Enterovirus  71 (EV71)

EV71 is one of a number of non-polio enteroviruses associated with an increased likelihood of neurological complications. This strain has caused several outbreaks in NSW in recent years, with affected children presenting with an acute febrile illness and neurological complications including meningitis, encephalitis, and acute flaccid paralysis. This can be sometimes followed by rapidly progressive, and potentially fatal, cardio-respiratory collapse due to neurogenic pulmonary oedema.

During EV71 outbreaks people are predominantly affected with mild forms of disease, such as hand, foot and mouth disease (HFMD), but in a small number of cases neurological disease can occur.

Children under 5 years of age, particularly those under 2 years, are most likely to develop severe disease. Hand, foot and mouth disease (HFMD), or a history of contact with a case of HFMD, are occasional but not consistent findings in these children.

Signs of complicated EV71 infections include the following:

• Myoclonic jerks, particularly in sleep
• Urinary retention
• Ataxia, weakness, or any focal neurological signs​
• ​Hypertension and/or bradycardia
• Severe, unexplained or persistent tachycardia or poor perfusion
• Altered level of consciousness or excessive irritability
• Tachypnoea or any other signs of respiratory distress
• ​Pulmonary oedema on chest X-ray

 Human parechovirus (HPeV)

HPeV was detected in a number of neonates and young infants admitted to NSW hospitals in spring/summer 2013 and again in 2015. Infants presented very unwell with a rapid onset of acute sepsis-like symptoms. This was often followed by an erythematous, often confluent rash. There were also a number of cases involving abdominal complications such as volvulus, intussusception and bowel ischemia.

Children under 3 months of age are most likely to develop severe disease, but older infants may also be at risk. Most recover with supportive treatment.

Signs of complicated HPeV infections in neonates or young infants with sepsis-like illness and fever >38°C include the following:

• ​Excessive irritability and appearing to be in pain
• ​Distended abdomen, diarrhoea
• ​Myoclonic jerks
• ​Seizures
• ​Unexplained or persistent tachycardia
• ​Altered level of consciousness
• ​Tachypnoea or any other signs of respiratory distress
• ​Hepatitis

Enterovirus D68 (EV-D68)

EV-D68 is known to cause mild to severe respiratory illness, ranging from fever, rhinorrhoea, cough and myalgia, to wheezing and difficulty breathing resulting in hospital admission. It has also been associated with cases and clusters of polio-like neurological symptoms, including paralysis and meningo-encephalitis.

Although EV-D68 has only rarely been detected in Australia, there has been increased reporting of cases overseas in recent years, including many case reports from the USA and Canada during 2014. The US CDC reported additional cases in 2016. Infants, children, and teenagers are believed to be more likely to have symptomatic infections and complications. Children with asthma may have a higher risk for severe respiratory illness caused by EV-D68 infection.

EV-D68 should be considered as a possible cause of disease in patients with severe unexplained acute respiratory infection and/or with unexplained neurological symptoms, when:

• other respiratory virus screens are negative OR
• if an enterovirus is initially detected.

In particular, EV-D68 should be suspected for clusters of severe acute respiratory disease, or unexplained neurological symptoms.

Initial management - enteroviruses and HPeV

Infants presenting to NSW hospitals with a fever, sepsis-like signs and/or neurological signs, including excessive irritability, should be assessed and treated for suspected sepsis using local protocols and discussed with an Emergency Consultant or Paediatrician. Cases presenting outside of a hospital setting should be immediately transferred to an Emergency Department for assessment. 

• Always consider the possibility of bacterial meningitis, including invasive meningococcal disease, and empirically treat.
• Well children with uncomplicated EV infections (e.g. with fever, pharyngitis, rash including HFMD) may be discharged with follow-up planned and clear advice given regarding warning signs. Children should be isolated at home until the rash, if present, has gone, all blisters have dried up and any fever has settled.
• Consider enterovirus infection, especially during summer and autumn, as a possible cause of acute, unexplained severe acute respiratory illness, even if the patient does not have fever.
• Consider laboratory testing of faecal or respiratory specimens for enteroviruses; and consider enterovirus typing for specimens that test positive for enterovirus in consultation with Infectious Diseases (see testing advice and contact details below).
• Report suspected clusters of unexplained severe acute neurological or respiratory illness to your local public health unit on 1300 066 055. Non-polio enteroviruses and HPeV are not notifiable infections, but local public health units can assist with outbreak control and prevention activities.

Investigations

Collect a stool specimen (or viral rectal swab) and throat swab or NPA for enterovirus PCR. A stool specimen is preferable to a rectal swab.

• If CSF is collected it should also be sent for routine microbiology, culture and sensitivities (MCS), biochemistry (glucose and protein) and enterovirus PCR (+/- other investigations, e.g. HSV PCR). Urine cultures can also help to detect bacterial sepsis. Human parechovirus (HPeV) PCR should also be requested in infants less than 12 months of age.
• Note that standard enterovirus PCR will not usually differentiate between particular enterovirus stains and will not detect human parechoviruses.
• HPeV PCR and enterovirus strain differentiation is available at some public health reference laboratories, such as NSW Health Pathology - Prince of Wales Hospital Laboratory (SAVID), the Children’s Hospital Westmead (CHW), NSW Health Pathology -  ICPMR at Westmead Hospital, and the Victorian Infectious Diseases Reference Laboratory (VIDRL) in Melbourne. Confirm with the laboratory that the specialist testing is available prior to sending clinical samples.
• If CNS imaging is required note that MRI is more sensitive for the detection of brain abnormalities than ultrasound.

Referral for specialist Paediatrician review is recommended after recovery from the acute illness in cases of infant parechovirus or severe enterovirus infection for assessment and advice regarding on-going management and follow-up.

Infection prevention and control

Enteroviruses and parechoviruses are spread from person to person by contact with respiratory secretions or faeces of infected people.

Standard precautions should be supplemented with contact and droplet precautions, and hand hygiene re-enforced.

Further advice on clinical management

Consult with infectious disease clinicians at the Children’s Hospital Westmead (02 9845 0000 pager 6675) or Sydney Children’s Hospital (02 9382 2222 pager 44893 or via the switchboard).