Lecture 12: TB Flashcards
What is the pathogenesis of TB?
Airborne droplet spread
Inhaled – deposited in terminal airspaces
Macrophages ingest bacilli – replicate within endosomes
Transported to regional lymph node
What are the four outcomes of TB that has spread to lymph nodes?
Killed
Multiply → primary TB
Dormant → asymptomatic (LTBI if exposed to host immune system)
Proliferate after period of latency → reactivation disease
What is the % risk of developing TB over a lifetime?
5-10%
This is considerably increased for those with immunodeficiency
What do we know about the TB bacteria?
Aerobic bacillus
Divides every 16-20 hours (slow)
Cell wall, but lacks phospholipid outer membrane
Does not stain strongly with Gram stain (weakly positive)
Retains stains after treatment with acids
Acid fast bacillus
What is meant by granulomatous inflammation?
Rim of lymphocytes
Fibroblasts
Central infected macrophages (giant cells)
Central necrosis – caseation
Secretion of cytokines (IFNγ) – activate macrophages to kill bacteria
AFBs in granulomas
What can be used to visualise M.tuberculosis?
Ziehl-Neelsen stain - bright red bacilli on blue background
Auramine-rhodamine stain
Fluorescent microscopy
What may increase the risk of transmission?
Close contacts of infectious cases
Contact with high risk groups
Immune deficiency
Lifestyle factors
Genetic susceptibility (twin studies of gene polymorphisms)
What are some causes for immune deficiency?
HIV Steroids Chemotherapy and biologics Nutritional deficiency (vit D), Diabetes End stage renal failure
What lifestyle factors may increase the risk of getting TB?
Drug / alcohol misuse
Homelessness / hostels / overcrowding
Prison inmates
What % of cases are primary TB?
1-5%
Bacilli overcome immune system soon after initial infection
What % of cases are latent TB?
2-23% cases – reactivation disease
Risk of reactivation increases with immunosuppression
HIV + risk 10% per year
HIV – risk 1%
How can you diagnose active TB?
Identify the infected area
Isolate the organism
Obtain information regarding susceptibility to antibacterials
How can you diagnose latent TB?
Identify immune response to TB proteins or TB-specific antigens
What is the basis for the mantoux test?
Circulating memory T-lymphocytes ability to mount a delayed hypersensitivity reaction
What are the problems with the mantoux test?
Cross reactive with other Mycobacterial antigens so non-specific
Maybe be falsely negative in severely ill or immunosuppressed individuals
What can be used as an alternative to mantoux?
ELISPOT/ELISA: Enzyme linked immunological assay of release of interferon-gamma in whole blood following stimulation by specific tuberculosis antigen
What are the advantages and problems with the ELISA test for TB?
Advantages:
- More specific than Mantoux
- Correlates better with degree of exposure than Mantoux
Problem:
- Does not differentiate between latent infection and disease
What % of cases are pulmonary TB?
55%
What are the clinical features of pulmonary TB?
Cough Weight loss Haemoptysis Fever Chest pain Night sweats
How can you diagnose pulmonary TB?
Chest imaging
Sputum/BAL
What sites may be affected by extra pulmonary TB?
Lymph nodes CNS Bone (Pott’s disease of the spine) Genitourinary system GI tract Disseminated/miliary
What is TB lymphadenitis?
Infection of LN
Often get worse on treatment - paradoxical reaction
Can form sinus tracts with chronic discharge
Cold abscess formation
What are the symptoms of miliary TB?
Fevers, sweats, weight loss and malaise very common
Respiratory symptoms in majority
GI or CNS symptoms in 20% (abdo pain, diarrhoea, hepatomegaly in 50%, headache or confusion - altered mental state in 20%)
What is the standard pharmacological treatment of TB?
2 months (initial phase) of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol
Followed by: 4 months (continuation phase) of Isoniazid and Rifampicin
How must the standard pharmacological treatment be taken?
All together on an empty stomach 1 hour before breakfast; compliance is essential for cure.
What about the treatment changes if there is CNS involvement?
The continuation phase of treatment is extended to 10 months making a 12 month full treatment plan
What are the side effects of pyrazinamide?
Nausea Skin rashes Hepatoxicity Joint pain N&V
What are the side effects of rifampicin?
Nausea
Skin rashes
Hepatoxicity
Reddish colour to urine
What are the side effects of isoniazid?
Nausea Skin rashes Hepatoxicity Fever Peripheral neuropathy Optic neuritis
What are the side effects of ethambutol?
Nausea Skin rashes Peripheral neuropathy Optic neuropathy Gout
What is the order of most hepatoxicity to least?
Pyrazinamide
Rifampicin
Isoniazid
