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Flashcards in Tuberculosis Deck (32):
1

general characteristics of Mycobacterium tuberculosis

aerobic, non-spore forming, non-motile bacillus

high cell wall content of high-molecular-weight lipids

4.4 Mb circular genome - a very large proportion of genes encode enzymes involved in lipogenesis and lipolysis

slow growing - 22-24 hour generation time and visible growth takes 3-8 weeks on solid media

2

TB pathogenesis

airborne droplet nuclei

initial focus on subpleural in the midlung zone - ventillation greatest in the middle and lower lobes

ingested by alveolar macrophages

infected macrophages carried to regional lymph nodes

may spread hematogenously to lymph nodes, kidneys, epiphyses of long bones, vertebral bodies, meninges and the apical posterior areas of the lung

3

tuberculin reactivity

hypersensitivity to tuberculin appears 3-8 weeks after infection and makrs the development of cellular imunity an dtissue hypersensitivity

before this reaction, bacterial growth is uninhibited, both in the intial focus and in metastatic foci

4

Ghon complex

antigen concentration int he primarily complex after the acute TB infection

consists of the Ghon focus (pulmonary focus) and draining regional nodes

visible calcification on CXR

 

5

Ziehl-Neelsen stain

fixed smear covered with carbol-fuschin is heated, rinsed, decolorized with acid-alcohol, and counterstained with methylene blue

6

Kinyoun stain

modified Ziehl-Neelsen stain to make the heating step unnecessary

7

Fluorochrome stain (auramine-rhodamine)

slightly modified acid-alcohol decolorization step and potassium permanganate counterstaining - fluorescent mycobacteria can be easily seen with a x20 or x40 low-magnification objective

8

characteristic structure of granulomas

necrotic center (if caseating)

surrounded by macrophages

surrounded by T cells

9

caseating granuloma

cells within the ring of macrophages are lysed contributing to centralized necrosis

extracellular bacteria reside within necrosis

prevents bacteria from spreading

also prevents immune cells from reaching and eliminating those trapped bacteria

10

Langhans giant cell

consissts of fused macrophages oriented around tuberculosis antigen with the multiple nuclei in a peripheral position

represents the most successful type of host tissue response

11

What are the most important determinants of transmission of infection?

close contact and infectiousness of the source

source infectivity is a function of the number of TB in bacilli in respiratory secretions and frequency and magnitude of the cough

12

What does reactivation tuberculosis typically look like in chest x-rays in young people?

apical posterior infiltrates, often with cavitation

apical localization attributed to high oxygen content in the apices and the the aerobic nature of the tubercle bacillus

an alternate theory attributes it to deficient lymphatic flow at the lung apices, especially the posterior apices, wher ethe pumping effect of respiratory motion is minimal

13

latent TB

all bacteria are harbored within a few infected macrophages within the granuloma

diagnosis is traditionally by tuberculin skin testing - may cross reaction with BCG, have operator error, or be mistaken for other mycobaccteria

interferon-gamma release assays (IGRAs) are used today

14

reactivation TB

extracellular bacterial levels increase when the immune system is unable to control infection

15

limitations of PPD skin testing

requires follow-up visit for interpretation

"operator error" - application and interpretation

corss reactions with BCG and MAI

negative in ~25% with active disease

16

interferon-gamma release assays (IGRAs)

quantify release of the interferon-gamma from lymphocytes in the whole blood incubated overnight with specific M. tuberculosis antigens - early secretory antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10)

as sensitive and more specific than tuberculin skin testing in identifying the latent TB infection

downside is that they are expensive

17

clinical presentation of TB

fever, night sweats, weight loss, shortness of breath, hemoptysis

cough > 2 weeks

history of exposure to infectious TB or positive TST

18

common CXR findings in TB

upper lobe infiltrate

cavitary infiltrate

hilar/paratracheal adenopathy

19

primary vs. reactivation active pulmonary tuberculosis

primary - more common in young children, elderly, and immunosuppressed hosts; presents as lower or middle lobe infiltrates, often with hilar or mediastinal adenopathy

reactivation - typical in adolescents and adults, presents with several weeks of malaise, fever, sweats, weight loss, cough; CXR shows apical posterior infiltrates - often cavitary

20

milliary tuberculosis

presents as diffuse reticulonodular infiltrates

reflects widespread dissemination of TB

can occur in almost any organ, especially the lymph nodes, vertebrae, and meninges

CXR findings may not suggest TB in 50% of individuals

21

tuberculous meningitis

untreated death ensues within 5-8 weeks of illness onset

early diagnosis often based on CSF formula - lymphocytic or mixed pleocytosis, high protein, low glucose, negative cultures

22

types of media used for culture of mycobacteria

egg-based (Lowenstein Jensen) and agar-based  (Middlebrook 7H11) - 3-8 weeks of incubation

liquid broth (Middlebrook 7H12) - 1-3 weeks of incubation

23

Xpert MTB/RIF test

automatic nucleic acid amplification test for TB and rifampin resistant TB

very sensitive and specific

takes about an hour to get results

24

first-line drugs for TB treatment

isoniazid

rifampin

rifapentine

rifabutin

ethambutol

pyrazinamide

25

second-line drugs for TB

moxifloxacin

levofloxacin

streptomycin

amikacin/kanamycin

cycloserine

ethionamide

p-aminosalicylic acid

capreomycin

bedaquiline

26

treatment for latent TB

isoniazid x9 months

or

rifampin x 4 months

or

isoniazid plus rifapentine weekly x2 months (directly observed therapy)

27

treatment for active TB

standard regimen - 2 months of isoniazid, rifampin, thambutol, and pyrazinamide followed by 4 months of isoniazid plus rifampin

extended treatment is recommended for cavitary disease on initial CXR and positive sputum cultures at 2 months of treatment

28

What is multi-drug resistant TB? What are the categories of MDRTB?

TB that is resistant to at least INH and rifampin

primary - patient initially infected with MDR-TB

acquired - poor adherence to Rx, selection of resistant bacteria

29

Why does drug resistance emerg during therapy? What is the likelihood of this happening?

selection - resistant variants pre-exist in the bacterial population

about 108 bacteria in a cavity

1in 108 are rifampin resistant

1 in 106 are isoniazid resistant

1 in 105 are ethambutol resistant

overall resistance probability to isoniazid and rifampin is 10-14

30

extensively drug resistant TB (XDR-TB)

resistance to INH and rifampin plus any fluoroquinolone and any one of the second-line anti-TB injectable drugs

31

totally drug-resistant TB (TDR-TB)

resistant to all first and second-line agents

32

BCG (Bacillus Calmette-Guerin) vaccine

significant protection vs. fatal TB in children

>80% protective vs. TB meningitis

variable protection vs TB infection

not very effectve vs. adult TB

effective only for a limited period of time - benefit lasts no more than 10-20 years

booster doses ineffective