tuberculosis Flashcards
what is the epidemiology of TB
Commonest cause of infectious disease related mortality worldwide
WHO ¼ of global population have latent TB infection
Global incidence is falling
8% HIV positive
1.5 million deaths per year
Increasing drug-resistance
what is the epidemiology of TB in the UK
TB now declining rapidly in UK
Example of major multiagency intervention
Less than 500 new cases
People born outside UK account for 72% of cases
what is the pathogenesis of TB
Airborne droplet spread
Inhaled – deposited in airspaces
Macrophages ingest bacilli – replicate within endosomes
Transported to regional lymph node
Killed
Multiply – primary TB
Dormant – asymptomatic (LTBI if exposed to host immune system)
Proliferate after period of latency – reactivation of disease
Natural history of TB infection
Exposure - elimination/inability to control (transmission)/immune control - latent TB elimination/lifelong containment/reactivation to active TB
Approx 50% develop active disease within 5 years of exposure
Risk of developing active TB 10-15% over lifetime in immunocompromised
HIV+ risk 10% per annum
what is TB
Aerobic bacillus
Divides every 16-20 hours (slow)
Cell wall but lacks phospholipid outer membrane
Does not strain with gram stain (weakly positive)
Retains stains after treatment with acid (acid fast bacillus)
what is the pathology of TB
Granulomatous inflammation
Rim of lymphocytes
Fibroblasts
Central infected macrophages (giant cells)
Central necrosis – caseation
Secretion of cytokines (IFNy). – activate macrophages to kill bacteria
AFBs in granulomas
What are transmission risks of TB
Close contacts of infectious cases (smear +)
Contact with high risk groups:
High incidence country
Frequent travel to high incidence areas
Immune deficiency – HIV, steroids, chemo and biologics, nutritional deficiency (vit D), diabetes and end stage renal failure
What lifestyle factors influence TB contraction
Drug/alcohol missuse
Homelessness/hostels/overcrowding
Prison inmates
Genetic susceptibility (twin studies of gene polymorphisms)
how does primary TB progress
1-5% cases, bacilli overcome immune system soon after initial infection
how does latent TB progress
majority (immune memory of exposure to TB), 2-23% cases – reactivation disease, risk of reactivation increases with immunosuppression (HIV + risk 10% per year and HIV risk 1%)
how is active TB diagnosed
Principles – identify the infected area, isolate the organism, obtain information regarding susceptibility to antibacterials
how is latent TB diagnosed
Principles – identify immune response to TB proteins or TB specific antigens
what is the tuberculin TB test
mantoux
Requires
Circulating memory T lymphocytes
Ability to mount a delayed hypersensitivity reaction
Cross reactive with other mycobacterial antigens so non-specific
Maybe falsely negative in severely ill or immunosuppressed individuals
what are interferon gamma release assays
ELISPOT/ELISA enzyme linked immunological assay of release of interferon-gamma in whole blood following stimulation by specific tuberculosis antigen
More specific than Mantoux
Correlates better with degree of exposure than Mantoux
Does not differentiate between latent infection and disease
T-spot TB or quantiferon gold
what is pulmonary TB
Majority (55%) of cases
Infection risk, cavitatory diease – more infectious