Tuberculosis: microbiology of diagnosis and management Flashcards
What is tuberculosis?
infection caused by mycobacterium tuberculosis
- affects any part of the body
- curable following 6 months therapy
contagious
- if affecting the lungs - pulmonary
- transmission via airborne particles
What happens if you inhale TB organisms?
granuloma formation
- macrophages engulf TB (epithelioid histiocytes)
- fuse to form giant cells with central necrosis
- “ghon focus” = lung
- “ghon complex” = + lymph nodes
What is the difference between primary disease and latent infection?
primary disease = organisms continue to divide, poor immune systems
Latent infection = organism not dividing, sleeping/dormant TB
What does it mean by secondary TB?
latent TB reactivates
- organism wakes up and starts dividing
- decline in health and immunity
What are the latent TB screening methods?
Tuberculin skin test
Interferon gamma release assay (IGRA) - quantiferon and T-spot
If they react = do they have TB? if negative do they need BCG?
What is TB prevalence associated with?
poor sanitation
overcrowding
unpasteurized milk
What are the symptoms of TB?
Long history (slow growing organisms)
- fever => infection
- weight loss and fatigue => prolonged inflammatory state
- night sweats => TNF alpha
consumption
cough, haemoptysis, abdominal pain, headache, back pain
What are the differential diagnoses for the symptoms of TB?
fever, weight loss, night sweats
- cancer (lymphoma, leukaemia, lung, bowel, metastasis)
- infection (bacterial, fungal)
granulomas
- sarcoidosis
- crohn’s disease
- granulomatosis with polyangitis
- infection (fungal, parasitic)
What is the treatment for TB?
RIPE
- rifampicin - 6 months
- izoniazid - 6 months
- pyrazinamide - 2 months
- ethambutol - 2 months
What is the main side effect of rifampicin?
bright orange urine
What are the treatments for drug resistant TB?
Longer = 9-24 months depending on resistance pattern
- mono/poly resistance
- multi drug resistant (MDR) = rifampicin and isoniazid
- extensively drug resistant (XDR) = MDR + quinolones and injectables
What microbiological samples need to be sent off to diagnose TB?
sputum x3 broncho-alveolar lavage gastric lavage blood CSF tissue
What are the features of mycobacterium tuberculosis?
aerobic bacilli (upper lobes) = acid fast (neither gram +ve or -ve- has a high lipid content (mycolic acid)), slow growing
>85 species
- mycobacterium TB complex = TB, bovis (cows and human hosts), africanum = BCG
- mycobacterium lepraw
- non-tuberculos mycobacteria (NTM) - environmental, cause disease in immunocompromised pts
How are acid fast stains used to diagnose TB?
1) auramine stain (auramine phenol) => fluorescent
- “smear positive” = highly infectious
- initial screening of sputum
2) ziehl neelson stain (carbol fuchsin) => red on blue
- confirmation of mycobacteria
- can comment on morphology
How can you grow TB?
1) solid media (conventional) => lowenstein jensen (only needs one organism)
2) liquid media (rapid) => MGIT (mycobacteria growth indicator tube) = needs 1-10 organisms)
What are the new developments to increase the speed of diagnosing TB?
1) TB polymerase chain reaction (PCR)
2) whole genome sequencing (WGS)
How does TB PCR work?
(geneXpert, Xpert, Cepheid) - straight from sputum - detects MTBc - can predict resistance to rifampicin diagnose same day and 2-4 weeks to determine drug resistance
What does WGS do?
detects single nucleotide variations (polymorphisms) between 2 isolates
TB mutates at 1 SNP every 2 years
- 0-5 SNPs difference between strains = most probably linked
- 5-12 SNPs may be linked
- >12 SNPs less likely to be linked
What are the benefits of WGS?
Faster drug susceptibility prediction
- more confident treatment regimens
- less likely to induce resistance
more informed contact tracing
Where does XDR most likely originate?
likely origin is E. Europe - within transmission in the UK
Where does MDR most likely originate?
likely origin is E. Africa
What is still needed in TB diagnostics?
WGS on sputum directly
smear negative
childhood Tb - sputum hard to get
biomarkers to detect LTBI with high risk of progression to active TB
