Enteroviruses

Question 1

Where in the body do enteroviruses replicate?

Answer 1

Oropharynx and intestine, hence why THS and stool are good sample types

Question 2

Patients with deficiencies in which cells are most at risk of severe enterovirus disease?

Answer 2

B cell deficiencies

Question 3

Clinical syndromes of enteroviruses

Answer 3

Respiratory
Pharyngitis/sinusitis/otisis media
Hand foot and mouth/herpangina
Haemorrhagic conjunctivitis
Bornholm disease/epidemic pleurodynia
Pancreatitis
Myopericarditis
Pneumonia
Aseptic meningitis
Encephalitis
AFM
Poliomyelitis

Question 4

Which wild polio serotypes have been eradicated? Where is the remaining serotype circulating?

Answer 4

PV2 and PV3 have been eradicated
PV1 still circulates in Afghanistan and Pakistan

Question 5

Why does vaccine derived poliovirus still circulate?

Answer 5

Due to low vaccine coverage
VDPV is excepted in stool for 3-6 weeks (2 weeks in saliva)
IPV will be required for polio eradication

Question 6

What samples would you request for entero PCR to investigate acute flaccid paralysis? (as per UKHSA guidelines)

Answer 6

Two stool samples 48 h apart

Throat/NPA

CSF

Question 7

Which enterovirus types can cause acute flacid myelitis?

Answer 7

EV-D68, EV-A71, echovirus 11 and polio

Question 8

Clinical symptoms and types of enterovirus causing hand, foot and mouth

Answer 8

Blisters in hands, feet, buttocks and mouth
Fever
Usually mild and self limiting
Can cause serious neurological symptoms

Mostly caused by coxsackie A16

Also A71, cocksackie A5, A9, A10

Question 9

Clinical symptoms of EV-D68 and sample types for testing

Answer 9

Respiratory disease
Pneumonia
Acute flaccid myelitis and cranial nerve dysfunction
Brainstorm and spinal chord lesions

Respiratory sample important as not always detected in stool/CSF

Question 10

Name two enterovirus types causing haemorrhagic conjunctivitis

Answer 10

D-70 and coxsackie A24

Question 11

Epidemiology of EV-A71

Answer 11

Can cause HFMD

Polio like disease/encephalitis/meningitis- under 5 y most at risk

Outbreaks of severe disease with high rates of brain stem encephalitis and 20% mortality in SE Asia - despite worldwide distribution

The most neurotropic non-polio EV

Two inactivated A71 vaccines are licensed in China

Question 12

Transmission route, risk factors, symptoms, when to suspect and how to treat neonatal enterovirus.

Answer 12

Transmission: vertically at birth or from close contact

Risk factors: PUO in mum

Symptoms: first two weeks of life - fever, irritability, lethargy, poor feeding, rash.
Sepsis, meningoencephalitis, myocarditis, pneumonia, hepatitis (most common), coagulopathy

Suspect: in septic baby with high ALT (marker of poor prognosis), thrombocytopenia and deranged clotting

Treatment: High dose IVIG in first 3 days

Question 13

Which enteroviruses are most associated with neonatal disease?

Answer 13

Coxsackie B (80%)
Echovirus
EV-A71

Question 14

Treatment for enterovirus myocarditis/encephalitis

Answer 14

IVIG - but benefits unclear

Question 15

What is the mechanism of action of pleconaril, what are the caveats to treatment?

Answer 15

Enterovirus specific capsid inhibitor, blocks virus uncoating and RNA release

No longer available and no activity against A71

Question 16

Experimental cocktail of drugs which have been used for treating life threatening enterovirus disease

Answer 16

High dose IVIG plus Favipirivir (or molnupiravir) with ribavirin, fluoxetine and nitazoxinide

Case reports only. Aim to hold off infection whilst host immune response reconstitutes

Question 17

Factors impacting develop of enterovirus vaccines

Answer 17

Lack of animal models

Lack of cross reactivity between expansive number of types of EV

Recombination between enteroviruses