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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

HHV6 & HHV7

Dr Kate Ward

UCLH

seizures
SEIZURES

13% (21/160) c. 1O HHV-6

Median age 14 months

2 children hospitalised for seizures

NEJM 331 (1994) 432

slide4

HHV-6 & -7 ANTIBODIES IN BRITISH CHILDREN

Ward. J Clin Virol (2005) 183-193

slide5

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

slide6

ENCEPHALITIS IN FIRST 3 YEARS – THE STUDYDesign: Prospective thro’out UK & Republic of IrelandPopulation: Children aged 2-35 months

3.4.25

slide7

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

slide10

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 1 o hhv 6 infection case 6 age 11 months
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 - -

proof of causation
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 1 o hhv 6 7 cases
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

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
THANK YOU TO:

Microbiologists

Paediatricians

Virologists

BPSU

CDSC

Wellcome Trust