Mycobacterium Flashcards
Granulomas
Walling off of organism that can’t be eliminated
- mycobacteria, bacteria (Bartonella), fungi
- autoimmune - sarcoid, Crohn’s, rheumatoid
- particulate - berylliosis
Mostly mononuclear - macrophages -> epithelioid, lymphocytes around edges, PMN, eosin
- fibroblasts, collagen
- Langhan’s giant cells
Caseating -> think TB
Mycobacterium overview
Weakly Gram + bacilli
Acid fast - red phenol -> mycolic acid -> doesn’t wash out
- mycolic/fatty long chain acids in cell wall (high lipid content)
- trehalose dimycolate -> cords in culture
- Nocardia has C50 mycolic acids -> weakly acid fast
- also Cryptosporidia, Actinomyces, Isospora, Cyclospora
Non-motile, non-spore, non-encapsulated
No toxin production
Obligate aerobes (except M bovis) -> upper lung lobes
Very slow growing (gen time = 18 hrs)
- ex leprae cannot be cultured
- 3-8 weeks for visible growth of others
- fastidious culture media
M leprae -> leprosy
M tuberculosis complex (tuberculosis, bovis, bovis-BCG)
Non-tuberculous - M avium, rapidly growing (RGM)
M tuberculosis complex
Group of 5 species/subspecies:
- tuberculosis
- africanum
- bovis
- bovis-BCG
- cannetti
History - “white plague”, scrofula, phthisis, consumption
- 1:4 deaths England 1815
Villemin proved contagious (innoculum)
Now 1.7 B prevalence, 9 million incidence, 2 million deaths
- US 10 million prevalence (4% population)
Tuberculosis pathogenesis
Droplet -> inhalation -> macrophages -> eliminated or transient bacteremia, granuloma formation ->
- primary disease
- latent infection (LTBI)
- latent -> reactivation disease
- highest risk of progression is in first 2 years
- HIV+ -> annual risk of 10% (vs lifetime risk of 10% healthy)
“Disease” = symptomatic
Can be disseminated (esp if immunocompromised)
- lymph nodes = scrofula
- bones (Potts = spine)
- meningitis
- kidney
Tuberculosis transmission
Droplets - 1 micron diameter = 10 bacteria
- can linger in air up to 8 hours
- shared airspace is key -> 30% of “close/household” contacts
Prevention - diagnostic suspicion -> isolation in Negative air pressure + N95 for personnel
- wear mask (or patient wears mask)
- ventilation
- annual TST or IGRA
- in US most acid-fast are M avium, but assume TB until known
Tuberculosis clinical presentation
Radiography:
- Ghon focus = granuloma of healed TB
- Ghon complex = focus within lymph node
- Ranke complex = calcified Ghon complex
Caseous - “cheesy” dry amorphous material
Tubercle = granuloma + fibrous + caseous center
Miliary - many small lesions - children, immunocompromised
Pulmonary -> cough, weight loss, fever
- cavity - parenchyma liquefies (high bacterial burden)
- hemoptysis - ex Rasmussen’s = pulmonary artery
Disseminated -> depends on site
Tuberculosis diagnosis
Acid fast bacillus (AFB) smear - rapid (same day)
- low sensitivity (requires 10>5/mL)
- low specificity - non-tuberculosis Myco, etc
Culture - more sensitive, more $$
- Lowenstein-Jensen egg -> 3-8 weeks
- automated CO2 detection -> 2-3 weeks
- can get sensitivity, DNA fingerprinting
PCR amplification
Mycolic acids -> LAM urine test
Clinical findings (ex CXR, granulomas)
Latent:
- IgG release assays (IGRA) - immune cells -> test in vivo
- skin test (TST) - inject partially purified derivative (PPD)
- positive at 2-10 weeks
- “induration” = palpable hardness
- interpretation depends on patient status
- cross-reacts with BCG, requires multiple visits
Tuberculosis treatment
Standard is directly observed therapy
“RIPE”:
Isoniazid (INH) - cidal, s/e hepatic, neuropathy
Rifampin (RMP) - cidal, s/e hepatic, flu, drug reactions
Pyrazinamide (PZA) - cidal for intracellular, s/e hepatic, GI, rash, myalgia
Ethambutol (EMB) - static (prevent resistance), s/e ocular
2 months intensive (all four) -> 4 month continuation (INH, RFA)
MDR = at least INH, RFA -> complicated to treat
- different mechanisms, chromosomal -> usually inadequate tx
XDR = MDR + fluoroquinolone and injectable -> ??, surgical??
Latent:
- INH x 9 months (best)
- RFA x 4 months
- INH + RFA weekly x 12 weeks
Mycobacterium bovis
Causes TB in cows -> GI disease
- can cause direct human disease (3% in Africa)
- transmission cow-> human or human -> human
BCG strain - attenuated live vaccine
- childhood - reduced disease by 80%, prevents meningitis, bacteremia/progressive - recommended in endemic
- 50% effective in adults
- also protects from other Mycobacteria
- immunostimulant for bladder cancer?
- > can convert PPD though usually <10 mm (increases with repeated testing)
- IGRA not affected
Mycobacterium leprae overview
Preferred: Hansen’s disease
Falling globally but still common in Brazil, Uganda, India
- 200-300 US cases in Louisiana (immigration, unknown)
Hosts - humans, armadillos
- transmission resp or through breaks in skin
- NOT highly contagious
- genetic predisposition? only 5% susceptible
- incubation 2-5 years
- > forced segregation is unnecessary and unethical!
Attacks skin, peripheral nerves, URI, eyes
Grows best in cooler temps
Never cultured!
M leprae clinical presentation
Varies with degree of cellular vs humoral immunity!
Cellular -> “paucibacillary”, no AFB reaction, lepromin +
- tuberculoid, non-caseous granuloma (+ CD4 in lesion)
- skin macules/papules - white, red, brown, also to PNS
- good prognosis
Humoral -> multibacillary, high AFB count, lepromin (-)
- > sheets of foamy macrophages in dermis
- loss of specific T cells, only suppressor T cells, non-specific Ig
- > nodules, thickening, disfiguration
M leprae treatment
Combo therapy x2-3 years
- dapsone
- rifampin
- clofazimine (-> skin s/e)
-> improves lesions, nervous fx, less contagious
Still need long-term care for disabilities
Overview of non-tuberculous Mycobacterium (NTM)
Ubiquitous in soil, water, animals - no human-human transmission
- livestock, showers, cigarettes
Incidence increasing!
Runyon classification (I-IV) - speed of growth, pigments grow in light vs dark (ex III slow no pigment)
Positive AFB -> contaminant? colonizer?
- can be pathogenic in compromised or normal
- often need PCR to distinguish from TB
- NTM is more common than TB in US!! (even for pulmonary)
M avium complex (MAC) Rapidly growing (RGM)
M avium complex (MAC)
Most common NTM, increasing
Found in soil, water, birds
-> cervical adenitis = scrofula
-> pulmonary in chronic lung, older women
-> disseminated in AIDS, severe compromise
Tx: multidrug x18 months
Rapidly growing Mycobacterium (RGM)
Type of non-tuberculous (NTM)
Ex: M chelonae, fortuitum, abscessus
Soil, water, birds ->
- > skin (compromised, surgical, direct innoculation)
- > prosthetics
- > pulmonary in chronic lung (ex CF)
- > disseminated in advanced immune compromise
Tx: long and multidrug, test susceptibility
