GP/ medicine - Tuberculosis Flashcards
What microorganism causes TB?
Mycobacteria tuberculosis
But can also be caused by Mycobacteria bovis and Mycobacteria africanum
Is Mycobacteria tuberculosis a bacillus or a coccus?
A bacillus (rod)
Can normal gram stain differentiate M.tuberculosis from other bacteria?
NO!
M.tuberculosis is special in the sense that it cannot be stained by normal gram stain i.e. neither gram + nor gram.
It’s an acid-fast bacilli, which means it can only be stained with acid-fast stain
What acid-fast stain do we normally use to identify mycobacteria? what color does that stain have?
Ziehl-Neelsen stain
It’s a light-blue stain
On a CXR, where would you usually see the consolidation in a patient with TB?and why?
- Upper lung lobes (usually at the apex) because it’s where most oxygen is present and TB is an aerobe!
- Cavitation, pleural effusion, mediastinal or hilar lymphadenopathy
Oxygen makes TB have orgasm!!!!
Compare and contrast TB and pneumonia
Where in the world TB is usually found?
Asia, Africa, South America, Eastern Europe
How is TB transmitted?
Aerosol inhalation causes pulmonary infection
Then from the lungs, it can spread all over the body through blood (haematogenous spread), causing extrapulmonary TB
What is the pathology/ pathogenesis of TB?
- Infected aerosols inhaled into the lungs
- Alveolar macrophages engulf the bacteria and carry them to hilar lymph nodes in attempt to control infection
- The lung lesion (Ghon focus) + hilar lymph nodes = Ghon complex
- Small granulomas (tubercles) are formed by macrophages to wall off and contain TB, preventing it from spreading.
- Granulomas are basically a collection of epitheliod histiocytes, lymphocytes and Langerhans giant cells surrounding a cheese-like core, which indicates caseous necrosis in the centre
- If infection is not adequately contained by granulomas, it can invade the bloodstream and cause Extrapulmonary TB and Miliary TB
- The inflammatory response is mediated by a type 4 hypersensitivity reaction
- Progression of TB then follows one of two paths:
- Active disease (primary TB) - symptomatic and infectious - the most common presentation (> 50%), OR
-
Latent disease - asymptomatic and NOT infectious - of which there are 2 outcomes:
- Heals spontaneously and no disease develops - common in healthy individuals
- Reactivation –> secondary TB (or post-primary TB) which is an active disease - patient is symptomatic and infectious
- Usually occurs if a patient becomes immunocompromised e.g. old age, HIV, malignancy, steroids, malnutrition
-
The lungs remain the most common site for secondary TB, however, extrapulmonary TB and miliary TB may occur in immunocompromised patients, esp in the following areas:
- CNS –> TB meningitis (most serious complication)
- Vertebral bodies –> Pott’s disease
- Cervical lymph nodes –> Scrofuloderma
- Renal
- GI tract
What are the risk factors for TB?
PMHx of TB
Close contact with someone with TB
Born in a country with high TB incidence e.g. India, Pakistan, Bangladesh
Foreign travel to country with high TB incidence
Immunosuppression e.g. HIV, organs transplant recipients, renal failure/ dialysis, malnutrition, diabetes, steroids, chemotherapy
Hx of alcohol excess, smoking, and IVDU
Children < 5 yrs old (higher risk of developing extrapulmonary TB)
Give 3 complications of TB
Bronchiectasis
Multi-drug resistance (MDR) TB
COPD
Cor pulmonale
What are the symptoms and signs of pulmonary TB?
Symptoms of pulmonary TB:
- Persistent productive cough with purulent sputum
- Fever
- Weight loss
- Drenching night sweats
- Haemoptysis (late)
- Dyspnoea
Signs:
- Crackles and bronchial breathing
- Pleural effusion
- If severe –> atelectasis, pneumonia, bronchiectasis
What are the clinical features of extrapulmonary TB?
- Genitourinary - sterile pyuria, salpingitis, abscess, epididymitis in males, haematuria
- MSK - arthritis, pott’s disease (back pain), osteomyelitis
- CNS - TB meningitis (headache, photophobia, neck stiffness, confusion, cranial nerve abnormalities, vomiting)
- GI - Ileocaecal lesions - abdominal/ pelvic pain, constipation, bowel obstruction, hepatosplenomegaly
- Skin - erythema nodosum, scrofuloderma
- Lymph nodes - lymphadenopathy often affecting cervical or supraclavicular lymph nodes
- Cardiac - TB pericarditis (pericardial rub, Kussmaul’s sign, fever, cardiomegaly, cough, SOB, chest pain, ankle swelling) –> pericardial effusion and tamponande
- Kussmaul’s sign = a paradoxical rise in jugular venous pressure (JVP) on inspiration, or a failure in the appropriate fall of the JVP with inspiration.
Miliary (disseminated)
. .
What are the differentials for haemoptysis?
PE
Bronchiectasis
TB
Pneumonia
Lung cancer
What investigations would you carry out to screen for latent TB?
CXR
quantiFERON (IGRA) or T-spot test
Mantoux test (tuberculin sensitivity test)
What are the limitations of quantiFERON?
- It only tells you whether you have previously been infected with TB i.e. latent TB infection. It doesn’t differentiate between active and latent TB
* A + quantiFERON test does not mean that the patient has active TB and a - quantiFERON test does not mean that the patient doesn’t have active TB - Patients with immunosuppression may not release IFN-y, causing false negatives
- It can’t pick up non-TB mycobacteria
How does quantiFERON work?
It detects the amount of IFN-y released by T cells when they are exposed to proteins found on mycobacteria. Pre-exposed cells release more IFN-y
Why is IGRA a better test over the Mantoux test?
- It can distinguish latent TB from previous BCG vaccine
- It can distinguish TB mycobacteria from non-TB mycobacteria, so it won’t give any false positives if the patient is infected by non-TB mycobacteria. It only gives a positive result if it’s caused by TB-mycobacteria
What is Mantoux? How is it being carried out?
0.1 mL of purified protein derivative (PPD) injected intradermally
Result read 2-3 days
Erythema and induration > 10 mm = positive result - this implies previous exposure to TB including BCG vaccine
If strongly positive (> 15 mm), TB is likely (as response to previous BCG decreases with time), needs further investigation including e.g. CXR, sputum smear
Causes of false-positive Mantoux test
Previous BCG vaccination
Infection with non-TB mycobacteria
Incorrect method of TST administration
Incorrect interpretation of reaction
Causes of false-negative Mantoux test
Immunosuppression - miliary TB, AIDS, steroids
Sarcoidosis
Lymphoma
Extremes of age
Fever
Hypoalbuminaemia, anaemia
How do you differentiate active TB from latent TB?
Usually based on symptoms and findings on CXR
But the following investigations can help too:
- Sputum smear microscopy (with Ziehl-Neelsen stain)
- TB culture
- NAAT
- Histology - TB granuloma
Which group(s) of people needs IGRA screening for latent TB ?
IGRA tests are used in asymptomatic patients who are at high risk of latent TB infection:
- Immigrants from high TB prevalence countries
- Healthcare workers
- People who have been in contact with a person with active pulmonary or laryngeal TB
- Patients who are immunocompromised e.g. HIV + patients, organ transplant recipients
- For people who have evidence of TB scarring or untreated fibrotic changes on chest X-ray but have not completed treatment as planned
What investigations would you carry out in someone with active TB?
- CXR - cavitation/ pleural effusion/ mediastinal or hilar lympadenopathy
- CT - lymphadenopathy/ nodes with central necrosis
- MRI - leptomeningeal enhancement in TB meningitis
-
TB culture (gold standard) - however this can take 6 weeks:
- Pulmonary TB - send 3 sputum samples for sputum smear microscopy and culture
- Meningeal TB - lumbar puncture
- Pericardial TB - pericardiocentesis
- Gastrointestinal TB - colonoscopy + biopsy
- Lymph node TB - biopsy of lymph node
- Histology - shows caseating granulomas
- Blood tests - FBC, U&Es, LFT
- HIV test
- Check vitamin D
In primary care:
- CXR + 3 sputum samples if active pulmonary TB
- Be aware that false negative results are more common in children and the immunocompromised, such as people with HIV.
What investigations would you carry out in pulmonary TB?
Pulmonary TB - x3 sputum samples for sputum smear microscopy with Ziehl-Neelsen stain
- If ‘smear +’ = high bacterial load and high infectivity –> start anti-TB treatment right away as there is a high chance it will culture
- If ‘smear -‘ –> bronchoscopy +/- EBUS (endobronchial ultrasound guided biopsy) of pulmonary lymp nodes –> start anti-TB treatment
CXR
CT chest if clinical features/ CXR atypical
What investigations would you carry out with meningeal TB?
MRI head followed by lumbar puncture
- MRI head shows leptomeningeal enhancement
- Lumbar puncture for TB culture and TB PCR - shows low glucose, high protein, lymphocytosis, fibrin web
(Note that ALL patients with miliary TB should have a lumbar puncture + CT/MRI head done to exclude TB meningitis as TB meningitis the most serious complication)
What are the clinical features of TB meningitis?
Headaches, photophobia, neck stiffness, confusion, vomiting, personality change
More insidious onset compared to viral/bacterial meningitis
What investigations would you do for pericardial TB?
Pericardiocentesis for TB culture
What clinical features will you see in pericardial TB?
Pericardial rub, Kussmaul’s sign, fever, cardiomegaly, cough, SOB, chest pain, ankle swelling
It can cause pericardial effusion and cardiac tamponade
What investigations would you carry out for disseminated/ miliary TB?
- CXR/ CT - shows widespread consolidations
- MRI head followed by lumbar puncture to exclude CNS involvement
What is the initial management for TB?
- ABCDE
- Admit to side room + start infection control measures e.g. masks and negative pressure room
- If productive cough: send 3 sputum samples for sputum smear microscopy and TB culture
- If no productive cough but pulmonary TB suspected –> bronchoscopy
- Routine bloods (FBC, U&Es, LFTs) + HIV test and check vitamin D levels
- CT chest if pulmonary TB suspected but clinical features or CXR atypical
- CT/ MRI head + lumbar puncture if miliary TB is suspected to exclude CNS involvement
- If diagnosis between pneumonia and TB is unclear: always treat it initially as pneumonia, so start Abx for pneumonia according to CURB-65 score, while investigating for TB
- If patient critically unwell and high likelihood of TB (no time to wait for sputum results) then start anti-TB therapy AFTER sputum samples sent
- TB is a notifiable disease so inform case to TB nurse specialists and public health team + start contact tracing
What is the pharmacological mangement of TB?
For latent TB:
- Rifampicin + Isoniazid (+ pyridoxine) for 3 months
- Assess risk of hepatotoxicity
For active TB:
- Standard RHZE treatment for 6 months for all sites EXCEPT for CNS TB (which needs 12 months):
- Rifampicin + Isoniazid (+ pyridoxine) + Pyrazinamide + Ethambutol for 2 months, then continue Rifampicin + Isoniazid (+ pyridoxine) only for 4 months
- For meningeal/ pericardial/ spinal TB:
- Give steroids at the start of treatment on top of the standard RHZE treatment to prevent paradoxical reaction
- For meningeaI TB:
- Standard RHZE treatment for 12 months + steroids at the start of treatment
- Rifampicin + Isoniazid (+pyridoxine) + Pyrazinamide + Ethambutol for 2 months, then continue Rifampicin + Isoniazid (+ pyridoxine) only for 10 months + steroids at the start of treatment
- Standard RHZE treatment for 12 months + steroids at the start of treatment
- For disseminated/ miliary TB:
- Do CT/ MRI head + lumbar puncture to see if there is CNS involvement
- If no CNS involvement –> standard RHZE treatment for 6 months (+ steroids if pericardial involvement)
- If there is CNS involvement –> standard RHZE treatment for 12 months + steroids at the start of treatment)
- Do CT/ MRI head + lumbar puncture to see if there is CNS involvement
- For MDR and non-MDR resistant TB
- Usually seen in patients from abroad, esp in those who have had incomplete treatment for TB previously
- Treatment regimen is decided by the consultant
- Infection control - manage patients in a negative pressure room + staffs wear PPE/ masks
Does latent TB require notification to public health? does it need contact tracing?
NO and NO
Before starting RHZE treatment, what must you monitor?
Baseline LFTs (as rifampicin, isoniazid, pyrazinamide are hepatotoxic)
Visual acuity (as ethambutol can cause reduced visual acuity)
What should you do if LFTs become deranged during standard RHZE treatment?
Treatment can either be stopped and the drugs gradually reintroduced once LFTs have normalised, OR a “liver friendly” regimen can be given (e.g. amikacin, levofloxacin, and ethambutol) but the treatment duration is longer, up to 24 months
How long should you give RHZE treatment for non-meningeal TB?
6 months
(4 drugs for 2 months, then 2 drugs for 4 months)
How long should you give standard RHZE treatment for meningeal/ CNS TB?
12 months
(4 drugs for 2 months, then 2 drugs for 10 months)
Which extrapulmonary TB needs steroids at the start of treatment to prevent paradoxical reaction?
Meningeal/ pericardial/ spinal TB
What drug must you give alongside isoniazid to prevent peripheral neuropathy?
Pyridoxine (vitamine B6)
What are the side effects of rifampicin?
- Rifampicin
- Orange tears and urine
- Hepatitis
- Rashes
- Rifampicin is a CYP450 enzyme inducer, so it can increase the rate at which drugs like warfarin and COCP being metabolised in the liver
What are the side effects of isoniazid?
Isoniazid:
- Peripheral neuropathy (reduced by pyridoxine)
- Hepatitis
- Rashes
- Psychosis
- Colour blindness
• Pyrazinamide – Hepatitis, rashes, vomiting, arthralgia • Ethambutol – Retrobulbar neuritis Therefore, MUST do a baseline visual acuity test and LFT’s which must be monitored closely
What are the side effects of pyrazinamide?
Pyrazinamide:
- Hepatitis
- Rashes
- Vomiting
- Arthralgia
Ethambutol – Retrobulbar neuritis Therefore, MUST do a baseline visual acuity test and LFT’s which must be monitored closely
Which anti-TB drug causes arthralgia as a side effect?
Pyrazinamide
What are the side effects of Ethambutol?
Ethambutol:
- Retrobulbar neuritis –> reduced visual acuity
How is contact tracing performed?
Test household contacts with either CXR or quantiFERON and treat any latent TB
What vaccine do you give to babies to prevent TB infection? What type of vaccine is that?
BCG vaccine (live attenuated vaccine)
What are the guidelines for infection control for TB?
- Staffs do NOT need to wear masks/ aprons unless MDR TB is suspected or they are performing an aerosol generating procedure e.g. giving a nebuliser
- Patients with smear + TB need to wear a mask when leaving their room until they have completed 2 weeks of treatment. After 2 weeks of treatment, patients are generally considered non-infectious to immunocompetent individuals
- Patients with non-resistant pulmonary TB should be nursed in a side room
- If the ward also manages immunocompromised patients, including HIV (i.e our ward!) then patients with pulmonary TB need to be nursed in a side room until discharge regardless of whether they are smear positive or negative
Give 3 differential diagnoses for TB
Viral URTI
Asthma
COPD
What advice can you give to the patient with TB?
Advice:
- Encourage adherence to the treatment regimen
- Lifestyle changes - stop smoking and drinking
- Advise that pulmonary TB can be transmitted to close contacts, and screening via contact tracing will be arranged for high-risk contacts (usually household contacts)
- Advise on symptoms suggesting relapse after treatment completion and the need to inform local TB team or primary care immediately
- Safety netting: If symptomatic or if acutely deteriorating, call 999 and inform local TB team
When should you refer TB patients?
- Suspected active TB
- If the person has known active or latent TB but has not completed treatment as planned
What investigation is best used for assessing drug sensitivities in TB?
Sputum culture
