Host-pathogen Interactions in Meningococcal Disease: Finding the Key That Fits the Lock

Study Overview
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Brief Summary
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At any time, around 10% of people carry meningococcal bacteria in the nose and throat, which can cause meningitis, blood poisoning and other serious illnesses. Most people carry these bacteria and never become ill, yet a very small proportion go on to develop these illnesses which can result in life long disabilities or death. The mechanism by which this happens is poorly understood and has been studied in various ways, usually focussing on the bacteria or on the individual, but none has given a definitive answer. This study will be the first of its kind and will assess the interaction between the host and the bacteria at the genetic level, through genetic mapping, helping us to understand what makes some people susceptible to this infection.

Detailed Description
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At any time, around 10% of people carry meningococcal bacteria in the nose and throat, which can cause meningitis, blood poisoning and other serious illnesses. Most people carry these bacteria and never become ill, yet a very small proportion go on to develop these illnesses which can result in life long disabilities or death. The mechanism by which this happens is poorly understood and has been studied in various ways, usually focussing on the bacteria or on the individual, but none has given a definitive answer. This study will be the first of its kind and will assess the interaction between the host and the bacteria at the genetic level, through genetic mapping, helping us to understand what makes some people susceptible to this infection.

Official Title
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Host-pathogen Interactions in Meningococcal Disease: Finding the Key That Fits the Lock

Conditions
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Meningitis

Intervention / Treatment
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* Other: Meningitis cases


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: any individual with culture-confirmed IMD in England from 01 September 2015 to 31 August 2019 written informed consent from the individual, the parent (for children aged <16 years) or next-of-kin (for non-survivors) Exclusion Criteria: any individual who does not fulfil the inclusion criteria Temporary Exclusion Criteria: Critically-ill patients and/or their family member will be only approached when the patient starts recovering from their illness or after they are deceased, on the advice of their clinical team.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| meningitis cases<br>any individual with culture-confirmed IMD in England from 01 September 2015 to 31 August 2019 with written informed consent from the individual, the parent (for children aged <16 years) or next-of-kin (for non-survivors) | Other: Meningitis cases<br>* None - blood draw only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| informed consent obtained for all culture-confirmed IMD to sequence their genome. | enrol cases | up to 55 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| creation of a functional database linking anonymised whole genome human and meningococcal sequences with data collected through national surveillance | construction of reference database | up to 55 months | 
| detailed genetic analysis on human-pathogen pairs, focussing particularly on (but not restricted to) the human complement system and the respective meningococcal binding proteins. | Genetic analysis | up to 55 months | 
| visualising potential host-pathogen interactions through computer modelling | computer modelling | up to 55 months |