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
What are the clinical features of pulmonary TB
Cough Haemoptysis Chest pain Weight loss Fever Night sweats Diagnosis Chest imaging Sputum/BAL
how is pulmonary TB seen on X-ray
Upper lobe consolidation, can be bilateral too
Hilar lymph node changes (Hilar lymphadenopathy)
TB pleural effusion
what are other types of TB
Extra pulmonary disease More common in non-UK born Asian origin Reactivation Sites Lymph nodes, CNS, none (pott’s disease of the spine), genitourinary system, GI tract and disseminated/military
what is TB lymphadenitis
Often get worse on treatment – paradoxical reaction
Can form sinus tracts with chronic discharge
Cold abscess formation
what are symptoms of disseminated/miliary TB
Fevers, sweats, weight loss and malaise very common
Respiratory symptoms in majority
GI or CNS symptoms in 20%
Abdo pain, diarrhoea, abnormal LFTs, hepatomegaly in 50%, headache or confusion, altered mental state in 20%
What are other forms of TB
Skeletal TB
Around 15-30% of all extrapulmonary cases
Genitourinary TB
Kidney/bladder/pelvic involvement, pus in urine but repeatedly negative standard cultures (sterile pyuria)
TB enteritis
Ileo-caecal commonest weight loss, diarrhoea, blood in stools
TB of the eye
Any part of eye, probably more common than we think
Pericardial TB
CNS TB
TB meningitis, TB arachnoiditis, Tuberculoma, spinal cord compression – extension of discitis
What is the epidemiology of extra pulmonary forms of TB
1% all TB cases
6%. Extrapulmonary TB in immunocompetent host
More common in HIV coinfected
Mortality 15-40% despite effective Rx (CDC)
How is TB controlled
Government global policy
Consider the diagnosis
Early diagnosis and treatment (even if negative cultures/smear)
Optimal treatment and adherence (DOT/VOT/section)
Contact tracing
Prevention – BCG
Latent treatment programs, prevent TB becoming active
how is TB treated
Standard treatment for TB is minimum 6 months
2 months (initial phase) – standard quadruple therapy (isoniazid, rifampicin, pyrazinamide and ethambutol)
4 months (continuation phase) of I and R, standard dual therapy
TB treatment taken all together on empty stomach 1 hour before breakfast, compliance essential for cure
(CNS- 12 month treatment)
Latent: 3 months R or 6 months I
what are the main treatment side effects
P: hepatoxicity, joint pain and N&V
R: hepatoxicity, reddish colour to urine
I: hepatoxicity, fever, peripheral neuropathy and optic neuritis
E: peripheral neuropathy, optic neuropathy and gout
All: nausea and skin rashes
