6 & -7 IgG AVIDITY TESTS Use indirect immunofluorescence: 1. Ag fixed on slide. 2. Incubate with test serum. 3. Wash off serum +/- urea (Urea breaks low avidity Ag-Ab bond) 4. Incubate with FITC-anti human IgG 5. Compare ab titres – 8-FOLD REDUCTN = LOW AVIDITY Ward et al., J. Clin. Micro 2001 Ward et al., J. Virol. Methods 2002 3.5.4.
EXAMPLE: 1O HHV-6 INFECTIONCase 6 - Age: 11 months _______________________________________Days Serum HHV-6 IgG HHV-7 IgG DNA Titre Avidity Titre Avidity _____________________________________________ 3 <8 - <8 - HHV-6 7 <8 - <8 - HHV-6 13 2048 Low NT - - 58 512 High <16 - -
QUESTION:HAVE THE1O INFECTIONS COINCIDED BY CHANCE WITH NEUROLOGICAL DISEASE?
HHV-6 1O infections 13 v 1.66 expected P<0.001 HHV-7 1O infections 14 v 1.34 expected P<0.001 PROOF of CAUSATION
Comparison of 1O HHV-6 & -7 cases HHV-6HHV-7 No. of cases 13 15 Days in hospital 9 5 Max temperature O C 39 38.7 No. c. convulsions None 1 0 <15 minutes 2 1 15-30 minutes 3 1 >30 minutes (status epilepticus) 7 13 No. ventilated/sedated 6 6
CONCLUSIONS 1O HHV-6 & -7 infections: 1. Are equally important causes of febrile status epilepticus in the first 2 years of life. 2. Burden of disease at c. one year old around time of MMR vaccine. HHV-6/7 tests needed to exclude misdiagnosis of neurological disease as a vaccine reaction.
THANK YOU TO: Microbiologists Paediatricians Virologists BPSU CDSC Wellcome Trust