Lecture 19- Tuberculosis Flashcards
What is TB caused by?
Mycobacterium tuberculosis
- Aerobic
- Acid and alcohol fast bacilli
- Slow growing
Demographics and risk factors
- Non-UK born/recent migraines
- South Asia 54%
- Sub-Saharan Africa 29%
- HIV
- Immunosuppressed
- Homeless
- Drug users, prison
- Close contacts
- Young adults (also higher incidence in elderly)
How can we stain for tuberculosis?
Sputum smear stained with Ziehl-Nielsen method
Takes 2-6 weeks to grow colonies
–> cant tell if TB alive or dead
in the UK TB is mainly found in
non-UK born
How does TB transmit from person to person?
- infected droplets from coughing and sneezing
- Infectious dose 1-10 bacilli
- Contagious, but not easy to acquire infection
- Need prolonged exposure to facilitate transmission (at least 8-hours /day up to 6 months)
- Households
- Prisons
- School
- Lots of factors need to be fulfilled for transmission
Where is the most common site of pulmonary TB?
Right lung apex as high pO2 in these areas compared to the rest of the lungs
pathogenesis of TB
- Alveolar macrophages phagocytose MTB but cannot kill them as cell wall lipids of MTB block fusion of phagosome and lysosome
- Macrophages initiate cell mediated immunity so activated macrophages can come and kill MTB, takes about 6 weeks
- Granulomatous reaction from macrophages
primary complex (Ghons focus and draining lymph node) can have 3 outcomes
- Active primary disease (5%)
- Initial containment of infections
- Heals/self cure
- Post primary infection TB
What could cause a latent TB infection to reactivate?
- HIV
- Chemotherapy
- Malnutrition
- Old age
- corticosteroids
- immunosuppressive therapy e.g. organ transplant
What is the likelihood of someone being infected with TB actually developing the active disease?
10% lifetime risk
- 5% develop primary TB at initial infection when primary complex does not heal
- 5% develop post primary TB up to 60 years after initial infection
TB with symptoms=
infectious
Primary TB become symptomatic after first exposure to TB
- Ghon focus/complex
- Limited by CMI
- Usually asymptomatic
- Rare allergic reactions include erythema nodosum
- Occasionally symptomatic and can also disseminate
- i.e. military and extra pulmonary
The general symptoms of TB disease include
Unexplained weight loss
Loss of appetite
Night sweats
Fever
Fatigue
Chills
The symptoms of TB of the lungs include
Coughing for 3 weeks or longer
Hemoptysis (coughing up blood)
Chest pain
Post-primary TB
- reactivation by exogenous re-infection
- latent –> disease
- much more symptomatic
- >5 years after primary infection
- 5-10% risk per lifetime
- Clinical presentation
- Pulmonary or extra-pulmonary
how can we test for latent infection
IGRA (QuantiFERON)
Tuberculin skin test
IGRA (QuantiFERON)
MTB antigens can make the body produce interferon gamma. Lymphocytes from the patient are cultured with MTB antigens and if T lymphocytes have been exposed before they will produce interferon gamma. The MTB antigen is not present in BCG or atypical mycobacteria so can distinguish latent from BCG vaccine
Tuberculin Skin Test:
Protein from MTB injected intradermally. Skin reaction 48-72 hours later indicates previous TB exposure, type IV hypersensitivity reaction to MTB
indicates sensitive T cells
positives and negatives of tubercukin skin test
Positives
- Cheap
- Lab infrastructure not required
- Evidence to support ability to predict active disease in those that are latently infected
Negatives
- False positives- BCG non TB
- False negatives (immunocompromised i.e. HIV/drugs/ advanced disease)
positives and ngeatives of IGRA
Advantages
- Antigens are only found in M. tb (not in BCG)
Disadvantages
- Cannot distinguish latent and active TB
- Similar problems with sensitivity and specificity
What are some of the changes a patient may have with post primary TB?
- Cavity formation: liquefaction of caseous material. Fibrous tissue usually around periphery of lesions
- Haemorraghe: extension of caseous process into vessels. leads to haemoptysis
- Spread to rest of lung
- Pleural effusion: seeding of TB into pleura or hypersensitivity
- Miliary TB: rupture of caseous pulomnary focus into blood vessel so widespread dissemination through body
What are some sites of extrapulmonary TB?
Miliary TB
- Bacteria spreading through the blood stream –> widespread infection
- Lymph nodes
- Bones
- Joints
- CNS
- GI tract
- Urinary tract
- brain (tb meningitis)
when does milliary tb occur
- Either during primary infection or during reactivation
- Lungs are always involved- but few respiratory symptoms
- Fever, very unwell, dry cough
- Often multiple organs involved
- Other organ involvement is variable
- Headaches suggest meningeal involvement
- Pericardial- pleural effusions small
- Ascites may be present
- Retinal involvement (Choroid tubercles seen)
What are some clinical features of pulmonary TB?
- Gradual onset over weeks or months
- Tiredness
- Malaise
- Weight loss
- Fever
- Sweats
- Cough with haemoptysis
- Can be asymptomatic even when CXR abnormal
- Crackles may be present
- Signs of pleural effusion or fibrosis
What does a CXR of TB look like?
Ghons focus
- Patchy solid lesions
- Cavity solid lesions
- Streaky fibrosis
- Flecks of calcification
How do we diagnose active TB?
- radiology most important
- microscopy
- culture
- histology
TB microscopy
- Rapid and cheap test
-
Zeal-neelson (ZN)stain used (acid-fast)
- Pink bacilli
- For test to be positive = need at least 5000 bacilli
- Smear positive case
- For test to be positive = need at least 5000 bacilli
- Cannot differentiate MTB from NTM
- Cannot differentiate live and dead organisms
- Pink bacilli
why doesnt the TB gram stain
encapsulated
TB culture- second most important
*
- Remains gold standard for TB diagnostics
- One of the most sensitive methods for detecting mycobacteria
- Solid and liquid culture system
- Has improve automated culture technology
- Allows identification and susceptibility testing
types of TB culture
Lowenstein jensen slopes
Automated TB culture
Additional test
Lowenstein jensen slopes
- Bacilli takes a long time to grow in this (2-6 weeks)
- Will need to be sent for microscopy identification
Automated TB culture
- Liquid culture medium
- Sample goes into automated machine
- Much more sensitive than solid cultures
- Detect growth of TB bacilli by measuring the change in pH (CO2 conc)
- Can detect growth much earlier (10-14 days)
additional tests
- Nucleic acid amplification test (NAAT)
- Rapid diagnosis of smear positive
- Drug resistance mutations
- GWAS
What does TB look like using histology?
- Granuloma with central caseous necrosis (cheese) surround by epitheliod macrophages, langhans giant cells and lymphocytes
How do we treat TB?
- Rifampicin (red urine)
- Isoniazid (INAH)
- Pyrazinamide
- Ethambutol
All 4 drugs for 2 months and then just R and INAH for a further 4 months. Give pyridoxine with INAH to stop peripheral nerve damage
low compliance
multidrug therapy
Why do we give 4 drugs for TB?
One drug would allow selection of resistant strains, less likely to be resistant to all three drugs
pts at risk- those not taking the medication
What should you do if you diagnose a patient with TB?
- Isolate and notify public health
- PPE
- Contact trace and vaccinate
difference between latent and active disease
adverse affect of drugs
What are some extra-pulmonary signs of miliary TB?
- Headaches as meningeal involvement
- Pericardial and pleural effusions
- Retinal involvement
- Ascites
Offer prophylactic drugs to pts with
latent TB – to kill dormant TB- reduce number of people with active disease
BCG- Bacilli Calmette-Guerin vaccine
- Live attenuated M.bovis strain
- Given to babies in high prevalence communities
- 70-80% effectiveness in preventing severe childhood TB
- Protection wanes
- Little evidence in adults
- Not part of routine childhood vaccination schedule only given to neonates/ infants / older children thought to have an increased risk of coming into contact with TB
- Other indication
- New entrants from high-risk areas
- Health workers
- Close contacts of active resp TB
- Other groups- ref green book
- Always consider HIV testing where appropriate before giving BCG
Ghon focus
ghon focus- granuloma with associated WBC
ghon comples- ghon focus with associated lymph node
granuloma formation
- Granuloma
- A collection of epithelioid histiocytes (macrophages) with surrounding lymphocytes
May also see giant cells within granuloma
