Tuberculosis Flashcards
What bacterium causes TB infection?
- tubercule bacilli
- mycobacterium tuberculosis (MTB) in humans
- mycobacterium bovis for cows
- non-tuberculous (atypical) mycobacterium does NOT cause tb but causes pulmonary diseases that resemble TB
What is the most common cause of infectious disease related mortality worldwide?
TB
how many new cases of TB a year?
9.6 million
What % of TB cases are HIV positive?
8%
increasing drug resistance in TB
1/2 million
What is the definition of high incidence of casees?
40/100,000
What % of TB cases in those born outside the UK?
72%
Who is at risk of TB?
- Deprivation: homeless, malnutrition, overcrowding and vitamin D deficiency
- alcohol abuse
- prisons
- immunocompromised: diabetes mellitus, HIV, steroid use
- elderly
- contact with high risk groups (travel to areas of high incidence)
How is TB transmitted?
- spread by droplets from cough by people with pulmonary TB
- bacillus inhaled into the lung
- macrophages ingest bacillus and these replicate within the endosome
- can then spread to other parts of the body
- 80% of cases affect the lungs
Where/how can Tb spread to within the body?
- haematogenous (bloodstream)
- lymphatics to hilar lymph nodes and other lymph nodes
- direct extension (eg pericardium)
Clinical presentation of pulmonary TB?
- productive cough: not improving with standard antibiotics
- haemoptysis
- chest pain
- fever
- night sweats
- fatigue
- weight loss
Could your patient have TB abbreviation?
- THINK TB
- troublesome cough (3 weeks or longer)
- Hemoptysis
- Involuntary weight loss
- Night sweats and fevers
- Known exposure to TB
- Tiredness
- Breathlessness
TB initial hypersensitivity
acute presentation is similar to acute sarcoidosis
erythema nodosum (redness on arms and legs)
phlyctenular conjunctivitis (red spots around eyes)
Pathogenesis of TB
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Progression of TB
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Which is a latent infection of TB, cavitary TB, miliary TB?
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Pulmonary MTB
- majority of cases (55%)
- infection risk
- cavitary disease - more infections - Ghon Focus in lungs:
- granuloma, area of central caseation and
fibrosis - calcified with few dormant bacteria
- granuloma, area of central caseation and
MTB bacillus: features:
- aerobic or anaerobic?
- how often division occurs?
- organelle features
- gram positive or gram negative?
- aerobic bacillus (needs O2 to live)
- divides every 16-20 hours (slow)
- cell wall, but lacks a phospholipid outer membrane
- weakly gram positive
- retains stans after treatment with acids = acid fast bacillus
Microbiological diagnosis of MTB
- sputum/BAL
- Ziehl-Neelsen stain = bright red bacilli on blue background
- TB cultures 6-8 weeks:
- confirm diagnosis
- drug sensitivities - Nucleic acid amplification
- identify MTB complex
- distinguish from non-tuberculous
infection - PCR:
- mycobacterial DNA
- pleural fluid/CSF/urine
Which stain used on this Tb?
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Ziehl-neelson
Histology of MTB
- granulomatous inflammation: rim of lymphocytes, fibroblasts, central infecteed macrophages
- central necrosis: caseation
- secretion of cytokines (IFN - gamma) which activates macrophages to kill bacteria
- AFBs in granulomas
Mantoux/Tuberculin Test
- 10 units (0.1ml) of Purified Protein Derivative (PPD) is injected intradermally and the size of the induration is measured after 48-72 hours
- the cutaneous immune response is measured
- response affected by the BCG vaccination status of the individual as those who have has the BCG vaccine will show a mild response even when they are not infected with MTB
- a strong positive tuberculin response (Grade 3 or 4) should be investigated further with clinical assessment, chest x-ray and samples for culture as appropriate
- > 5mm is positive
- > 15mm is strongly positive
The mantoux test requires
circulating memory T lymphocyte ability to mount a delayed hypersensitivity reaction
Is the mantoux test specific?
No
cross reactive with other mycobacterial antigens so non-specific
When can the mantoux test be falsely negative?
- in severely ill or immunocompromised individuals
IGRA/T spot test
- the interferon gamma release assay is an in-vitro test that measures T-cell activation by MTB antigens
- blood taken must be analysed within a few hours
- The Quantiferon Gold assay and the T-spot TB assay are available in the UK
If a patient has a positive IGRA/T-spot test, do they have TB?
- the results of these investigations must be interpreted carefully together will all the other information availble as a positive test on its own does not necessarily mean the patient has TB
Which is more specific; the mantoux test or the IGRA (interferon gamma release assay)?
Interferon Gamma Release Assay (IGRA)
Does the IGRA (interferon gamma release assay) correlate better with degree of exposure to TB than Mantoux?
Yes
Does the IGRA (interferon gamma release assay) differentiate between latent infection and disease?
No
Diagnosis of TB:
- Hx of contact with smear positive Tb
- signs and symptoms suggestive of TB
- abnormal chest x ray
- positive tuberculin/ positive T spot test
- culture of mycobacterium TB
- always consider a HIV test
CXR
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CXR
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CXR
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TB Disease progression:
- primary TB (active):
- 1-5% cases
- bacilli overcome immune system soon
after the initial infection - latent infection:
- majority of cases (immune memory of
exposure to TB)
- 2-23% cases = reactivation of disease
- risk of reactivation increases with
immunosuppression
What % of patients never become ill with TB?
90% (unless they are HIV positive)
What % of patients will progress to symptomatic and infectious TB (active TB)?
10%
When are the chances of progressing to active TB the greatest?
- within 1-2 years of infection and decrease steadily after this
Active TB occurs by
reactivation of latent Tb or re-infection
Latent TB vs Active TB:
- bacilli in/number?
- symptoms?
- sputum smear and culture positive or
negative?
- chest x ray normal or abnormal?
- Mantoux tuberculin test positive or negative
- IGRA test positive or negative
- infectious or not infectious?
- tuberculin skin test reaction?
- T spot blood test?
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Differential diagnoses for TB:
- bilateral hilar lymphadenopathy
- clinical symptoms (B symptoms):
- sarcoidosis
- lymphoma - B symptoms: fever, drenching night sweats, weight loss
Extrapulmonary MTB is more common in which ethnicity in the UK?
- more common in non-UK born of asian origin
Extrapulmonary MTB is generally a first infection or reactivation?
Reactivation of latent infection
Extrapulmonary MTB: sites:
- lymph nodes
- CNS
- Bone (Pott’s disease of the spine)
- Genitourinary system
- GI tract
- disseminated = miliary TB
TB lymphadenitis
- often gets worse on treatment
- paradoxical reaction
- can form sinus tracts with chronic discharge
- cold abscess formation
TB lymphadenitis
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Disseminated Miliary TB symptoms and percentage of patients that experience this
- fevers, sweats, weight loss and malaise very common
- respiratory symptoms in majority
- GI or CNS Symptoms in 20%:
- abdominal pain, diarrhoea, abnormal
LFTs
- hepatomelagy in 50%
- headache or confusion; altered mental
state in 20%
miliary TB CXR
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miliary TB CT
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Extrapulmonary TB can affect (5):
- pericardium
- skeleton
- genitourinary
- eye
- gastrointestinal
Tuberculous meningitis can affect
the central nervous system
TB can also be found in cerebral spinal fluid.
True or False?
True
Extrapulmonary TB is most commonly found in those who are
co-infected with HIV
Mortality from extrapulmonary TB
15-40%
Historical treatment of MTB:
- sanitorium
- surgical treatments:
- thoracoplasty
- rib resection
- lobectomy
- pneumonectomy
- artificial pneumothorax
- plombage - streptomycin (1950s)
Standard Quadruple Therapy for TB: First Line Drugs: Initial phase:
(how many months treatment?)
- 2 months
- isoniazid
- rifampicin
- pyrazinamide
- ethambutol
Standard Quadruple Therapy TB: First Line Drugs: Continuous Phase:
(how many months treatment?)
- 4 months
- isoniazid
- rifampicin
First Line Drugs: TB meningitis: how long?
- TB meningitis
- affects central nervous system
- 12 months
Side effects of drug treatment for MTB (4)(1):
- Pyrazinamide: Hepatoxicity, joint pain, N&V
- Rifampicin: Hepatoxicity, reddish colour to
the urine, tears - Isoniazid: Hepatoxicity ,fever, peripheral
neuropathy and optic neuritis - Ethambutol: peripheral neuropathy, optic
neuropathy and gout - All: nausea and skin rashes
What does MTRB stand for?
- multi-drug resistant TB
When does MDRTB occur?
- failure of treatment with first line drugs: lack of compliance
MDRTB mainly occurs in which conntinents?
majority from africa or indian sub-continent
Why has rated of MDRTB doubled in the UK?
Immigration
Patients with MDRTB must be —— as they pose a huge public health risk
isolated
What % of all TB deaths are caused by MDRTB worldwide?
10%
To treat MDRTB
a prolonged course of second line drugs for upto 24 months may be required
third line drugs sometimes required
Why should patients complete treatment?
to reduce the risk of:
- drug resistant TB
- onward transmission
- relapse of disease
- dying
What % of TB patients complete a six month treatment?
83%
TB is curable with
antibiotics
Latent TB treatment
- 3 months of rifampicin and isoniazid
- 6 months of izoniad
Screening for latent TB:
- close contacts of index case
- pre-employment for healthcare workers
- some new entrant to UK “looked after children”
- those who are going to have biologics treatment (immunosuppressive): Rheumatoid arthirits, Crohn’s disease, Psoriasis
Prevention of spread of TB:
- BCG vaccination
- contract tracing
- directly observed therapy (DOT)
- problems with TB treatment: stigma
BCG vaccination
- the only vaccine available against TB
- 70-80% protection against severe and disseminated TB in children, but its protective efficacy against adulthood, pulmonary TB is limited
- offer to infants aged 0-4 weeks
- if born in high incidence area
- if parent or grandparent born in high incident area
- if family history of TB in the last 5 years
- reduces risk of TB meningitis and miliary /tb
What is the cornerstone of TB control?
contact tracing
Index case?
the patient with TB is identified
Contact Tracing:
- close household contacts
- if any of these are positive, then extend: other family members, school, work etc
Contact tracing for TB: screening of contacts:
- chest x ray
- IGRA
Contact Tracing for TB: screened contacts show chest x ray normal and IGRA positive, what is the next course of action?
- latent TB treatment
Contact Tracing for TB: screened contacts show chest x ray abnormal, symptoms and positive IGRA, what is the next course of action?
6 month TB treatment
Directly Observed Therapy (DOT)
- used in treatment of Tb
- to ensure compliance
- adults who need supervision:
- alcoholics
- chaotic lifestyle
- previous TB
- mental health problems - done in hospital/via videa/local pharmacy
- recommendation daily tablets
- if not possible then 3x a week
- lack of compliance results in a poor outcome, development of multi-drug resistant TB
Monitoring of TB treatment
- blood tests (liver function) at baseline
- Ishihara test to check if you are going colour blind
- colour vision
- monitor liver function tests
34 year old male cleaner born in Zimbabwe, in UK last 10 years. Recent productive cough last few months with a 2 day history of haemoptysis, decreased appetite and weight loss 10 kg over 6 months . No history of travel in last year. Had BCG ( TB vaccine ) as a child. Smoker 4-5 /day.
On examination: thin, moist cough, afebrile, not clubbed, no lymphadenopathy , respiratory rate 18 /min normal, chest expansion and percussion normal, crackles right upper zone, O2 saturation 95%, pulse normal and heart rate 90/min heart sounds normal, no organomegaly.
What exams to be ordered?
CXR
Sputum:
IGRA
2 year old child contact traced as contact of aunt living in household diagnosed with smear positive, fully sensitive MTB
Initially asymptomatic, Mantoux negative, T Spot negative with index case on Rx for 2 weeks
Missed BCG child of Nepalese parents
what happens next?
repeat mantoux test in 6 weeks
2 year old child contact traced as contact of aunt living in household diagnosed with smear positive, fully sensitive MTB
Initially asymptomatic, Mantoux negative, T Spot negative with index case on Rx for 2 weeks
Missed BCG child of Nepalese parents
Repeat at 6 weeks Mantoux positive 10 mm
What examinations ordered?
T spot
Full blood count
chest x ray
2 year old child contact traced as contact of aunt living in household diagnosed with smear positive, fully sensitive MTB
Initially asymptomatic, Mantoux negative, T Spot negative with index case on Rx for 2 weeks
Missed BCG child of Nepalese parents
Repeat at 6 weeks Mantoux positive 10 mm
T Spot positive; Fbc ESR LFTs all negative ;CXR normal
What diagnosis?
latent TB
2 year old child contact traced as contact of aunt living in household diagnosed with smear positive, fully sensitive MTB
Initially asymptomatic, Mantoux negative, T Spot negative with index case on Rx for 2 weeks
Missed BCG child of Nepalese parents
Repeat at 6 weeks Mantoux positive 10 mm
T Spot positive; Fbc ESR LFTs all negative ;CXR normal = latent TB
what treatment prescribed?
- treated 3 months anti-TB drugs
- isoniazia
- rifampicin
- vitamin supplement pyridoxine
What differentiates between Active and Latent TB?
1 = AFB in sputum
2 = Age of patient
3 = Positive Mantoux test
4 = Positive IGRA test
5 = Previous BCG vaccination
1
A 27 year old doctor arrives in the UK to work for the NHS. He is very well. His pre-employment health check reveals a normal CXR and a positive IGRA test. What treatment, if any, does he require?
1 = BCG vaccination
2 = 3 months of quadruple therapy
3 = 3 months of Isoniazid and Rifampicin
4 = 6 months of quadruple therapy
5 = No treatment needed
3
Which of these is a risk factor for developing active TB?
1 = living in low altitude
2 = male gender
3 = malnutrition
4 = obesity
5 = smoking
3
