Genetic Susceptibility to Severe Streptococcal Infections
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.
Invasive Streptococcal Infection
Invasive Group A Streptococcal Disease
Invasive Group B Streptococcal Disease
|Study Design:||Observational Model: Family-Based|
|Official Title:||Genetic Susceptibility to Invasive Streptococcal Disease|
- 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) [ Time Frame: The outcome is measured once by genetic testing using a sample collected on enrolment ('baseline'). There is no follow-up period. ] [ Designated as safety issue: No ]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.
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.
|Study Start Date:||December 2013|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Individuals who have previously experienced an episode of invasive streptococcal infection or necrotising fasciitis.
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.
|University of Oxford Wellcome Trust Centre for Human Genetics||Not yet recruiting|
|Oxford, Oxon, United Kingdom, OX3 7BN|
|Contact: Tom Parks, BA MB BChir MRCP +447795082724 firstname.lastname@example.org|
|Principal Investigator: Tom Parks, BA MB BChir MRCP|
|Principal Investigator:||Tom Parks, BA MB BChir MRCP||University of Oxford|