7/5/2019

1

Everything Enterovirus

EV PCR

Colby-Brown Collaborative

45th Annual “Progress in Pediatrics”

Michael Koster, MD

July 12th, 2019

Disclosures

I have no financial disclosures

No off label medication recommendations

Objectives

• Review the various clinical presentations of

enteroviruses

• Identify signs and symptoms that require

immediate attention

• Increase awareness of emerging infectious

diseases

http://www.aafp.org/afp/990515ap/2761.htmlhttp://www.aafp.org/afp/990515ap/2761.html

7/5/2019

2

Picornaviruses

Rhinoviruses Enteroviruses

Hepatoviruses

Polioviruses Enteroviruses A-D

Over 70 serotypes:

Group B coxsackie

Echovirus 11

EV-D68, EV-A71Severe

Disease

Parechoviruses*

Enteroviruses

• Small single-stranded RNA viruses

• Replicate in lymph tissue—viremia

• Incidence: 10-30 million/year

75,000 meningitis

2,500 neonatal sepsis

• Predominately in summer and fall

• Immunodeficient hosts and neonates are at risk for serious infection

7/5/2019

3

Diagnostic Tests for Enteroviruses

• Viral culture

– Specimens: stool, oropharynx, CSF

– quick growth 4 to 7 days

– not all enteroviruses grow (e.g. Coxsackie B)

• Serology - helpful in epidemics/myocarditis

• PCR is now gold standard

– Not able to type EV

– Can’t distinguish enterovirus from rhinovirus in respiratory samples

Case Presentation 1

• CC: “My baby has fever, not eating well”

• HPI: 37+ wk BB, NSVD

– Discharged with mom on DOL# 2

– Sweating with feeds, last 2 days

– Presents DOL# 10 with fever, and in extremis

7/5/2019

4

Case Presentation 1

• PMx: Single umbilical artery, ECHO nl

• IMM: Hep B #1 at birth

• Maternal Hx: G3P2, GBS+ tx with AMP, other

prenatal labs negative

– Mom had fever and induced delivery due to

concern for chorioamnionitis

• FSHx: 2 y/o sibling with URI sx/sx and a

healthy 5 y/o sibling

Case Presentation 1

• PE: T 95, RR 80, HR thready, BP 40/palp

• Gen: pale, listless

• HEENT: tense fontanelle

• CV: holosystolic murmur

• Abd: hepatomegaly

• Ext: cool, cap-refill >>2sec

• ABG: 7.01/31/76/78/-22

Case Presentation 1

• WBC: 30.8>13.5/41.2

7/5/2019

5

Infant Disease Manifestations

• Sepsis

• Pneumonia

• Meningioencephalitis

• Myocarditis

• Hepatitis

– Coagulopathy

Presentation: Neonates

• 2/3 of mothers report illness: fever, URI, etc

• Neonates: fever or hypothermia, irritability,

lethargy, anorexia, decreased perfusion,

jaundice, abdominal distention, emesis,

occasionally diarrhea

• Biphasic pattern: mild dz—better—severe dz

– This is most common w/ myocarditis

7/5/2019

6

Risk Factors: Neonates

• Absence of neutralizing antibodies

• Maternal illness prior to delivery

• Prematurity

• Illness onset in first few days of life

• Multiorgan involvement

• Severe hepatitis

• Positive serum viral culture

• Infecting serotype

National Enterovirus Surveillance System – CDC

Passive reporting

Case 2

• CC: “He’s having fever and his head hurts”

• HPI:12 yo, 4 days headache, 3 days fever,

mild photophobia, emesis x3

• PMHx: healthy

• FSHx: no chronic illnesses, lives with

parents, 16 yo sib well

7/5/2019

7

Case 2

• PE: T 102, HR96, RR 22, BP 102/74

• Gen- well appearing

• HEENT: mild neck stiffness, OP clear

• CV: RRR, no M/R/G

• Pulm: CTA, no W/R/C

• Ext: cap refill

7/5/2019

8

Performance of BMS

0

200

400

600

800

1000

1200

1400

1600

1800

Number of

Patients

0 1 or more

Bacterial Meningitis Score

Aseptic meningitis

Bacterial meningitis

JAMA 297(1): 52-60, 2007

Considering Lyme Meningitis

• Rule of 7’s

–

7/5/2019

9

Seasonality of EV

CDC -NESS

PNAS first published March 5, 2018

Outbreaks – Emerging Infections

• 2012 – Integumentary

• 2014 – Pulmonary

• 2014-18 – CNS

7/5/2019

10

Case 3 - 2012

• CC: “her eczema got really bad”

• HPI: 16mo with hx of eczema, presents

with spreading rash, 3 days fever, no URI

symptoms

• FSHx- father with asthma, atopic

dermatitis, lives with parents, only child, in

daycare

Case 3

• PE: T 99.9 HR 102 RR 26 BP 80/64

• Gen: non-toxic, large diffuse rash covering

more than 50% of the body

• HEENT: oral mucosa normal, OP clear

• Skin: rash confluent in extensor areas,

with areas of small “punched-out lesions”

that satellite the larger areas, some skin is

denuded and appears raw

• DDX?

7/5/2019

11

7/5/2019

12

Coxsackievirus A6 (CVA6)

Mathes et al., Pediatrics 2012; 132:e149-157

7/5/2019

13

HFMD

http://aapredbook.aappublications.org.revproxy.brown.edu/content/images/large/2006/1/042_22.jpeghttp://aapredbook.aappublications.org.revproxy.brown.edu/content/images/large/2006/1/042_22.jpeghttp://aapredbook.aappublications.org.revproxy.brown.edu/content/images/large/2006/1/042_14.jpeghttp://aapredbook.aappublications.org.revproxy.brown.edu/content/images/large/2006/1/042_14.jpeg

7/5/2019

14

Mathes et al., Pediatrics 2012; 132:e149-157

Vesiculobullous CVA6

Gianotti-Crosti Syndrome

41

7/5/2019

15

Case 4 - 2014

• CC: “I can’t catch my breath”

• HPI: 9 yo with hx of wheezing as a child,

URI 4d, acute respiratory distress 1d

• PMHx: bronchiolitis at 1 and 2yo

• FHx: no asthma in the family

• SocHx: no smokers at home, no allergy

precautions taken at home

Case 4

• PE: T 98.9 HR 88 RR 32 O2Sat 93%

• Gen: moderate resp distress

• Lungs: tachypnea, intercoastal rxn’s,

diffuse bilateral wheeze, no crackles

• CV: RRR no M/R/G

• Abdomen: belly breathing, no HSM

• Ext: cap refill < 2secs

• Viral testing positive for Rhino/Enterovirus

7/5/2019

16

What’s going on here?

• In 2014, EV D-68 swept the country

– Accounted for 68% of identified types in 2014

– Four-fold increase from last highest reported

• Mostly asthmatics, hx of wheeze, but also

many with no hx of wheeze or asthma

• Asthma exacerbations “worse” than typical

• Treatment: steroid+beta-agonist therapy

7/5/2019

17

National Enterovirus Surveillance System – CDC

Passive reporting

Case 5 - 2018

• CC: “he’s arm is weak, and slurred

speech”

• HPI: 8 yo, URI 10d prior, p/w arm and leg

weakness, ataxia, dysarthria, new fever

• PMHx: eczema, concussion at 7yo

• SocHx: parents A&W, 3 sibs, 2 also had

URI 1-2wks ago

Case 5

• PE: T 101.5, HR 96 RR 22, BP 102/68

• Gen: seems distressed, not walking

• HEENT: drooling

• Neck: supple, mild shotty LAD

• CVS and Pulm- normal

• Neuro: CN 7 palsy, 3/5 UE strength, 4/5

LE strength, absent UE and decreased LE

reflexes

7/5/2019

18

Case 5

• MRI: Brain stem enhancement, and

cervical grey matter, including anterior

horn enhancement spanning 3 vertebral

spaces

What’s going on here?

7/5/2019

19

AFM: Features in Children

• weakness and loss of muscle tone and

reflexes in the arms or legs

• facial droop or weakness

• difficulty moving the eyes

• drooping eyelids

• difficulty swallowing

• slurred speech

Diagnosis

• Acute flaccid limb weakness

• MRI: spinal cord gray matter dz, spanning

one or more intervertebral spaces

• Pleocytosis: >5 WBC in CSF

• Pathogen testing: CSF, blood, stool and

respiratory specimens should be obtained

Treatment

• No clear definitive treatment

• Main empiric therapies

– IVIG

– Steroids

– Plasma exchange

• Considerations:

– Fluoxetine

– Antivirals

7/5/2019

20

Enteroviruses in AFM

• EV-D68 related to rhinoviruses

– clustering with AFM

– most commonly detected

• EV-A71 related to poliovirus

– worldwide outbreaks with neuroinvasive dz

• Strong association with EVs

– no absolute causality

– needs further investigation

Take Homes

• EV in neonates has high mortality rate

– Poor feeding, diaphoresis– myocarditis

• EV is seasonal and associated with several

recent outbreaks

• Limb weakness, swallowing/speaking

difficulties, and/or facial droop need

immediate attention

Post Lecture Question 1

• In 2014, an outbreak of acute respiratory

illness occurred in the United states

among children. What specific enterovirus

was isolated most frequently?

A. EV-A71

B. CVA16

C. EV-D68

D. Echo 11

7/5/2019

21

Post Lecture Question 2

• In addition to Hand Foot Mouth Disease,

CVA6 has been associated with which

other dermatological descriptions?

A. Lymphangitis

B. Eczema coxsackium

C. Vesiculobullous lesions

D. Delayed nail changes

E. All the above

F. B,C,D only

Post Lecture Question 3

• The majority of Enteroviruses and their out

breaks have typically occurred during what

time of the year?

A. Winter

B. Spring

C. Autumn

D. Early Summer