Mycobacterium Flashcards
Staining characteristics of Mycobacterium sp.
Weak gram positive staining rods
Acid fast positive staining rods
Large amounts of lipids (mycolic acids) in the cell wall
The type of pathogen Mycobacterium sp. are
Facultative intracellular pathogens
Survive inside macrophages
Immunity is cellular (Th1 response)
Type of inflammatory response produced by Mycobacterium sp.
Cause granulomatous inflammation
Virulence factors of Mycobacterium sp.
Mycolic acid containing cell wall lipids - facilitate survival in macrophages (facultative intracellular pathogens)
Cell protein antigens - Tuberculin (purified protein derivative)
Important diseases caused by Mycobacterium sp.
Mammalian tuberculosis = M. tuberculosis complex - M. tuberculosis, M. bovis, M. africanum, M. microti
Avian tuberculosis = M. avium subsp. Avium serotypes 1-3
Leprosy = M. leprae (human), M. lepraemurium (cat)
Johne’s Disease = M. avium subsp. paratuberculosis
Tuberculous Group of Mycobacterium
Forms caseous granuloma
M. tuberculosis
M. bovis
Non-tuberculous Group of Mycobacterium
Forms non-caseous granuloma
M. avium complex
Pathogenesis of Tuberculosis
Infection (inhalation or ingestion) -> disease -> innate control -> spontaneous healing or containment in the body (latency) -> reactivation and disease transmission
Cell mediated immune response is important in the destruction of bacilli
If the bacilli survive, infected macrophages are killed following release of macrophage-derived cytotoxins and enzymes (Type IV hypersensitivity or Delayed type hypersensitivity)
Tuberculosis lesions
Tubercles are the classic lesion of tuerculosis
Granulomas with central areas of either solidly packed epithelioid macrophages (hard tubercle) or caseous necorsis (soft tubercle) surrounded by epithelioid cells and multinucleated giant cells (Langerhan’s cells)
Elements of a tubercle
Activated macrophage/epithelioid cells Lymphocytes Fibrosis (fibroblasts/collagen) Mineralization may occur Coagulative/caseous/liquefactive necrosis may be present
Mycobacterium tuberculosis hosts
Humans are the main reservoir
Can infect dogs, cats, pigs, nonhuman primates
Psittacine birds and canaries are susceptible
Diagnosing Mycobacterium tuberculosis
Diagnositc imagin
Tuberculin testing (Mantoux testing)
TB is a treatable and curable disease
Anti-tubercular Drugs
Drugs are always used in combinations to treat tuberculosis
Primary Drugs - Isoniazid, Rifamycins, Ethambutol, Pyrazinamide
Secondary Drugs - Aminoglycosides, Fluoroquinolones
Problems with TB treatment
Combination drug therapy is needed
Need prolonged treatment
Poor drug distribution in walled off lesions
Multidrug Resistant TB (MDR) = resistant to isoniazid and rifampin
Extensively drug resistant TB (XDR) = resistant to isoniazid and rifampin, fluoroquinolones and at least one of three injectable second-line drugs
Mycobacterium bovis hosts
Widest host range of all TB organisms
Maintained primarily in bovine species
Mycobacterium bovis pathogenesis
GI tract is the main portal of entry
Chronic progressive, and latent infections
Disease is seldom apparent until it has reached advanced stages
Organisms can remain dormant in the body for lifetime without causing progressive disease
Causes disease indistinguishable from that of Mycobacterium tuberculosis of humans
Mycobacterium bovis lesions
Advanced disease = enlarged regional lymph nodes and generalized wasting (cachexia)
Early stages = lesions are difficult to find at necropsy
Later stages = nodular lesions in target organs and associated lymph nodes
Diagnosis of Mycobacterium bovis
Tuberculin hypersensitivity skin tests
- screening test in caudal tail fold with single-strength dose of M. bovis purified protein derivative (PPD)
- reactors in screening test are subsequently tested by paired cervical tests with double strength M. bovis PPD and M. avium PPD in separate areas of the neck to rule out cross reactions with M. avium subsp. paratuberculosis
Mycobacterium avium subsp. paratuberculosis
- disease names
- type of disease
Johne’s disease, or paratuberculosis
A chronic progressive granulomatous enteritis
Mycobacterium avium subsp. paratuberculosis hosts
Primary hosts = ruminants (cattle)
Young animals are most susceptible to infection with an incubation period up to two years before symptoms appear
Pathogenesis of Mycobacterium avium subsp. paratuberculosis in cattle
Infection through ingestion of contaminated milk or in-utero
Localizes in macrophages in the intestine, local lymph nodes
Animal will either clear the infection, or delayed progression to disease
Develops granulomatous enteritis, cachexia (wasting of the body)
“Iceberg Effect” - numerous asymptomatic shedders
Diagnosis of Mycobacterium avium subsp. paratuberculosis
Detection of Host Response to Infection:
Humoral immune response - ELISA or Agar gel immunodiffusion test used for herd testing when there have been prior cases or high infection prevalence in herd
Cell mediated immune response - Johnin hypersensitivity skin test; Interferon Gamma Release Assays (IGRA) or Lymphoblast Stimulation Assays
Johne’s ELISA
Widely used in cattle herd to detect animals infected with Mycobacterium avium subsp. paratuberculosis
Detect humoral immune response to MAP
Low sensitivity in early stages of diseases
False positives can occur (specificity issues)
False negative results in advanced stages of disease due to mechanism called anergy
Mycobacterium avium complex (MAC)
Opportunistic granulomatous infections in humans, animals, and birds
Widespread in soil and water, including treated municipal tap water
Mycobacterium ulcerans
Causes Buruli Ulcer, a mysterious devastating disease
Mycobacterium leprae
- disease names
- disease caused
Leprosy or Hansen’s Disease
Chronic granulomatous debilitating disease
Anaesthetic skin lesions, peripheral neuropathy, and nerve thickening
Mycobacterium leprae transmission
Transmission from shedding through nose, not from skin
Animal reservoir = Nine banded Armadillo in southern United States
2 types of Mycobacterium leprae leprosy
Tuberculoid leprosy - paucibacillary
- paucibacillary = few AFB+ in the lesion
- few acid fast positive bacilli in the lesion
Lepromatous leprosy - multibacillary
- multibacillary = numerous AFB+ in the lesion
- no cell mediated reponse, sever disease with numerous aid fast positive bacilli
Mycobacterium lepraemurium
- disease names
- disease caused
Feline and Murine Leprosy
Solitary to multiple cutaneous nodules or ulcerated lesions
Granulomatous Dermatitis Panniculitis
Diagnosis of Mycobacterium lepraemurium
Geimsa or Acid Fast Staining
In Geimsa or Gram stain-Negative stained (not Gram negative) bacilli are generally observed