• Causative agents
• Epidemiology
• Clinical Manifestation
• Laboratory Diagnosis
• Patient Management
• Infection Control Measures
• Reporting of Cases

Enquiry : Please contact the hospital Infection Control Unit or medical microbiologist/virologist.

Causative agents :
The genus Enterovirus belongs to a group of small RNA viruses within the family Picornaviridae. It comprises four species, namely Polioviruses (3 serotypes), Coxsackieviruses (group A: 23 serotypes, group B: 6 serotypes), Echoviruses (31 serotypes) and Enteroviruses (4 serotypes).

Epidemiology :
Enteroviruses enter the body via ingestion. They are shed in the faeces and from the oropharynx. Enteroviral infections tend to peak in summer in temperate regions. Outbreaks of infections have been reported world-wide. Young children are its main target and reservoir but adults can also be infected. The viruses are mainly transmitted by the faecal-oral route but can also be spread by direct contact with respiratory secretions. The incubation period is 3 to 6 days for Hand-Foot-Mouth Disease (HFMD).

Clinical Manifestation :
Enteroviral infections are mostly subclinical. The same virus can cause several different clinical syndromes. Conversely, the same clinical picture can be caused by different enteroviruses, such as meningoencephalitis (Echoviruses, Enterovirus 71); acute flaccid paralysis (Polioviruses; Enterovirus 71; Coxsackievirus A7); myocarditis/pleurodynia (Coxsackievirus B); herpangina (Coxsackievirus A), HFMD (Coxsackievirus A9, A16; Enterovirus 71); acute haemorrhagic conjunctivitis (Enterovirus 70); respiratory infections (Coxsackievirus A21, A24).

• Enterovirus infections in Taiwan have been associated with HFMD and neurological complications in some of the cases. A distinct and new clinical pattern of brain stem failure was described which progressed from the mild early phase (with symptoms of fever, poor appetite, oral/skin manifestations, cough ) lasting up to 3 days to the more severe phase (with symptoms of irritability, insomnia, panic attack, abdominal distension, vomiting, photophobia) followed by the toxic manifestations including apathetic look, sleepiness, myoclonic jerks, hallucinations, shortness of breath, cold sweating, poor peripheral circulation, tachycardia (>160/min), limb weakness, ataxia, conjugated ocular disturbance, and cranial nerve paresis. Further deterioration could result in hypothermia, respiratory disturbance, neurogenic shock, haemorrhagic crisis, cardiopulmonary failure, and ARDS.
• In Hong Kong, most of the EV/EV-71 infections to date were simple uncomplicated cases. However, we believe that the clinical experience from Taiwan could facilitate our early detection of complicated cases.

Laboratory Diagnosis :

1. Standard methods
   • Virus Isolation : Enteroviruses can be isolated by cell culture but this is of variable sensitivity. Specimens (as stated above), except CSF, should be put in viral transport medium (T/M) and kept in low temperature during transport to the laboratory. Serological test is also available for diagnosis but of limited value. Paired serum samples (acute and convalescent) should be taken at least 14 days apart.
   • Viral studies for enteroviruses should focus on hospitalised patients with any of the following conditions :
     • HFMD/Enterovirus infection with rapid clinical deterioration or complications;
     • Children with fever and rapid clinical deterioration;
     • aseptic meningitis / encephalitis;
     • acute flaccid paralysis;
     • myocarditis.
   • Specimens should be taken in the early phase of the disease. The specimens of choice include :
     • faeces (shedding continues up to a few weeks);
     • NPA / throat swab (within the first few days of onset of illness);
     • others as appropriate - vesicle fluid, CSF, eye swab and tissue;
     • paired serum samples.
   • Specimens should be sent to the Government Virus Unit or Virology Laboratory of PWH, following existing arrangement.
2. Rapid Methods
   • Refer to Information on rapid diagnosis for enteroviral infections provided by HA designated centres (appendix 1) for the details.
   • The primary aim of these tests is to provide prompt enteroviral diagnosis for management of patients with severe complications.
   • The tests provided are rapid (Shell vial) culture and molecular technique (RT-PCR) for direct detection.
   • These tests are available at three HA designated centres, namely QMH, QEH and PWH]
   • Doctor in-charge or the hospital microbiologist should consult the medical microbiologist/virologist of the designated centre before ordering any such tests.

Patient Management :

1. At Accident & Emergency Department (AED) / Out-Patient Clinic :
   • Most cases of HFMD/enterovirus infection are mild and do not require hospitalisation.
   • Cases showing the severe symptoms/signs, especially when they are secondary cases in the household, should be considered for hospitalization for investigation and treatment. The following are important warning signs :
     • irritability, insomnia, panic attack, abdominal distension, repeated vomiting, photophobia, sleepiness, myoclonic jerks, hallucinations, shortness of breath, cold sweating, poor peripheral circulation, tachycardia (>160/min), limb weakness, unsteady gait, conjugated ocular disturbance, and cranial nerve paresis.
   • The "Advice on Enterovirus Infection" (see appendix 2) should be given to parents of patients who are discharged with HFMD or fever.
2. In-patient Management :
   • Specific anti-enteroviral agents are not available. Prompt supportive treatment is the mainstay of patient management.
   • Secondary cases from household contact could be more severe and require closer observation.
   • Early detection of signs of CNS involvement (especially brain stem) is important.
   • Patients should be closely monitored for cardiopulmonary decompensation (HR, RR, BP, SaO₂).
   • Careful monitoring and assessment of fluid balance and left ventricular function are important.
   • When deterioration is noted, early intubation is desirable since the patient might progress to pulmonary edema rapidly.
   • Consider left ventricular failure and perform early echocardiogram if patient fails to respond to fluid resuscitation.
   • The use of intravenous immune globulin (IVIG) for the treatment of severe enteroviral infections has been suggested for patients showing signs of encephalitis/myelitis or carditis based on the assumption that it might exert either an immunomodulation effect or anti-viral effect. However, it efficacy has not been fully established. Its use should therefore be regarded as empirical and the patient should be clearly informed.
   • Upon discharge;
     • the "Advice on Enterovirus Infection" should also be given to parents/patients.
     • Remind parents that recovery from HFMD does not necessarily confer protection against other enteroviruses and the patient should therefore maintain personal hygiene and observe precautions especially hand-washing when in contact with other children suffering from HFMD.
   • Inform parents/patients (even if discharged) when the diagnosis of Enterovirus infection is confirmed by the Department of Health.

Infection Control Measures :

• Contact Precautions is the key in preventing hospital outbreak and should be strictly observed.
  1. Wash hands immediately and thoroughly after handling patients secretions or excretions irrespective of whether or not gloves are worn.
  2. Wear gloves and gown during patient-care activities that are likely to involve contact with patient's secretions or excretions.
  3. Put on personal protection (as in Universal Precautions) when carrying out procedures that will generate splashes to mucous membranes.
• Place the patient in a private room or cohorting (i.e. in a room with other patients who has active infection with the same organism) with other patients.
• Restrict the direct contact of patients suffering from HFMD/enterovirus infection with other patients.
• Disinfect the patient items properly by following existing guideline on disinfection.
• Health care workers could also contract the disease from patients and strict compliance to the above recommendations is therefore important. If infected, they should avoid direct patient care especially for infants, neonates or immunocomprised patients, until symptoms resolve.

Reporting of Cases :

1. Ward Staff
   • Inform the hospital's Infection Control Unit of any patients admitted for :
     1. Hand-Foot-Mouth disease (HFMD)/herpangina;
     2. Febrile illness in children with rapid clinical deterioration;
     3. Aseptic meningitis or encephalitis;
     4. Acute flaccid paralysis (AFP);
     5. Myocarditis / Cardiomyopathy.
   • For in-patients under category 2-5 who also has HFMD (i.e. severe complications associated with HFMD), please also fill in the DH report form and send it to the hospital's Infection Control Unit.
   • Inform the hospital's Infection Control Unit of any reported patients whose clinical condition become "critical" (among the four categories of clinical conditions for case reporting).
2. Infection Control Staff
   • Inform Duty Microbiologist daily on cases under categories 2-5 and weekly on HFMD.