Thorough clinical investigation of the host-pathogen interaction in chronic and recurrent otitis media.

Otitis Media (OM) is one of the most frequent diseases in childhood and the
primary reason for children to visit a physician (1;2). In many countries it is
the most common reason to prescribe antibiotics (3;4), or to undergo surgery
(5). Costs for general health care are expanding, and are estimated to be 3-5
billion dollar anually in the United States (2;6-8).
Although OM management has no universal standard yet, it may imply watchful
waiting, antibiotic treatment, adenoidectomy, insertion of tympanostomy tubes
or vaccination. Approximately 80% of the acute otitis media (AOM) cases is
self-limiting within 2-14 days and also otitis media with effusion (OME)
resolves spontaneously: 60% of newly detected OME resolves within 3 months (9).
However, in a part of the OM population persistent or recurrent episodes of OM
are responsible for a significant morbidity for both children and parents,
despite variable treatment options (10).
Through the set up of a new prospective cohort and investigation in a clinical
setting, relevant patient characteristics, the role of bacterial and viral
pathogens, the role of recurrent infection in relation to biofilm formation,
and the host response at protein level will be studied in detail. This project
is expected to increase the understanding of the underlying mechanisms of OM
disease, and to support future treatment and prevention strategies. Towards a
rational, multi valent vaccine development a better understanding in OM
pathogenesis is warranted.

PROPOSAL PART I - TYMPANOSTOMY TUBE INSERTION
Objective: Regarding children suffering from Acute or Chronic Otitis Media:
Are there biological markers present in blood (and middle ear fluid), which
will inform us about:
1. The risk of recurrent infection
2. The severity of disease

PROPOSAL PART II - BIOFILM FORMATION
Objective: Regarding children suffering from Acute or Chronic Otitis Media:
Are there biological markers present in middle ear biofilm related pathogens,
which will inform us about:
1. The severity of disease (virulence factors)
2. The risk of recurrent infection

PROPOSAL PART I - TYMPANOSTOMY TUBE INSERTION
Setting Radboud University Nijmegen Medical Centre, Nijmegen
Canisius Wilhelmina Hospital, Nijmegen
Study Period 01-11-2007 to 01-09-2009
Samples Questionnaire, Blood sample, Middle ear fluid,
Nasopharyngeal swab
Analyses At study entry and after 2-3 months :
1. Questionnaire: risk factors
2. Blood : FACS analysis, Proteomics,
Transcriptomics,
3. Nasopharyngeal swab: Bacterial culture,
Bacterial PCR, viral multiplex PCR.
4. Only at study entry: Middle ear fluid:
Bacterial Culture, Bacterial (rt)-PCR, Viral multiplex PCR,
FACS analysis.

PROPOSAL PART II - BIOFILM FORMATION
Setting Radboud University Nijmegen Medical Centre,
Nijmegen Canisius Wilhelmina Hospital, Nijmegen
Study Period 01-11-2007 to 01-09-2009
Samples At study entry:Middle Ear Mucosa biopsy or Old
Tympanostomy tubes
At study entry and after 2-3
months:Nasopharyngeal swab
Analyses Culture, (rt)-PCR, SE Microscopy, RT-(rt) PCR, Therapy
resistance

Burden

PROPOSAL PART I - TYMPANOSTOMY TUBE INSERTION
2x Questionnaire
2x Blood sample
2x Nasopharyngeal swab
1x Collection of middle ear fluid during surgical insertion of tympanostomy
tubes


PROPOSAL PART II - BIOFILM FORMATION
2x Questionnaire
2x Nasopharyngeal swab
1x Collection of 3 biopsy specimens during surgical debridement of the middle
ear.