Tuberculosis Flashcards
Regions with highest cases of TB
China
India
Regions with highest incidence of TB
Sub-Saharan Africa
What populations is TB concentrated in the uk?
Urban poor IVDUs Poor Alcoholics Inmates Alcoholics
Risk factors/social risk factors for TB
Urban homeless IVDU AIDS/HIV Alcohol misuse Prison Deprivation
How many main mycobacterial species are in the ‘Mycobacterium tuberculosis complex’
4: M.Tuberculosis M.bovis M.aricanum M.microti
What does TB grow inside of, and what does this make it?
Macrophages
Obligate intracellular parasite
What stains TB red?
Zeheil-Neilson stain
Shape of TB:
Rod-shaped
Is TB anerobic or aerobic?
Strict aerobe
Why does TB have a waxy cell wall?
Mycolic acid
Once inhaled, what happens to TB?
Taken up by alveolar macrophages
What can happen to TB once taken up by alveolar macrophages (4)
- Cleared
- Heal with scaring
- Lie dormant
- Primary progressive disease
What cell primarily makes up granuloma?
Macrophages
Gohn focus =
Primary lesion. Small area of granulomatous inflammation
When is a Gohn focus detectable on CXR?
When it calcifies
Gohn complex =
Gohn focus + infection of lymphatics
Ranke complex =
Gohn focus undergoes fibrosis and calcification
Milliary TB =
Widespread dissemination of TB via hematogenous route
When is miliary TB more common?
Immunosuppressed patients
What is very important in Tb immunity?
Cell mediated immune response
What cytokines are important in TB/markers of infection
TNF-a
INF-y
Name some clinical conditions which increase risk of TB infections
HIV
SIlicosis
Diabetes
Chronic renal failure
What treatments can increase risk of TB infection
TNF-a therapy
Solid organ transplants
How does silicosis increase TB risk?
Disrupts macrophages/granulomas
How does HIV, diabetes and chronic renal failure increase TB risk?
Impairs cell mediated response
How can infectious particles be aerosolised?
Coughing
Sneezing
Talking (if laryngeal)
What secretions aren’t too important for infection?
Large secretions
fomites
Fomites =
Inanimate objects that carry disease
How long does unrestrained TB multiplication occur before cell mediated response kicks in?
Weeks (2-3 weeks)
What do alveolar macrophages do when infected with TB?
- Form granuloma: release TNF, adhesion molecules
- Cellular influx: chemokine secretion
- IL-6 secretion
- MHC II expression - CD4+ cells
- IL-10 secretion: limit inflammatory response
Function of IL-10
Limit inflammatory response
Tissue necrosis occurs if antigen load is
High
Necrosis in TB =
Caseous
Symptoms of TB
Productive, chronic cough
Chest pain
Haemoptysis
Systemic: chills, fecer, night sweats, appetite loss, weight loss, fatigue
Standard view of CXR =
PA (posterior-anterior)
What can trigger post-primary tuberculosis?
Age Immunosuppression Disease Alcohol Drugs
What is post-primary TB?
Reactivation of latent TB
Extra-pulmonary TB occurs in what % of cases?
50%
Whats more infectious, pulmonary or extra-pulmonary TB
Pulmonary
Examples of metastatic organ spread:
Kidneys Bone Brain Muscle Retina Lymph nodes
Features of metastasis to kidneys:
Hematuria
Proteinuria
Back pain
Potts disease =
Vertebral TB
Features of metastasis to brain
Tuberculomas in brain
In muscle, TB may cause a
Cold abscess
How many/when should sputum specimens be collected?
3 specimens, 3 consecutive days
If patient not producing enough sputum, what can be used to induce it?
Hypertonic saline solution
If patient cannot induce sputum, what can be used for specimen?
Gastric aspirate
Bronchoscopy
Baseline diagnostic exams for TB:
CXR
Sputum specimen - AFB microscopy and mycobacterial cultures
Drug-susceptibility testing
CEPHAID test
Detects DNA sequences specific for M.tuberculosis and rifampicin resistance by PCR
How long does a CEPHAID test take?
90 mins
Ways to diagnose latent TB/corroborate active TB
Heaf test
Mantoux test
INF-y test
Mantoux test looks for
Immune response to mycobacteria antigens
What can the mantoux test react to that the INF-y test doesn’t?
BCG vaccine
INF-y test measures what
- Amount of INF-y (ELIZA)
- Number of T cells producing INF-y (ELISPOT)
More specific test =
INF-y test
When should you consider treating for TB:
Postive AFB smear
Hx of cough and weight loss
Characteristic CXR findings
Emigration from country of high incidence
Once treatment stats, what should you do:
- HIV test
- CD$+ count for HIV+
- Liver and vision baselines
4 1st line TB treatments:
Isonazid
Rifampin
Pyrazinamide
Ethambutol
Ex of 2nd line TB class
Fluoroquinolones
Fluoroquinolones suffix
-floxacin
Moa of fluororquinoles
Topoisomerase II inhibitor (DNA gyrase)
MOA rifampin =
RNA polymerase inhibitor
MOA Ethambutol
Cell wall inhibitor
MOA pyrazinamide
Cell membrane
MOA isoniazid
Cell wall inhibitor
Combos for Tb treatment:
- first 2 months –> rifampicin + isonazid + pyrazinamide +/- ethanmbutol
- 4 months (OR 7 IF SMEAR +VE) –> rifampicin + isoniazid
Pyridoxine =
B6
What should B6 be given with
Isonazid
What can turn urine orange
Rifampicin
Why does rifampicin interact with other drugs strongly
Potent cytochrome p450 inducer
Ex of drugs rifampicin can interact with
Warfarin
Contraception
Analgesia
MDR-TB =
Multi-drug resistant TB. Resistant to isoniazid and rifampicin
At risk of MDR-TB
- Hx of treatment
- Contact with or from country with MDR-TB
- Smears +ve despite 2 months treatment
- Lack of compliance
- Single drug therapy
- Dispencing error
XDR-TB =
Extensively drug resistant TB
Resistant to any flurorquinole and at lead 1 of 3 injectable 2nd line drugs
