Condensed Notes

Tuesday, August 19, 2014

6:33 PM

Learning Objectives
- Describe unique structure, transmission, and pathogenesis of M.tuberculosis and M.leprae
M.tuberculosis (TB)
Structure
1/3 world pop infected
MDR (Multi-drug-resistance) becoming a global health emergency
Resistance is chromosomal, not due to a plasmid
Mycobacteria Gram stain very poorly, but are almost uniquely acid-fast

Grows in vitro, but very slowly, and requires special nutrients

M.leprae doesn't grow in vitro = very hard to study/research
Obligate aerobe: colonization is restricted to O2-rich parts (CNS, kidney, lung, lymph nodes, ends of long bones)
Does not produce any toxins (mycobacteria don't produce toxins)
Pathogenesis
Humans are reservoir, therefore human-human transmission is typical via resp droplets
Resides in macrophages (uses it as a trojan horse) and proliferate
Exudative lesions (lesions that "exude" out/excrete things out) in lungs @ initial infection; acute inflammatory response
Exudative lesions that are calcified + draining lymph nodes = Ghon Complex
TB if reactivated can then travel from Ghon complex systemically via macrophage
Granulomatous lesions (when TB is encapsulated)
Reactivation lesions may occur in neck (scrofula), kidneys, brain, and bone as well as lower lung
This is seen in immunocompromised or debilitated ppl
Disease is controlled by cell-mediated-immunity (CMI) - Active TB becomes dormant/latent
Organism is very hard to clear completely
M.tuberculosis is intracellular (inside macrophage), and multiply slowly (have periods of metabolic inactivity)
Both of these protect it from drugs that kill rapidly-growing cells (which is how normal bactra would multiply)
M.leprae (Hansen's Disease)
Structure
Not culturable
Reservoirs are humans (major) and armadillos (minor)
14-day doubling time: slowest growing human pathogen
Prefers 30C for growth (unusual) --> this is why it sticks to periphery of humans
Pathogenesis
Infec by prolonged cntct w/ infectious pt
Spread by nasal secretions and skin lesions
Most infectees (>90%) asymptomatically clear the bacteria
If colonized, intracellular replication in skin, endothelial cells, schwann nerve cells
This causes nerve dmg by both bacteria & CMI
Symptoms are a spectrum b/w 2 extremes
Tuberculoid leprosy
Strong CMI response contains the disease in granulomas
Few bacilli seen
Immunogenic nerve dmg
Lepromatin skin test (type of PPD) positive
Lepromatous leprosy
Poor CMI --> large number of bacilli in skin & mucous membrane
Foamy histocytes form
Nerve dmg by bacteria

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 Nerve dmg by bacteria

Lepromatin skin test negative
This is the really ugly leprosy
Treatment
For tuberculoid: 2 yrs of dapson + rifampin
+clofazimine if lepromatous
- List the steps of acid-fast differential staining for microscopy

Acid-fast staining of sputum or other specimens

If you see the characteristic clumps in the acid-fast smear staining, this is TB
However, if it is acid-fast staining smear negative, this does not rule out TB
Culture: liquid media (takes about 2 wks)
Begin susceptibility testing, but results will take weeks
- You are not responsible for the details of diagnosis and treatment this year, but be able to describe some of the challenges to each
Diagnosis
Exam: fever, fatigue, night sweats, weight loss
Pulmonary TB: cough, hemoptysis
Scrofula
Miliary TB: multiple disseminated lesions (like "millet seeds")
Meningitis: high-inflammation
For children, check for Brudzinski's sign (bend the neck, and if legs go up with it)
Osteomyelitis (Pott's Disease): if you see a sign of osteomyelitis, don't delay treatment, or else patient might be paralyzed
Osteomyelitis = infection + inflammation of bone
GI TB: abdominal pain and diarrhea, obstruction or hemorrhage in ileocecal region
This may be TB (b/c you swallow sputum that has active TB in it) or M. bovis (from unpasteurized milk)
Renal TB: dysuria (painful urination), hematuria (presence of RBCs in blood), flank pain (abdominal pain), "sterile pyuria"
(pus-containing urine)
AIDS + TB = many symptoms & rpaid decline
Remicade-activated TB: pt receiving Remicade for rhemuatoid arthritis, Chron's, etc may reactivate latent infection
PPD skin test: PPD injected --> diamter of erythema & induration (aka skin condition) from tuberculin is measured
15mm = positive
10mm: positive if also has major risk factors
5mm: positive if has deficient CMI (immunosuppressed)
Misleading weak positives may result from past disease or vaccination
Treatment
At least 6 months of multidrug courses featuring ISONIAZID
Directly Observed Therapy (DOT) is standard: pt come to the office @ least 3x/wk so a nurse can watch them take the pill
Prevention
Good housing & nutrition go a long way: strong CMI induces latency
Semieffective vaccine is available made based on BCG, a live M. bovis (used where TB is common enough that it's cost-effective)
Can prevent up to 70% of symptomatic infections, but has wide batch variation (meaning the actual prevention will probably be
much less)
Also, this does not prevent latent infection
- Be aware of the existence of and potential for confusion w/ atypical mycobacteria
Atypical mycobacteria are environmentally-acquired that do not cause TB or leprosy
Group 1: Photochromogens
M.kansasii is environmental (unknown reservoir) --> produces lung disease resembling TB in immunosuppressed pts
M.marinum found in fresh & salt water --> forms graulomatous ulcerating lesions
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 M.marinum found in fresh & salt water --> forms graulomatous ulcerating lesions
Group 2: Scotochromogens
M.scrofulaceum found in water --> produces scrofula (like TB)
This is more common than TB in pediatric scrofula b/c they put shit in their mouth
Group 3: nonchromogens
M.avium/M.intracellulare are very difficult to distinguish; they are jointly called MAI/C --> causes pulmonary disease
indistinguishable from TB in severely immunocompromised pts
Environmentally widespread (found in soil and water)
Highly drug resistant

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