Tuberculosis Flashcards

1
Q
  1. Explain the epidemiology of M. tuberculosis, including trends worldwide, in the US and in Wisconsin.
A

TB has plagued mankind throughout history, for decades isolation in sanitoriums was a major control method

development of streptomycin and isoniazid ‘46-‘52 made outpatient treatment possible and curtailed TB in industrialized countries

resurgence 1984 due to deterioration of TB public health infrastructure, HIV/AIDS epidemic and deco of MDR orgs

Mtb is estimated to infect ⅓ of the world’s population; 2 billion effected, 9 million develop it yearly

TB kills 1.5 million people each year, mostly in SE asia, sub-Saharan Africa and Eastern Europe, immunocompromised are most at risk.

in US 15million are infected M. tb with the greatest number of TB cases occurring among foreign-born from high prevalence countries, racial or ethnic minorities and those in congregate settings

over 40% cases reported in Wisconsin occurred in Milwaukee county, 50% of cases in people born outside the US

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2
Q
  1. Describe the structure and physiology of M. tuberculosis, including virulence factors/mechanisms.
A

M tb produces an unusual, waxy coating on the cell surface, primarily composed of my colic acid (impermeable to usual stains; classified as acid fast because they retain carbol fuchsin stain (alt. fluorescent aura mine-rhodamine dye)

M tb is an intracellular pathogen and ingest but not killed by macrophages due to inhibition of phagolysosome fusion; its ability to multiply in macrophages is key to virulence
cord factor- surface glycolipid found only in virulent strains, triggers TH1 response and enhances survival in macrophages

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3
Q
  1. Describe the transmission of TB infection and TB disease.
A

reservoirs of persons with caviar lung lesions, and expelled into environment via coughing, singing or sneezing

small droplets 1-5 microns may reach alveoli where infection can begin

infection depends on # organisms expelled, ventilation and size of room, length of time exposed/ rate ventilation and immune status of the exposed person

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4
Q
  1. Explain the significance of co-infection with HIV and the mycobacteria involved.
A

any compromise in CMI may result in a poor outcome with active disease or disseminated disease

for most 10% lifetime risk of infection progression to disease with 50% of risk in first 2 years

disseminated/miliary TB is most common in immunocompromised (organs are seeded with millet like lesions) which is commonly seen in persons co-infected with HIV –> high mortality if not treated

high burden of co-infection in sub-Saharan Africa

HIV is the strongest risk factor for someone with latent TB to progress to active disease, w/o proper treatment 90% people living with HIV die within months of contracting TB

HIV modifies the clinical presentation of TB (radiographically atypical)

persons with HIV risk development of environmental mycobacteria, dx. with blood cultures

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5
Q
  1. Discuss why young children need to be identified soon after contact with an individual who has active disease, including predisposing factors.
A

children have an increased risk for developing severe disease within weeks to months of infection; are also at increased risk for TB meningitis (often results in deafness, blindness, paralysis and mental impairments)

dx. can be difficult if child is unable to produce sputum for lab tests or have extra-pulmonary TB lesions

extra pulmonary TB occurs more commonly in children
disseminated/miliary TB is common in children (organs are seeded with millet like lesions)

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6
Q
  1. Discuss the laboratory tests available to diagnose M. TB.
A

several stains can demonstrate acid fast bacilli: Ziehl-Neelsen, Kinyoun and Flurochrome

to detect AFB in smear 5,000-10,000 bacilli/mL needed (50-80% of patients)– positive smear presumed to be TB until proven otherwise

Nucleic acid amplification, fast but low sensitivity, neg test does not exclude TB dx.

difficult to grow and slow growing, may take 5 weeks before a M tb positive specimen can be ID’d and drug susceptibilities known by traditional techniques

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7
Q
  1. Explain the rationale of targeted tuberculin testing and why the tuberculin reaction occurs.
A

reason to test include find latent TB that would benefit form tx. or TB disease that should be treated

PPD should only be done in higher risk groups for exposure or disease once infected

reaction to PPD is due to type IV hypersensitivity (TH1 activation and cytokine release)

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8
Q
  1. Explain the importance of timely reporting of all TB cases (or suspected cases) to local public health departments.
A

all TB cases or suspected TB cases are to be reported to local health dept. within 24 hrs., delay can result in delays of treatment plan and protecting contacts

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9
Q
  1. Discuss the role of non-tuberculous mycobacteria in human disease.
A

aka environmental mycobacteria, or atypical mycobacteria can be acquired from environment by aspiration or inoculation and can resistance to many 1st line antituberculous agents

NTM cause more disease in WI than M tb

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10
Q
  1. Explain the concepts that are important in effective treatment of TB disease and LTBI with antimicrobials.
A

for DISEASE: tx. must be prolonged (6-9mo) because M tb are slowly dividing, intracellular pathogens

more than one drug used to combat resistance, monitoring for drug reactions are important, with adherence, patients are non-infectious within 2-3 weeks

LTBI: rule out TB disease, standard tx. is isoniazid for 9 mo.

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11
Q
  1. Of the 7 mycobacteria that comprise Mycobacterium tuberculosis complex which are most significant to human health ?
A

[M. tuberculosis, M bovis, Mafricanum, M microti, M canetti, M caprae and M. pinnipedii]

M. tb is the primary cause of TB, M bovis and M aftricanum are rare causes

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12
Q
  1. Describe the basics of how TB is spread and what serves as a reservoir of TB. How is most likely to be susceptible to TB?
A

humans are the only natural reservoir of M. tb
TB is spread person-to-person by aerosols
TB equally affects females and males
an increased risk of mortality exists at extremes of age

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13
Q
  1. Describe the transmission and pathogenesis of TB infection and TB disease.
A

circulating macrophages engulf M tb in the alveoli and bring them to regional lymph nodes accompanied by a silent bacteria

unrestrained replication proceeds both in the initial foci and metastatic foci for several weeks until concentration reaches 10^3-10^4 which can elicit the CMI response

activated T cells and macrophages surround and form granulomas, most of these granulomas heal through fibrosis and calcification. well oxygenated lesions (apical lungs) the bacilli may be walled off but remain viable –> LTBI

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14
Q

What is TB disease?

A

active or clinical disease; patient has M tb and symptoms are present

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15
Q

What is the action of BCG vaccination?

A

does not prevent infection but induces a more rapid response by alveolar macrophages and helps to prevent bacteremia (contraindicated in pregnancy and anyone with compromised immune response)

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16
Q

Describe resistance pattern of multi drug-resistant TB.

A

resistant to all first line anti-TB, the fluoroquinolones and at least one of the three injectable second-line anti TB drugs (capreomycin, kanamycin and amikacin)

molecular drug-resistance tests can provide info of resistance of several first line antiTB drugs within 1-2 days

17
Q

What could lead to a false negative PPD test?

A
cutaneous anergy
recent or overwhelming TB infection
very old TB infection
very young age (less than 6mo)
recent live-virus vaccination or infection
18
Q

What is the booster effect?

A

some people with latent TB may have false negative test, which may convert if primed with a PPD in a two test protocol, these should not be confused with new infection by doing two tests 2 weeks apart (takes 3 weeks to convert)

19
Q

Discuss the advantages and disadvantages of IGRAs (interferon-gamma release assays).

A

increased specificity, one visit required, not as subjective, not effected by prior BCG vaccine

more expensive, processing must be within 12 hours of collection, can cross with NTM; difficult to interpret results on children and immunosupressed

20
Q

What is mycobacterium leprae?

A

cause of leprosy (Hansen’s disease) which is a chronic granulomatous disease of the peripheral nerves and superficial tissues

disease ranges from slowly resolving skin lesions (tuberculoid) to disfiguring lesions (lepromatous)