Respiratory Tract Infections: Tuberculosis

Question 1

Bacteria that causes Tuberculosis

Answer 1

most commonly: myobacterium tuberculosis

m. bovis, m.africanum, m.microti

Question 2

Characteristics of M.tuberculosis

Answer 2

obligate aerobes - grow in tissues with a high O2 content
facultative intracellular pathogens, usually affecting mononuclear phagocytes
slow-growing
hydrophobic - high lipid content in the cell wall, less permeable to usual bacterial stains
acid-fast bacilli - once stained, resist decolourisation

Question 3

Transmission and early response to TB

Answer 3

spead by airborne droplet nuclei which can remain airborne after coughing for several hours
droplets inhaled lodge into alveoli and is taken up by alveolar macrophages
slow replication and spread via lymphatic system to hilar lymph nodes

Question 4

What happens around 2-8 weeks after infection?

Answer 4

in most individuals: cell-mediated immunity develops, positive tuberculin skin test
activated T cells and macrophages form granulomas that limit further replicaiton and spread
bacterial cells remain in centre of necrotic ‘caseating’ granulomas
most individuals are asymptomatic and never develop active disease

Question 5

Main clinical features of TB

Answer 5

systematic - fever, weight loss, night sweats
respiratory - cough, SoB, haemoptasis, chest pain
pulmonary disease
CNS - TB meningitis, tuberculomas

Question 6

Other clinical features

Answer 6

infection of:
skin/soft tissue - cervical lymphadenitis (firm, discrete, painless lymph nodes)
bone and joints - Pott’s disease
genitourinary tract - prostatitis, orchitis or renal lesions
disseminated disease - many organs involved simultaneously

Question 7

Methods for diagnosing TB

Answer 7

samples
ziehl-neelsen stain
microscopy
culture: slow and rapid
antibiotic sensitivity tests
genomic tests

Question 8

Samples

Answer 8

sputum, bronchoalveolar lavage, pus/tissue, urine, CSF

Question 9

Ziehl-Neelson stain

Answer 9

rapid, cheap, simple

moderate specificity and sensitivity

Question 10

Microscopy

Answer 10

auramine staining (UV microscopy), sensitive but not highly specific
ZN stain may be used to confirm auramine positive samples

Question 11

Slow culture

Answer 11

2-8 weeks
reqquires specialised media
culture performed in category 3 facility
beige, dry, rough colonies
cauliflower or verrucose colonies
M.kansasii - chromogenic when grown in light

Question 12

Rapid culture

Answer 12

1-2 weeks
liquid media eg. Kirchner’s liquid medium
automated system - Mycobacteria Growth Indicator Tube

Question 13

Antibiotic sensitivity tests

Answer 13

agents: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol
important to detect resistance, especially multi-drug resistant
tuberculosis = XDR, resistat to R, I and any member of quinolone and at least one second line anti-TB agent (kanamycin, capreomycin or amikacin)

Question 14

Genomic test for mycobacteria

Answer 14

PCR
DNA probes allows speciation
rapid detection of Rifampicin resistance

Question 15

Standard treatment of pulmonary TB

Answer 15

initial: 2 months of 4 drugs - rifampicin, isoniazid, pyrazinamide, ethambutol
continuation: 4 months of rifampicin and isoniazid
if resistance suspected: 5 drugs may be used initially, longer courses required with second line agents

Question 16

What happens if early diagnosis and treatment is made?

Answer 16

‘open’ (ZN stain +ve) pulmonary diseas usually made non-infectious after 2 weeks of effective therapy
contact tracing and detection of latent infection:
tuberculin skin test, chest radiography, in vitro interferon-gamma release tests
contacts treated if evidence of infection

Question 17

Prevention of TB

Answer 17

vaccination
BCG - live attenuated m.bovis strain
protecting children against severe disease (meningitis and miliary)