24b Mycobacterium TB from Notes then NTM Flashcards
What are the general properties of mycobacteria? Gram status? Shape? Capsule status? Motility? Spore status? O2 status? Intra or Extra cellular status?
Gram + non-encapsulated rod Not motile Non-spore forming Obligate aerobe Intracellular
What is the host response to Mycobacterium tuberculosis (MTB)?
Name the cells involved and their cytokines.
Macrophages ingest MTB >> present to CD4 cells >> Th cells release IL-2 to clonally expand CD4 cells and release IFNg activate Macrophages. Activated macrophages release TNFa to self-induce phagolysosomal fusion and kill intracellular MTB Activated macrophages (epithelioid cells) have enhanced cidal activity against MTB
What does the gene NRAMP1 do for MTB susceptibility?
What does “tt” vitamin D receptor polymorphism do for MTB susceptibility?
NRAMP1 makes more susceptible (regulates phagolysosomes)
tt vit D receptor makes less susceptible
Epidemiology of MTB…
How many cases? How many deaths?
In the US, which groups are more susceptible?
Transmission?
Spread… If one person is untreated, how many new cases does tha person spread MTB to?
6-8 million cases, 2-3 million deaths
Minorities and people living in close proximity
Respiratory droplets
1 untreated person spreads to 10 people
What is the distinction between infection and disease in MTB?
What is the steps from infection to disease?
Organism inhaled»_space; macrophages»_space; transient bacteremia»_space; granuloma formation in organs
Infection is detected by PPD skin test
Disease is identified by culture of MTB from granuloma
Detail: Among the 100 newly Dx cases of TB each year in the U.S. some are truly new infections and others are reactivated latent infections.
Most are reactivated infections.
.
What is a Ghon lesion?
What is a Ranke Complex?
Ghon lesion is cell-mediated and contained MTB infection
Ranke complex is a further development of the Ghon lesion that has become calcified
What is difference between cavitary pulmonary TB and disseminated miliary TB?
Cavitary Pulmonary TB is localized in the lung with one or more granulomas
Disseminated miliary TB is an infection that spreads to many organs with many small granulomas. It is fatal, even with treatment.
What are common locations that TB spreads to?
Note: this can be either “pulmonary” or miliary TB.
Lymphatics aka scrofula
Skeletal aka Pott’s disease
Genitourinary
CNS and Menigitis
What is the relationship between HIV and Mycobacterium tuberculosis?
HIV weakens CD4 cells and so if a person is infected, they are more likely to develop tuberculosis disease
What techniques are used to Dx active tuberculosis?
Acid-Fast Bacillus (AFB) smear of sputum
Culture on Lowenstein Jensen egg
Nucleic acid amplification (PCR?) then confirm with TB-specific probe
What are the advantages and disadvantages to…
1) Acid-Fast Bacillus (AFB)?
2) Culture on Lowenstein Jensen egg?
3) Nucleic acid amplification?
1) Same day results, but needs at least 10^5 organisms in sputum for detection
2) Standard practice. More senstive than AFB and allows for testing sensitivity to antibiotics, but takes 2 to 8 weeks and is costly.
3) Same day results, but is high tech
How is Multidrug Resistant (MDR) defined with Mycobacterium tuberculosis?
Resistance to Isoniazide and Rifampin.
What are risk factors for Multidrug Resistance in Mycobacterium tuberculosis?
What mechanism increases risk of MDR?
What illnesses increase risk of MDR?
What populations are at increased risk of MDR?
Prior exposure, especially inadequate treatment, with drugs (eg, monotherapy or incomplete Rx)
HIV and Cavitary TB
Low SES populations, incarcerated people, and people from certain geographical locations (like Russia, Dominican Republic, and others)
In terms of numbers of TB organisms in an infected person, why are more severe infections more drug resistant?
What is the purpose of multidrug therapy as a first line of Tx?
Persons with cavitary disease may have 10^9 organisms
In terms of numbers, 1 in 10^8 organims is INH resistant, 1 in 10^9 organisms is rifampin resistant, and 1 in 10^16 organisms is INH and rifampin resistant.
Multidrug therapy is there to wipe out as many organisms as possible the first time, so that resistant lines are not selected for by incomplete Tx
What is XDR-TB?
A super multidrug resistant strain that is resistant to Isonaizide Rifampin Fluouroquinolone and other injectable Rx
What are the 4 standard drugs for active Mycobacterium tuberculosis?
(Directly Observed Therapy = DOT)
R.I.P.E. Rifampin INH (Isoniazid) Pyrazinamide Ethambutol
What are the mechanisms for... Rifampin INH (Isoniazid) Pyrazinamide Ethambutol
Name the Mechanism, whether it is Intracellular or Extracellular, and whether it is Static or Cidal.
R: blocks DNA-dependent RNA polymerase, works agains intracellular TB, Cidal
I: blocks Mycolic acid formation (the cell wall of TB), works against extracellular TB, Cidal
P: creates acidic intracellular environment for the TB bacilli, works against intracellular TB, both Static and Cidal
E: blocks Mycolic acid formation, doesn’t say intra or extracellular, helps prevent resistance, Static
What are the side effects for... Rifampin INH (Isoniazid) Pyrazinamide Ethambutol
R: influenza syndrome, HEPATITIS, orange urine, drug interactions
I: HEPATITIS, neuropathy, mild CNS, B6 DEFICIENCY
P: GI, HEPATITIS, arthalgias, uric acid
E: optic neuritis, rash
What is the length of drug Tx for active TB:
RIPE for two months
RI for four months
Adminsiter all drugs by Directly Observed Therapy (DOT)
Detail: What is Directly Observed Therapy (DOT) in TB?
Contains five elements
1) Government commitment (including both political will at all levels, and establishing a centralized and prioritized system of TB monitoring, recording and training)
2) Case detection by sputum smear microscopy
3) Standardized treatment regimen directly observed by a healthcare worker or community health worker for at least the first two months
4) A regular drug supply
5) A standardized recording and reporting system that allows assessment of treatment results
