LECTURE 13 (Mycobacteria) Flashcards
Describe Mycobacteria
- Gram +ve
- Slim, poorly staining bacilli
- Non-motile, Non-spore forming
- OBLIGATE AEROBES
- Acid fast bacteria
[cell wall contains long-chain fatty acid (MYCOLIC ACIDS) and a transmembrane polysaccharide (LAM)] - Do not produce exotoxins or endotoxins!!!
Describe the growth of Mycobacteria
- Aerobes that grow very slowly (14-15 hours)
- Optimum temp is 37 C
- Grow only in specially enriched media containing egg, asparagine, potatoes, serum and meat extract
- Colonies appear in 2-8 weeks
What are the clinically important species of Mycobacteria?
- Mycobacterium tuberculosis
- Mycobacterium leprae
- Mycobacterium avium-intracellulare
- Mycobacterium kansasiii
- Mycobacterium chelonae
What are the disease processes that the host responds with?
- A DELAYED-TYPE HYPERSENSITIVITY REACTION (DTH) = destruction of non-activated macrophages containing multiplying organisms
- CELL MEDIATED IMMUNITY (CMI) = activates macrophages, enabling them to destroy mycobacteria contained within their cytoplasm
Describe Mycobacterium Tuberculosis
- Slim, strongly acid-alcohol-fast rod
- Grows at 37C which is very slow (12-24 hrs)
- Dry, rough, buff coloured colonies usually appear after 3-6 weeks of incubation
- Resistant to drying, most disinfectants and acids and alkalis -> BUT sensitive to heat + pasteurisation
- Individual organisms in droplet nuclei are susceptible to inactivation by UV light
What are the Virulence factors of Mycobacterium Tuberculosis?
- SULFATIDES (sulfolipids in cell envelope) = inhibits phagosome-lysosome fusion -> allows intracellular survival (if fusion occurs, waxy nature of cell envelope reduces killing effect)
- CORD FACTOR (trehalose dimycolate) = causes serpentine growth in vitro, inhibits leukocyte migration, disrupts mitochondrial respiration + oxidative phosphorylation
- TUBERCULIN (surface protein) along with MYCOLIC ACID = delayed hypersensitivity
What is Mycobacterium Tuberculosis?
A gram-positive mycobacteria that causes Tuberculosis
EPIDEMIOLOGY:
- Transmitted from person-to-person via respiratory aerosol from “smear-positive” people + initial site of infection is lung
- Humans are the natural reservoir
- Can be infected through GI tract by ingestion of milk from tuberculous cows
- The healthy person will not become infected if TB bacteria are destroyed inside the nasal passage of throat
PATHOGENESIS:
- PRIMARY TUBERCULOSIS: respiratory alveoli bacteria are recognised by MACROPHAGE COMPLEMENT RECEPTORS + phagocytosed + multiply in macrophages due to virulence factors -> Macrophages + dendritic cells release cytokines (tumour necrosis factor, IL-12 & IFN gamma) which attract T cells + other inflammatory cells to site -> CD4 T-cells initiate TH1-type immune response over the following 3-9 weeks in which IFN-gamma is the primary activator of macrophages -> As bacteria multiply, mycobacterial proteins trigger a DTH (delayed-type hypersensitivity) response -> TH1 immune + DTH responses manifest in a GRANULOMA -> As granuloma grows, degeneration causes CASEOUS NECROSIS
- LATENT TUBERCULOSIS: oxygen + nutrient deprivation -> LATENCY! waxy nature of MTB cell wall helps survival + organisms lie waiting for reactivation for months years or decades later
- REACTIVATION TUBERCULOSIS: caused by depression in hosts’ immunity + located in body areas with high oxygen
MANIFESTATIONS:
- ASYMPTOMATIC PRIMARY INFECTION: fever and malaise + radiographs show infiltrates in mid-zones of lung + enlarged draining lymph nodes in area around hilum
- SYMPTOMATIC PRIMARY TUBERCULOSIS: common in children, elderly + immunocompromised adults
- REACTIVATION/SECONDARY TUBERCULOSIS: occur after 50 + common in men + reactivated by alcoholism, diabetes, old age and drastic change
DIAGNOSIS:
- Small amount of PPD tuberculin is injected below skin of inside forearm -> within 48-72 hrs, swelling is checked at injection site
[Positive TB skin test/TB blood test only tells if person is infected with TB, no if person has latent TB or has progressed to TB disease]
- Chest X-ray: isolated granuloma, Ghon focus, Ghon complex, old scarring in upper lobes or active tuberculous pneumonia
LABORATORY TESTS:
- Pulmonary tuberculosis = sputum
- Renal tuberculosis = urine
- Tuberculous meningitis = CSF
[Early morning sputum samples should be collected for 3 days in a sterile container + Renal tuberculosis 3-6 morning samples collected]
- Acid-fast smear and culture
- Nucleic amplification tests
TREATMENT:
- Isoniazid
- Rifampin
- Ethambutol
- Pyrazinamide
[treatment course is 6-9 months]
What are the manifestations of Tuberculosis depending on the site of reactivation?
- PULMONARY TUBERCULOSIS: most common site of reactivation tuberculosis
- PLEURAL + PERICARDIAL INFECTION: fluid collections around lung or heart respectively
- LYMPH NODE INFECTION: most common extra-pulmonary infection
- KIDNEY: red + white blood cells in urine but no bacteria seen by Gram stain or grow in culture -> “sterile pyuria”
- SKELETAL: thoracic + lumbar spine -> destroys intervertebral discs + adjacent vertebral bodies (Pott’s disease)
- JOINTS: usually a chronic arthritis of 1 joint
- CNS: subacute meningitis + forms granulomas in the brain
- MILIARY TUBERCULOSIS: granulomas disseminated all over body
What are the signs and symptoms of Tuberculosis?
- Coughing that lasts 3 or more weeks + coughing up blood
- Chest pain or pain with breathing or coughing
- Unintentional weight loss
- Fatigue + fever
- Night sweats + chills
- Loss of appetite
Describe Mycobacterium Leprae
- Not grown in artificial media/cell culture -> grown in animals (e.g mice)
- Optimal temp for growth (30C) is lower than body temp -> grows preferentially in skin + superficial nerves
- Grows VERY slowly -> antibiotic therapy must be continued for a long time (usually several years)
What is Mycobacterium Leprae?
A mycobacterium that causes leprosy
EPIDEMIOLOGY:
- Incubation period is 2-7 years or up to 4 decades
- Infection acquired by prolonged contact with patients with LEPROMATOUS LEPROSY who discharge M. leprae in large numbers in nasal secretions + form skin lesions
- Humans are natural hosts
PATHOGENESIS:
- Obligate intracellular parasite that must multiply in host cells to persist
- Target Schwann cells (glial cells of the peripheral nervous system) -> Schwann cell injury + demyelination of peripheral nerves which precedes but is enhanced by DTH immune response to M. leprae -> invasion + demyelination of peripheral sensory nerves causes local anaesthesia + changes in skin depending on location + degree of immune response
MANIFESTATIONS:
- Tuberculoid Leprosy = development of macula’s or large, flattened plaques on the face, trunk and limbs with raised, erythematous edges and dry, pale, hairless centres
- Lepromatous Leprosy = skin lesions are infiltrative, extensive, symmetric and diffuse, particularly on the face with thickening of the looser skin of lips, forehead and ears
DIAGNOSIS:
- Lepromatous leprosy -> acid-fast stain of skin lesions or nasal scrapings
- Tuberculoid form -> appearance of typical granulomas is sufficient for diagnosis
- Cultures are NEGATIVE because organism doesn’t grow on artificial plates
- PCR
TREATMENT:
- SULFONES (blocks para-aminobenzoic acid metabolism in M leprae) -> combined with RIFAMPIN, DAPSONE controls/cures tuberculoid leprosy when given for 6 months
- In lepromatous, CLOFAZIMINE is added to prevent resistant mutants + treatment for at least 2 years
Describe Tuberculoid Leprosy
- When the bacterium has invaded peripheral nerves -> the lesions are anaesthetic
- The disease is indolent with simultaneous evidence of slow progression and healing
- Usually non-contagious (due to small number of organisms present)
Describe Lepromatous Leprosy
- Damage may be severe with loss of nasal bones and sputum, sometimes of digits and testicular atrophy in men
- Peripheral neuropathies may produce deformities or non-healing painless ulcers
- Organism spreads systemically with involvement of reticuloendothelial system
