Tuberculosis Flashcards
what is BCG
bacille calmette-Guerin
isolated from mycoplasma bovis
vaccine
what are diseases of importance that mycobacteria cause
tuberculosis - mycobacterium tuberculosis, mycobacterium bovis and leprosy (mycobacterium leprae)
what do mycobacteria cause
granulomatous lesions (tubercules) in tissues of a wide range of domestic and wild animals and humans
where does the mycobacteria survive and replicate in the host
macrophages of the host
is mycobacteria an anerobic or aerobe
aerobic
does mycobacteria form spores
non spore forming
is mycobacteria motile
non motile
is mycobacteria gram negative or positive
positive
what is the shape of mycobacteria
rods
how is mycobacteria stained
acid fast
bind phenol dyes (carbon fuchsin) and resist acid alcohol decolorization (ziehl neelsen stain)
is mycobacteria easy to grow
yes relatively simple
is mycobacteria rapid or slow growing
rapid (<7d) or slow growing (weeks or months)
what is unique about mycobacteria cell walls
lipid rich
acid fastness related to presence of peptidoglycan but particularly glycoplipids
lipids in cell wall related to pathogenicity (survival in phagolysome of macrophages, resists drying, extreme pH and other stresses)
what do the lipids in the cell wall of mycobacteria relate to
lipids in cell wall related to pathogenicity (survival in phagolysome of macrophages, resists drying, extreme pH and other stresses)
what are mycobacterium spp of clinical importance
- Mycobacterium tuberculosis*
- Mycobacterium bovis*
- Mycobacterium avium subspecies paratuberculosis*
- Mycobacterium avium complex* (including subspecies avium)
- Mycobacterium leprae*
- Mycobacterium lepraemurium, M. ulcerans, M. kansasii, M. fortuitum and M. chelonae*
what does Mycobacterium tuberculosis cause
TB in humans
Cats, dogs, chickens, pigs, parrots, canaries, guinea pigs, mice (cattle — rare)
what does Mycobacterium bovis cause
Bovine tuberculosis
TB in humans (badgers, deer) other ruminants, pigs and more rarely horses, dogs, cats, sheep
what does Mycobacterium avium subspecies paratuberculosis cause
Johne’s disease in cattle, sheep, goats, and deer (rarely other animals)
what does Mycobacterium avium complex (including subspecies avium) cause
TB in birds, poultry very susceptible
Pigs susceptible but not cattle
Sporadic cases in horses, dogs and cats
Opportunist in humans (AIDS — M. avium)
what does Mycobacterium leprae cause
Leprosy
Human, mice, armadillos
what does Mycobacterium lepraemurium, M. ulcerans, M. kansasii, M. fortuitum and M. chelonae cause
Skin ulceration and lymph node involvement in many different species
Chronic RTI
what is shown here
mycobacteria in acid fast (ziehl neelsen) stain
what do the mycolic acids do in the cell wall of mycobacteria
Resist phagocyte digestion
what do the sulfatides in the mycobacteria cell wall do
Sulfatides
Prevent phagocyte activation and phagosome-lysosome fusion
what do trehalose di-mycolate (Cord factor) do in the cell wlal of mycobacteria
Trehalose di-mycolate (cord factor)
Inhibits phagocyte chemotaxis, activation, phagosome-lysosome fusion and digestion
what do the lipoarabinomannan (LAM) do in the cell wall of mycobacteria
Lipoarabinomannan (LAM)
Prevents phagocyte activation and digestion within the phagocyte
what do the mycosides of the cell wall of mycobacteria do
Mycosides
Prevent intracellular killing and digestion
what do the cell wall antigens of mycobacteria do
Cell wall antigens in general induce delayed type hypersensitivity (DTH)
what determines the outcome of infection with mycobacteria (TB) in humans
the ability to mount an effective activated macrophage response
what are the outcomes of a TB infection (4)
- Infects, killed by immune response, no disease
- Infects, lies dormant for many years, no disease (infection contained) (most common)
- Infects, lies dormant for many years, re-activates and causes acute disease
- Infects, causes rapid acute disease, may disseminate (children, immunocompromised, HIV)
what is the immune response to mycobacterial infections
Antibody response irrelevant to protection
- Th1 (CMI) required to limit the disease and provide protection
Immune status of host important
- Active response results in lymphocyte infiltration, central necrosis in the lesion, tubercule many limited by a fibrin capsule
Response kay kill the bacteria but often is only able to restrict the disease
Reactivation occurs with stress/immunosuppression
IFN gamma from CD4 lymphocytes activates macrophages to all intracellular mycobacterial infected cells
CD1 restricted T cells recognize glycolipids
Exposure to environmental mycobacteria provides some cross-protection which may limit the disease caused by virulent species (also complicates skin testing)
what are the outcomes of bovine tuberculosis infection
how is bovine TB spread
Is promoted by high densities of animals and immune suppression
what usually occurs after exposure in bovine TB
Leads to tubercules in the lungs and associated lymph nodes (bronchial and retropharyngeal)
how does bovine TB spread throughout body
Spread to intestine (via sputum) and serosal surfaces
Pleural lesions
- Pearls disease
Further disease spread (usually hematogenous) to liver, spleen, kidney, brain etc
how is bovine TB treated
Antibiotic treatments are long term and very expensive
- Tuberculin testing and culling of exposed animals
what lesions are seen in PM of bovine TB
multifocal to coalescing caseous granulomas
describe the epidemiology of bovine TB
Cattle transmit infection to cattle via infected respiratory droplets –> Resp route
Badgers transmit M. bovis between themselves by respiratory route and biting
Mums transmit to cubs
Cattle may get M. bovis from badgers via grazing on pasture contaminated with badger urine, feces and bronchial pus or badgers urinate and defecate in cattle feeders
Aerosol transmission via coughing may be possible or via dried badger saliva in cattle houses
This may apply to battle to badger transmission
how is TB controlled by badger culling
Badger culling has significant impacts on the incidence of bTB in cattle
Culling of badger in define areas prevents infection on farms
Culling badgers in areas with no barriers makes survivors wander and spread infection further
Need vaccine for cows and wildlife
BCG works well in badgers both IM and orally
BCG in neonatal calves, adults?
how well does the TB vaccine work in cattle
Will protect cattle against TB
The degree of protection varied considerably between studies
Neonatal or young calves can be protected at least as well as older calves
Systemic as well as mucosal (oral or endobronchial) delivery of BCG leads to protection
Its (or another better vaccine) use in cattle and other domestic animals will require the development of a diagnostic test that can be used alongside vaccination to differentiate vaccinated and infected cattle (DIVA test)
what are the options of control of bovine TB
Culling — Ireland (with vaccination of badgers using BCG)
Culling — England (achieve certain percentage in high TB areas to decrease disease?
Vaccination of badgers — Wales
Badger vaccination across UK? — needles, baits?
Cattle vaccination
how is mycobacterial infection diagnosed
Immunological detection
Microscopy
Culture
how is mycobacteria diagnosed using immunological detection
Tuberculin testing using PPD (purified protein derivative) from the relevant bacterial species
PPD contains a mixture of proteins, carbohydrates, lipids and DNA
Gamma interferon assay
how is mycobacteria diagnosed using lab
Microscopy
- Ziehl Nielsen staining, rhodamine/auramine fluorescent stain) of appropriate specimens from site of infection
Culture
- Lymph node, tissue lesions, sputum, aspirates, milk
- Decontamination of specimens with sodium hydroxide
- Lowenstein Jensen medium (slants) incubated for up to 8 weeks
- ID by growth rate, colonial appearance, biochemical techniques, now increasingly molecular techniques (DNA probes, specific species primers for PCR)
what is the intradermal test for bovine TB
The tuberculin test is carried out at 1, 2, 3, or 4 year intervals depending on the freq of TB in the area
Animal ID and two sites prepared on the side of neck
Inject PPD
Re-measure fold after 72 hours
If reaction to M. bovis PPD is 5mm greater than to M. avium then defined a reactor
If 1-4mm then retested within 40-60 days
Measure lymphocyte infiltration into site
If previous exposure increased TB specific lymphocytes in lesion hence increase in size
Rest of herd analyzed using ‘severe interpretation’ which is 3mm
what infection does mycobacterium avium cause
non human primates, cattle and pigs infection is confined to the lymph node
causes disseminated disease in HIV/AIDs patients
describe the pathogenesis of paratuberculosis (Johne’s disease)
what is the gross pathology of John’es disease
thickened corrugated infection of ileum
what does Mycobacterium leprae cause
Leprosy in humans and primates, cutaneous lesions and nerve damage
Irradiated mice foot pads, nine banded armadillos
Tuberculoid leprosy:
- Little disfigurement
- Few organisms in well-contained granulomatous lesions in tissue
Lepromatous leprosy:
- Disfigurement, nodular swellings full of bacteria
- Anesthesia
- Shortening of toes and fingers in response to repeated unfelt trauma; spontaneous
what does Mycobacterium lepraemurium: cause
Skin lesions (especially on head and tail) of cats and rodents
what does Mycobacterium ulcerans: cause
Skin, nodules (skin granulomas) which can ulcerate
mainly humans
what does Mycobacterium marinum cause
Fatal infections common in poikilotherms
Fish tank/swimming pool granuloma from humans
