Tuberculosis Flashcards
epidemiology of TB - worldwide
incidence rate worldwide is falling 2%/yr
number 1 killer of comunicable disease (> HIV and malaria combined)
2/3 of all cases in 8 countries: India, China, Indonesia, Philippenes, Pakistan, Nigeria, Bangladesh, South Africa
30 high TB burden countries account for 87% of all the world’s cases
~2bln people infected worldwide
epidemiology of TB - national
major problem in London - immigration from high incidence areas
39% of TB cases in UK are in London
2/3 cases born abroad
clusters in cities
vulnerable groups in the UK
those from high prevalence countries
70% are non-UK born, most aged 15-44
HIV +ve, immunosuppressed
elderly, neonates, diabetics
homeless, alcoholics, IDUs, mental health problems, prison - 1/10 of all cases
mycobacteria
numerous species, ubiquitous in soil, water
which species of mycobacteria cause human disease
Tuberculosis (M. TUBERCULOSIS, M. africanum, M. bovis (bovine TB, BCG strain)
non-tuberculosis mycobacteria, NTM infections/atypical mycobacteria
Leprosy (M. leprae)
why does TB take a long time to treat
non-motile bacillus, very slow growing
disease is slow, treatment is long
cultures take a long time to grow to recieve results back
is TB aerobic or anaerobic
aerobic - predilection for apices of lungs where there is a higher oxygen conc
describe the cell wall of mycobacteria
uniquely has a very thick fatty cell wall - have to treat with many antibiotics for a long period of time
resistant to acids, alkalis and detergents
resistent to neutrophil and macrophage destruction
acid and alcohol fast bacilli - Ziehl Nielson stain
are all AAFBs TB
NO
can’t differentiate mycobacteria from TB on initial stain
how is TB spread
airbone - pulm and laryngeal TB
someone with TB bacteria in their lungs coughs/sneezes/yells
TB bacteria attached to aerosol droplets which remain suspended in air for many hours esp w/ poor air circulation
someone else breathe in the bacteria
usually requires prolonged closed contact
what is TB NOT spread by
shaking hands sharing food touching surfaces sharing toothbrushes kissing
what are outdoors mycobacteria eliminated by
UV radiation
dilution
what is the exeption to the spread of TB
M. bovis
can be spread by the consumption of unpasteurised infected cow milk
why do HIV patients respond worse to TB
Their T cell response is impacted
what does the T cell immune response cause
tissue destruciton
immunopathology of TB
activated macrophages –> epithelioid cells –> Langhan’s giant cells
accumulation of macrophages, epithelioid and Langhan’s cells –> Granuloma
central caseating necrosis which may later calcify
is the Th1 cell mediated response good or bad
eliminated/reduces number of invading mycobacteria
tissue destruction is a consequence of activation of macrophages
what affects the outcome of TB infection
infection - virulence, number
susceptibility - genetics, nutrition, age, immunosuppression
primary TB infection
no preceding exposure or immunity
mycobacteria spread via lymphatics to draining hilar lymph nodes
usually no symptoms
can be fever, malaise, erythema nodosum, rarely chest signs
associated with development of immunity to tuberculoprotein
what happens in the majority of 1y TB infections
> 85%
initial lesion and local lymph node (1y complex)
heals w/ or w/o scar
may calcify (Ghon focus and complex)
what are the 3 different outcomes of 1y TB infections
progressive disease
contained latent
cleared cured
tuberculous bronchopneumonia
small number of 1y infections (1%) progress
1y focus continues to enlarge - cavitation
enlarged hilar lymph compress bronchi, lobar collapse
enlarged lymph node discharges into bronchus
poor prognosis
miliary TB
occurs in 1-3% of 1y TB infections
hematogenous spread of bacteria to multiple organs
fine mottling on X ray, widespread small granulomata
CNS TB in 10-30%
post-1y disease
most common outcome
only in humans
typically 1-5yrs after exposure
2 main theories:
1. TB bacteria enter dormant stage with low/no replication over prolonged time period
2. balanced state of replication and destruction by immune mechanisms
clinical presentation of TB
cough - present with pulmonary TB
fever
sweats (mainly night)
weight loss
all 3 symptoms
what % of patients have extra-pulmonary TB
50
in what % of patients are CRP and ESR normal
CRP - 15%
ESR - 21%
in what % of pts are symptoms absent
fever - 37%
sweats - 39%
weight loss - 38%
all 3 absent in 25%
appearance of pulmonary TB on CXR
classical: apices, soft ‘fluffy/nodular’ upper zone, cavitation in 10-30%
lymphadenopathy rare
normal CXR in 13% of definitive pulm TB (22% in HIV)
when to consider CT
normal CXR but clinical suspicion miliary TB cavitation and other differential lymphadenopathy, alternative diagnosis targets for BAL
appearance of 1y TB on CXR
mediastinal lymphadenopathy (mainly unilateral, 15% bilateral)
pleural effusion
miliary (hematogenous spread, 1-3%)
pnuemonic lesion w/ enlarged hilar nodes - consider 1y TB
(no swollen lymph nodes in pneumonia)
how to sample the bacteria
sputum: 3 samples, 8-24hrs gap, at least 1 early morning sample
induced sputum if they can’t cough
bronchoscopy with BAL
endobronchial US with biopsy
lumbar puncture (CNS TB)
urine (urogenital TB)
aspirate/biopsy from tissue (lymph node, bone, joint, brain, abscess)
mantous/IGRA are NOT routinely used in diagnosing active TB
what are the 4 drugs used to treat TB
isoniazid (H)
pyrazinamide (Z)
rifampicin (R)
ethambutol (E)
rules of TB treatment
multiple drug therapy is essential - single agent treatment leads to drug resistant organisms within 14 days
therapy must continue for at least 6 months
legal requirement to notify all cases
test for HIV, hep B and C (risk of hepatotoxicity)
standard TB treatment
2 mths R/H/Z/E + 4 R/H
6 mths duration minimum
other drugs used in TB treatment
pyridoxine (vit b6) with isoniazid to reduce risk of neuropathy
steroids (CNS, miliar, pericardial)
vit D substitute?
when is TB treatment >6mths
7-9mths - monoresistance
12 mths - CNS TB, h monoresistance extensive disease
9-12-18-20 mths - MDR RR TB
treatment in the brain/drug resistance takes longer
how long does it take to kill the MTB
90% MTB dead in 2 days when using isoniazid
99% MTB dead in 14days when also using rifampicin
side effects of rifampicin
orange urine/tears/lenses - indicates tablet is being absorbed
induces liver enzymes, prednisolone, anticonvulsants
all hormonal contraceptive methods ineffective
hepatititis
rash
side effects of isoniazid
hepatitis
peripheral neuropathy - pyridoxine B6 to prevent this
rash
side effects of pyrazinamide
hepatitis
gout
rash
side effects of ethambutol
optic neuropathy
rash
BCG vaccination
given selectively to risk groups
neonates or unvaccinated children under 5, whose parent/grandparents were born in a country with an annual incidence of TB of 40/100 000 or greater
unimmunised contacts of cases
unimmunised high risk employees
latent TB screening
screen: contacts of people with active pulmonary/laryngeal TB who are <65 (hepatotoxitity increases with age), new entrants from high endemic areas, pre-biologics (TNF-alpha inhibitors), outbreaks
asymptomatic with normal CXR and norma examination AND +ve mantous/IGRA test
treatment of LTBI
always rule out actie TB rifampicin and isoniaid for 3 mths OR isoniazid only for 6mths OR rifampicin only for 6mths OR rifapentine and isoniazide once weekly for 12 weeks (underserved population)
