TB Flashcards
What is TB
Tuberculosis (TB) is a granulomatous disease caused by Mycobacterium tuberculosis.
Epidemiology of TB
- 1.7 billion people worldwide have latent TB
- Common in South Asia and sub-Saharan Africa
- Prevalent in immunocompromised individuals
RFs of TB
- Contactwith a person with active TB
- Endemic regions:South Asia or sub-Saharan Africa
- Homelessness
- Alcohol or drug abuse
- Immunocompromised: e.g. secondary to HIV, steroid use, malnutrition, immunosuppression medication
- M.bovis (animals) can cause abdominal TB
Why do macrophages struggle to clear M. tuberculosis?
due to its waxy mycolic acid capsule which confers protection (the waxy membrane also prevents binding with normal stains - known as acid fastness).
TB very slow dividing bacteria with high oxygen demands
How does TB spread?
via respiratory droplets from patients with active disease. After primary infection, immunocompetent patients can harbour the infection and remain asymptomatic (latent TB)
What happens in immunocomprised patients with TB?
reactivation and failure to contain the bacteria can manifest as secondary TB. It can then spread systemically, resulting in miliary TB.
What happens in primary TB?
1 initial exposure of tb with alveolar macrophage
2 macrophage attempts to form a phagosome but tb has protein which inhibits this
3 weeks later a granuloma form known as a ghon focus , the contents become necrotic
4 ghon focus and Hilar lymph nodes = ghon complex
5 on CXR seen as ranke complex
What type of hypersensitivity reaction is a granuloma with caseous necrosis in centr?
Type IV
What happens in Latent TB?
- This occurs after primary infection.
- Patients remain asymptomatic and the bacteria remains dormant, resulting innegative sputumcultures but apositive Mantoux test.
- These patients arenotinfectious.
- However, if patients areimmunocompromised, the disease can progress or reactivate at a later stage to becomeactive TB.
- Maybe tiny granulomata that become calcified
- detectable CMI to TB on tuberculin skin test
What happens in secondary infection?
- Immunocompromised patients may develop secondary TB when latent TB reactivates, resulting in clinical features e.g. haemoptysis and fever.
- Patients are infectious.
- Reactivation typically occurs in thelung apexwhere pO2is highest, as mycobacteria are aerobic.
- The bacteria can spread locally, to form caseating granulomata, or systemically (miliary TB).
What happens in Miliary TB?
This occurs due to lympho-haematogenous spread to multiple organs e.g. heart, lungs, spleen, liver, bone marrow, pancreas and brain.
2-5% of people develop clinically evident primary pulmonary disease - what are the features
As granuloma grows it develops into a cavity.
More likely in apex of lung as there is more air and less blood supply / immune cells
The cavity is full of TB bacilli, which are expelled when patient coughs
Bacilli + macrophages coalesce to form a granuloma, this is called the Primary (Ghon) focus
mediastinal lymph nodes enlarge.
Primary focus + mediastinal LN = Ghon Complex
S + S of TB
Auscultation - crackles may be present
Clubbing
Cough
Dyspnoea
Chest pain
Fever
Lethargy
Malaise
Anorexia
Extra pulmonary Tmanifestations for TB
CNS - TB meningitis, CN palsy
Heart - pericardial TB
Adrenals - Addisons
Liver - hepatitis
GI - ascites, ileal malabsorption
Bone - pain or swelling of joint, Potts disease + spinal cord lesion
Genito-urinary TB - epididymitis, dysuria, haematuria
Investigation for Latent disease of TB?
Mantoux screening - used to look for previous immune response to TB -
Interferon- gamma release assay (IGRA) - sample of blood and mixing it with antigens from TB in bacteria - more sensitive than Mantoux - used if Mantoux positive or inconclusive or if Mantoux falsely negative
Mantoux Test/ TST tuberculin skin test
Antigenic protein derived from Mtb surface
injected intradermally (technically difficult)
stimulates ‘type 4 delayed hypersensitivity’ reaction
Antigen Presenting Cell takes up antigen and presents this to T cells
if Mtb specific memory T cells present they produce cytokines (IFNy) that cause local inflammatory reaction
What are the problems with the mantoux test
Less sensitive in immunosuppressed or miliary TB (false negatives)
only moderately specific (false positives) e.g. if prior BCG
And
Won’t distinguish latent TB infection from active TB disease and a negative does not rule out active TB
Interferon gamma release assays (IGRAs)
Stimulates memory T cells with antigens specific to M. tuberculosis ESAT-6 and CFP10
If TB specific memory T cells are present, they react by producing IFN-g
so detects real TB exposure and not just BCG (Bacille-Calmette-Guerin) live attenuated version of TB used in vaccination
98-99% specific – better than TST but still a risk of false positive depends on background exposure risk
Chest X- RAY for active disease
- Primary TBmay show patchy consolidation, pleural effusions and hilar lymphadenopathy
- Latent disease may show ghon complex
- Reactivated TBmay show patchy or nodular consolidation with cavitation (gas filled spaces in the lungs) typically in the upper zones
- DisseminatedMiliary TB show “millet seeds” uniformly distributed throughout the lung fields
Other than Chest x-ray what other tests can be done for Active disease?
-
Microbiology/ microscopy- Definitive, AFB PCR CULTURE:send three deep cough sputum samples; analyse with Ziehl-Neelsen stain (will turn red) and Mycobacterium culture
- Bronchoscopy with lavage if sputum can’t be obtained
- Lymph node aspiration for biopsy
- Nucleic-Acid Amplification Test (NAAT): rapid diagnostic test conducted on sputum or urine if specific criteria are met e.g. co-existing HIV, risk of multi-drug resistance or, aged < 15 years
- HIV and hepatitis status:assess for co-infection
What vaccine is given for TB?
BCG vaccine: intradermal injection of live attenuated (weakened) TB.
Latent TB Management
- Isoniazid + Rifampacin 3 months : People <35 if hepatotoxicity is concer
- Isoniazid 6 months: interaction with rifampacin are a concern
- Pyridoxine
Active TB management
- Notify within 3 days
- Contract tracing
- Isolate in negative pressure rooms
- RIPE : rifampicin, isoniazid, pyrazinamide and ethambutol 2 months
- Continuation phase: R + I for 4 months
What happens if the TB is multi drug resistant?
treatment will be extended for 1-24 months, with at least six drugs
Rifampicin and Isoniazid +/- any others
Rifampicin monoresistance effectively same as Rifampicin so critical
Pyridoxine (Vit B6)
Extreme drug resistance TB
MDR + second line drugs such as fluoroquinolones
Extrapulmonary management
Usually longer continuation phase of antibiotics + corticosteroids
Complications of TB
- Empyema
- Aspergilloma
- Bronchiectasis
- Pneumothorax: TB is a cause of secondary spontaneous pneumothorax
- Miliary TB:
- Extrapulmonary diseases
Rifampicin
Inhibits bacterial RNA polymerase - prevents transcription of DNA to mRNA
SE: red urine, hepatitis, flu like symptoms
Isoniazid
- Inhibits mycobacterial cell wall synthesis
- SE: hepatitis, peripheral neuropathy, agranulocytosis
Pyrazinamide
- Bactericidal initially, less effective later
- Hepatitis
- Gout - due to hyperuricaemia
- Arthralgia and myalgia
Ethambutol
- Causes inhibition of mycobacterial cell wall synthesis
- Optic neuritis
- Requires dose adjustment in renal impairment
Pott’s disease of the spine
This patient has presented with Pott’s disease, or tubercular spondylitis, one of the commonest extrapulmonary manifestations of tuberculosis. Risk factors for infection with tuberculosis include prolonged exposure to poor living conditions and being immunocompromised. Clinical features include localised back pain, neurological deficits and radiographic findings indicative of vertebral body involvement. A biopsy demonstrating granuloma formation is highly suggestive of a tubercular process.
