Enterovirus- and parechovirus infection in Dutch children: epidemiology, diagnosis and prognosis

Enterovirus (EV), a picornavirus, is a common cause of infection in children.
The incidence of EV infection in Dutch children is not exactly known. There is
no official registration. EVs cause a broad range of clinical syndromes from
gastro-enteritis to meningitis. The clinical presentation changes between the
several subtypes. Human Parechovirus (HPeV), also a member of the
Picornaviridae, is recently identified, and is associated with similar symptoms
as EV infection. EV and HPeV can be diagnosed with viral cultures, reverse
transcription polymerase chain reaction (PCR) of feces, urine, throat swab,
blood or cerebrospinal fluid (CSF) or with serology. Hypotheses:
(1) EVs are one of the most important viral agents of infection in Dutch
children
(2) EVs are the major cause of meningitis in Dutch children
(3) PCR is more sensitive than viral culture and serology in the detection of
EV and HPeV infection in children
(4) HPeV is a major cause of serious infection in younger children (<=2 year)
with psychomotoric and cognitive develop deficiencies

Primary objectives:
(1) To describe the incidence of EV and HPeV infections in Dutch children
(2) To determine the major symptoms of EV/HPeV infections in children
(3) To evaluate the epidemiology and symptoms of the different subtypes of EV
and HPeV
(4) To compare the sensitivity and specificity of different laboratory
techniques to detect EV or HPeV during infection: viral culture, PCR and
serology
(5) To determine the sensitivity and specificity of the different body fluids
in diagnosis of EV or HPeV infection: feces, urine, throat swab, blood, CSF
(6) To determine the sequelae after an EV/HPeV central nervous system (CNS)
infection till 5 years after infection


Secundary objectives:
(1) To describe the morbidity of EV and HPeV infection (hospitalization,
duration of hospitalization, duration and severity of symptoms, average school-
and work absence, duration use of antibiotics)
(2) To evaluate the use of antibiotics before and after the diagnosis

Observational multicenter study with nested case-control follow-up study. To
identify EV or HPeV infection we will examine feces, urine, throat swab, blood
and CSF. The definition of cases and controle in the follow-up study is as
follows:
Cases: Children with an CNS infection with EN/HPeV, proven with EV/HPeV in
liquor (meningitis or encephalitis)
Control group 1: No EV/HPeV meningitis, however EV/HPeV positivity in feces,
urine, throat swab or blood
Control group 2: No EV/HPeV or other viral (or bacterial) infection proven
Approximately 2 weeks after the infection, the patient will be invited for
check-up for a standardized questionnaire, physical examination and for the
second vena puncture. The further follow-up will consist of taking standardized
questionnaires and developmental and cognitive tests at 6, 12, 24 and 60 months
after the infection.

- 1 extra vena puncture for blood sample (2ml) for convalescent serological
test 15 days after the begin of the infection. This is routineprocedure with
no extra risk involved and will be coupled with the check-up visit by the
paediatrician.
- 4 follow up visits at 6, 12, 24 and 60 months after infection for
standardized questionnaire, physical examination and developmental tests
(m-ABC/ BSID-II).
- Duration: 75 minutes
- Study with minors: burden and risks are extremely minimal. The laboratory
tests are routine acts. The follow-up studies are not invasive. Study with
minors because especially very young children can become very ill from an EV or
HPeV infection.