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99 Cards in this Set

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Properties of Mycobacteria
Acid-fast nonmotile
SPORE-forming
NON-encapsulated RODS
obligate AEROBES
compare growth rate of MYCOBACTERIA to E. coli
many mycobacteria are very slow growing
Mycobacterium leprae cannot be cultured on artificial media, all other mycobacteria exhibit mostly what type of growth?
facultative intracellular growth
mycobacterial cell walls
triple layer
contain MYCOLIC (fatty) acids
acid fast bacteria
mycobacteria
and
Nocardia
distant relative of mycobacteria, also contain mycolic acids (but shorter length ~35 Carbons)
NOT acid fast
Corynebacteria
these bacteria w/ C50 mycolic acids are weakly acid fast
NOCARDIA
Mycobacteria have C#-# mycolic acids
C78-92 mycolic acids
what is cord factor?
two mycolic acids attached to the disaccharide TREHALOSE,

associated with virulence in Mycobacterium tuberculosis
what gives mycobacteria a high lipid content?
MYCOLIC ACIDS
40-60% dry weight = lipid

also contain WAX D
what is Freund's complete adjuvant?
mycrobial lipids used by immunologists to increase the immune response to various antigens
mycobacterial lipids are probably involved in what type of immune response, often seen in mycobacterial infections?
cell-mediated
what features is involved in the characteristic resistance of mycobacteria to drying and chemicals
lipids (mycolic acids and Wax D)
high lipid concent and associated decreased permeability may contribute to
the slownesss of mycobacterial growth
generation time for TB =
15-20 hours for TB
compared to 1 hour for most common bacterial pathogens
visible growth on solid media takes how long for TB?
3-8 weeks
prevalence of Leprosy
in the US: 300-400 in National Leprosarium in LA (800-1100 undiagnosed or arrested cases)

12-15million cases in world, widespread in Brazil and India
why is prevalence of leprosy falling worldwide?
because of control programs and multi-drug Tx
causative agent of LEPROSY
Mycobacterium leprae (aka: Hansen's bacillus)
Mycobacterium leprae
-where is it found?
-characteristics
found intracellularly in leprosy lesions
ACID-FAST RODS

has never been cultivated in artificial media
leprosy lesions are found:
skin, nose, mucous membranes of upper respiratory tract

temp pref 27-33 C

humans and armadillos are only known natural hosts
transmission of leprosy
probably respiratory, perhaps sometimes through breaks in skin
age group most susceptible to leprosy
children >> adults
primary lesions of leprosy
a skin macule, may be hypo-pigmented or erythematous or raised and brown wheal-like papule, like mosquito bite
incubation period for leprosy
usually 2-5 years, though can be few months to 30 years
Leprosy primarily involves what tissues?
primarily involves skin (esp. low temp areas) and nerves

cases with long duration show amyloidosis of kidneys, liver and spleen
Types of Leprosy
LEPROMATOUS
INTERMEDIATE
TUBERCULOID
Lepromatous Leprosy
-Genesis
-# of bacteria involved
-Result of Lepromin skin test
-Immunity
-Genesis: M0 or Histiocyte takes up bacilli

-Many bacilli (5x10^6/ gram infected tissue)

Lepromin skin test NEGATIVE

Ability to mobilize T cells is POOR
Tuperculoid Leprosy
-Genesis
-# of bacteria involved
-Lepromin skin test
-Immunity
-Genesis: more like TB; chronic granulomatous lesions, epithelioid and giant cells present w/o caseation

-Few, if any, bacteria toward the center of the lesion

-POSITIVE Lepromin skin test

-Immunity: CAN mobilize T cells, DTH intact
why type of leprosy has a POORER prognosis?
Lepromatous
(old nodular)
poor immune response
many bacteria
supressor T cells in skin lesion
hypergammaglobulemia
correlation of cellular immunity with Tuberculoid Leprosy
Lepromin skin test +
In vitro T cell responses- lymphocyte transformation, M0 and leukocyte migration inhibition, gamma-interferon production

normal IgG
polyclonal hypergammaglobulinemia is seen in what type of Leprosy?
lepromatous
Erytheme Nodosum Leprosum (ENL) is a complication resembling what?
immune complex disease
Antibody to M. leprae
specific for phenolic glycolipid, but not protective
potential mechanism for failure of cell-mediated immunity in lepromatous patients?
possible induction of Supressor T cells by a unique component of lepromin (perhaps a phenolic glycolipid)
Dx of Lepromatous Leprosy
difficult, based on gross appearance of lesions, histological examination, acid-fast stains of material from nodules, margins of flat lesions or nasal scrapings
Chemotherapy of Lepromatous Leprosy
3 drug treatment (typically for 2-3 years)
1) Dapsone (sulfonamide-like action)
2) Rifampin- bactericidal
3) Clofazimine
*treat ENL complication with immune supression
control/prevention of Leprosy
evaluation of household ocntacts for up to 5 years, treatment of 2ndary cases

BCG (TB vaccine) offers some protection
causative organism of TB
mycobacteria tuberculosis
mycobacteria tuberculosis may remain viable for ??? at 4 C
for weeks
extremely resilient
hydrophobic waxy triple-layered cell walls
host defenses against MTB
M0s injest, release IL-12/present to (cd4) T cells

CD4 T cells release lymphokines to:
-expand CD4 clone (IL-2), and
-activate M0 (IFNg) to release TNF to induce pagolysosomal fusion and kill intracellular MTB
activates M0s (aka EPITHELIOID CELLS) have enhanced ???? activity against MTB?
cidal activity
NRAMP1
a gene that appears to regulate the pagolysosomal environment

variant allele may confer increased susceptibility to MTB (common in W. Africans, rare in Europeans)
what type of polymorphisms are associated with protection against TB in W. Africa?
polymorphisms in vit. D receptor gene (tt genotype)
# of new active TB cases/year worldwide
(# of deaths/year)
6-8 million new active cases/year
2-3 million deaths/year
TB epidemics are favored by:
crowded living conditions
populations with little native resistance
US cases of TB occur disproportionately among what groups?
minorities
foreign-born (from TB endemic countries)
institutionalized persons
HIV-infected persons
TB transmission
person to person
most from inhalation of droplet nuclei produced by coughiing or talking; droplet nuclei remain suspended for long periods and reach terminal respiratory tree
one case of untreated active (smear +) TB is estimated to cause:
-how many new infections/year?
-what rate of infection among family contacts?
10 new infections/year
30-50% of fam contacts develop infection
this bacteria from contaminated milk produces clinical picture of TB (developing countries)
mycobacterium bovis
mode of TB entry
organisms are inhaled, injgested by alveolar M0s, transient bacteremia, granuloma formation in lung (+/- other parenchymal sites such as brain, liver, kidney)
TB infection
organism in the M0
ID by PPD
TB disease
id by culture of MTB from lung or other site
or by compatible clinical syndrome
Primary TB infection can proceed to
--> latent infection (90% remain latent, 5% develop reactivation disease)
--> 5% progressing primary disease (w/in 2 years)
in the united states
-% of cases attributed to new infection
-% of cases presumed to be reactivation of old latent infection
10% new
90% reactivated
information learned from interviewing index case:
approx 10% able to id exposure
information gained by molecular epidemilogy
digestion of MTB DNA followed by probe for a MTB insertion sequence deomstrates 40/100 cases clustered in urban US areas (represent new infections)
would you expect % of clustered cases in a TB endemic country in developing world expected to be higher or lower than in the use?
probably more clustered new infections, due to higher
Ghon lesion, Ranke complex:
healed primary MTB infection
cavitary (pulmonary) TB
-bacterial burden
mayb be 10^9
TB and HIV, strong association due to:
critical role of CD4 cell in mycobacterial immunity
in the US approx what % of new TB cases occur in HIV positive persons?
10% of new cases

(50-70% of new cases in developing world)
TB is the most common cause of death in what group?
HIV +
HIV positive individuals are not at increased reisk of unefction, but are CLEARLY at INCREASED RISK OF
ACTIVE DISEASE
10% risk /year (vs. 10% lifetime risk)
-increases productive HIV infection in mononuclear cells (via TNF) and increased incidence of extrapulmonary TB
MDR
multiple drug resistance

defined as resistance to at least INH and rifampin

chromosomally mediated, thus most commonly occur in those with prior Rx, esp inadequate Tx
risk factors for MDR TB
HIV, cavidary TB, low socioeconomic status, incarcerated persons, and initial acquisition in certain geographic areas
% of TB isolates in the US that are INH-Resistant)

% of isolates that are MDR
8-10% INH-R

2% MDR
XDR is defined as
extremely drug resistant
resistant to at least 3 of six second line drugs
Dx of TB disease
AFB smear,
Nucleic acid amplification
Culture
IFNg response
AFB smear for TB Dx
examination of sputum sample (requires at least 10^5 orgs/mL)
-limited sensitivity and specificity
Nucleic acid amplification for Dx of TB DISEASE
can be used direclty on sputum sample on day one to amplify DNA then use TB-specific proble to confirm (more sensitive than AFB smear, high tech)
Dx of TB DISEASE using culture
visible growth takes 3-8 weeks, automated broth systems reduces time to 2-3 wks
more sensitive than smear, but more labor intensive and costly

permits testing sensitivity to antibiotics and performance of DNA fingerprinting for epidemiology
Dx of TB DISEASE using IFNg response
mononuclear cells from patients with TB infection or disease and normal T cell immunity, produce IFN in response to TB specific antigens (ESAT, CFP10)
rates of drug resistance in M. tb
INH 1:10^8-9
Rifampin 1:10^9
INH and rifampin 1:10^16
standard regimen for TB Tx
DOT= directly observed Therapy
RIPE (2 months= Intensive phase),
RI (4 months = continuation phase)
Rifampin (good for intracellular orgs)
INH (good for EC orgs)
Pyrazinamide
Ethambutol
(P&E prevent drug resistance)
Rx for MDR TB
INH, rifampin, pyrazinamide and fluoroquinolone + one or more additional drugs x >9-12 months
Rx for TB in HIV infected individual
same as HIV negative, but if response is slow, Rx should be continued for 9 months or for 4 months after negative cultures

cannot use Rifampin with protease inhibs so use Rifabutin
possible complication of TB Rx in HIV +
IRIS Immune restoration inflammatory syndrome, may occur within first 2 months of starting Rx and may last 10-40 days
Follow up to TB Rx
monthly sputum cultures with expectation that 85% will be culture negative at 2 months, consultation recommended if still positive at 3 months
Dx TB Infection
Tuberculin Skin testing, STH to M. tubergulosis purified protein derivative (occurs at 2-10 weeks) and is measured by intradermal injection of PPD and measurement of induration at 2-3 days

size of induration correlates with infection 15mmPPD usual in TB infected individual with normal immunity

smaller reactions result from cross reactions with other mycobacteria
in vitro tuberculin testing
whole blood stimulated with TB specific antigens (ESAT, CFP, and interferon response quantitated) these tests will replace intradermal testing
Rx for Latent TB (LTBI)
INHx 9 months (preferred for HIV)
INH x 6 months
Rifampin x4 mos
PPD cutoff for Rx
>5mm HIV infection, transplant patient, TB contact
>10mm recent immigrant from high TB area, high risk worker, iv drug user, diabets, heme disorders, gastrectomy
>15mm persons w/o risk
TB infection control
key element is diagnostic suspicion and prompt TB isolation (negative air pressuire, respirator for those entering)

annual PPD for health care workers, additional testing 8-12 wks after exposure, pos AFB smears are more likely to grow M. avium than M. tuberculosis, but assumption should always be TB

wear mask or have patient wear mask
consider BCG vaccine
NTM
environmental nontuberculosis mycobacteria "atypical myobacteria"
M. marinum (infects soft tissue, rarely a contaminant)
M. fortuitum (infects soft tissue, often contaminant0
M. avium (infects lung, sometimes contaminant)
M. gordonae (infects lung (rarely), usually a contaminant)
most common NTM causing human infection
widespread distribution in WATER SOILD and BIRDS
common cause of TB in chickens
Human infections becoming more common
mycobacterium avium complex
(MAC)
clinical syndrome of MAC in kids
cervical adenitis
MAC pulmonary disease
seen in patients with chronic lung disease and in normal patients (more common in older women) impossible to distinguish rom TB, more common than TB in some areas of US
disseminated MAC infections seen in
advanced AIDS (affects 20-40% with CD4 count < 50
causes fever, weight loss, sometimes diarrhea
shortens survival by 5-7 months; prevention with macrolide (clarithromycin, azirothmycin)
Dx of disseminated MAC
special mycobacterial blood cultures positive
what might cause a large number of false positive PPD skin tests
prior MAC infections
Mycobacterium bovis, BCG strain
attenuated, used as a live vaccine against TB in humans
mechanism of BCG
induces a cellular immune response against mycobacteria
protection is offered against subsequent challenge with M. TB and other mycobacteria
Efficacy of BCG vaccine
reduces risk of childhood TB by ~80% and all TB by ~50%
also prevents infections due to other mycobacteria (eg leprosy, MAC)
greatest efficacy in TB against bacteremic complications (meningitis) and childhood forms of progressive TB
duration ~15 years
no known effective booster
variation in BCG efficacy may relate to:
-given at birth or later, after already infected with MTB or NTM
-vaccine strain
where is BCG used
used as intradermal childhood vaccine in most parts of the world where TB is endemic

some european countries have stopped admin

also used as immunostimulant in topical treatment of bladder carcinoma
compliations of BCG vaccine
local swelling and drainage for several weeks (scars)
local abscess with adenopathy (BCG-itis)
Osteomyelitis (esp. scapula)
disseminated BCG infection (AIDS, other immune deficiencies)
effect of BCG on PPD skin test
immunization usually converts PPD to + for several years, but reactions > 10mm unlikely from BCG alone, prior BCG infection with NTM can lead to gradual increase in PPD w/ repeated testing
effect of BCG on IFNg test with TB sepcific Ag
NOT AFFECTED