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.

Participants for the genetics study are divided into cases/survivors and family members (relatives and parents).

To participate as a survivor, the individual must meet criteria 1A. Their illness can have occurred anytime from birth up until enrolment, providing it happened after 1st January 1980. Family members can only take part if invited to do so by the survivor from their family at the request of the research team.

In families in which two or more survivors are identified, all the remaining first- and second-degree relatives of the survivors will be eligible to participate. The recruitment team subdivide those relatives on enrolment into healthy (Criteria 2) or intermediate (Criteria 3) phenotype.

In families in which there is only a single survivor, the recruitment team will assess whether the survivor meets criteria 1B. If so the parents of that survivor are eligible to participate if they have a healthy phenotype (Criteria 4).

Inclusion Criteria:

1. 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
     • Requirement for surgical procedure (including drainage of abscess or collection)

   • And:

     • Both parents alive at time of recruitment

2. Unaffected phenotype family member in multi-case pedigree

   • All of:

     • Biological first or second degree relative of a survivor meeting criteria 1A in a family in which two or more members meet those criteria
     • None of: severe streptococcal illness requiring hospital illness, recurrent tonsillitis or recurrent impetigo (recurrent is defined as more than one episode in two consecutive years)

3. Intermediate phenotype family member in multi-case pedigree

   • All of:

     • Biological first or second degree relative of a survivor meeting criteria 1A in a family in which two or more members meet those criteria
     • History of severe bacterial illness requiring hospital admission, recurrent tonsillitis or recurrent impetigo (recurrent is defined as more than one episode in two consecutive years)

4. Parent in mother-father-child trio

   • All of:

     • Biological parent of case meeting criteria for 1B
     • None of: severe bacterial illness requiring hospital admission, recurrent tonsillitis or recurrent impetigo (recurrent is defined as more than one episode in two consecutive years)

Exclusion Criteria:

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

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.