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

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.

Study Overview

• Status: Withdrawn
• Conditions: Meningitis
• Intervention / Treatment: Other: Meningitis cases

Detailed Description

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• United Kingdom
  • England, United Kingdom
    • All NHS hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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)

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
meningitis cases; 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; None - blood draw only

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Public Health England
• Investigators: Principal Investigator: Shamez Ladhani, MD PhD, Public Health England

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: March 9, 2016
• First Submitted That Met QC Criteria: April 1, 2016
• First Posted (Estimate): April 4, 2016

Study Record Updates

• Last Update Posted (Actual): April 5, 2017
• Last Update Submitted That Met QC Criteria: April 3, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningitis; Meningococcal Infections
• Other Study ID Numbers: Lock and Key

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO