Tuberculosis Flashcards
- Who discovered the mycobacterium?
- Which cells have a similar call wall to mycobacterium? Name 2 components of the mycobacterium cell wall
- MTB is an AFB. Name one other AFB
- MTB is an obligate aerobe. What is it susceptible and resistant to?
- Name the culture that is widely used for TB and describe it
- Robert Koch
- Similar to gram +. Liboarabinomannan and mycolic acid
- Nocardia is also an AFB
- It is susceptible to heat, UV light, pasteurization, and alcohol. Resistant to acids, bases, ammonium compounds.
- LJ culture- egg-glycerol-based, green dye. Inhibits growth of contaminants. Grows well at 35-37 degrees celsius and grows for 2-8 weeks.
TB DIAGNOSIS- MICROSCOPY
- Name the 2 sains used for TB microscopy and differentiate between them
- When is the sensitivity of microscopy lowered?
- ZN stain and Auramine stain
- ZN: cheap, LM BUT magnification, poor contrast, lower sensitivity, and time-consuming.
- Auramine- higher sensitivity and less time-consuming. BUT toxicity- mercury, requires a dark room, expensive.
- Sensitivity is lowered if HIV+, EPTB, pediatrics
TB DIAGNOSIS- CULTURE
- Culture is the gold standard in TB diagnosis. What are its two downsides?
- Name two types of cultures that we do
- Describe the typical TB colonies
- When is the culture contaminated and when is there actual MTB growth
- Time consuming and risk of contamination
- Solid media (LJ culture) and liquid media» decreased risk of contamination
- Typical TB colony- irregular edges, heaped center, ivory color/ nonpigmented.
- MTB growth: colony clumping + flaky grains present and contaminated: turbid, even suspension
IMMUNOASSAYS
- T/F immunoassays tell you about the active disease
- What do immunoassays elicit?
- Name two types of immunoassays we do
TST - What type of injection? - In which patients do we do it to and why? What type of hypersensitivity is it? - What does a false positive mean? What does a false negative mean
IGRAS
- How do these generally work?
- How do IGRAS differ from TST?
- what are the pros and cons
- False- they tell you about infection
- They elicit an antibody response
- We have TST and IGRAs
- intradermal injection
- Mostly pediatric patients for HIV prophylaxis
- Delayed hypersensitivity
- False positives: NTMs, BCG
- False positives: HIV, cancer, severe TB, malnutrition
IGRAS
- These work by exposing peripheral blood smear/ mononuclear cells to TB antigens and interpreter the results. The results usually involve IFN-y response, CD4 or CD8 response to antigen wells.
- Pros- one visit, more sensitive
- Cons- expensive, needs infrastructure and limited data on use in our setting
HUMORAL IMMUNITY
- What does this test try to elicit
- Why is it a generally not good test?
- Name a test that uses this technique and state in which patients we use it
- What are the WHO recommendations of a U-LAM test?
- Elicits antibody response against TB
Not a good test because TB antigens are expressed at different stages of the disease and different strains produce different antigens and antibody response is dependent on the patients’ immunity. - U-LAM for use in patients with <100 CD4.
- WHO recommends use in HIV+ with signs of TB or advanced HIV/ seriously ill or CD4<100 despite signs and symptoms. (advises against not assessing for TB symptoms or doing a U-LAM without TB symptoms and a known CD4 or without TB symptoms and a > 100 CD4)
DST
- There are two ways in which we do DST, namely?
- Describe how we do phenotypic DST and the two types we have in this category (differentiate between them)
- What does the genotypic technique look for?
- There are two types here:
GeneXpert Ultra and LPA (MTBDrPlus and MTBDrsl) what do each of these look for?
- Phenotypic and genotypic
- phenotypic: culture of patient’s inoculum and see if TB grows in the presence of a drug or not. We have 1st line and the 2nd line. 1st line is more studied, reproducible, reliable, and correlates with the clinical outcome. 2nd line is less well studied, has technical issues, unreliable, and not so reproducible except for in the case of fluoroquinolones.
- genotypic looks for already known TB mutations
GeneXpert ultra: looks for mutation of rpoB gene (INH and Rif resistance)
MTBDrPlus looks at the mutation of katG (high INH resistance) and inhA (low INH resistance, ethionamide resistance) and MTBDrsl looks for 2nd line drugs resistance.
Differentiate between the symptoms of:
- PTB
- EPTB
Differentiate between primary and secondary resistance
PTB- coughing for 2 weeks, fever, LOW, night sweats, tired/ fatigue
EPTB- lymph nodes, meningitis, anywhere in the body: pleura, peritoneum, bone. Miliary TB is not contagious (more in immunocompromised)
Primary resistance is where you get infected with an already DR-TB whilst secondary resistance is where you acquire resistance during the disease
- What is meant by a TRACE result?
- Which 3 groups of patients are at risk of getting TRACE results?
- T/F Molecular tests (GXP) show Rif and INH resistance
- What do you do if on GXP the results show Rif resistance?
- What do you do if on GXP where is TRACE?
- Detection of dead bacilli/ non-viable OR paucibacillary (in which case, it is an actual TB)
- HIV+, pediatrics, EPTB
- False. You may miss INH resistance
- If Rif resistance, repeat on LPA to confirm RR- resistance, and you do a second-line DST test on LPA.
- If trace, repeat GXP and do culture
DEFINE
- Mono-resistance
- Polyresistance
- RR-TB
- Pre-XDR TB
- XDR-TB
- MDR-TB
- Heretoresistant TB
Mono- Rif OR INH resistance
Poly- Rif OR INH and another 1st line
RR- Rif resistance with or without another resistance
MDR- RIF AND INH
Pre-XDR- RIF AND INH AND fluoroquinolone or injectables
XDR- RIF AND INH AND fluoroquinolones and injectables
DR-TB and DS-TB in the same patient- Lab diagnosis
MTB- IMMUNOLOGY There are many different immunological presentations of TB. Define each of these - Latent TB - Innate immune stage - Acquired immune stage - Quiescent immune stage - Replicative immune stage - Active TB stage
Latent TB- mostly asymptomatic. May have erythema nodosum and fever
Innate immune response- innate immune response, no memory
acquired immune response= innate and acquired immune response
quiescent- can’t eliminate TB but it is not growing so you can control it
Replicative: uncontrolled bacterial growth but you can still control the infection so no signs and symptoms yet.
Active TB stage: clinically apparent infection/ disease
- How does delayed hypersensitivity work?
-
The antigen is injected (intradermally) and processed by APCs. Th1 cells recognize the antigen and release cytokines on the vascular endothelium. phagocytes and plasma are recruited to the site and an induration forms
Explain the pathogenesis of TB
Infected macrophages and dendritic cells recruit monocytes and then form a granuloma, with the help of T cells. The granuloma has fibrotic walls and a necrotic center. The TB remains dormant until immunity decreases. Dendritic cells and macrophages then move to the lymph nodes and stimulate antigen-specific T cells. At this point, gohn complex has formed
The granuloma is hypoxic and so TB is therefore dormant and undetectable by ZN. The granuloma however disrupts (due to resuscitation promoting factors of metabolically active MTB) and TB flourishes in a liquefied environment and spreads.
TB consists of loss of immune memory and T cell phenotypes- explain
Loss of immune memory- exhaustion of memory as MTB changes its expression programs all the time
T-cell phenotypes-Th2 and regulatory cells suppress Th1 (IFN-y, TNF, IL1-2 are decreased)
Name 2 POTENT Anti-TB drugs
INH and moxifloxacin
Name two sterilizing anti-TB drugs
Rifampicin and PZA
