Investigations and Treatment

Question 1

what investigations should be done?

Answer 1

radiology

microbiological diagnosis

• microscopy of sputum using ZN stain
• culture on selective media
• PCR: direct from sample 1st line
• tuberculin skin test and IFNg if latent

Question 2

what signs may be seen on a CXR?

Answer 2

upper lobe predominance

CXR consolidation with or without cavitation

fibrosis

calcification

Pleural effusion

widening of the mediastinum

Question 3

why does a special stain need to be used for TB?

Answer 3

mycobacterium tuberculosis is acid alcohol fast bacilli and has a thick waxy coat

Question 4

how is the stain obtained?

Answer 4

red dye (carbol - fuchsin) added to smear 
it is heated to allow dye to penetrate the waxy coat 

acid/alcohol is added

Waxy coat of mycobacteria retain dye even after exposure to acid and alcohol

Non-waxy bacteria don’t (i.e other bacteria)

Counterstain added and Mycobacteria appear red

Question 5

what is the advantages and disadvatages?

Answer 5

they are cheap(ish) and rapid

dis: no indication of species or sensitivity

Question 6

what do the cultures require?

Answer 6

selective media - lowenstein jensen

Question 7

what characteristics are identified on growth culture?

Answer 7

colour, speed, texture, biochemical characteristics

Question 8

what are the disadvantages?

Answer 8

it is very slow growing but on the other hand it is very sensitive

Question 9

what is a disadvantage of PCR?

Answer 9

it does not tell you if the organisms are alive or dead

Question 10

what may give you a false -ve result on mantoux/ tuberculin skin test?

Answer 10

if previous BCG

Question 11

if the mantoux is positive what test do you do?

Answer 11

IFN gamma

Question 12

what do interferon gamma release assays detect?

Answer 12

T cell secretion of IFN g following exposure to tb specific antigens

Question 13

what happens in response to re-exposure to TB specific antigens if the person has been infected with TB already

Answer 13

activated T cells within their extracted whole blood secrete quantifiable levels of IFNg

Question 14

how is a diagnosis made for active TB?

Answer 14

if the CXR suggests TB, take sputum samples

(≥3, with one early morning sample, before starting treatment if possible) and send for MC&S for AFB (acid-fast bacilli resist acid on Ziehl–Neelsen (ZN) staining). If spontaneously produced sputum cannot be obtained, bronchoscopy and lavage may be needed.

Question 15

how is adiagnosis made for active non-resp TB?

Answer 15

Try hard to get samples: sputum, pleura & pleural flu- id, urine, pus, ascites, peritoneum, bone marrow or CSF. Send surgical samples for culture. Microbiologist should routinely do TB culture on these, even if it is not re- quested. All patients with non-respiratory TB should have a CXR to find coexisting respiratory TB. Incubate cultures for up to 12wks on Lowenstein–Jensen medium.

Question 16

what is the histological hallmark of TB?

Answer 16

presence fo caseating granulomata

Question 17

Immunological evidence of TB?

Answer 17

may be helpful: Tuberculin skin test: TB antigen is injected intradermally and the cell-mediated response at 48–72h is recorded. A +ve test indicates immunity. It may also indicate previous exposure or BCG. A strong +ve test probably means active TB. False–ve tests occur in immunosuppression (miliary TB, sarcoid, AIDS, lymphoma). Quantiferon TB Gold® and T-spot-TB® tests measure the delayed hypersensitivity reaction developed after contact with M. tu- berculosis; they use specific, complex M. tuberculosis antigens and are better than older Mantoux tests, which rely on reactions to serial dilutions of TB antigen.1

Question 18

what should be done if the histological and clinical picture indicate TB ?

Answer 18

start treatment without waiting for culture results and continue even if these are negative

contact tracing and public health notification are essential

Question 19

what should be done before treatment starts ?

Answer 19

stress importance of compliance/concordance (helps the patient & pre- vents resistance). Test colour vision (Ishihara chart) and acuity before and during treatment as ethambutol may cause (reversible) ocular toxicity.

Check FBC, U&E, LFT.

If pre- creatinine clearance=10–50mL/min: Rifampicin: dose by 50%. Ethambutol: monitor U&E; avoid if possible. No dose change for ethionamide or isoniazid.

Question 20

what is the treatment for the initial phase?

Answer 20

8 weeks on 4 drugs
need directly observed therapy

rifampicin, isoniazid, pyrazinamide, ethambutamol

Question 21

what are the side effects?

Answer 21

Rifampicin SE: discolouration of urine/tears, hepatitis, flu-like illness, inactivation of the pill, decreased platelets

Isoniazid SE: decreased WCC, stop if neuropathy and give pyridoxine, agranulocytosis, allergic reaction

Pyrazinamide SE: hepatotoxicity (rare), reduced renal excretion of urate, gout

Ethambutol SE: colorblindness developing into blindness

Question 22

what test is sensitive to rifampicin resistance

Answer 22

PCR

Question 23

what happens in the continuation phase?

Answer 23

(16wks on 2 drugs) rifampicin and isoniazid at same doses

consider steroids if meningeal or pericardial TB