EV71 (Enterovirus 71) Neurological Disease
Queensland Health Guidelines for Public Health Units
To be read in conjunction with Acute Flaccid Paralysis (AFP) and Poliomyelitis guidelines.
Full revision of guideline
The infectious agent is enterovirus 71.
Aseptic meningitis, encephalitis or AFP.
NB: while clinical evidence is required for classification/reporting purposes, only AFP is clinically notifiable under the Public Health Act.
Laboratory definitive evidence
Detection of enterovirus 71 by nucleic acid testing in CSF, throat swab, nasopharyngeal aspirate, faeces or vesicle swab
isolation of enterovirus 71 in CSF, throat swab, nasopharyngeal aspirate, faeces or vesicle swab.
NB: while laboratory evidence is required for classification/reporting purposes, EV71 is not laboratory notifiable under the Public Health Act.
Community outbreak criteria
Two or more cases within a one month period.
Attending Medical Practitioners/Medical Superintendents (or Delegates):
To notify on a provisional clinical diagnosis of AFP, by telephone or facsimile.
The public health unit should immediately notify the Communicable Diseases Branch (CDB) of confirmed and probable cases of EV71 neurological disease.
While AFP and poliomyelitis are notifiable conditions under the Public Health Act, EV71 neurological disease is not. The following case definitions should be used for public health response purposes.
A confirmed case requires both clinical and laboratory definitive evidence.
A probable case requires clinical evidence and an epidemiological link to a confirmed case of EV71.
To identify outbreaks so that appropriate public health action can be taken.
EV71 was first identified in 1969. It can cause both endemic and epidemic disease, predominantly of a mild nature eg. hand foot and mouth disease (HFMD) but also exhibiting a varying incidence of neurological disease. While some strains are more neurovirulent than others, the molecular genetics of neurovirulence are poorly understood. Understanding of endemic circulation of EV71 is limited as most studies have been done in outbreak situations.
Two patterns of EV71 neurological disease outbreaks have been described. Relatively small outbreaks with occasional patient deaths have been reported in developed countries including the United States, Sweden, Japan and Australia. Larger outbreaks with higher numbers of deaths have been reported in Eastern Europe (Bulgaria and Hungary) in the 1970s and in Asia (Taiwan, Malaysia and China) since the 1990s. Some of these outbreaks have been associated with HFMD outbreaks while some have not. While small outbreaks have also been reported in Asian countries, it is unclear why there have been no large outbreaks in developed countries.
In Australia, small outbreaks of EV71 neurological disease have been reported in 1972 (Melbourne - 39 cases), 1986 (Melbourne - 33 cases/Sydney - number of cases unclear) and 1999 (Perth - 14 cases).
The spectrum of illness in EV71 infection is varied. It usually causes a mild or asymptomatic infection. The most common clinical manifestations of EV71 infection are HFMD and herpangina.
EV71 infections have the propensity to involve the central nervous system (CNS). They can be complicated by a range of neurological diseases including encephalitis, aseptic meningitis and acute flaccid paralysis. The condition can be complicated by a rapidly fatal neurogenic pulmonary oedema.
Other less common manifestations include acute respiratory disease, myocarditis and other exanthems.
Humans, particularly young children.
EV71 infection is transmitted from person to person by direct contact with nose and throat discharges, saliva, fluid from blisters or from the faeces of infected people.
There are high rates of transmission in child care settings and within households.
The usual incubation period for HFMD is 3-5 days. It is not clear whether the incubation period for neurological disease differs.
The disease is infectious in the acute stage of illness and for as long as the virus is present in faeces, which could be up to several weeks.
Most symptomatic infections occur in children younger than 5 years of age with a peak incidence at 1 year of age. Very young children have a higher risk of developing encephalitis and AFP.
Confirmed and Probable Cases
EV71 neurological disease should be considered in any child under the age of 5 years who has aseptic meningitis, acute flaccid paralysis or encephalitis of unknown cause. Early recognition of the complications and aggressive management in facilities with paediatric intensive care support is necessary for the effective management of severe disease.
An incident management team should be convened for a single confirmed case.
In consultation with the attending medical practitioner, determine if the case attends childcare or another institution, and if there are any associated probable cases or recent HFMD cases. Arrange the collection of specimens for examination for EV71 for all probable cases where not already collected. Specimens for EV71 isolation should be collected as soon as possible after the onset of illness. The specimens (that may include CSF, NPA, throat swab, faeces and vesicle swab) should be sent immediately in viral transport medium at 4° Celsius to the virology laboratory of Royal Brisbane and Women’s Hospital or Townsville General Hospital. Upon detection or isolation of the enterovirus, specimens will be forwarded to Forensic and Scientific Services for typing.
NB: Routine specimen collection from uncomplicated cases of HFMD is not recommended.
In all cases of AFP in children less than 15 years of age, the Australian Paediatric Surveillance Unit (APSU) questionnaire should be completed (http://www.vidrl.org.au/labsandunits/polio/forms/qninitial.doc) and sent to the National Polio Reference Laboratory at the Victorian Infectious Disease Research Laboratory (VIDRL) with a copy to APSU as listed on the form. A further questionnaire will be sent by APSU to the treating clinician to complete at 60 days after the onset of illness (http://www.vidrl.org.au/labsandunits/polio/forms/qnfollowup.doc).
If the child is hospitalised, isolate with contact precautions.
Children with EV71 neurological disease should be excluded from childcare settings and schools until the virus is no longer being excreted in the faeces.
Children with HFMD should be excluded from child care settings and schools until all blisters have dried.
Advise the case/parents of the nature of the infection and its mode of transmission.
Any person in direct contact (that is, contact with nose and throat discharges, saliva, fluid from blisters or faeces) with the case, in settings including institutional (eg. school or child care), household, work or social.
Look for additional cases of neurological disease, especially in children. Also check whether any recent HFMD cases. Encourage prompt reporting of neurological disease among contacts to the relevant PHU.
Advise contacts of the nature of the disease and its mode of transmission. Emphasise the importance of good personal hygiene, particularly hand washing. Advise disinfection of contaminated surfaces with household bleach (at strength of 1000ppm).
More than one case of EV71 neurological disease over a one month period is considered an outbreak.
Once an outbreak has been declared the following strategies should be considered:
- Increased awareness: Alert relevant stakeholders eg. childcare settings, schools and health care professionals to the outbreak and provide advice on the prompt recognition of cases and infection control practices.
- Enhanced surveillance:
a. Ask Forensic and Scientific Services to report all positive EV71 test results.
b. Request relevant clinicians eg. emergency departments and paediatric units to report confirmed and probable cases of EV71 neurological disease
c. Consider asking relevant clinicians eg. GPs and settings eg. childcare to report HFMD cases/outbreaks to their respective public health units.
- Interrupting transmission:
a. Advise relevant stakeholders eg. childcare settings, schools and health care facilities to reinforce infection control practices including frequent hand washing, disinfection of soiled clothing, toys and surfaces and ensuring isolation/exclusion of affected children.
b. Closures of child care facilities may need to be considered in exceptional circumstances. When closure is necessary, they should remain closed for at least two incubation periods (10 days) from the date of onset in the last case.
Personal hygiene and infection control measures.
A human vaccine is currently not available.
In the event of an outbreak, prepare a report of the investigation and response for the Communicable Diseases Branch, Queensland Health, on request.
Gilbert GL, Dickson KE, Waters MJ, et al. Outbreak of enterovirus 71 infection in Victoria, Australia, with a high incidence of neurologic involvement. Paediatr Infect Dis J 1988; 7(7):484-8.
Kennett ML, Birch CJ, Lewis FA, et al. Enterovirus type 71 infection in Melbourne. Bull World Health Organ 1974;51:609-615.
McMinn P, Stratov I, Nagarajan L, et al. Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot and mouth disease in Western Australia. Clin Infect Dis 2001;32:236-242.
McMinn P. An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 2002;26:91-107.
Sanders SA, Herrero LJ, McPhie K, et al. Molecular epidemiology of enterovirus 71 over two decades in an Australian urban community. Arch Virol 2006;151:1003-1013.