Session 9 Flashcards
(44 cards)
Risk factors for tuberculosis?
• Non-UK born/recent migrants – South Asia 54.8% – Sub-Saharan Africa 29.5% • HIV • Other immunocompromised conditions • Homeless • Drug users, prison • Close contacts • Young adults (also higher incidence in elderly)
Microbiology of tuberculosis?
Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex
7 closely related species M tuberculosis M bovis M africanum
•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
Transmission of TB
Spread is by respiratory droplets –coughing, sneezing etc
•Droplet nuclei •<10µm particles •Suspended in air •Reach lower airway
•Infectious dose 1-10 bacilli
•Contagious, but not easy to acquire infection Prolong exposure facilitates transmission (at-least 8 hours / day upto 6 months)
Pathogenesis of TB
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Two forms of infection for TB
Clinical infection (TB)
Subclinical infection (LTBI)
90% of infection is latent infection Reservoir of potential disease
Progression risk is heterogeneous Highest risk with recent infection
First two years: 5% Rest of life time: 5% Total: 10%
TB vs LTBI
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Primary TB
– Ghon focus/complex – Limited by CMI – Usually asymptomatic – Rare allergic reactions include Erythema nodosum – Occasionally symptomatic & can also disseminate - i.e. miliary & extra pulmonary
Post-primary TB
• Reactivation or exogenous re-infection • >5 years after primary infection • 5-10% risk per lifetime
• Clinical presentation – Pulmonary or extra-pulmonary
Risk factors for Reactivation
• Infection with HIV • Substance abuse • Prolonged therapy with corticosteroids • other immunosuppressive therapy, • tumor necrosis factoralpha [TNF-α] antagonists • Organ transplant • Haematological malignancy • Severe kidney disease /haemodialysis • Diabetes mellitus • Silicosis • Low body weight Risk factors for Reactivation All suspected and confirmed cases of TB must have a HIV test
Sites of TB Disease table
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Pathology of TB
Caseating granulomata – Lung parenchyma – Mediastinal LNs
When to suspect TB
• 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
signs and symptoms of pulmonary TB
Symptoms
• Fever • Night sweats • Weight loss and anorexia • Tiredness and malaise
• Cough (most common) • Haemoptysis occasionally • Breathlessness if pleural effusion
Signs on examination
• Often no chest signs despite CXR abnormality • Maybe crackles in affected area • In extensive disease: – signs of cavitation, – fibrosis • If pleural involvement: typical signs of effusion
Investigations of Pulmonary TB
- Chest X Ray
- Sputum – 3 early morning samples minimum volume 5ml
- Induced Sputum
- Bronchoscopy (patients with a dry cough)
Radiology for TB
Pulmonary TB • Apex of the lung often involved as more oxygen there •Ill Pulmonary TB • Apex of the lung often involved •Ill defined patchy consolidation •Cavitation usually develops within consolidation •Healing results in fibrosis
Pleural TB- Pleural effusion defined patchy consolidation •Cavitation usually develops within consolidation •Healing results in fibrosis
Pleural TB- Pleural effusion
TB Microscopy
Remains the mainstay of TB Diagnostics Worldwide
Rapid test, cheap test Sensitivity is approximately 5x103AFB/ml of sputum
60% -70% of culture positive samples are microscopy positive
Indicates infectiousness ‘Smear positive case’
Cannot differentiate MTB from NTM
Cannot differentiate live and dead organisms
TB Culture
• Remains the Gold standard for TB diagnostics • One of the most sensitive methods for detecting Mycobacteria • Solid & liquid culture systems • Has improved with automated culture technology • Allows identification and susceptibility testing
Additional tests – Nucleic Acid Amplification Tests (NAAT) for TB
- Role of NAAT for primary samples? – Rapid diagnosis of smear +ve – Drug resistance mutations
- Whole genome sequencing (WGS)
Histology of TB
tuberculosis granuloma, caseous necrosis - cheese like
Tuberculin sensitivity Test (TST
Oldest diagnostic 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 Tuberculin Skin Testing Read 2-3 days later Subjective interpretation False positives (BCG, non TB ) False negatives (immunocompromised i.e HIV/ drugs/ advanced disease etc Cheap (???) Laboratory infrastructure not required Evidence to support ability to predict active disease in those that are latently infected
Interferon Gamma Assays for TB
• In-vitro test • T cell based assay • Measures Interferon Gamma (IFNg assay)
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Interferon Gamma Releasing Assays (IGRAs) •Detection of antigenspecific IFN-gamma production •T Spot TB •Quantiferon Gold •No cross-reaction with BCG •Cannot distinguish latent & active TB •Similar problems with sensitivity & specificity
Anti-TB drugs and TB treatment
First line medications
•Rifampicin •Isoniazid •Pyrazinamide •Ethambutol
Second line medications
•Quinolones (Moxifloxacin)
•Injectables •Capreomycin, kanamycin, amikacin •Ethionamide/Prothionamide •Cycloserine •PAS •Linezolid •Clofazamine
TB treatment
• Early and adequate treatment with Anti TB Drugs • Close monitoring of compliance • Makes the patient Non infectious • No secondary transmission and cases
• Multi-drug therapy
– Rifampicin • Raised transaminases & induces cytochrome P450 • Orange secretions / urine – Isoniazid • Peripheral neuropathy (pyridoxine 10mg od) • Hepatotoxicity – Pyrazinamide • Hepatotoxicity – Ethambutol • Visual disturbance • Vitamin D • Surgery
• 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)
Development and spread of 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
MDR & XDR TB
• Multi-drug resistant TB (MDR) – Resistant to rifampicin & isoniazid • Extremely drug-resistant TB (XDR) – Also resistant to fluoroquinolones & at least 1 injectable • Spontaneous mutation + inadequate treatment • Likelihood increased – Previous TB Rx – HIV+ – Known contact of MDR TB – Failure to respond to conventional Rx – >4 months smear +ve/>5 months culture +ve • 4 to 5 drug regimen, longer duration – Quinolones, aminoglycosides, PAS, cycloserine, ethionamide,
Miliary tuberculosis
- 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)
