The main objective of the MeninGene study is to identify genetic risk factors in host and pathogen influencing susceptibility to bacterial meningitis, and the rate of complications, unfavourable outcome and death.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Central nervous system infections and inflammations
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Online case-record forms will be used to collect data on patients* history,
symptoms and signs on admission, laboratory findings at admission, treatment
(including adjunctive treatment), clinical course, outcome and neurological
findings at discharge. Severity and clinical deterioration will be evaluated.
Data on complications will be collected according to predefined criteria.
Results of neuroimaging will be collected. At discharge, all patients undergo a
neurological examination performed by a neurologist, and the outcome is graded
according to the Glasgow outcome scale. A score of 1 on this scale indicates
death; a score of 2, a vegetative state (the patient is unable to interact with
the environment); a score of 3, severe disability (the patient is unable to
live independently but can follow commands); a score of 4, moderate disability
(the patient is capable of living independently but unable to return to work or
school); and a score of 5, mild or no disability (the patient is able to return
to work or school). A favourable outcome will be defined as a score of 5, and
an unfavourable outcome as a score of 1 through 4. The Glasgow outcome scale is
a well-validated instrument with good inter-observer agreement.
Secondary outcome
Niet van toepassing
Background summary
Meningitis is an inflammation of the membranes covering the brain and spinal
cord (the meninges). Each year 35,000 European patients suffer from bacterial
meningitis, leaving 7000 deaths and 7000 disabled.1,2 In developing countries,
the burden of disease is up to 20 times higher.3,4 Streptococcus pneumoniae and
Neisseria meningitidis are the most common etiologic agents accounting for 85%
of total cases.1 Although these bacteria are common inhabitants of the human
upper respiratory tract, in some individuals they spread to the bloodstream,
slip through the blood-brain barrier and cause meningitis, with devastating
consequences. Differences in susceptibility and outcome between individuals and
populations are poorly understood but genetics of host and pathogen are
considered crucial in this host-pathogen interaction.5,6 Recent studies have
shown that both host and pathogen genetic characteristics influence the risk of
acquiring meningitis, the response to treatment in bacterial meningitis
patients and the risk of unfavourable outcome.7-11,13 However, all of these
studies used a candidate single-nucleotide polymorphism approach, which is
unable to detect novel genetic variants influencing the disease and is likely
to overlook the most important genetic risk factors. In the recent years high
throughput sequencing methods have enabled massive parallel sequencing of genes
and whole genomes.
By sequencing whole genes in patients and whole genomes of bacteria we will be
able to
- Determine genetic risk factors for susceptibility to meningitis
- Determine genetic risk factors for unfavourable outcome, cerebrovascular
complications and death
- Determine virulence factors in the bacterial genomes
This may improve patient*s care in the following ways:
- By determining genetic risks factor for increased susceptibility to bacterial
meningitis protective measures such as vaccination and patient education on
early symptoms can be implemented. This will especially be useful patients with
recurrent meningitis and families with high incidence of meningitis, in which
genetic counselling may be given.
- By determining genetic risk factors for complications or unfavourable outcome
new treatments can be devised which counteract the pathophysiological mechanism
that leads to the increased disease severity.
- Genotypes may be used to identify patients at high risk for specific
complications. Physicians may, in the future, be able to use genetic
information to tailor immune-based therapy to modulate the response in a given
patient. Future therapeutic trials are likely to be designed to target specific
genotypes and associated cellular responses, thereby maximizing clinical
response and patient safety.14
- Identification of genetic variants in bacteria causing increased virulence
could lead to development of new vaccines that includes antigens specific for
virulent bacteria. This may result in vaccines preventing severe cases of
bacterial meningitis.
Study objective
The main objective of the MeninGene study is to identify genetic risk factors
in host and pathogen influencing susceptibility to bacterial meningitis, and
the rate of complications, unfavourable outcome and death.
Study design
We will conduct a prospective observational nation-wide cohort study in which
we will perform massive parallel sequencing of causative bacteria and genes in
patients and controls involved in the immune response in bacterial meningitis.
Study burden and risks
Patients do not have direct benefit from this study. Therapies identified as a
result of this study may be beneficial to a future episode of meningitis in
patients with recurrent meningitis (approximately 5%). The risks of the study
are limited to those of a venous blood withdrawal, which are minor.
Meibergdreef 9
1105AZ Amsterdam 1105AZ
NL
Meibergdreef 9
1105AZ Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1. Age >= 16 yr
2. Bacterial meningitis defined by positive bacterial culture or PCR of
cerebrospinal fluid
Exclusion criteria
1. Neurosurgical operation in the month previous to the meningitis episode
2. Head trauma in the month previous to the meningitis episode
3. Presence of neurosurgical devices in the central nervous system such as
cerebrospinal fluid catheters or deep brain neurostimulator.
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 | NL43784.018.13 |