Tb Flashcards
Escrow teh epidemiology
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What is theorganism that causes Tb
Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex
7 closely related species
M tuberculosis
M bovis
M africanum
Describe the features of mycobacterium tuberculosis
• Non-motile rod-shaped bacteria
•Obligate aerobe
•Long-chain fatty (mycolic) acids, complex waxes & glycolipids in cell wall
Structural rigidity
Staining characteristics
Acid alcohol fast
•Relatively slow-growing compared to other bacteria
Generation time 15-20h
Gives it integrity. It is very hard to kill.. ZN stain - strong acids and alcohol used. Ahence acid alcohol oil fast. Culturing the organism takes a lot of time bc of slow growth. Cultures are kept for 6-12 weeks.
Desribe transmission
Spread is by respiratory droplets –coughing, sneezing etc
•Droplet nuclei/airborne
•<10µm particles
•Suspended in air
•Reach lower airway macrophages
•Infectious dose 1-10 bacilli
Air remains infection or 30 min
Contaigios not easy to catch
Prolong exposure facilitates transmission (at least 8 hours / day up to 6 months)
Ss
If low grade infection - not producing many droplets - nee a big load to be infectios. And some people cough but its not productive. New person need to come into contact with droplets to get infected. Catching Tb is not infected? If someone is immunocompromised hey re more susceptible
Describe the pathogenesis
Inhaled aerosols
Engulfed by alveolar macrophages
Local lymph nodes
Primary complex (Ghon’s focus + draining LN) 5% -> (Progression to Active disease (5%) Primary)
95%->
Initial Containment of the infection
Latent Infection
-> Heals / Self cure (95%)
Or -> Post Primary TB
Compare ltbi vc Tb
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What are the manifestations of primary Tb
• Primary TB – Ghon focus/complex – Limited by CMI – Usually asymptomatic – Rare allergic reactions include EN – Occasionally symptomatic miliary /disseminated • Latent TB Generally asymptomatic. Diagnosies sometimes when being investigated for something esle. Not much damage to lung when exposed for first time. Not enough damage happening so nto fully symptomatic
What is post-primary Tb
• Reactivation or exogenous re-infection • >5 years after primary infection • 5-10% risk per lifetime • Clinical presentation – Pulmonary or extra-pulmonary Can be exposed a second time
What are risk factors for reactivation
- Infection with HIV
- Organ transplant
- Substance abuse
- Haematological malignancy
- Prolonged therapy with corticosteroids
- Severe kidney disease /haemodialysis
- other immunosuppressive therapy,
- Diabetes mellitus
- tumor necrosis factor- [TNF-α] antagonists
- Silicosis
- Low body weight
What is pulmonary, extrapulmonary and miliary Tb
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How does host immune response affect outcome
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Describe teh pathology
Caseating granulomata
– Lung parenchyma
– Mediastinal LNs
Describe teh typica Tb patient
• Non-UK born/recent migrants - Recent arrival or travel
• HIV
• Other immunocompromise states (i.e. cancers)
• Homeless
• Drug users, prison inmates
• Close contacts of patients with TB
• Specific clinical features:
Unexplained Fever, weight loss, Malaise, Anorexia
What are the symptoms of pulmonary Tb
Fever, night sweats, weight loss and anorexia, tiredness and malaise, cough, haemoptysis occasioanlly, breathlessness if pleural effusion
What are teh signs on examination o pulmonary Tb
Often no chest signs despite cxr abnormality, maybe crackers in affected area, in extensive disease - signs of cavitation, - fibrosis, if pleura involvement: typical signs of effusion
What are the investigations of pulmonary Tb
• Chest X Ray
•Sputum – 3 early morning samples
minimum volume 5ml
•Induced Sputum
•Bronchoscopy (patients with a dry cough)
Radiology is not diagnostic. Must get bacteria sample
Describe teh radiology
Pulmonary TB • Apex of the lung often involved • Ill defined patchy consolidation • Cavitation usually develops within consolidation • Healing results in fibrosis
Descrbe Tb microscopy
Microscopy is universal worldwide. Rapid test. Sample of sputum on a slide. Cheap test, but very low sensitivity to see Tb bacilli. Need at least 5000 bacilli in an ml of sputum. Not sensitive. Always have to perform microscopy bc we measure infectiosness on whether microscopy is present or not. If we see it -> patient is smear positive -> can transmit Tb from one. Person to another.
Cant be 100% certain whether it’s Tb or non Tb mycobacteria. You also cat differentiate live and dead organisms. May be still postivie but they could be dead.
Then need to do a zn stain
Describe Tb culture
- Remains the Gold standard for TB Lowenstein diagnostics Jensen (LJ) slopes
- One of the most sensitive methods for detecting Mycobacteria
- Solid & liquid culture systems
- Has improved with automated culture technology
- Allows identification and susceptibility testing
What is NAAT
• Role of NAAT for primary samples? – Rapid diagnosis of smear +ve – Drug resistance mutations • Whole genome sequencing (WGS) Cepheid Xpert MTB/RIF and Xpert MTB/RIF Ultra
Describe teh histology
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What si the tst
Tuberculin sensitivity test
Oldest diagnostic (TST)
tests in use (1890) Measures CMI, in the form of DTH to PPD of M tuberculosis
Tuberculin injected intradermally The induration is read 48-72 hrs later
Sensitised t lymphocytes come to sites where Tb antigen has ben introduced. They set up a delayed hypersensitivity . If you have been previously exposed, t lymphocytes come to that spot,. Test tells us that patent has been exposed to Tb. Exposure doesnt = disease. Not a test to diagnose disease. It is a test to find out who has been exposed.. there is a big pool who has been exposed who has latent Tb .mycobacteria that are not causing Tb can be shown so false positive. Limitations. So new test developed.
False negatives. (Hi/immunocompromised)
Cheap
Laboratory infrastructure not required Evidence to support ability to predict active disease in those that are latently infected
What is Igra
Interferon Gamma Releasing Assays (IGRAs)
•Detection of antigen- specific IFN gamma production
•T Spot TB
•Quantiferon Gold
•No cross-reaction with BCG
•Cannot distinguish latent & active TB
•Similar problems with sensitivity & specificity
Blood sample. Measure amount to fin game as a measure of exposure to Tb
Only way to diagnosed is sending sputum samples, radiology, cuulvibatting bacili
• radiology, microbiology , history
How to. Diagnose latent: tst, igra,
What are anti Tb drugs
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Always treated with combination therapy. Give at least 4 drugs
Sedona line drugs if patient is intolerant to first lie, or if there is drug resistant. Always go with combination. Other recason to givec combination is bc natural history of Tb is when it multiplies . There is always option to .
2 reasons for combination therapy????????
Compliance for 4 drugs. Some of the mutations that emerge - for a population - progress to drug resistant Tb.
Describe Tb treatment
• Early and adequate treatment with Anti TB Drugs
• Close monitoring of compliance
• Makes the patient Non infectious
• No secondary transmission and cases
Straight forwards pulmonary Tb - 6 months. They have side effects too. Compliance is poor. Major problem. Major threat to control of b worldwide. Important public health implication
Descrbe the mult idrug therapy
• Multi-drug therapy (RHZE) – Rifampicin • Raised transaminases & induces cytochrome P450 • Orange secretions – Isoniazid • Peripheral neuropathy (pyridoxine 10mg od) • Hepatotoxicity – Pyrazinamide • Hepatotoxicity – Ethambutol • Visual disturbance • Vitamin D • Surgery
Describe the duration and adherence
• Duration – 3 or 4 drugs for 2/12 – Then Rifampicin & Isoniazid 4/12 – 18/12 if CNS TB – Cure rate 90% • Adherence – Directly observed therapy (DOT) – Video observed therapy (VOT)
Describe teh development and spread f drug resistance
Natural history – during multiplication small number of naturally drug resistant organisms arise through spontaneous mutations
Improper drug regimens / poor drug compliance leads to selection of these mutants
Single and multi drug resistance
Diagnostic delays, overcrowding and inadequate infection control facilitates transmission of drug resistance
What is MDT and CD-R Tb
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What is miliary Tb
• Milia (latin) = seed
• Bacilli spreading through the blood stream – widespread infection
• 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 variable
– Headaches suggest meningeal involvement
– Pericardial, pleural effusions small
– Ascites may be present
– Retinal involvement (choroid tubercles seen)
Can happen in primary or post primary. Can affect other organs too
What is extrapulmonary Tb
• Lymphadenitis • Scrofula • Cervical LNs most commonly • Abscesses & sinuses
Gastrointestinal • Swallowing of tubercles • Peritoneal • Ascitic or adhesive • Genitourinary • Slow progression to renal disease • Subsequent spreading to lower urinary tract •Bone & joint Haematogenous spread Spinal TB most common Pott’s disease •Tuberculous meningitis Chronic headache, fevers CSF – markedly raised proteins, lymphocytosis
Descb the preventation
All forms of tuberculosis are compulsorily notifiable under the Public Health Act 1984 • The doctor making or suspecting the
diagnosis is legally responsible for notification.
• A decision to commence treatment (but not
chemoprophylaxis) indicates a level of suspicion which should trigger notification for all forms of tuberculosis
Descrbe teh notificatoin
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Descrbe teh control of Tb
• Treatment of index case Detection and treatment of cases and contacts • Prevention of transmission – Personal protective equipment – Negative pressure isolation • Reduce susceptible contacts – Address risk factors – Vaccination
What s bcg
Bacille Calmette-Guerin (BCG): live attenuated M. bovis strain Given to babies in high prevalence communities only (since 2005) 70-80% effectiveness in preventing severe childhood TB Protection wanes Little evidence in adults
