RCSI BMFL2 Streptococci Past Paper PDF

Leading the world to better health Streptococci Dr. Rachel Grainger Clinical Lecturer, Dept. of Clinical Microbiology, RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in...

Leading the world to better health Streptococci Dr. Rachel Grainger Clinical Lecturer, Dept. of Clinical Microbiology, RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Session ID: BMFML2 Streptococci Class: Year 1 Course: Undergraduate Medicine Lecturer: Dr. Rachel Grainger Date: 6th November 2024  LEARNING OUTCOMES By the end of the lecture you will be able to……… 1. Outline the basic laboratory features of clinically important streptococci 2. Discuss the epidemiology of clinically important streptococci 3. Describe the pathogenesis of infections caused by clinically important streptococci 4. Recognise & describe the clinical features and complications of infections caused by clinically important streptococci 5. Outline the diagnosis of infections caused by clinically important streptococci 6. Choose the appropriate antimicrobial agents to treat infections caused by clinically important streptococci 7. Use the appropriate measures to prevent the acquisition and spread of streptococcal infections INTRODUCTION Streptococci represent a diverse group of gram positive organisms Many normally colonize mucosal membranes – Predominant component of respiratory, gastrointestinal and genital tract – Many of low virulence – However may also invade normally sterile body sites, causing significant disease STREPTOCOCCI: BASIC LABORATORY FEATURES Gram-positive cocci – Chains (long or short) or pairs (diplococci) Optimal growth media supplemented with blood – May cause haemolysis (destruction of red blood cells) on blood agar Catalase* negative Most are facultative anaerobes – Some are strict (obligate) anaerobes *For more on catalase see Staphylococci lecture  CLASSIFICATION SYSTEMS Most commonly used classification systems: 1. Based on their actions on blood-containing agar (Haemolysis) 2. Based on antigens contained in their cell walls (Lancefield classification) 3. Molecular classification (newer) - based on emm gene (encodes for M protein) Some clinically important streptococci often referred to by both Lancefield group and haemolysis pattern  Streptoco cci   γ haemolyti haemolyti haemolyti c c c Reduce Hb and Lyse blood cells & No change in cause a greenish cause complete blood agar discolouration of clearing of blood blood agar agar in the vicinity of their growth LANCEFIELD CLASSIFICATION Serological system of grouping streptococci Based on specific antigens present in their cell walls Groups A-G of most clinical significance Basis of test: – Antibody / antigen reaction – Positive if agglutination is detected CLINICAL CASE 1 A 10yo male attends his GP with a sore throat On examination he has swollen, erythematous tonsils with exudate. Cervical lymph nodes are swollen & tender Which one of the following is the most likely diagnosis in this instance? A. Bloodstream infection B. Cellulitis C. Erysipelas D. Pharyngitis E. Scarlet fever A throat swab is taken and following culture, Gram staining and microscopy, the following is seen. Which one of the following best describes this Gram stain? A. Gram-negative cocci in chains B. Gram-negative diplococci C. Gram-positive coccobacilli D. Gram-positive cocci in chains E. Gram-positive diplococci Which one the following is most likely causing this infection? A. Corynebacterium diptheriae B. Streptococcus pneumoniae C. Staphylococcus aureus D. Streptococcus pyogenes E. Staphylococcus epidermidis Streptococcus pyogenes displays which one of the following haemolytic patterns on blood agar? A. Alpha haemolysis B. Beta Haemolysis C. Gamma haemolysis Beta-Haemolytic Strep are further classified using which one of the following classifications systems? A. Biofilm formation ability B. Catalase production C. Coagulase production D. Lancefield grouping E. O antigen classification CLINICALLY IMPORTANT STREPTOCOCCI 1. Strep. pyogenes (Group A, -haemolytic) 2. Strep. agalactiae (Group B, -haemolytic) 3. Other -haemolytic streptococci 4. -haemolytic streptococci - “viridans” streptococci - Strep. pneumoniae (pneumococcus) 5. Enterococci (Group D, - or non-haemolytic) 6. Peptostreptococcus (anaerobic or non-haemolytic) 1. STREPTOCOCCUS PYOGENES (GROUP A, -HAEMOLYTIC STREPTOCOCCI) Beta-haemolytic streptococci Possess the Lancefield group A antigen Commonly colonise oropharynx of children & young adults – Colonisation is transient – Influenced by acquired immunity & competition from other organisms in the oropharynx Among the most prevalent of human bacterial pathogens Major cause of bacterial pharyngitis  GROUP A STREPTOCOCCI: IRISH EPIDEMIOLOGY Invasive group A strep = notifiable disease Source: HPSC GROUP A,  HAEMOLYTIC STREPTOCOCCI: VIRULENCE MECHANISMS Several virulence factors involved in causing disease: Structural components: Capsule: resists phagocytosis Cell wall: peptidoglycan can activate alternative complement pathway M-proteins : >80 types, mediate attachment to cells, anti-phagocytic Major virulence factors – some types associated with greater severity of disease M-like proteins…. Bind IgG/ IgM  GROUP A,  HAEMOLYTIC STREPTOCOCCI: VIRULENCE MECHANISMS Cytolysins: Pyrogenic (erythrogenic) Streptolysin O/S exotoxins exotoxins Responsible for rash, fever – ASOT titre Potent activators of immune Hyaluronidase system (toxic shock syndrome) – Tissue destruction, Activation of T-cells leads to allowing spread of increased secretion of pro- infection inflammatory cytokines Leucocidin Produced by both antigen Haemolysins presenting cells and T Streptokinase lymphocytes  PATHOGENESIS (FROM THE BACTERIA'S PERSPECTIVE…) 1. Droplet spread Get in – Colonises oropharynx 2. Direct contact Portal of Invades epithelial cells with e.g., Entry infected wounds Get out and M protein Attach to spread cells further M proteins Capsule = resists Exotoxins phagocytosis Haemolysins Cause Defeat/evade Hyaluronidase damage to the immune Leucocidin host cells system Streptokinase CLINICAL INFECTIONS Suppurative infection: 1. Pharyngitis 2. Scarlet fever 3. Erysipelas, cellulitis, necrotising fasciitis 4. Toxic shock syndrome, bloodstream infection Post-Infectious immune-mediated complications: – Rheumatic fever* May later develop rheumatic heart disease – Glomerulonephritis *(Note GAS a very unusual case of infective endocarditis (IE) – but RHD predisposes to IE by other organisms later on) (Commonly confused by students) 1. STREPTOCOCCAL PHARYNGITIS One of the most common bacterial infections of childhood Occasionally due to Group C or G Spread: Person-to-person via droplets (saliva or nasal secretions) Facilitated by overcrowding Incubation period: 2-4 days History: Sore throat Fever, headache Nausea + vomiting (especially children)  1. STREPTOCOCCAL PHARYNGITIS On examination: Redness, oedema, lymphoid hyperplasia Enlarged tonsils with exudate, enlarged tender lymph nodes Fever Laboratory findings positive throat culture immunological Hyperaemic, enlarged tonsils (antibody) response with exudate Slide: A Colour Atlas of Infectious Diseases, Emond (anti-streptolysin O titre, ASOT) COMPLICATIONS 1. Suppurative complications: – Quinsy – peritonsillar abscess – Otitis media – Acute mastoiditis 2. Non-suppurative (immunological) sequelae: – Acute glomerulonephritis – Acute rheumatic fever Main reason for antibiotic treatment is to prevent rheumatic fever A FOUR YEAR OLD GIRL PRESENTS TO THE GP WITH AN ERYTHEMATOUS, PAPULAR, BLANCHING RASH ON HER ARMS AND TRUNK THAT HAS A “SAND- PAPER” FEEL. WHICH OF THE FOLLOWING IS THE MOST LIKELY INFECTION? A. Cellulitis B. Erysipelas C. Impetigo D. Necrotising fasciitis E. Scarlet fever  2. SCARLET FEVER ‘Scarletina’ Delayed-type skin reactivity to pyrogenic toxin produced by the organism Pharyngitis + rash May also occur following impetigo 3. SKIN AND SOFT TISSUE INFECTION Impetigo Erysipelas Cellulitis Necrotising fasciitis These will be covered in more detail in the ‘Skin and Soft Tissue Infections Lecture’ 4. OTHER SERIOUS INFECTIONS Streptococcal toxic shock syndrome Soft tissue inflammation followed by pain, fever, chills, multi-organ failure Pyrogenic exotoxin production Rapidly progressive Bloodstream infection Mortality approaches 40% COMPLICATIONS: RHEUMATIC FEVER & GLOMERULONEPHRITIS Post-streptococcal auto-immune complications Affect a minority of people who have group A streptococcal infection Immune reaction: Development of antibodies to some fraction of the organism – In rheumatic fever: the antibodies cross-react with cardiac tissue  immune complex deposition on the heart – In post-streptococcal glomerulonephritis: immune complexes are deposited on the glomerular basement membrane – Molecular mimicry  ACUTE RHEUMATIC FEVER Associated with streptococcal pharyngitis but NOT with streptococcal skin infections Occurs 2-3 weeks later Fever, joint pains and carditis May also get neurological involvement (Syndenham’s chorea) With recovery, affected heart valves become thickened and deformed Antibiotic prophylaxis required if undergoing procedure that may put patient at risk of endocarditis Diagnosis is based on the Jones Criteria Documented evidence of a recent GAS infection and clinical findings ACUTE GLOMERULONEPHRITIS Associated with streptococcal pharyngitis AND sometimes with streptococcal skin infections Oedema, puffy face, swollen extremities Due to sodium and water retention Hypertension With albumin and blood in the urine Majority of young patients recover completely However, may lead to permanent renal damage May warrant lifelong dialysis or renal transplantation Or may be fatal 2. STREPTOCOCCUS AGALACTIAE (GROUP B, -HAEMOLYTIC STREPTOCOCCI) Colonise the lower GI and GU tract 10-40% women intermittently carry S. agalactiae in vagina May be carried in the throat Important cause of neonatal sepsis Neonatal colonization usually occurs via the mother’s genital tract Risk factors: Maternal colonisation Premature delivery / Premature rupture of membranes Prolonged labour Low birth rate Intra-partum fever  GROUP B STREPTOCOCCI: IRISH EPIDEMIOLOGY Year Pathogen 2016 2017 2018 2019 2020* Number laboratoriesby year-end 38 37 39 38 36 %Coverage of population 97% 99% 100% 100% 93% Group Bstreptococci (from 1st January 2019) Number of isolates † † † 176 102 %Erythromycin-R* † † † 41.9% 31.9% † No data; data collection for this pathogen commenced in 2019 *2020 data missing from 2 laboratories Source: HPSC GROUP B -HAEMOLYTIC STREPTOCOCCI: VIRULENCE MECHANISMS Capsule polysaccharide – Different serotypes based on capsular polysaccharides – Types Ia, III to V most commonly associated with colonisation and disease Haemolysins Hyaluronidase Surface proteins - adhesins You will learn more about Group B streptococci and neonatal sepsis in Year 4 3. OTHER -HAEMOLYTIC STREPTOCOCCI Can cause similar diseases as Group A streptococcus But without the immunological complications Group C streptococci Puerperal fever Tonsillitis Wound sepsis Group G streptococci Upper respiratory tract infections Endocarditis 4. -HAEMOLYTIC STREPTOCOCCI A. “viridans” streptococci B. Streptococcus pneumoniae (‘pneumococcus’)  4A:“VIRIDANS” STREPTOCOCCI Oropharynx, GIT & GU Strep. sanguis tract Strep. mitis Most lack Lancefield Commonest viridans strep Tooth biofilm antigens Infective endocarditis Exception S. bovis Strep. mutans (Group D) Dental caries Clinical infection: Strep. anginosus (milleri) Several associated with Purulent infections: brain dental caries and & liver abscesses endocarditis Strep. bovis Invasive disease often Linked to colon cancer related to breech in Infective endocarditis mucosal surfaces CLINICAL CASE 2 An 80yo female presents with: – Productive cough – Shortness of breath – Pleuritic chest pain – Fever One week previously she was diagnosed with influenza. WHICH ONE OF THE FOLLOWING STREPTOCOCCI IS THE MOST LIKELY CAUSATIVE PATHOGEN? A. S. agalactiae B. S. mitis C. S. oralis D. S. pneumoniae E. S. pyogenes WHEN S. PNEUMONIAE IS CULTURED ON BLOOD AGAR, WHICH ONE OF THE FOLLOWING HAEMOLYTIC PATTERNS IS MOST LIKELY TO BE SEEN? 1. Alpha haemolysis 2. Beta Haemolysis 3. Gamma haemolysis  4B: S. PNEUMONIAE -haemolytic Gram-positive cocci in chains or diplococci Carried in nasopharynx by: – 5-10% of healthy adults – 20-40% of healthy children Polysaccharide capsule – > 90 serotypes – Allow typing of strains – Vaccines available against Gram-positive diplococci, i.e. some serotypes Pneumococcus Variety of clinical infections (Humphreys, Willatts & Vincent) INVASIVE PNEUMOCOCCAL DISEASE (BLOODSTREAM AND MENINGITIS) IN IRELAND https://www.hpsc.ie/a-z/vaccinepreventable/pneumococcaldisease/epidemiologicaldata/ annualreportsoninvasivepneumococcaldisease/Streptococcus%20Pneumoniae%20(invasive) %20in%20Ireland,%202023.pdf  VIRULENCE FACTORS & PATHOGENESIS (FROM THE BACTERIA'S PERSPECTIVE…) Direct person to Get in – person spread Portal of Colonises via respiratory Entry oropharynx – droplets mediated by adhesin Get out and Attach to spread cells further Invasion promoted by cell wall, adhesins + cytotoxin pneumolysin Defeat/ Cause evade the damage to Pneumolysin & immune host cells system cell wall polysaccharide Risk factors: immunodeficiency, capsule: activates splenectomy, asplenia complement and Antibiotic resistance facilitates disease cytokine release Capsular polysaccharide: anti-phagocytic  PNEUMOCOCCAL PNEUMONIA (MORE DETAIL LATER IN RESP MODULE) Symptoms: Pleuritic chest pain Shortness of breath Purulent sputum Classically  “lobar” pneumonia May cause bronchopneumonia especially in the elderly Complications: Parapneumonic effusion Empyema / Lung abscess Bacteraemia Influenza infection a major predisposing factor  SINUSITIS & OTITIS MEDIA S. pneumoniae is a common cause of acute infection of the paranasal sinuses and ear Usually preceded by upper respiratory tract infection Otitis media usually affects young children Sinusitis affects all ages PNEUMOCOCCAL MENINGITIS & BSI Meningitis: BSI / Bacteraemia Leading cause of 25-30% of patients with meningitis in adults pneumococcal How does it get to the pneumonia central nervous system? May accompany During a bacteraemia meningitis Chronic ear infection RARELY occurs with Sinus infections cases of sinusitis or After head trauma otitis media  5. ENTEROCOCCI 18 species: E. faecium and E. faecalis most common Previously classified as Group D streptococci Bowel flora – usually low virulence Facultative anaerobes Haemolytic pattern varies Alpha or beta Grow in presence of bile salts i.e grow on MacConkey agar Vancomycin resistance is common!  VIRULENCE FACTORS & PATHOGENESIS (FROM THE BACTERIA'S PERSPECTIVE…) Get in – Most infections = Portal of endogenously 1. CONTACT from Entry (bowel flora) hands, environment, 2. Contaminated food or water Attach to Get out and cells spread further Protein and carbohydrate factors enable binding to cells Defeat/ Cause evade the damage to immune Haemolysinshost cells system Antibiotic resistance (intrinsic / acquired) facilitates survival and multiplication ENTEROCOCCAL INFECTION At-Risk Patients: Types of Infection: Recent surgery 1. Urinary tract infection Underlying disease a) Particularly urinary catheter-related Malignancy Burns or trauma 2. Endocarditis Recent antibiotics 3. Bloodstream infection cephalosporins or 4. Wound infections aminoglycosides 5. Intra-abdominal Prolonged infections hospitalization Especially ICU  INFECTIVE ENDOCARDITIS (MORE IN CV MODULE IN SEMESTER 2) Turbulent flow through the heart provides a surface for bacteria to attach Bacteria enter blood usually after a procedure that damages epithelial barriers e.g. dental extraction, Vegetation on heart valve cystoscopy (Slide: A Colour Atlas of Infectious Bacteria attach to damaged Diseases, Emond) valves and vegetations form 6. ANAEROBIC STREPTOCOCCUS PEPTOSTREPTOCOCCUS >25% of anaerobes from clinical specimens Colonise oral cavity, GI & GU tracts, and skin Infections include Aspiration pneumonia Sinusitis and brain abscess Intra-abdominal abscesses Pelvic infections GENERAL ASPECTS OF DIAGNOSIS OF INFECTION (THIS WOULD APPLY TO ANY STREP INFECTION) Clinical suspicion based on clinical features Appropriate samples sent to the laboratory based on site of infection – Blood (if invasive disease suspected) – CSF (meningitis) – Urine – Throat swab (pharyngitis) In the laboratory: – Gram stain on sterile site sample (blood, CSF, pus) – Culture: takes 24 – 48 hours Samples incubated aerobically and anaerobically Blood agar (haemolysis) MacConkey agar (enterococci)  LABORATORY DIAGNOSIS Identification Lancefield Grouping Bacitracin susceptibility (GAS) Optochin sensitive (pneumococcus) Bile solubility (enterococci) Serology Detect recent Group A infection in suspected rheumatic fever & glomerulonephritis i.e. ASO titres (ASOT) PCR Blood, CSF Urinary antigen (for pneumococcus) S. PYOGENES LAB DIAGNOSIS Bacitracin disk Gram-positive cocci in chains ß-haemolytic Catalase negative Group A Group A ß-haemolytic streptococci showing bacitracin susceptibility (clearing around bacitracin disc)  S. PNEUMONIAE LAB DIAGNOSIS Gram-positive cocci in chains or diplococci -haemolytic Catalyse negative Optochin disk Susceptible to optochin i.e. growth inhibited by optochin  ANTIMICROBIAL RESISTANCE IN PNEUMOCOCCI Pneumococci can alter the structure of penicillin- binding proteins (PBPs) that are found on their surface – β lactam antibiotics (e.g., penicillin) cannot bind to pneumococci and destroy their cell wall Different levels/degrees of resistance – Low-level or intermediate resistance – High-level or full resistance Important to know if patient has been in area where there is high level of resistance ANTIMICROBIAL RESISTANCE AND S. PNEUMONIAE 2023 Data: HPSC STREPTOCOCCI: ANTIBIOTIC TREATMENT Most commonly use cell wall active agents: Penicillins – Nearly all -haemolytic streptococci susceptible Cephalosporins – For penicillin-resistant pneumococci – Used for treatment of meningitis – ceftriaxone (3rd gen) – Used if rash with penicillin – Do not use for enterococci (are intrinsically resistant) Vancomycin – If -lactam anaphylaxis – If resistance to -lactams suspected ENTEROCOCCI ANTIBIOTIC TREATMENT First line treatment for enterococci = amoxicillin – If resistant to this (many E. faecium are!) then vancomycin However VRE (vancomycin resistant enterococci) problematic (i.e. can’t use vancomycin) Patients may become colonised, +/- develop significant infection due to VRE Limited treatment options, with significant potential side effects and interactions – Linezolid PREVENTION & CONTROL - VACCINATION Pneumococcal vaccine available against some serotypes 2 types of vaccine available – PPV 23 – only used if >2 yrs, recommended for >65 yrs of age – PCV 13 – Immunogenic from 6/52 of age, part of childhood vaccination schedule, given at 2, 6 and 13 months At risk groups should also be offered vaccination IMPACT OF VACCINATION PRINCIPLES OF INFECTION PREVENTION & CONTROL Infection Prevention & Control a) Group A strep - isolate in a single room if iGAS confirmed until 24 hours on appropriate antimicrobial therapy b) Notifiable diseases – public health Which one of the following is a well-recognised post-infectious immune mediated complication of untreated Group A streptococcus pharyngitis? A. Blindness B. Deafness C. Gastroenteritis D. Meningitis E. Rheumatic fever YEAR 1 STUDENTS IN NEED OF ASSISTANCE RCSI Student Assistance Programme – If you need urgent emotional support contact our student assistance programme available 24/7/ 365. This service provides counselling free of charge to our students: Freephone: 1800 851 340 International: 00353 1 518 0277 WhatsApp: Text 'Hi' to 087 369 0010 RCSI Centre for Mastery: Personal, Professional & Academic Success (CoMPPAS) – A multidisciplinary team of RCSI professionals and specialists working collaboratively to empower students to achieve their academic, personal and professional goals: – Moodle page: https://vle.rcsi.com/course/view.php?id=2583 General Queries: [email protected] Career Development: [email protected] Academic Development: [email protected] Learning Support (Disability) : [email protected] Student Welfare : [email protected] Niteline: 1800 793 793 (Instant messaging on https://niteline.ie 9pm-2.30am every night of term). Late-night listening, support and information service run by students for students in the greater Dublin area. RCSI Security Emergency Contact (+353) 01-402219 : – If require urgent assistance from RCSI, or you are on campus you can contact security at 01 402 22 19. This number will not result in an in person response. Please note that in an emergency your safest action is to contact the local emergency services (112/999). If you are an International Student you should also contact your Embassy/ Sponsor to advise them of your circumstances. Mercers Medical Centre (General Practice) for health/COVID advice: – https://www.mercersmedicalcentre.com/rcsi-students For urgent medical advice/emergency outside regular hours contact DubDoc (Out of Hours GP) (+353) 01- 4545607 https://www.dubdoc.ie/ – DubDoc provides urgent medical care to patients that cannot wait to be seen by their usual GP. Emergency Services dial 999/112. Thank you