Mycobacterium Tuberculosis PDF

Mycobacterium tuberculosis  Genus Mycobacterium Gram-positive irregular bacilli Acid-fast staining: mycolic acids Strict aerobes Catalase + No capsules/No flagella/ No spores Grow slowly Resistant to drying and chemicals Intracellular survival and replic...

Mycobacterium tuberculosis  Genus Mycobacterium Gram-positive irregular bacilli Acid-fast staining: mycolic acids Strict aerobes Catalase + No capsules/No flagella/ No spores Grow slowly Resistant to drying and chemicals Intracellular survival and replication in macrophages  What is Tuberculosis? Tuberculosis is a disease caused by tiny germs that enter your lungs when you breathe them in; It is called Tubercle bacillus “TB” Produces no exotoxins or enzymes that contribute to infectiousness Virulence factors - contain complex waxes and cord factor that prevent destruction by lysosomes or macrophages TB are most commonly found in the lungs, but sometimes they can move to other parts of the body Contagious  Acid Fast Bacilli Mycobacterium tuberculosis : aerobes, tubercles ( infection sites) due to cell- mediated response: hypersensitivity test transmitted person-person airborne droplets  Risk of TB 1. People with weakened immune systems 2. Predisposing factors include: inadequate nutrition, poor access to medical care, lung damage, and genetics. 3. AIDS patients  Common Symptoms of TB Disease Cough (haemoptysis) Chest pains Fever Night sweats Feeling weak and tired Losing weight No appetite  TB Infection vs. TB Disease TB Infection TB disease Primary Secondary Initial infection May follow months, years or decades after the initial disease Stay in lungs Stay in lungs or move to other parts of body (Miliary) Latent pathogen Re-activation from latent Do not multiply or make you sick Multiply, and make you sick Cannot pass TB germs to others Can pass the TB germs to other people 90% 10% Diagram of a Granuloma NOTE: ultimately a fibrin layer develops around granuloma (fibrosis), further “walling off” the lesion. Typical progression in pulmonary TB involves caseation, calcification and cavity formation.  Primary TB Infectious dose 10 cells Phagocytosed by alveolar macrophages: multiply intracellularly - If the organism does not cause immediate infection, the organism can be “walled off” in a granuloma. Granulomas can break down in future and the organisms can cause infection later. After 3-4 weeks immune system attacks, forming tubercles granulomas consisting of a central core containing bacilli surrounded by WBCs –tubercle If center of tubercle breaks down into necrotic caseous lesions, they gradually heal by calcification.  Pathology Alveolar macrophages (infections) Macrophages activated Tubercules (small granulomas in tissue) Caseation Invade blood stream (miliary TB)  Diagnosis 1. Microbiology (sputum) Microscopy (Ziehl-Neelson stain or Acid-Fast Stain) - Report in 1 day Culture - Definitive diagnosis - Report in 2-6 weeks 2. Mantoux skin test : Protein purified derivative (PPD) 3. X rays Chest X-Ray of Patient with Active Pulmonary Tuberculosis  Mantoux skin test consists of an intradermal injection of exactly 0.1mL of PPD tuberculin The size of induration is measured 48–72 hours later. 10mm induration (palpable raised hardened area) for positive test Erythema (redness) should not be measured.  Treatment 1. Initial phase: isoniazid, rifampin (in combination to kill bacteria and prevent emergence of drug resistance) x 2 months 2. Continuation phase: isoniazid, rifampin x 4 months 3. Suspected drug resistance: IM streptomycin for 12 months Prevention/Vaccination BCG (Bacillus-Calmette- Guérin) vaccine – an attenuated strain of M. bovis HELICOBACTER PYLORI H pylori is a spiral-shaped gram-negative. It has multiple flagella at one pole actively motile oxidase positive and catalase positive is a strong producer of urease. H pylori is associated with 1. gastritis 2. duodenal (peptic) ulcer disease 3. gastric ulcers 4. gastric adenocarcinoma 5. gastric mucosa-associated lymphoid tissue (MALT) lymphomas. H. pylori virulence factors 1. Outer membrane proteins: a. The adhesions: adhesion to host cell b. Porin proteins, iron transport and flagella proteins 2. The lipopolysaccharide (LPS) 3. The exotoxins: The vacuolating (Vac A) toxin (gastric mucosal injury) 4. The secretory enzymes: a. The urease : Neutralize gastric acid b. The mucinase, lipase and protease (mucosal injury) 5. The flagella ( motility) 6. The effector cytotoxin: The cytotoxin associated gene A (Cag A). Pathogenesis H pylori grows optimally at a pH of 6.0–7.0 and would be killed or not grow at the pH within the gastric lumen. Gastric mucus is impermeable to acid and has a strong buffering capacity. On the lumen side of the mucus, the pH is low (1.0– 2.0); on the epithelial side, the pH is about 7.4. H pylori is found deep in the mucous layer near the epithelial surface where physiologic pH is present. H pylori produces a protease that modifies the gastric mucus and reduces the ability of acid to diffuse through the mucus. H pylori produces potent urease activity, which yields production of ammonia and further buffering of acid.  H pylori is quite motile, even in mucus, and is able to find its way to the epithelial surface. H pylori overlies gastric-type but not intestinal-type epithelial cells. With its flagella and its spiral shape, the bacterium drills into the mucus layer of the stomach, and can either be found suspended in the gastric mucosa or attached to epithelial cells. In human, ingestion of H pylori resulted in development of gastritis and hypochlorhydria (deficiency of stomach acid). There is a strong association between the presence of H pylori infection and duodenal ulceration. Antimicrobial therapy results in clearing of H pylori and improvement of gastritis and duodenal ulcer disease. Toxins and lipopolysaccharide may damage the mucosal cells, and the ammonia produced by the urease activity may also directly damage the cells. Gastric-biopsy specimen showing Helicobacter pylori adhering to gastric epithelium and underlying inflammation H. pylori infection, resulting in ulceration of the stomach. Histologically, gastritis is characterized by acute and chronic inflammation. Polymorphonuclear and mononuclear cell infiltrates within the epithelium and lamina propria. Destruction of the epithelium is common, and glandular atrophy may occur. H pylori thus is a major risk factor for gastric cancer. Clinical Findings Acute infection can yield an upper gastrointestinal illness with nausea and pain vomiting Fever Poor appetite Weight loss Heart burn Dyspepsia After colonization, the H pylori infection persists for years and perhaps decades or even a lifetime.  Diagnostic Laboratory Tests Diagnostic test are of two kinds: A. Invasive test Endoscopy guided multiple biopsies can be taken from gastric mucosa and are subjected to: a. Histopathology b. Microbiological methods. Gram staining. Culture media. Biochemical tests (Oxidase and catalase are positive ) C. Biopsy urease test (Rapid urease test) B. Noninvasive test a. Urea breath test b. Stool antigen assay c. Antibody detection d. Polymerase chain reaction (PCR) Treatment 1st line triple drug therapy Omeprazole + Clarithromycin + Metronidazole or Amoxicillin given for 7 -14 days Urea breath test is done If the 1st line regimen fails (Urea breath test +ve) 2nd line quadruple drug therapy Omeprazole + Bismuth subsalicylate + Metronidazole + Tetracycline Given for 14 days If 2nd line quadruple drug therapy fails then – Culture of endoscopic guided biopsy is done and treatment is Given based on antimicrobial susceptibility test Control H pylori is present on the gastric mucosa of fewer than 20% of persons younger than years 30 but increases in prevalence to 40–60% of persons age 60 years, including persons who are asymptomatic. In developing countries, the prevalence of infection may be 80% or higher in adults. H. pylori bacteria are usually passed from person to person through direct contact with saliva, vomit or stool. H. pylori may also be spread through contaminated food or water. There is no vaccine or other specific preventive measure.