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101 Cards in this Set

  • Front
  • Back
What causes TB?
Mycobacterium tuberculosis
Rarely M. bovis, M. africanum and M. microti
Why was TB named like this?
Describes the granuloma (tuber = potato growth)
What is consumption?
TB
How is TB spread?
Airborne droplet nuclei expelled by a TB carrier mostly with coughing
<5um
How many droplet nucleai spread by a cough?
3000
How long do droplet nuclei remain in air?
Several hours
How long are TB baccilli viable in environment?
Longer than other bacteria due to waxy coat
What factors determine the probability of transmission of TB?
Infectiousness of index case
Environment of exposure
DUration of exposure
What is an "open case" of TB?
One who expells TB
What does probability of infection with TB depend on?
Extent of exposure
- high risk if close prolonged contact
- low risk if sputum smear neg and extrapulmonary dz
Susceptibility of infection
How many persons does an open case of tb infect each year?
12-15
Describe TB pathogenesis
TB ingested in lung by macrophages
Bacilli multiply in macrophages
Spread occurs via bloodsream
Normally infection checked by immune system, DISEASE is prevented
Once infected, how long infected?
Years, perhaps life
What percent infected develop TB disease?
10% in HIV neg (asx - only evidence is + PPD)
Once infected, how often do HIV + progress to dz?
Increase 10% per year
What increases risk of infection progressing to dz?
HIV
Substance abuse
Recent infection
CXR showing previous dz
DM
Silicosis
Prolonged steroids
Other immunosuppression
Malnutrition
Impaired cell mediated immunity
What is the natural outcome of dz, if not treated in 5 years?
50% pulmonary tb die
25% self cure
25% ill with chronic infectious tb
What are the stages of TB dz?
Primary infection "primary complex"
Latent TB infection (LTBI)
Post primary TB (by reactivation or reinfection)
What is a Ghon focus
An area in lung with locally lodged bacilli (normally R upper)
What is a Ranke complex?
Ghon focus (in r upper lung) and hilar lyphadenopathy"
What is the "primary complex" of TB?
Ranke complex (Ghon focus plus hilar lymphadenopathy)
What happens after Ranke complex in TB?
Apical scarring in some -- reidual bacteria calcified
Immune response in 4-6 weeks

10% pulmonary/pleural infection, disseminated dz; 90% no clinical dz/(+) PPD
What is post-primary TB?
Months to years after latent period
TB reactivated
Upper lobe infiltrates
Extensive lung destruction (caseation)
Cavity formation
(+) sputum smear
Are most TB cases primary or post primary?
Post primary
When does post-primary TB most commonly occur?
Adulthood
WHen does primary TB most commonly occur?
Childhood
Describe a TB granuloma
Central necrosis, surrounded by epithelial cells, angerhands giant cell, and lymphocytes on the outer edge
What are the sx of post-primary TB?
Cough > 3 weeks
Sputum
Weight loss
Fever, night sweats, fatigue, anorexia, chest pain, hemoptysis, breathlessness
Common sites of TB dz? (7)
Lungs
Pleura
CNS
Lymphatic
GU system
Bones/joints
Disseminated (miliary)
Is positive sputum smear necessary for TB+
No
Does HIV increase risk for TB infection?
NO
But increases risk for dz
What is the role of immunity in TB dz process?
Chronic antigenic stimulus causes macrophage activation, release of reactive metabolic intermediates/hydrolases
Loss of balance
So, immune response creates some of the damage (granulomas, cavitations, caseation, fibrosis)
What are the most infectious TB lung lesions?
Cavitations (as big pockets of TB infection communicating with outside world)
Does AFB cording relate to virulence?
Cords grown on culture
Used to thing yes, increased virulence
Now know the answer is "No"
Is there possible genetic susceptibility to TB?
Yes (africans twice as likely to become infected than Europeans)
What is the Lubeck disaster?
1926 Germany
BCG vaccine mixed up with virulent TB (!!)
251 children injected
31% died
50% xray confirmed dz
19% no evidence dz
SHOWS INDIVIDUAL VARIABILITY OF PROGRESSION TO DZ
Describe mycobacterium tuberculosis microscopy?
Straight/sl curved rods
Cannot gram stain
Waxy lycolic acid/lipid cell wall prevent gram stain
Acid fast stain needed
Are TB slow or fast growing in culture?
Slow! 12-24 hour generation time (vs. 20 min in E coli)
What does TB look like by AF stain?
Thin bacilli, singly or in bundles "beaded appearance"
How to acid fast stain:
Expose specimen to hot carbol fuchsin dye...which penetrates the waxy coat.
Heat bound dye does not wash off with solvents.
Wash with 3% acid alcohol
Counterstain with blue or green dye
How to M. tuberculosis look on acid fast stain?
Pink or a green/blue background
How to Dx TB?
PPD
CXR
Sputum smear for AFB
Culture for mycobacteria
Rapid dx by DNA probes
What is LTBI?
Presence of M Tuberculosis without sx or xray evidence of dz
How to dx LTBI?
PPD
IGRAs
What is the IGRA test?
Interferon Gamma Release Assay
Measures IFN-y release by sensitized T cells stimulated with M. TB antigens
Done via blood test
What is anergy
No reaction to PPD
How is a + PPD defined?
> 15mm
>10mm in child
>5mm in HIV +
Can cxr be nagative in pulmonary TB?
Yes...hard to differentiate from LTBI
Normally have another sx (f/c, sweats, cough, wt loss, anorexia) or a positive sputum smear
Who to test for LTBI?
Contacts with known TB case
Foreign born endemic areas
Residents/employees high risk settings
HCW serving high risk clients
Medically underserved/poor
High risk racial/ethnic populations
Children exposed to high risk adults
IV drug users
Homeless
Jail
Who are high-risk for TB dz once infected?
HIV
Recent M. tb infection
Immunocompromised
IV drug users
Hx inadequate treatment TB
PPD width cutoff?
15mm - no risk
>10mm - immigrant, IVDU, children < 4, immunocompromised, exposed infants/children/adolescents; TB lab workers; emplyees/residents of congregate settings
>5: HIV+, organ transplant, close TB contact, CXR with prior tb
How to dx TB in a lab with microscopy?
AFB smear
auramine stained smear (fluorescent)
Histopathology (stained bx of lesion)
How to dx TB by culture/sensitivity?
Conventional: Lowenstein-Jensen media, x 6 weeks
New: BACTEC, MGIT
How to dx TB by molecular methods?
PCR
DNA probe
Molecular typing
(for id'ing strains/track outbreaks)
Do you need to cx TB if smear is positive?
Yes
What is Lowenstein Jensen?
The solid medium (LJ Medium) thats used to cx tb
What is a true pathogen?
If one organism found (like an M. tb), indicates dz
Why is TB testing hard?
Many samples low # AFB
Mycobacteria hard to distinguish from each other
Antibody test not useful
TB can infect almost any tissue
Slow growing on cx (7-42 d)
How to treat TB?
Isoniazid (INH) and Rifampicin (R) -- most powerful bacteriocidal
Pyrazinamide (kills some)
Streptomyin (kills some, esp extracellular)
Ethambutol (bacteriostatic)
What is normal TB treatment regimen?
4 drug therapy (HRZE), drop E when ssceptibility comes back?
What does a dosing regimen of 2H3R3Z3E3/4H3R3 mean?
2 months of first group, followed by 4 months of second.

Each drug given 3x/week
What is MDR-TB
Multidrug resistent TB
Always resistant to INH and Rifampin
May have other resistances
What is XDR-TB
Extensively drug resistant TB
Found first in South Africa
MDR(HR) plus resistance to any FQ and to one injectable (amikacin, capromycin, kanamcin)
XDR rates in US?
76% foreign born
12% black
41% asian
What is the white plague?
TB outbreak in 17th/18th century europe
Nearly 100% infected
25% of all deaths caused y TB
What caused the black plague?
Yersinia pestis
How much of the world is infected with TB
1/3
What was the first WHO declared public health emergency?
1993 - TB
Why is TB still out of control?
Inadequate control programs
Increased drug resistance
Neglected by governments
High rates population growth
HIV epidemic
How many new TB cases each year?
9 million
How many people die each year from TB?
1.6 million (4400 per day)
What percentage of people with untreated TB die from the dz?
50-70%
Why is meant by TB inequity?
98% of deaths in low to middle income nations
What is the leading cause of death in HIV?
TB
How many people fail to get access to TB treatment each year?
1.8 million
Where is the highest incidence TB (2006)
Africa 363/100,000/year
Where was the highest prevalence of TB in 2006?
India
China
Africa
(69%)
Why does HIV make TB worse?
Reactivates latent TB
Rapid progression in infection due to lack of CMI
What is the lifetime risk of TB in HIV positive?
10%
Does HIV increase TB infectivity?
Yes, high TB prevalence in HIV population leads to increase transmission to non HIV positive
Why a spike of TB cases in the US in 1992?
Decline in control programs
Number of TB cases in US in 2008?
12,904
Mortality rate of TB is US?
4.2
Who are the biggest population of TB + in us?
60% foreign born
What caused the spike in TB cases by 20% in US between 1985 and 1992?
HIV
Imigration of persons from high prevalence
igh risk environ transmission (prisons, hospital, nursinghome, homeless shelters)
Deterioration of TB public health infrastructure
What are concerns re: US TB?
Limited DOT available
15 million persons infected -- 10% will turn positive
Drug resistant TB growing
When did Do Not Board list begin?
June 2007
What country has the highest TB burden?
India
505/100,000
2 million incidence
What is DOTS
Directly Observed Therapy, Short course
What are the 5 elements of DOTS? KNOW THIS
Sustained political committment
Access to quality assured TB microscopy (NOT CX)
Standardized short course chemo
Uninterrupted supply of quality drugs
Recording and reporting system enabling outcome assessment
What is the big problem with DOTS?
Requires patients to seek treatment
Targets only active TB (not LTBI)
How does HIV impact DOTS?
Rise in TB rates seen, despite DOTS
How is DOTS different than other control programs?
Control doesn't aim at uninfected population, but decreasing infectivity of infected
WHO TB goals?
2015: reduce prevalence by 50% relative to 1990
2050: Eliminate TB as a public health problem
WHO TB targets (know)
Increase detection to 70%
Increase successful treatment to 85%
What is the problem of WHO detecting cases by smear postiives?
Sputum smears + in only 44% of cases
17% of sputum smear negatives transmit infection
Problems with TB control?
No new drug
HIV
MDR and XDR
No good field test
No effective vaccine
What is BCG?
Live attenuated vaccine from M. bovis
Reduced in lab till gene turned off
Decreases TB meningitis
Helpful in non-endemic areas (but not endemic areas)
Why do HIV positive patients have more drug resistance in TB?
Malabsorption due to dz
Too many drugs/compliance prob
Drug interactions?
When was BCG developed?
Early 1990s
Where is BCG recommended?
WHO: All infants in countries with high TB rates
CDC: Pediatric pops where TB transmission high, Healthcare workers possibly exposed to resistant strains