GIHEPL2 GNB SalmShigHP24Stud PDF

Aerobic Gram-Negative Bacilli (GNB) 2 Dr Aoife Kearney Clinical Lecturer Dept of Clinical Microbiology, RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Gram-negative bacilli: Salmonella, Shigella, Helicobacter Class Year 2 Semester 1 C...

Aerobic Gram-Negative Bacilli (GNB) 2 Dr Aoife Kearney Clinical Lecturer Dept of Clinical Microbiology, RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Gram-negative bacilli: Salmonella, Shigella, Helicobacter Class Year 2 Semester 1 Course Undergraduate Medicine Lecturer Dr Aoife Kearney Date 11th September 2023  LEARNING OUTCOMES At the end of this session, you should be able to……. 1. Discuss the epidemiology of clinically important Salmonella & Shigella species and Helicobacter pylori (H. pylori) 2. Outline the basic laboratory features of clinically important Salmonella & Shigella species and H. pylori and explain the biological role of each in the pathogenesis of infection 3. Describe the pathogenesis of infections caused by clinically important Salmonella & Shigella species and H. pylori 4. Recognise and describe the clinical features and complications of infections caused by clinically important Salmonella & Shigella species and H. pylori 5. Outline the laboratory diagnosis of infections caused by clinically important Salmonella & Shigella species & H. pylori and describe their laboratory features e.g. Gram stain appearance etc. 6. Choose the appropriate antimicrobial agents to treat infections caused by clinically important Salmonella & Shigella species & H. pylori 7. Use the appropriate measures to prevent the acquisition and spread of infections caused by clinically important Salmonella & Shigella species & H. pylori 1. Salmonella  Salmonella (2610) Salmonella bongori Salmonella enterica Subsp. v Subsp. I Subsp. II Subsp. IIIa Subsp. IIIb Subsp. IV Subsp. VI (23) enterica salamae arizonae diarizonae houtenae indica (1547) (513) (100) (341) (73) (13) Cause 99% of human & animal infection Typhoidal Salmonella Non-typhoidal Salmonella (Humans only) (Humans & Animals) Typhoid Paratyphoid Gastroenteritis Extra-intestinal fever fever e.g. S. typhimurium S. typhi S. paratyphi S. virchow S. enteritidis S. Dublin  Salmonella enterica – Overview Enterobacterales: Gram-negative bacilli Facultative anaerobes 1. Typhoidal/ Enteric fever 2. Non-typhoidal Salmonellae Salmonellae Serotype Typhi Serotype Enteritidis Serotype Paratyphi Serotype Typhimurium Humans the only host Humans and animals can be hosts – Enteric fever – Zoonoses i.e., pathogens of – Carrier state animals, man is an incidental host – Food poisoning / gastroenteritis  Virulence factors Adhesion Motility Intracellular invasion Anti-phagocytic Toxin production Source: Brock Biology of Microorganisms 11th edition  Salmonella Electron Micrograph Peritrichous flagellae Fimbriae  Salmonella (2610) Salmonella bongori Salmonella enterica Subsp. v Subsp. I Subsp. II Subsp. IIIa Subsp. IIIb Subsp. IV Subsp. VI (23) enterica salamae arizonae diarizonae houtenae indica (1547) (513) (100) (341) (73) (13) Cause 99% of human & animal infection Typhoidal Salmonella Non-typhoidal Salmonella (Humans only) (Humans & Animals) Typhoid Paratyphoid Gastroenteritis Extra-intestinal fever fever e.g. S. typhimurium S. typhi S. paratyphi S. virchow S. enteritidis S. Dublin  Typhoidal Salmonella (Humans only) ENTERIC FEVER Typhoid fever Paratyphoid fever SALMONELLAE S. typhi S. paratyphi SALMONELLA TYPHI SALMONELLA PARATYPHI A,B & C  Enteric Fever: Pathogenesis 1. Ingestion (faecal-oral spread) 2. Adheres to & penetrates epithelium over Peyer’s patches in the distal ileum using fimbriae 3. Ingested by macrophages 4. Bacilli remain alive inside macrophages and are carried via lymphatics to mesenteric lymph nodes 5. After multiplying in mesenteric lymph nodes, they enter the bloodstream and cause a primary bacteraemia 6. Invade and multiply in liver, gall bladder, spleen, bone marrow 7. Re-enter the bloodstream (secondary bloodstream infection) 8. From gallbladder, re-infect intestinal tract – Re-infects mesenteric lymph nodes and Peyer’s patches- can cause necrosis of Peyer’s patches with associated bleeding or perforation – Shed in stool  Enteric Fever: Pathogenesis (RES) Liver, spleen, bone marrow Gastrointestinal Symptoms (10-14 days)  Enteric Fever: Epidemiology Typhoid + paratyphoid fever – S. typhi causes typhoid fever – S. paratyphi A, B and C cause a milder form Transmission: Faecal-oral route Sources: – Person-to-person spread by chronic carrier – Faecally-contaminated food or water Incubation period: 7-21 days - up to 30 days Worldwide ∼ 22 million cases/ year – Mainly in underdeveloped areas with poor sanitation – Travel to endemic countries  Enteric Fever: Clinical Features If left untreated - Three clinical stages (each lasts about a week) Followed by slow improvement Potential to become chronic carriers Week 1 - Body temperature rises gradually - Headache - Relative bradycardia - Constipation or diarrhoea Early diagnosis & antibiotic treatment leads to lower complication and mortality rates. If undiagnosed, the disease progresses…..  Enteric Fever: Clinical Features Week 2 Fever persists (39-40°C) Signs & symptoms progress – – abdominal distension / splenomegaly – Profuse ‘Pea-soup’ diarrhoea – Confusion/ altered mental state – Rose spots (30%) Flanks, buttocks, costal margins Salmon-coloured, blanching, maculopapules Resolve within 2-5 days Bacterial emboli to the dermis  Enteric Fever: Clinical Features Week 3 Additional complications in untreated patients: 1. Hepatic, renal & bone marrow dysfunction 2. Severe abdominal distension, perforation / peritonitis (necrotic Peyer’s patches), secondary bacteraemia 3. Osteomyelitis- especially spinal 4. Relapse (10-15%), especially if treatment inadequate Week 4 (if survives) Fever, mental state, abdominal distension improve Intestinal complications may still occur in surviving untreated individuals Weight loss & debilitating weakness for months  Salmonella Typhi: Chronic carriage Definition: positive stool cultures 12 months after overcoming the disease Incidence: up to 6% become chronic carriers Potential to transmit S. typhi indefinitely Usually asymptomatic May have increased risk of gallbladder cancer Treatment: ciprofloxacin for at least 1 month Chronic carriers are not allowed to work in the food industry Who was this? Paratyphoid Fever Paratyphoid A – Similar to typhoid except rarely see rose spots and less severe Paratyphoid B – Usually a diarrhoeal illness  Enteric Fever: Diagnosis Culture and PCR of various specimens – Blood: 80% + in 1st week, 20-30% in 3rd week – Faeces: 2nd week onward – Urine: 3rd week – Bone marrow culture May be positive even if treated with antibiotics Widal test – Was the mainstay of diagnosis for decades. – Agglutination test: O or H antigens from Salmonellae added to patient’s serum – Not done now – poor sensitivity and specificity  Enteric Fever: Treatment 1. Fluid & electrolyte replacement and supportive management 2. 10-14 days antibiotics Ceftriaxone 1st line empiric treatment - resistance to other agents (e.g. ciprofloxacin) increasing (Ciprofloxacin, Azithromycin- only if susceptibilities known) - XDR typhoid fever in Pakistan Up to 6% of patients become chronic carriers after symptoms have resolved  Enteric Fever: Prevention Public health measures – Safe drinking water & sanitary disposal of excreta Precautions – Good food hygiene (storage, preparation) – Hand hygiene – When travelling: boil it, cook it, peel it, or forget it! Vaccine – WHO recommended to those travelling to high-risk areas 1. Subunit vaccine (Vi polysaccharide) 2. Live attenuated oral vaccine  Salmonella (2610) Salmonella bongori Salmonella enterica Subsp. v Subsp. I Subsp. II Subsp. IIIa Subsp. IIIb Subsp. IV Subsp. VI (23) enterica salamae arizonae diarizonae houtenae indica (1547) (513) (100) (341) (73) (13) Cause 99% of human & animal infection Typhoidal Salmonella Non-typhoidal Salmonella (Humans only) (Humans & Animals) Typhoid Paratyphoid Gastroenteritis Extra-intestinal fever fever e.g. S. typhimurium S. typhi S. paratyphi S. virchow S. enteritidis S. Dublin  Non-typhoidal Salmonella (Humans & Animals) SALMONELLA Gastroenteritis Extra-intestinal GASTROENTERITIS e.g. S. Typhimurium S. Virchow S. Enteritidis S. Dublin CAUSED BY NON-TYPHOIDAL SALMONELLAE E.G. SALMONELLA ENTERITIDIS SALMONELLA TYPHIMURIUM  Salmonella Gastroenteritis (Non-typhoidal Salmonellae): Epidemiology Over 2,200 different serovars Source: GIT animals & reptiles (pets) & the environment Transmission – Foodborne (next slide) Improperly handled/ inadequately cooked/ stored food contaminated by animal or human faecal material – Faecal-oral From other humans or at farms or from pets Incubation period: 18-72 hours  Salmonella Gastroenteritis Epidemiology: Food Sources 1. Poultrycommonest source, up to 20% contaminated 2. Eggs from infected poultry, oviduct infected & eggs contaminated by transovarian spread 3. Beef & beef products, meat contaminated in the abattoir from animal’s intestines 4. Unpasteurised milk, infected from cow’s faeces  Salmonella Gastroenteritis Pathogenesis (Non-typhoidal Salmonellae) Salmonella Gastroenteritis Pathogenesis (Non-typhoidal Salmonellae) 1. Ingestion 2. Adherence: complex, multiple genes, fimbriae important 3. Invasion – Induce nonphagocytic cells (e.g., enterocytes) to internalize them – Then survive and replicate within modified phagosome Virulent strains of Salmonella induce multiple host inflammatory responses and cytokines (mediated by lipopolysaccharide in the cell wall)  Salmonella Gastroenteritis (Non-Typhoidal Salmonellae) Clinical Features Abrupt onset, short course, self-limiting gastroenteritis (usually lasts 3-7 days) Diarrhoea, nausea, headache, malaise; vomiting rare Severe infection with dehydration a problem in – Extremes of age – Immunocompromised  Non-Typhoidal Salmonellae Chronic Excretion Up to 4 weeks after acute illness Prolonged excretion increased by – Antibiotics (hence only treat if indicated) – HIV – Inflammatory bowel disease – Diverticulosis  Non-Typhoidal Salmonellae Complications (esp. if immunosuppressed) Bloodstream infection (BSI) – 4% of cases of acute gastroenteritis. – more likely with certain strains (e.g., S. Dublin or S. Choleraesuis) Systemic disease – Osteomyelitis (esp. sickle cell disease) – Meningitis – Endovascular + prosthetic material infection (Localised in tissues with pre-existing damage & survive in macrophages) Reactive arthritis  Management of Salmonella gastroenteritis (Non-Typhoidal Salmonellae) 1. Fluid & electrolyte replacement and supportive management = sole treatment required for most cases 2. Antibiotics not routine ONLY if severe illness & high risk of invasive disease –