Discover diagnostic biomarkers for disease severity. Increase the insight in the epidemiology of viral infections in the primary, secondary and tertiary care facilities and in the pathogenesis of and immunological response against viral infections…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Identification and validation of genes and proteins that can be used as
diagnostic biomarkers.
Secondary outcome
1. To study the epidemiology of acute LRTI*s in children presenting at primary,
secondary and tertiary care facilities. We specifically analyse:
a) The distribution of the causative viruses at the three levels of
care facilities.
b) The individual role of the various viruses in causing respiratory
tract disease in children.
c) The burden of disease by the various viruses on the health care
facilities.
2. Identification of viral host interactions and factors influencing
susceptibility for viral infections and / or severity of disease.
3. Identification of novel respiratory viruses.
Background summary
Viral lower respiratory tract infections (LRTI*s) are a leading cause of
morbidity and mortality in young children. The most commonly identified viruses
are Respiratory Syncytional Virus (RSV), rhinovirus, parainfluenzavirus, human
metapneumovirus and influenzavirus. We expect that additional novel viruses may
be discovered in the near future. Currently, insight in the clinical
epidemiology of viral respiratory infections in children is limited, due to the
fact that studies have focussed on groups of children presenting either at
primary care facilities or in the hospital. In addition, the variability in
disease severity caused by a particular virus is not well understood, neither
is the interaction between virus and host at the molecular and cellular levels.
A better understanding of the pathogenesis and immune response of the host is
very important for the development of new therapeutic and preventive strategies
and optimalisation of diagnostic tools (biomarker discovery).
Study objective
Discover diagnostic biomarkers for disease severity. Increase the insight in
the epidemiology of viral infections in the primary, secondary and tertiary
care facilities and in the pathogenesis of and immunological response against
viral infections.
Study design
This is a prospective descriptive multi-centre study for viral LRTIs in
children. We expect to include 1000 children (0-6 years) presenting at the
primary, secondary and tertiary care facilities during three consecutive years.
Children with an acute viral LRTI will be scored on clinical symptoms, the need
for nasogastric feeding and/or oxygen supplementation. Nasopharyngeal aspirates
(NPA) will be analysed for the presence of viruses and bacterial colonisation.
Samples from patients that remain negative will be used for the detection of
novel viruses. Blood samples (6 ml) will be obtained in hospitalised children.
3 ml. will be used for transcriptome analysis, the other 3 ml. will be used for
immunological assays. We will also study the effect of single nucleotide
polymorphisms on disease severity and susceptibility. This last part will focus
only on RSV infections.
Study burden and risks
In this study we will include children as subjects. Young infants and children
have an immature immune response. This is the reason why viral infections are
often more severe in young children in comparison with older children and
adults, resulting in a higher morbidity and mortality. Therefore this study is
group related.
In all children an oral swab and a nasopharyngeal aspirate will be taken. These
procedure are not painful. A NPA is not pleasant for a child, however it is a
fast procedure. Children who have been admitted are asked for a 6 ml. blood
sample. This is often standard procedure (69% in a previous study). In these
cases only the amount of blood drawn is increased without performing an extra
puncture. With local anaesthetics the discomfort of a venapuncture will be
diminished. A small hematoma might occur. No more than two attempts will be
taken to draw blood. When a child is admitted because of severe LRTI, an
additional blood sample and NPA will be asked 4 to 6 weeks after hospital
admission. There are no direct or only small benefits of this study for the
participating children and their parents. The benefits may be related to the
future development of novel diagnostic and therapeutic tools, including the
development of vaccines. The confirmation of an viral origin of disease may
lead to an earlier discontinuation of antibiotics or less antibiotic
prescriptions. Also for parents it may be comforting to know which virus causes
their child*s illness.
Kapittellaan 29
6500 HB Nijmegen
NL
Kapittellaan 29
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Patient younger than 6 years. (meaning not older than five years)
Clinical signs of a lower respiratory tract infection:
Tachypnea OR
Subtractions or nasal flaring OR
Wheezing OR
Apnoea
Exclusion criteria
No informed consent. Corticosteroid use (in the previous 6 weeks, exception start within 24 hours), known primary or acquired immunodeficiency, children using immunosuppressive medications.
o Exclusion criteria for blood drawing for transcriptomics: blood transfusion. If blood transfusion in history: natriumheparin tube only.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL32886.091.10 |