Tuberculosis Flashcards
TB is the commonest cause of infectious disease-related mortality worldwide?
True or false?
True
What fraction of global population have latent TB infection?
1/4
Is the global incidence of TB rising or falling?
Falling
Is the drug resistance prevelance rising or falling?
Rising
What % of TB patients are HIV infected?
8% HIV positive
The global prevelance of multi-drug resistant TB is lower in previously treated cases.
True or false?
False
Globally proportion of new cases with MDR TB is 3.4% new cases and 18.4% of previously treated cases
Is TB rising or falling in the UK?
Falling - less than 500 cases a year
People born outside of UK account for ____% of cases
72%
What is the pathophysiology of TB?
- Airborne droplet spread
- Inhaled – deposited in terminal 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 disease
Complete the diagram
50%
What is the risk of developing active TB?
How is this risk different in HIV+ patients?
Risk of developing active TB 10-15% over lifetime in immunocompetent
HIV+: risk 10% per annum
What are the microscopic features of TB?
- 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 will you see in pathology in TB patients?
Granulomatous inflammation
- Rim of lymphocytes
- Fibroblasts
- Central infected macrophages (giant cells)
- Central necrosis – caseation
- Secretion of cytokines (IFNγ) – activate macrophages to kill bacteria
- AFBs (acid fast bacillus) in granulomas
What does this show?
Granulomatous inflammation
Who is at higher transmission risk?
- Close contacts of infectious cases (smear +)
- Contact with high risk groups:
- High incidence country
- Frequent travel to high incidence areas
•Immune deficiency:
- HIV
- Steroids
- Chemotherapy and biologics
- Nutritional deficiency (vit D),
- Diabetes
- End stage renal failure
•Lifestyle factors:
- Drug/alcohol misuse
- Homelessness/hostels/overcrowding
- Prison inmates
Genetic susceptibility (twin studies of gene polymorphisms)
What is anti-TNF-alpha treatment?
Medication for TB causing immunosurpression
What happens during primary TB?
–Bacilli overcome immune system soon after initial infection
What risk factors increase reactivation?
–Risk of reactivation increases with immunosuppression
HIV + risk 10% per year
HIV – risk 1%
What point of disease progression are the majority of TB cases in?
Latent period
What percentage of TB latent cases will reactivate?
2-23% cases – reactivation disease
How is active TB diagnosed?
- Identify the infected area
- Isolate the organism
- Obtain information regarding susceptibility to antibacterials
How is latent TB diagnosed?
Identify immune response to TB proteins or TB-specific antigens
What does the the tuberculin skin test (Mantoux) require?
–circulating memory T-lymphocytes
–ability to mount a delayed hypersensitivity reaction
What are the negatives of the tuberculin skin test (Mantoux)?
- Cross reactive with other Mycobacterial antigens so non-specific
- Maybe be 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
What are the pros and cons of using Interferon Gamma Release Assays to test for TB?
- More specific than Mantoux
- Correlates better with degree of exposure than Mantoux
- Does not differentiate between latent infection and disease
Name 2 Interferon Gamma Release Assays machines
T-Spot TB®
Quantiferon Gold®
What type of TB makes up the majority of cases (55%)?
Pulmonary TB
Which type of TB has infection risk and why?
Pulmonary TB
Cavitatory disease – more infectious
What are the clinical features of pulmonary TB?
Cough
Weight loss
Haemoptysis
Fever
Chest pain
Night sweats
How is pulmonary TB diagnosed?
–Chest imaging
–Sputum/BAL
What does this chest x-ray show?
Upper zone consolidation - white upper zone air opacification
Prominent hilar lymph node
Where is consolidation usually found on TB chest x-rays?
Upper zone
What does this chest x-ray show?
Bilateral consolidation
Where can extra-pulmonary disease from TB effect?
–Lymph nodes
–CNS
–Bone (Pott’s disease of the spine)
–Genitourinary system
–GI tract
–Disseminated/miliary
What makes extrapulmonary disease more likely?
- More common in non-UK born Asian origin
- Reactivation
What does this chest x-ray show?
Hilar Lymphadenopathy
What is this?
TB Lymphadenitis
What is TB Lymphadenitis?
•Often get worse on treatment
–Paradoxical reaction
- Can form sinus tracts with chronic discharge
- Cold abscess formation
What does this show?
Tuberculous Pleural Effusion
What are the clinical features 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 does this chest x-ray show?
Miliary TB
What other forms of TB are there?
•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 the eye
–Probably more common than we think
- Pericardial TB
- CNS TB
–TB meningitis
–TB arachnoiditis
–Tuberculoma
–(Spinal cord compression – extension of discitis)
–1% of all cases of TB
–6% of extrapulmonary TB in immunocompetent host
–More common in HIV coinfected patients
–Mortality 15-40% despite effective Rx (CDC)
How is TB controlled in the UK?
- Government global policy
- Early diagnosis AND treatment (even if negative cultures/smear)
- Optimal treatment and adherence (DOT/VOT/Section)
- Contact tracing
- PreventioN - BCG (Vaccination)
- Latent treatment programs. Prevent TB becoming active
What are the first line drugs for TB?
Standard treatment for TB is a minimum of 6 months:
2 months (initial phase) of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol. Known as standard quadruple therapy.
Followed by:
4 months (continuation phase) of Isoniazid and Rifampicin Known as standard dual therapy
TB treatment is taken all together on an empty stomach 1 hour before breakfast; compliance is essential for cure.
N.B. If there is central nervous system involvement the continuation phase of treatment is extended to 10 months making a 12 month full treatment plan.
What is first line treatment for latent TB?
Latent treatment : 3 months Rifampicin/Isoniazid 6 M isoniazid
What are the side effects caused by the TB drugs?
- Pyrazinamide: Hepatoxicity, joint pain, N&V
- Rifampicin: Hepatoxicity, reddish colour to the urine
- Isoniazid: Hepatoxicity ,fever, peripheral neuropathy and optic neuritis
- Ethambutol: peripheral neuropathy, optic neuropathy and gout
All: nausea and skin rashes
