Tuberculosis Flashcards
1
Q
Microbiology of tuberculosis infection:
A
- TB caused by members of the M.tuberculosis complex - M. tuberculosis, M. bovis, M. africanum, M. micronoti, M.canetti, M. caprae
- Aerobic, thin curved rod
- Cell envelope is distinguishing characteristic
- Gram positive on staining. Ziehl-Neelson stain or fluorescent dye (auramine) to identify AFB (though does not distinguish from non-tuberculous mycobacteria) - sensitivity on non-sputum samples generally lower. Generally consider smear negative patients non-infectious (if subsequent positive culture)
- Growth - slow, requires 3-4 weeks. M. tuberculosis reduces nitrate allowing it to be distinguished from other mycobacterial species
2
Q
What are the 4 potential outcomes of inhalation aerosol droplets of M. tuberculosis:
A
- Immediate clearance
- Primary disease - immediate onset of active disease
- Latent infection
- Reactivation disease - onset of active disease many years following a period of latent infection
- If no underlying medical problems - 5-10% of latent infections will reactivate. Increased risk with HIV
3
Q
Notes on TB Primary Disease
A
- 5-10% infected develop active disease - 50% within 2-3 years following infection
- Bacilli → droplets → alveolar space → proliferate inside alveolar macrophages → migrate from lungs to other tissues
- Lungs: develop granulomatous structure called tubercle → enlarges (Ghon focus). Bacilli enter local draining lymph nodes → lymphadenopathy (lymph node enlargement/calcification + Ghon focus = Ranke complex)
- Cell-mediated immune response develops within 2-10 weeks (CMI). Failure to amount effective CMI → progressive destruction of lung and caseating necrosis
- Unchecked growth = disseminated TB
- Miliary TB, bacilli can spread mechanically by erosion of caseating lesions into airways (host becomes infectious). Death in 80% without treatment
4
Q
Disorders that cause caseating necrosis:
A
- TB
- Syphilis
- Histoplasmosis
- Cryptococcus
- coccidioidomycosis
5
Q
Notes on reactivated TB
A
- Proliferation of previously latent bacteria seeded at the time of the primary infection
- Reactivation A/W immunosuppresion:
- HIV, CKD, DM, lymphoma, corticosteroids, TNF-a inhibitors, cigarette smoking, diminution in cell-mediated immunity associated with age
- Tends to be localised - little regional lymph node involvement and less caseation
- Lesion typically at lung apices - disseminated disease unusual unless severely immunocompromised
- Latent TB confers some protection against subseqeunt TB infection, prior TB disease A/W increased risk of subseqeunt TB disease
6
Q
Risk factors for TB
A
Host factors:
- Immunosuppression - HIV, glucocorticoids, DM, TNF inhibitors, transplant
- Substance abuse - drug (plus epidemiological factors A/W this e.g. homelessness), tobacco, alcohol
- Systemic disease - silicosis, malignancy (haematological, and head and neck cancers), DM, CKD, cirrhosis, COPD, gastric resection for PUD
- Nutritional status - underweight, vitamin D deficiency
Social/Environmental factors
- Household contacts
- Birth in a TB endemic area → Philippines, Vietnam, China, India
- Low socioeconomic static - crowding, poor nutrition, poor access to medical care, unemployment, low education
7
Q
Investigations for pulmonary tuberculosis:
A
- CXR
- Sputum - 3 x early morning sputum for AFB and culture
- Induced sputum preferred - more sensitive than bronchoscopy in dx pulmonary TB in subjects who are AFB negative
- If bronchoscopy required - BAL produces better yeild than “bronchial washings’
8
Q
CXR findings in TB:
A
- Features of active pulmonary disease (need to be followed up with sputum):
- Patchy consolidation or infiltration
- Definite infiltration/consolidation/cavitation
- Features of inactive/fibrotic changes with high probablity progession (need to send sputum)
- Minor lobar scarring, large focal areas of scarring, patchy/definite lobar consolidation/infiltration
- Features of previous TB with low probability of reactivation (do not need sputum testing unless immunosuppressed)
- Calcified lymph node or pleura, minor apical pleural thickening, single calcified granuloma <10mm
- Cavity formation uncommon in primary TB
- Miliary - evenly distributed nodules - disseminated TB
- Pleural and mediastinal lymph node disease are classified as extra-pulmonary TB
9
Q
Investigations for suspected pleural TB:
A
- Pleural biopsy more sensitive than pleural fluid TB culture
- ADA (adenosine deaminase) - useful in diagnosis suspected TB pleural effusion
10
Q
Notes on CNS tuberculosis:
A
- Chronic presentation - malaise, headache, mental change, meningism and focal neurological signs - presentation can be broad (headache → coma)
- May be no evidence of pulmonary disease
- Investigations:
- CT/MRI - r/o raised ICP, posterior fossa disease, obstructive hydrocephalus
- CSF (large volume): leucocytosis (lymphocyte predominant), raised protein, low glucose, send CSF for NAAT, AFB found <20% cases, 45% with suspected TB meningitis have negative CSF cultures
- Moxifloxacin better CNS penetration than ethambutol
11
Q
Other abnormalities of blood tests/routine blood tests that should be done in TB:
A
- CBC - leucoctosis, of leukopaenia
- Anaemia
- Pancytopaenia if extensive bone marrow involvement
- Hyponatraemia - production of ADH like hormone in diseased tissue
- Hypercalcaemia - mild and usually responds to TB treatment
- Mild LFT derangement
- Hypoalbuminaemia
- All patients with suspected TB should have HIV test
12
Q
Standard treatment regimens for pulmonary tuberculosis
A
- 2RZHE/4RH
- Intensive phase:
- 2 months of rifampicin, isoniazid, ethambutol and pyrazinamide
- Continuation phase:
- 4 months isoniazid and rifampicin
Update 2022
4 month regimen now supported by WHO
8 weeks rifapentine, isoniazid, pyrazinamide, moxifloxacin, then 9 weeks rifapentin, isoniazid, moxifloxacin
Problems with international supply of rifapentine
13
Q
Standard treatment regimens for extrapulmonary tuberculosis
A
- Generally same 6 month regimen except for meningeal TB, intracranial TB, and TB of bones and joints
- Meningeal TB = 12 months therapy
- 2RHZE/10RH
- Intracerebral TB = 18 months
- 2RZHE/16RH
- If disseminated TB treat for 9 months and look for CNS involvement and extend treatment accordingly
- 9-12 months for bone and joint TB (given difficulties in assessing treatment response)
- Longer duration of treatment also recommended in the presence of severe disease, extensive disease, drug resistance or clinical or radiological improvement that is slower than expected
14
Q
Predictors of drug-resistant TB:
A
- Previous TB treatment
- Progressive clinical and/or radiographic findings while on TB treatment
- Origin from, history of residence in or frequent travel to a region/country with high rates of drug resistance
- Exposure to an individual with infectious drug-resistant TB
15
Q
Treatment of drug resistant tuberculosis:
A
Isoniazid resitant tuberculosis:
- 6REZM (isoniazid replaced with moxifloxacin)
Rifampicin resistant tuberculosis
- Very uncommon, should raised suspicion of MDR-TB. Requires longer duration of treatment if loss of rifampicin from regimen
Pyrazinamide resistant tuberculosis
- M. bovis naturally resistant to this
- 2RHE/7RH. Add moxifloxacin if extensive disease
16
Q
Notes on multidrug-resistant TB
A
- TB that is resistant to rifampicin and isoniazid
- Pre-XDR TB (extensively resistant) → resistance to rifampicin + isoniazid + fluroquinolones
- XDR TB → Above + at least one additional Group A drug
- Therapy for 18 months with at least 5 drugs that are likely to be effective - work way through groups as below (note Bangladesh regimen allows 9 months of therapy only)
- Daily DOT mandatory for all patients with MDR-TB
- Elective partial lung resection may be used alongside a recommended MDR-TB regimen
29
Q
Tests used to diagnose latent TB - Mantoux
A
- Mantoux
- Intradermal injection of 5 tuberculin units of purified protein derivative (PPD) - derived from cultures of M.tuberculosis
- If prior M tuberculosis infection patient will develop a delayed type hypersensitivity reaction
- High sensitivity in immunocompetant individuals
- Potential for confounding of the test result by prior BCG vaccine and exposure to non-tuberculous mycobacteria
31
Q
Treatment regimens for LTBI
A
- WHO recommendation options:
- 9 months isoniazid → up to 15% world’s TB resistant, severe hepatotoxicity in <2% but increases with age
- 4 months rifampicin → note drug interactions, higher completion rates and less hepatotoxic
- Prevent TB trial: 9H vs 3 months of weekly H and rifapentine → higher completion rates, less hepatotoxic, higher rates of hypersensitivity, non-inferior
34
Q
WHO update May 2022 on treatment of drug resistant TB
A
