TB Flashcards
What % of those exposed to TB will develop disease?
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
Diagnostic screening
3 weeks of cough +/- weight loss / night sweats
“official” best diagnostic tool?
- 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
1) Additional more practical diagnostic tools in acute TB
2) Diagnostic tools in screening programs
- 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
Best marker of response to treatment?
Best marker of ongoing infectivity?
1) Weight!
2) Active cough
TB drug treatment?
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
How long will cultures stay positive for?
Up to 60 days!
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
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
How do we definte Pulmonary tb (PTB) versus Extrapulmonary TB?
NB: pleural and hilar TB AREN’T pulmonary because outwith the parenchyma they confer much less transmission risk
Which drugs most commonly develop resistance?
Isoniazid and Rifampicin.
New TB 11% / 5 % resistance
Previously treated 30% / 25%
(Lima)
Paradoxical Reactions in TB
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
Adjunctive therapies in TB
Steroids?
Apprently better in pericardial TB and Meningeal TB but unclear benefit in those with HIV
MDTB : Multi drug resistant tb
Which drugs?
IZONIAZID AND RIFAMPICIN.
Isoniazid Resistant = 10% of all TB in london
Rifampicin : 95% of those with rifampicin resistance also have Isoniazid resistance
MDR TB treatment: duration and options
Shite options until V recently.
20-24 months.
8 months of daily injectibles
Mechanism of MTB resistance
Sporadic gene mutations, NOT plasmid transfer
How is the type of resistance diagnosed?
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
Defintions of resistance
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
Whats the method for regimen selection (do NOT MEMORISE ALL OF THIS)
What are the new MDRTB drugs with 6 month courses?
BPaL regimen – 90% relapse-free cure
Bedaquiline
Pretonamid
Linezolid
Prophylactic rx for families exposed to MDR TB?
Shite evidence.
Some prophylaxis. (??)
Key: aggessive surveillance and diagnosis
What’s different in Diabetes + TB
- More likely to contract it
- More likely to get sick with it
- More likely to die from it
- More likely to fail TB treatment
5 Increased recurrence rates
Screening in TB & DM
You should screen ALL new TB patients for DM. It is EXTREMELY common, often unknown or known and neglected
Management of DM in TB
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)
What adjuvant treatments should you give patients with DM + TB?
- Aspirin
- Pyridoxine
- Vit D
- Statins
- What is a “classic” TB CSF pattern?
- ) What are the caveats?
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.
CSF TB Diagnosis?
- Cell counts(^), protein (^^), Glu(vv)
- CSF Culture - roughly 60% accurate, higher volumes and multiple cultures help with dx
- CSF PCR (approx 70% accurate)
- Treatment of Meningeal TB?
- How does it differ?
- Steroids?
- RHZE as perpulmonary tb
- Rifampicin has piss poor CSF penetration, must give high dose IV to compensate.
- Might help, less so in HIV and v difficult to wean. Help in paradoxical IRIS
