Mycobacteria - Fan 4/28/16 Flashcards
mycobacteria
general chars
thin, rod-shaped
non-motile
obligate aerobe
cell walls contain N-acetyl glucolylmuramic acid (instead of N-acetyl muramic acid) → high lipid content, stains differently
- Ziehl-Neelsen acid fast staining w/ carbol fuschin
- resistant to destain by acid/alcohol
- fluorochrome stain (sputum)
- more sensitive than ZN acid fast stain → binds mycolic acid
v slow growing
2 primary complexes: Mtb complex vs. non-Mtb complex
Mtb complex
5 organisms
- M. tuberculosis, M. bovis, M. bovis BCG, M. africanum, M. microti, M. canetti*
- non-pigmented colonies
1/3 of the world’s pop is infected
pathogenesis
- 15-20% inhalation
- M. bovis from milk
- M. bovis BCG from vaccine (in immunocompromised people)
- small percentage of pts : disseminated disease
- disease may occur many years after exposure
spectrum of disease
- low grade fever, night sweats, anorexis, weight loss
- productive cough with pulm infection & fever, sweating, chills, myalgia
- GI, LN, CNS, bone/jt, peritoneal, pericardial, laryngeal involvement
- HIV+ individuals especially susceptible
TB transmission
airborne via droplet nuclei
only 5% of pts become infectious BUT those that are are highly infectious
TB pathogenesis
droplet nuclei containing TB bacilli are inhaled → travel to alveoli
- infection can also occur via inoculation/ingestion
- infection depends on host, virulence, dose
typically, bacilli multiply in alveolar macrophages
2-8 wks: cell mediated immunity kicks in, activated macrophages surround bacilli, form a barrier shell (granuloma) that keeps bacilli contained and under control
- aka LTBI : latent TB infection
- if immune system can’t keep up with infection and keep it contained…*
focal granulomata break down → organisms escape, replicate, can disseminate
- can occur in multiple places → considered active disease
- progressive primary infection, reactivation, or reinfection
***tissue injury is a consequence of immune response (not toxins or virulence factors)
- host destroys itself in attempt to control intracellular growth
TB lab/histo findings
DTH test
histo low power: granulomas
histo high power: Langerhan’s cells (macrophages)
in most people, TB remains latent due to delayed type hypersensitivity (type IV)
tuberculin skin test (Mantoux test)
- Mtb extract or purified protein derivative of Mtb injected
- 48-72 hours later: ring of induration: >5, >10, >15
- positive for: high risk, moderate risk, all pops
- issues: failure to follow up, incorrect reading/inconsistent interp, cross-reactivity with other mycobacteria, positive due to BCG vaccination
interferon gamma release assay
- T lymphocytes of people who have been infected with Mtb will release IFN gamma in presence of Mtb antigen
- 3 separate measurements:
- whole blood (baseline)
- whole blood plus non-specific activator of WBC (control for WBC response and IFN gamma secretion)
- whole blood plus Mtb peptides (recombinant, specific → not cross-reactive with BCG)
should you do TST (tuberculin skin test) or IGRA (IFN gamma release assay)?
IGRA can be used in place of (not in addition to) TST
IGRA better when
- patients might not return for reading
- BCG vaccine administered
TST better when
- testing < 5yo (IGRA data not available for this group)
risk factors for Mtb progression
HIV+
children < 5 yo
people receiving immunosuppressive therapy
- TNF alpha antagonists (etanercept, adalimumab, infliximab)
- systemic corticosteroid tx
- post organ transplant tx
people with recent infection (< 2 yr) OR infection with no/inadequate tx
silicosis, diabetes, chronic renal failure, leukemia, lymphoma
malnutrition (incl gastrostomy or jejunoileal bypass)
smokers
people in high incidence locations
differentiating latent TB vs active TB
latent TB
- no symptoms
- not contagious
- skin test or blood test indicating infection BUT normal CXR, negative sputum smear
- need treatment to prevent progression to active
- usually INH for 9 mos
active TB
- symptoms incl:
- bad productive cough (3+ weeks) w bloody sputum, chest pain
- weakness, fatigue, weight loss
- no appetite
- fever, chills, night sweats
- contagious
- skin test or blood smear showing infection; also abnormal CXR or negative sputum
- tx: multiple drug therapy
miliary TB xray
- occurs when TB-infected lymph node erodes a vessel wall → tubercule bacilli spread through bloodstream
- “miliary” due to diffuse appearance like that of millet seeds
TB test specimen processing, visualization
if from a normally sterile site:
- concentrate, stain/inoculate
if from a site with other contamination:
- N-acetyl-L-cysteine liquefaction
- NaOH to kill contaminating bacteria
- neutralize
- concentrate
then…
- visualize via
- acid fast staining → look for cording
- fluorochrome stain (more sensitive)
*need to consider contamination by other acid fast orgs! (Nocardia, Rhodococcus, L. micdadei, Cryptosporidium, Isospora)
new best practice for TB testing:
NAAT
nucleic acid amplification testing
- use in conjunction with conventional smears
- advantages
- greater specificity (95% PPV)
- greater sensitivity (50-80% of smear-/culture+ specimens show up NAAT+)
NTM
non-tuberculous mycobacteria
ubiquitous in environment
infection via trauma, inhalation of aerosol, ingestion
clinically important NTM (Runyan classification)
- photochromogens (Group I) → develop pigment under light
- schotochromogens (Group II) → develop pigment with or without light
- nonphotochromogens (Group III) → no color formation
- rapid growers (5 days, no pigment) (Group IV)
M. kansasii
chronic pulmo infection involving upper lobes
major reservoir: tap water
dissemination rare except in AIDS
photochromogenic
slow grower so…
- dx: DNA probe
tx: rapid response to antimicrobial therapy
M. marinum
cutaneous infection associated with exposure to salt/freshwater after trauma
- swimming pool/fish tank granuloma
photochromogenic
slow growth at 30 C, no growth at 37 C
ID: molecular identification
M. gordonae
non-pathogenic (no tx required)
found in soil, water
colonizes resp tract
scotochromogen
ID: DNA probe
