Epidemiology, Pathophysiology, Diagnosis & Treatment Of Tuberculosis, Nocardia, And Actinomyces

Front 1

in general what kind of infections do mycobacteria and actinomycetes cause

Back 1

cause granulomatous infectious disease

Front 2

what is a granuloma

Back 2

an organized collection of macrophages; a ball-like collection of immune cells which forms when the immune system attempts to wall off substances that it can't eliminate

Front 3

what stains do you use to identify mycobacteria

Back 3

Ziehl-Neelsen
auramine-rhodamine stains

Front 4

what are some general microbiologic characteristics of mycobacteria

Back 4

1. acid fast bacilli
2. aerobic
3. non-motile
4. non-spore forming
5. unusual cell wall with large amount of high molecular weight lipids

Front 5

what are the two main species of mycobacteria

Back 5

mycobacterium tubercolosis and mycobacterium bovis

Front 6

what is mycobacterium tuberculosis reservoir and how is it transmitted?

Back 6

human reservoir, transmission is only human to human

Front 7

what is one way to differentiate between mycobacterium tuberculosis and myobacterium bovis?

Back 7

mycobacterium tuberculosis does nitrate reduction, mycobacterium bovis doesn't do nitrate reduction.

Front 8

mycobacterium bovis reservoir

Back 8

cows

Front 9

how long does mycobacterium tubercolosis take to grow in culture?

Back 9

grows slowly 3-6 weeks in culture so you need to make guesses about what you are treating before you diagnosis it as tb

Front 10

in general how quickly do granulomatous infectious diseases take to grow?

Back 10

they grow slowly

Front 11

how long does mycobacterium bovis take to grow in culture

Back 11

slowly, it takes 3-6 weeks

Front 12

what drug is mycobacterium bovis resistant to?

Back 12

pyrazinamide

Front 13

how can you get mycobacterium bovis from a cow

Back 13

you drink the infected milk. not a big problem anymore because of better animal husbandry

Front 14

what cytokines do Th1 cells make after antigenic stimulation

Back 14

IFN-y, IL-2, TNF

Front 15

what cytokines do Th2 cells make after antigenic stimulation

Back 15

IL-4, IL-5, IL-10, IL-13

Front 16

what type of immunity is the most important for mycobacteria

Back 16

type 1 immunity (ie Th1 arm of CD4+ system)
1. cytokines of Th1 activate macrophage into better killers of phagocytosized pathogens
2. cytokines of Th1 make macrophages into better antigen presenters to stimulat more T cells
3. IFN-y and TNF are critical for granuloma inflammatory response development
4. Th1 help CD8 CTL develop, these kill cells infected with intracellular parasites
5. type 1 immunity is what we are measuring with a PPD DTH test (INF and TNF are direct mediators of this)

Front 17

what is type II immunity good for?

Back 17

Th2 CD4 cells are good for extracellular pathogens via Ab and allergies (IgE)

Front 18

what is the PPD test used for and what can't it be used for?

Back 18

diagnose latent TB infection
doesn't tell you if you have active TB, does not predict protective immunity

Front 19

are delayed type hypersensitivity reactions involved in TB pathology

Back 19

yes, Th1 causes the DTH response. granulomatous responses are DTH responses that cause bystander damage

Front 20

for what population does the granulomatous response cause tissue damage?

Back 20

granulomatous response is part of the problem for people that have intact immune systems

Front 21

how do HIV and TB interact?

Back 21

1. HIV increases risk of reactivation
2. HIV enhance primary disease progression
3. MTB activates HIV disease progression
4. delayed response to anti-TB therapy

Front 22

can you infect other people when you have latent TB

Back 22

no, your system has contained it so no infectiousness and no symptoms of active disease.

Front 23

what is a primary disease progresion in Tb

Back 23

when you move on to active disease without going through a latent stage

Front 24

how does MTB enhance HIV disease progression

Back 24

CD4 cells that have been activated to proliferate are better hosts for HIV. these CD4s support HIV replication much better

Front 25

what does delayed response to anti-TB therapy mean for treating HIV patients with TB

Back 25

you have to keep them isolated longer because they may still be able to infect people.

Front 26

how is diagnosing TB complicated by HIV

Back 26

they don't have a positive PPD because they have no immune system to mediate the DTH reaction.

Front 27

for HIV patients, the lower your CD4 count the more likely you will progress to

Back 27

active TB

Front 28

what is one way to tell if you were infected by a specific someone's TB strain?

Back 28

use molecular fingerprinting: you take their TB cut it up with specific restriction endonucleases and run it all on a gel. same pattern = same strain

Front 29

what does HIV do to the risk of TB reactivation?

Back 29

it increases the risk greatly that you'll get reactivation if you have a latent infection

Front 30

what drugs are multi-drug resistant TB strains resistant to

Back 30

Isoniazid (INH) and rifampin (RIF)

Front 31

what drugs are XDR-TB resistent to

Back 31

Isoniazid (INH), rifamprin (RIF), fluoroquinolones and aminoglycosides

Front 32

what is a way to prevent drug resistance in microbes in general?

Back 32

use polyclonal drug therapy. monoclonal drug therapy selects for drug resistant strains

Front 33

what is MDR-TB in saint louis like?

Back 33

there is an ongoing MDR-TB epidemic in St. Louis. this strain is resistant to a third drug as well.

Front 34

most MTB transmission is ____ but you can also get TB from ____

Back 34

respiratory, skin contact with fluids that have drained from lymph nodes to the skin (wear protective gear)

Front 35

why do we treat latent TB sufferers?

Back 35

to prevent them from moving to active TB by curing them. you are only infectious when you have active TB

Front 36

when do we stop respiratory isolation in immunocompetent TB sufferers?

Back 36

when they get from a positive sputum smear test to a negative sputum smear test

Front 37

describe TB disease progression

Back 37

after primary infection you can go to primary active disease but most people don't unless you're immunocompromised. usually contain orgs in a granulomatosous region. it hibernates in there. but if you get old, cancer therapy, HIV, basically immunosuppressed you can get activated TB.

Front 38

reactivation TB occurs in the ______. primary disease TB progression happens in the _______

Back 38

immunocompetent (10% lifetime risk of this), immunosuppressed

Front 39

when is risk of progression to active disease greatest

Back 39

first 2 years after infection, that's why you want to treat people early (5% disease progression risk in the first 2 years.)

Front 40

if you have untreated active TB disease for 5 years what is your fate

Back 40

50% dead, 30% "cured" (your immune system has contained it enough so you aren't immediately going to die and you aren't infectious, but most of time you will relapse again to active TB)

Front 41

where can TB cause disease

Back 41

it can replicate in any part of the body and cause extrapulmonary disease but most disease in the immunocompetent is in the lungs

Front 42

how is TB presentation location different in the immunocompromised compared to immunocompetent

Back 42

immunocompetent = mostly pulmonary disease
immunosuppressed = 50% of cases are extrapulmonary disease

Front 43

what do the lung xrays look like for reactivation TB

Back 43

you see patches of lung scarring and cavities with some fluid and air. it mostly affects the apical regions first then it works it way down to affect other areas of the lungs. this is progressive disease that affects both sides of the lungs

Front 44

if you dissect a reactivation TB lung what do you see?

Back 44

whole lung is blackened. see a caseous necrosis region (endpoint of granulmatous response. made up of dead tissue with tons of MTB. it sits in the airways and is coughed out spreading disease)

Front 45

what does reactivation TB look like microscopically

Back 45

with H and E you see a sea of blue dots which are the nuclei of inflammatory cells. hallmark is giant cell (macrophages fuse to form multinucleated giant cells [a ring that tries to contain the mycobacteria])

Front 46

what are the macrophages in granulomas called sometimes

Back 46

epithelioid

Front 47

what does the xray look like for primary TB disease progression

Back 47

you were never able to get to latent stage so the damage is in areas where you breathe the most, midlung. it is not in the apices of lungs, there's no scarring.

Front 48

is primary TB disease hard to diagnose from Xrays

Back 48

yes cause there's a lot more variability in lung X rays compared to reactivation TB

Front 49

active TB vs latent TB differences

Back 49

active: infectious, immediate risk to public health, kills people, need multiple drugs to treat
latent: not infectious, no immediate risk to public, don't kill you, use a sing drug to treat like (isoniazid)

Front 50

symptoms of pulmonary TB

Back 50

chronic (2 weeks or more) productive cough, green sputum, hemoptysis (cough up blood), chest pain (from things like caseus necrosis and hemoptysis)

Front 51

main things you look for in reactivation TB xray that isn't too far advanced

Back 51

apical scarring that's maybe bilateral in the lungs

Front 52

systemic symptoms of TB
(know both sides)

Back 52

fever (102-105), chills (can't get warm no matter how many blanket you use), PROFUSE night sweats, easy fatigability, loss of appetite, weight loss

Front 53

symptoms of chronic basilar meningitis (know both sides)

Back 53

headaches (over weeks or months), change in mentation, cranial nerve findings (e.g. one eye not coordinated [III palsy]), hemiparesis, cerebellular signs, stupor/coma (this is the end stage of the disease)

Front 54

what do you see if you dissect someone with meningeal TB's brain

Back 54

see thick inflammatory goo cake of exudate at base of brain. this messes with cranial nerve roots as they exit from the brain and cause the cranial nerve palsies

Front 55

what do you see in someone's MRI if they have meningeal TB

Back 55

lots of little hyperintense white spots. with treatment these can melt away

Front 56

TB can infect the lungs, where else can it infect (major areas)

Back 56

pulmonary TB, meningeal TB, vertebral osteomyelitis, peripheral skeletal osteomyelitis, genitourinary TB, miliary TB

Front 57

describe vertebral osteomyelitis
Sx when patient first walks in

Back 57

patient presents with fever and back pain. you should do xray right away if they have these symptoms to check for vertebral osteomyletis

Front 58

describe vertebral osteomyelitis aka and pathology

Back 58

called Pott's disease. when tb infects the disk space between vertebrae of the anterior thoracolumbar vertebrae, destroying them, and causing abscesses

Front 59

what does vertebral osteomyelitis look like on xray

Back 59

you see erosion between the vertebrae so they get closer together (tumors attack the body first and then only until later hit the intervertebral area)

Front 60

peripheral skeletal osteomyelitis symptoms

Back 60

can have fever, chronic arthritis of one joint (e.g. weight bearing joint), painful extremity

Front 61

what does peripheral skeletal osteomyelitis look like on xray?

Back 61

for example, bone has been punched out (lesions) on both sides of the joint

Front 62

what does genitourinary TB look like? Sx

Back 62

1. low grade, chronic renal/prostatic infection
2. dysuria, gross hematuria & flank pain
3. sterile pyuria (you won't be able to grow anything in the urine because TB takes so long to grow)
4. destruction of urinary collecting system (progression destruction destroys it, caseus necrosis may be evident in areas like the kidneys on autopsy)

Front 63

how do you distinguish genitourinary TB from a standard UTI

Back 63

sterile pyuria

Front 64

describe miliary TB

Back 64

1. extensive hematogenous disease (i.e. spread through the body via blood)
2. pathologic lesions resembling millet seed (all organs get little inflammatory granulomatous areas, e.g. lungs or adrenal gland)
3. increased frequency in immunosuppressed (happens most in them)
4. most patients anergic (so don't respond to skin test cause they don't have a functioning immune system)
5. minimal Chest X ray findings

Front 65

milary TB Xray

Back 65

chest X ray findings may be minimal but a chest film will sometimes show a millet-seed pattern throughout the lung

Front 66

can TB affect the adrenal gland

Back 66

yes. it can cause adrenal insufficiency by damaging the adrenal glands with milary TB

Front 67

TB is one of the great

Back 67

imitators because it can present disease pretty much anywhere in the body. we have diagnoses test for TB but they aren't that great

Front 68

what are some of the miscellaneous diseases TB can cause

Back 68

1. empyema/bronchopleural fistula
2. pericarditis
3. gastrointestinal TB
4. cutaneous TB
5. laryngitis
6. otitis
7. spontaneous peritonitis

Front 69

how can you diagnose TB

Back 69

1. PPD skin testing (can get false positives and negatives)
2. Quantiferon gold blood test (measures your Th1 response)
3. AFB smears
4. cultue and identification
5. histology & special stains
6. DNA probes
7. PCR

Front 70

what can cause a false positive TB PPD skin test

Back 70

BCG vaccination and infection with other mycobacteria

Front 71

what is diagnostic progression for TB?

Back 71

once you get a test indicating exposure to TB (PPD or interferon) you do a chest Xray (most common place for tb). if xray is weird do an AFB smear along with a sample to be cultured and identified. if you are worried that other tissues are infected get a biopsy of those tissues and do a culture of it

Front 72

are DNA probes and PCR good for diagnosing TB

Back 72

neither one is very sensitive yet.

Front 73

describe the DNA probe for TB

Back 73

you get enough organisms growing to get enough DNA to do a southern blot.

Front 74

what does AFB stand for

Back 74

acid fast bacillus test. you do a smear on a slide and check to see if you have acid fast bacteria on a microscope

Front 75

what are some reasons why a skin test would be false negative or false positive?

Back 75

false negative: immunosuppressed
false positive: if they've been exposed to atypical mycobacterium or if BCG vaccinated

Front 76

why do we do a 2 step PPD skin test?

Back 76

2 step PPD test is when you repeat a test 1-2 months after the initial test. do it to eliminate the booster effect.

Front 77

booster effect description

Back 77

tends to happen in people who get regular TB skin tests. it is a weak or no reaction to one TB skin test followed by a strong reaction from a second test but this doesn't mean that the person has become infected with TB. instead, the first test boosts the immune system to start reacting to the TB antigens on the second test because the person's immune system stopped reacting to the antigens.

Front 78

advantages of quantiferon test

Back 78

CDC recommends this over the skin test
1. it's better than the skin test because it only requires that you go to the doctor's office once
2. more specific than PPD

Front 79

why is quantinterferon test so specific?

Back 79

measures the same thing as PPD. it measures the IFN-y release using whole blood after stimulating the cells with antigens specific for MTB (ie not expressed on most atypical mycobacteria.). PPD uses antigens that aren't specific for MTB

Front 80

chest radiograph of classic reactivation vs primary disease vs HIV-infected TB

Back 80

apical infiltrates, mid lung fields, unusual appearance (i.e. no clear pattern seen for these; it can look like anything)

Front 81

can you use a chest xray to confirm TB diagnosis?

Back 81

no you need to do other tests like cultures, biopsies, etc

Front 82

how do you get specimens for sputum for TB

Back 82

use infection control precautions. you can induce sputum or use bronchoscopy to collect it yourself. you need to get at least 3 sputums for smear and culture because the concentrations of TB may be so low that you get a false negative on just one sputum culture.

Front 83

what qualifies as a positive TB smear?

Back 83

greater than 10000 CFU per mL

Front 84

is it easy to find mycobacteria on an acid fast slide sputum smear using a microscope?

Back 84

no there are a lot of other organisms there (epitheloid cells, neutrophils, multinucleated cells, macrophages). if you are skilled you may see the thin, purple curved organisms that are the mycobacteria

Front 85

because it is so hard to find mycobacteria on a smear using acid-fast stains what do you do instead

Back 85

mycobacteria will fluoresce green when you use an ormene rotamean stain and then fluorescence microscopy. if this is positive for mycobacteria you then do acid fast staining or culture to confirm that it is mtb

Front 86

how do you test for drug susceptibility for a TB strain? how long does it take

Back 86

only way to test susceptibility is to see what kills the TB in culture. to do this you have to usually takes about 2 months for antibiotic susceptibility test results; culture the MTB for 10-14 to get enough orgs, then wait another 10-14 days to see if the drug kills the MTB

Front 87

how do you confirm the existence of extrapulmonary TB

Back 87

you have to biopsy the tissue

Front 88

why do you culture TB? how long does culturing take?

Back 88

to confirm TB diagnosis. it takes 10-14 days to get the results

Front 89

how do you test for tb meningitis

Back 89

do a lumbar puncture and then do a smear. the CSF in infected individuals will have high protein, low glucose and large number of lymphocytes (mononuclear pleocytosis: abnormally high number of mononuclear cells). smears aren't diagnostic as they are likely to be negative. you need to collect 3-4 samples to get enough sensitivity (ie 80%) for these tests (each test by itself has low sensitivity)

Front 90

why is it harder to diagnose HIV patients

Back 90

because of immunosuppression, PPD is less diagnostic and there is no tissue damage to allow more organisms to be spewed out into the tissue sample

Front 91

complications of diagnosing HIV patients (PPD test, sputum AFB smears, bronchoscopy AFB) smears

Back 91

positive if greater than or equal to 5 mm, sputum AFB smears are less sensitive compared to immunocompetent, bronchoscopy tissue samples may be negative for mtb even if they have TB

Front 92

tell me about testing for mtb in HIV patients blood

Back 92

if you collect blood and do a culture you will find it in their blood 25-50% of the time

Front 93

what are the priority guidelines for TB control

Back 93

identify cases, isolate cases, treat cases, evaluate contacts, do chemoprophylaxis on latent disease people

Front 94

what does negative pressure room do?

Back 94

allows nothing to get out into the hospital hallway, filter air to get rid of organism, rapid air circulation to get rid of organism

Front 95

when do you discontinue isolation for immunocompetent TB cases who have active TB?

Back 95

discontinue isolation only after: 1. clinical improvement. 2. three negative AFB smears 3. if the patient has MDR-TB you don't release them until they are culture negative

Front 96

what are two ways to prevent drug resistence in treatment of active TB?

Back 96

directly observed therapy (DOT) to insure long term compliance of drug taking, use multiple drugs

Front 97

what are the first line drugs to treat active TB (non resistent strains)?

Back 97

first of all you have to use multiple drugs. secondly INH plus RIF are the most effective drugs for nonresistent strains

Front 98

what is the treatment course for infants with active TB (non drug resistant strain

Back 98

2 months with INH, RIF, PZA, and STM (not ETB because that is toxic to the optic nerve). then 4 months with INH and RIF if they are found to have a non drug resistent strain

Front 99

what is the treatment course for adults with active TB (non drug resistant strain)

Back 99

2 months with INH, RIF, PZA, and ETB. then 4 months with INH and RIF if they are found to have a non drug resistent strain

Front 100

how is the treatment course for pregnant women different from regular adults (non drug resistant strain)?

Back 100

give them INH and RIF for 9 months. don't give them PZA because it is a teratogen. but because PZA shortens the amount of time for therapy because of its rapid intracellular killing activity, the pregnant woman has to do the treatment for 9 months instead of a total of six months

Front 101

how do you modify the treatment for active TB in HIV patients (non drug res)

Back 101

rule of thumb is to treat them for at least six months even after their cultures are negative. replace rifampin with rifabutin because rifampin interacts badly with reverse transcriptase inhibitors

Front 102

how do you modify treatments for active TB in bone, miliary or the CNS?

Back 102

treat them for at least 12 months

Front 103

how do you modify the time course for TB treatment in infants?

Back 103

treat them as soon as TB is suspected because they are at extreme risk for really bad disease

Front 104

how do you have to modify typical TB treatment for MDR-TB or XDR-TB?

Back 104

seek an expert's opinion, individualize their treatment (e.g. see what happens clinically and in the labs to figure out if you are doing the right treatment and if you need to modify it), use 4-5 different drugs in a prolonged treatment period

Front 105

what drugs work for MDR and for XDR TB?

Back 105

quninolones/aminoglycosides for MDR for XDR; other drugs for XDR

Front 106

what do you monitor to check for drug toxicity when treating active TB

Back 106

1. monthly LFTs, BUN/Cr, CBC, platelets (liver is the major toxicity target for TB drugs; kidneys can be damaged too but at a lower level than the liver)
2. monitor uric acid in patients taking PZA (PZA can cause gout so you gotta check for this)
3. monitor visual acuity in patients taking ETB
4. monitor audiometry in patients taking STM (streptomycin can cause audiotoxicity)

Front 107

when do you do chemoprophylaxis to treat latent infection (PPD-test wise

Back 107

>= 5, 10, 15 for high, medium, and low risk people

Front 108

who is in the high, mod, and low risk group for TB skin testing

Back 108

high: HIV, immunocompromised, contacts of TB patients, xray has TB findings
Mod: hospital workers, immigrants, IVDU, those with chronic disease (ie those that have had active TB that has caused some scarring but that are now latent again)
low risk: e.g. geographically low risk area and no other disease risks

Front 109

what is the preventative therapy for TB composed of?

Back 109

prophylactic INH alone for 6-9 months

Front 110

what are the complications that exist for prophylactic TB treatments

Back 110

treat longer than 9 months for HIV-infected children; you have to treat pregnant women; use RIF instead of INH when you are treating people who have been in contact with INH-resistant TB

Front 111

what are mycobacteria that aren't mtb called?

Back 111

atypical mycobacteria

Front 112

which atypical mycobacterium targets HIV patients

Back 112

m. avium-intracellulare causes disseminated disease at the end stages of AIDS

Front 113

how is m. leprae

Back 113

by direct human contact

Front 114

where do you find atypical mycobacteria

Back 114

find it in the US but it is more common in the rest of the world. if you see any atypical mycobacteria you make sure to consult with an infectious disease expert

Front 115

who is infected with mycobacterium avium-intracellulare

Back 115

advanced stage AIDS patients, elderly people with COPD or other chronic pulmonary disease, other people with lung problems (e.g. cystic fibrosis patients)

Front 116

is mycobacterium avium-intracellulare hard to diagnose?

Back 116

yes because you find it everywhere in the environment. so you have have repeated test to verify that you are infected with it

Front 117

how do you prevent AIDS patients from getting mycobacterium avium-intracellulare

Back 117

azithromycin prophylaxis in AIDS patients whose CD4 count drops lower than 50.

Front 118

is mycobacterium avium-intracellulaire difficult to treat

Back 118

it is relatively resistent to drugs. you treat it with 3-5 drugs

Front 119

how are the two types of leprosy different

Back 119

both are caused by mycobacterium leprae. arm of T cell immunity: T (Th1); L (Th2). acid fast bacilli (have to do with cell mediated immunity): T rare, L many. cell mediated immunity: T high, L low. antibody titers (have to do with Th2 response): T low, L high. nerve damage: T high, L low

Front 120

study clinical cases from lecture

Back 120

study clinical cases from lecture