TB

Question 1

What % of those exposed to TB will develop disease?

Answer 1

90% Latent 10% active. - HIV increases latent > active by 10% per year. - Childhood and immunosuppresion change not just the frequency of TB but the type. Extrapulmonary etc more common

Question 2

Diagnostic screening

Answer 2

3 weeks of cough +/- weight loss / night sweats

Question 3

“official” best diagnostic tool?

Answer 3

• Gene Xpert MTB / RIF
• Prohibitively expensive

Presumptive treatment when smears are negative has massively reduced the efficacy roll-outs in eg) SA compared with other dx tools

Question 4

1) Additional more practical diagnostic tools in acute TB
2) Diagnostic tools in screening programs

Answer 4

• Light microscopy MAINSTAY, Zeihl-Neilson staining
• LED microscopy (increases yeild)
• Cultures: 6-8 weeks, delaying dx and treatment
• Front Loading: taking two samples at clinic 1hr apart instead of three over three occasions including an “early morning” (patients forget and access is poorer)

2) Tuberculin skin tests ( Heaf / Mantoux) 5 / 10 / 15mm +ve in various populations. Shite. Also +ve in those who have had BCG.
3) Quantiferon Gold - gold standard blood assay for TB. QuantiFERON-TB Gold In-Tube uses an ELISA format to detect the whole blood production of interferon γ (produced in response to TB exposure) Cannot distinguish latent from active but does distinguish those from cured

Question 5

Best marker of response to treatment?

Best marker of ongoing infectivity?

Answer 5

1) Weight!
2) Active cough

Question 6

TB drug treatment?

Answer 6

Isonicotinic acid Hydrazide

H Isoniazid

R Rifampicin

Z PyraZinamide

E Ethambutol

Ideally treatment is directly observed
daily for intensive phase

Can be 3x/week in continuation phase

2HRZE/4HR or 2HRZE/4(HR)3

Question 7

How long will cultures stay positive for?

Answer 7

Up to 60 days!

Question 8

Definitions which must be allocated to all TB patients

1) Cured
2) Treatment Completed
3) Died
4) Lost to Follow-up
5) Not evaluated
6) Treatment success

Answer 8

outcome

1) Cured

+ve smear at start, 2x separate negatives by end of full course

2) Treatment Completed

Finished course, no proof negative sputum

3) Dead

for any reason

4) Lost-to follow up

Didn’t start OR didn’t complete / interrupted

5) not evaulated

nobody recorded an outcome

6) Treatment success

Cured + treatment completed are considered a “treatment success” by the WHO

Question 9

How do we definte Pulmonary tb (PTB) versus Extrapulmonary TB?

Answer 9

NB: pleural and hilar TB AREN’T pulmonary because outwith the parenchyma they confer much less transmission risk

Question 10

Which drugs most commonly develop resistance?

Answer 10

Isoniazid and Rifampicin.

New TB 11% / 5 % resistance

Previously treated 30% / 25%

(Lima)

Question 11

Paradoxical Reactions in TB

Answer 11

Paradoxical reaction (PR) in tuberculosis (TB):

” clinical or radiological worsening of pre-existing tuberculous lesions or the development of new lesions, in patients receiving anti-tuberculous medication who initially improved on treatment.

Self limiting

potential to cause serious morbidity and, on occasion, death

most likely that PR is due to an abnormal immune response or reconstitution of the immune system. For this reason PR is more commonly seen in HIV co-infected individuals

Question 12

Adjunctive therapies in TB

Answer 12

Steroids?

Apprently better in pericardial TB and Meningeal TB but unclear benefit in those with HIV

Question 13

MDTB : Multi drug resistant tb

Which drugs?

Answer 13

IZONIAZID AND RIFAMPICIN.

Isoniazid Resistant = 10% of all TB in london

Rifampicin : 95% of those with rifampicin resistance also have Isoniazid resistance

Question 14

MDR TB treatment: duration and options

Answer 14

Shite options until V recently.

20-24 months.

8 months of daily injectibles

Question 15

Mechanism of MTB resistance

Answer 15

Sporadic gene mutations, NOT plasmid transfer

Question 16

How is the type of resistance diagnosed?

Answer 16

GENOTYPIC (Genome sequencing)

Xpert MTB/RIF and the next-generation assay Xpert MTB/RIFare fully automated nucleic acid amplification assays that detect MTB and mutations affecting the rifampicin resistance determining region

Line probe assays (LPAs) are based on the PCR amplification of specific fragments of the MTB genome, followed by reverse hybridisation of the PCR products to oligonucleotide probes immobilised on nitrocellulose strips. Resistance is detected by lack of binding to wild type probes and also by binding to probes targeting specific mutations.

PHENOTYPIC

Phenotypic DST determines if a strain is resistant to an anti-TB drug by evaluating the growth (or metabolic activity) in the presence of the drug.

The reliability of DST varies from one drug to another

Question 17

Defintions of resistance

Answer 17

Primary: Infected with a resistant form

Secondary: developed during treatment

MDR: multi drug (Rif and Iso)

XTB: EXtensively drug resistant tb ) MTR + second line resistance

Question 18

Whats the method for regimen selection (do NOT MEMORISE ALL OF THIS)

Answer 18

Question 19

What are the new MDRTB drugs with 6 month courses?

Answer 19

BPaL regimen – 90% relapse-free cure

Bedaquiline

Pretonamid

Linezolid

Question 20

Prophylactic rx for families exposed to MDR TB?

Answer 20

Shite evidence.

Some prophylaxis. (??)
Key: aggessive surveillance and diagnosis

Question 21

What’s different in Diabetes + TB

Answer 21

1. More likely to contract it
2. More likely to get sick with it
3. More likely to die from it
4. More likely to fail TB treatment

5 Increased recurrence rates

Question 22

Screening in TB & DM

Answer 22

You should screen ALL new TB patients for DM. It is EXTREMELY common, often unknown or known and neglected

Question 23

Management of DM in TB

Answer 23

If unknown and

a) HBA1c <8% watch and wait
b) HBA1c >/= 8 <10 start 500mg metformin od and get help if unimproved after increasing to 1g after 2 weeks
c) >10% start 1g metformin od and get help starting insulin

LIFESTYLE: Smoking, BP, Renal function etc.
Target HBA1c in TB is >8 (normally <7)

Question 24

What adjuvant treatments should you give patients with DM + TB?

Answer 24

• Aspirin
• Pyridoxine
• Vit D
• Statins

Question 25

1. What is a “classic” TB CSF pattern?
2. ) What are the caveats?

Answer 25

a. ) VERY high protein
b. ) LOW glucose
c. ) WCC (very) raised, lymphocyte predominance but can be polymorphonulear in first ten days
d) V high opening pressures noted.
2. ) a) THIS IS HUGELY VARIABLE. Not having this profile by no means excludes the diagnosis!
b) HIV is particularly difficult to diagnose as these results are even less commonly seen.

Question 26

CSF TB Diagnosis?

Answer 26

1. Cell counts(^), protein (^^), Glu(vv)
2. CSF Culture - roughly 60% accurate, higher volumes and multiple cultures help with dx
3. CSF PCR (approx 70% accurate)

Question 27

1. Treatment of Meningeal TB?
2. How does it differ?
3. Steroids?

Answer 27

1. RHZE as perpulmonary tb
2. Rifampicin has piss poor CSF penetration, must give high dose IV to compensate.
3. Might help, less so in HIV and v difficult to wean. Help in paradoxical IRIS