Genetic Susceptibility to Severe Streptococcal Infections

NCT01911572 | Unknown

• 1 other identifier: GENIGASUK
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Invasive bacterial infection is a dangerous but relatively uncommon disease where bacteria spread deep into the body causing diseases like blood poisoning ('bacteraemia'), pneumonia, meningitis and others. The various bacteria of the streptococcus family are an important cause, often leading patients to require intensive care despite which, for some strains, one in five patients die. One notable form is called necrotising fasciitis, a condition where bacteria rapidly spreads through and destroys the layers of tissue just under the skin. As individuals vary greatly in their risk of developing such serious infections, investigating how the genome, the inherited blueprint of our bodies, of these patients differs from that of healthy volunteers can help to explain why the disease develops in some and not others. For some streptococcal bacteria such as Streptococcus pneumoniae this approach is already proving successful; for others such as the "Group A" strain (Streptococcus pyogenes) it has yet to be explored but carries excellent potential. The investigators have secured the support of the Lee Spark Necrotising Fasciitis Foundation to recruit from their membership survivors of streptococcal infections and some of their family members. The investigators will also ask infection specialists from NHS hospitals to invite patients they have looked after. The investigators also have a small existing collection. Taking part would involve registering information on a website, discussing the study on the telephone and then providing us with a sample of saliva from which the investigators can isolate DNA. The investigators would prepare the sample for analysis of the genome and compare the patients with both their family and an existing reference collection from healthy volunteers using technology that reads the DNA code. Our study will be a first key step in renewing efforts to understand the determinants of invasive streptococcal infection, which is important for developing better treatments and vaccines.

Conditions

Invasive Streptococcal Infection; Invasive Group A Streptococcal Disease; Invasive Group B Streptococcal Disease; Necrotising Fasciitis

Keywords

Streptococcus species; Streptococcus pyogenes; Streptococcus agalactiae; Necrotising fasciitis; Sepsis

Outcome Measures

Primary Outcomes (1)

• Number of genetic variants at which cases of invasive streptococcal infection (as defined in inclusion criteria 1) differ from their family members (inclusion criteria 2-4)

  This is an observational study comparing genetic data from cases (inclusion criteria 1) vs unaffected family members (inclusion criteria 2-4) and publically available genetic data from health volunteers in existing reference databases (e.g. UK10K - http://www.uk10k.org/). The case's illness (as defined in inclusion criteria 1) may have occurred anytime between 1st January 1980 and enrolment. The outcome is measured by genetic testing using a sample collected on enrolment. There is no follow-up period.

  The outcome is measured once by genetic testing using a sample collected on enrolment ('baseline'). There is no follow-up period.

Study Arms (2)

Survivors

Individuals who have previously experienced an episode of invasive streptococcal infection or necrotising fasciitis.

Family members

Parents of those survivors aged less than forty years without risk factors for streptococcal disease (forming mother-father-child trios), or first and second degree relatives of survivors from a family in which two or more individuals have been affected.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be identified through an invitation sent to the Lee Spark Necrotising Fasciitis Foundation and by infection specialists at NHS hospitals who will invite patients whose care they have been directly involved in. In addition, a small collection of existing samples held at Imperial College London will be used.

You may qualify if:

• Cases/Survivors
• A. All Cases (survivors in pedigree, trio or as simplex case; existing serum samples from Imperial College London collection)
• Either of:
• Isolation of Streptococcus species from a normally sterile site (e.g. blood, joint fluid, etc.) during an acute illness since 1st January 1980
• Severe clinical presentation - streptococcal toxic shock, necrotising fasciitis, pneumonia, puerperal sepsis, meningitis - since 1st January 1980 plus concurrent Streptococcus species isolated from non-sterile site (e.g. abscess, wound swab, pus)
• And:
• Admitted to an NHS hospital in England or Wales or Northern Ireland
• B. Trio case (survivor in trio)
• All of:
• Meets criteria for 1A
• Less than 40 years of age at the time of illness
• None of at the time of the illness: heart disease, diabetes mellitus, cancer, steroid use, chronic lung disease, immunocompromise, intravenous drug use and alcoholism
• Plus one of:
• More than one episode of illness meeting criteria for 1A
• Admission to high dependency or intensive care unit

You may not qualify if:

• \. Adults (age \> 16 years) unable to consent for themselves.

Sponsors & Collaborators

• University of Oxford: lead
• Public Health England: collaborator
• Imperial College London: collaborator

Study Sites (1)

University of Oxford Wellcome Trust Centre for Human Genetics

Oxford, Oxon, OX3 7BN, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Primarily we will collect saliva from which DNA will be isolated. Secondly, from a subset of individuals, we will request follow-up blood samples from which we will extract RNA and separate leukocytes for studies of function.

MeSH Terms

Conditions

Fasciitis, Necrotizing; Sepsis

Condition Hierarchy (Ancestors)

Fasciitis; Musculoskeletal Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tom Parks, BA MB BChir MRCP DTM&H

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2013
• First Posted: July 30, 2013
• Study Start: December 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2019
• Last Updated: May 18, 2018

Record last verified: 2018-05

Locations

GB (1)