Investigation of a cluster of Investigation of a cluster of ggcases of acute flaccid cases of acute flaccid

paralysis associated with paralysis associated with paralysis associated with paralysis associated with EnterovirusEnterovirus D68 infection D68 infection

(EVD68) in children in South (EVD68) in children in South East Scotland East Scotland 2016 2016 East Scotland, East Scotland, 2016 2016

Catriona Waugh Dr Kate Mark Dr Janet Stevenson Catriona Waugh, Dr Kate Mark, Dr Janet Stevenson, NHS Lothian, NHS Fife

F lt f P bli H lth C f A i 2017Faculty of Public Health Conference, Aviemore, 2017

Enterovirus D68 was first discovered in 1962, ,previously one of the rarest enteroviruses with less than 700 confirmed cases golbally between 1962 and 2014Single strand RNA virus – most well known enterovirus is polioTransmission can occur by faeco-oral or respiratory y p yspreadCan cause a range of clinical syndromes –from asymptomatic to acute respiratory infection requiring h i li ihospitalisationSporadically can cause neurological symptoms such as acute flaccid paralysis (AFP)AFP = a complex clinical syndrome: sudden onset of limb weakness in 1 or more limb or respiratory muscles due to disease of lower motor neurons.

Background to EVD68Background to EVD68

In mid August 2014, a large number of cases In mid August 2014, a large number of cases (1153) of EVD68 were detected in USA.107 cases of AFP and 14 deathsA n mbe of EU co nt ies also epo ted an A number of EU countries also reported an increase in severe enterovirus infections with a variety of different strains. yOnly 1 case of AFP in Europe (France).In 2015 - a number of countries also reported sporadic cases of EVD68 with reported sporadic cases of EVD68 with associated acute flaccid paralysis – Wales reported a cluster of cases of EVD68 with t i l G ill i B é t d atypical Guillain-Barré type syndrome.

Cluster included adults and children - 2 cases of confirmed EVD68 with AFP.

Global context 2014Global context 2014--20162016of confirmed EVD68 with AFP.

A review of respiratory samples collected in p y pSouth East Scotland in 2014 was carried out to determine an estimate of circulating EVD68. There was a marked increase in EVD68 There was a marked increase in EVD68 compared to previous years with 74 cases of EVD68 identified in 8359 respiratory samples sent to Specialist Virology Centre in Edinburgh sent to Specialist Virology Centre in Edinburgh. Nearly 30% of of enteroviruses were identified as EVD6861% of EVD68 e e in nde 5 ea olds ith 61% of EVD68 were in under 5 year olds, with majority male (68%)Cases of EVD68 had more severe markers of

f h h ( dinfection than other enteroviruses (admission to hospital, admission to ITU, length of admisison)

Scotland context: 2014Scotland context: 2014

Scotland context: September 2016Scotland context: September 2016

Between September and November 2016, 5 p ,cases of confirmed EVD68 with associated acute flaccid paralysis were reported to the NHS Lothian Health Protection Team by the RHSC.Lothian Health Protection Team by the RHSC.4 confirmed cases presented within a 2 week window in September 2016. 5th case presented in October 2016October 2016Aged between 2-6 years1 case in Fife, 3 in West Lothian, 1 in East LothianLothianAll previously well with history of minor illness only

The clusterThe cluster

All presented with prodromal symptoms of p p y pcoryza and fever. Neurological symptom onset was 1-6 days following prodrome.2/5 children had bulbar symptoms and required 2/5 children had bulbar symptoms and required ventilatory support in ITU (still required at 6 months)Asymmetrical limb weakness was a feature in all Asymmetrical limb weakness was a feature in all children Reflexes and tone were reduced in all children4/5 hild h d f i l i h f i l d4/5 children had facial signs such as facial droop2/5 had autonomic dysfunction (high BP and low HR) )Pain was a feature in all 5 children. Cognition was preserved in all children

Clinical featuresClinical features

CSF MRI Nerve conduction

IVIg

Steroids

Gabapentin

1 High WCC, normal protein, 40% lymphocytes

Abnormal signal pons, diffuse signal grey matter in cervical spinal cord

Suggestive acute motor neuropathy

Yes Yes Yes

2 No Abnormal signal in pons, diffuse signal grey matter in cervical spinal cord

Suggestive acute motor neuropathy

Yes No Yes

cord

3 No Abnormal signal in midbrain, high signal grey matter cervical

l d

No No No Yes

spinal cord

4 No Abnormal signal pons, high signal medulla, increased signal in grey

No Yes No Yes

increased signal in grey matter of cervical cord

5 High WCC, normal protein, predominantly

Abnormal signal medulla, through cervical spinal cord to T1/2

No Yes Yes Yes

predominantlylymphocytes

cord to T1/2, enhancement facial nerves bilaterally

Investigations & management

NHS Lothian urgently formed an IMT with multi-disciplinary NHS Lothian urgently formed an IMT with multi disciplinary input when initial 2 cases confirmed and 2 cases suspected. Case definitions agreedCase definitions agreedTrawling questionnaires were carried out by NHS Lothian HPT Parents of cases were interviewed shortly after cases were confirmed. Questionnaire covered previous 4 weeks Questionnaire covered previous 4 weeks. Exposures – vaccinations, travel, environmental, school/nursery, sick contacts were all explored - no common exposures identified common exposures identified Temporal and geographical link notedSurveillance data extracted for analysis

E id i l i l i i iE id i l i l i i i

yClinical alert letter sent to primary and secondary careCommunications statement prepared

Epidemiological investigationEpidemiological investigation

MapMap

Epicurve of EVD68 cases: South East Scotland

6

p cu e o 68 cases Sout ast Scot a d2014

4

5

1

2

3

0

1

EpicurveEpicurve: 2014: 2014

Epicurve of EVD68 cases: South East Scotland 4

p cu e o 68 cases Sout ast Scot a d2016

Non-neurological

Neurological3

Neurological

1

2

0

1

EpicurveEpicurve: 2016: 2016

Emerging infection: significant distress for Emerging infection: significant distress for families – uncertain outlook, poor prognosis, lack of informationLong term medical and psychological support Long-term medical and psychological support for children and familiesHCW support – lack of evidence base for ppmanagement Media interest – “The new polio”Challenges of infection control including Challenges of infection control, including communityPlanning services – ITU beds, isolation g ,precautions, long term careLargest cluster of confirmed EVD68 in Europe

Challenges for Public HealthChallenges for Public Health

Urgent need for an international collaborative gworkingRole of surveillance of circulating EVD68 – ‘tip of the iceberg’ as seen in USA in 2014the iceberg as seen in USA in 2014Surveillance in Europe challenging – not all countries have access to typing in laboratories. Missing data for Eastern Europe Missing data for Eastern Europe. Need to gain an understanding of of condition and risk factors for contracting EVD68, and de eloping AFPdeveloping AFPPreparedness for emerging infection – services, infection control and limiting anxiety Management of clinical conditionImproving long-term outcomesRole for a vaccine?

Future considerationsFuture considerationsRole for a vaccine?

We would like to thank:We would like to thank:◦ Dr Kate Templeton and Virology team in NHS LothianLothian◦ Dr Margaret Hanna and HPT in NHS Fife◦ Dr Paul Eunson and Clinical team at RHSC◦ Infection Control Team at RHSC◦ HPS

AcknowledgementsAcknowledgements

Questions?Questions?Questions?Questions?

Hay F, Horsley J, Guerendiain D, Hardie A, Harvala H, Templeton K E E t i D 68 i Edi b h 2014 2015 Cli i l d K.E. Enterovirus D-68 in Edinburgh, 2014-2015: Clinical and Epidemiological Features of Enterovirus D-68 in Comparison to Rhinovirus and Enterovirus InfectionHolm-Hansen CC, et al. Global emergence of enterovirus D68: a , gsystematic review. Lancet Infect Dis. 2016;16:e64–75.Lang M et al. Acute flaccid paralysis following enterovirus D68 associated pneumonia, France, 2014. Euro Surveill. 2014;19.Messacar K et al (2016) 2014 outbreak of enterovirus D68 in Messacar, K. et al. (2016), 2014 outbreak of enterovirus D68 in North America. J. Med. Virol., 88: 739–745. Pariani, E. Et al. (2017). Letter to the editor: Need for a European network for enterovirus D68 surveillance after d t ti f EV D68 f th B3 li i S d d detections of EV-D68 of the new B3 lineage in Sweden and Italy, 2016 . Eurosurveillance, 22(2), 30440. Williams CJ et al. Cluster of atypical adult Guillain-Barrésyndrome temporally associated with neurological illness due to y p y gEV-D68 in children, South Wales, United Kingdom, October 2015 to January 2016. Euro Surveill. 2016;21(4).

ReferencesReferences