Genetic Susceptibility to Severe Streptococcal Infections

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.