Tuberculosis: Microbiology of Diagnosis and Management Flashcards
50 year old Polish male
- 2/52 cough and weight loss
- GP gave amoxicillin – no improvement
- Attended A&E – sent home
What does this person?
Pulmonary TB
23 year old male
- 1/12 hx fevers, headache, weight loss
- Vomiting, ataxia, clonus, leg weakness
Tb of the brain
- 62 year old male, Sudanese
- 1 month history of fevers, rigors, lethargy and rapid weight loss - recent return from Sudan
Miliary Tb
19 year old male
• 2/12 history of shortness of breath, fatigue, weight loss and vomiting
What does this person have?
Pericardial TB
- 47 year old female
• Ascites, fevers, thickened peritoneum on CT
TB in the peritoneum - nodular pattern seen in omentum - rare
- 20 year old, lives in Pakistan
- Came to UK November 2018
- 3/52 cough, fever, night sweats
What could this person have?
Bilateral lymphadenopathy
Causes: TB, sarcoidosis, lymphoma
What is Tuberculosis?
Infection -Affects any part of the body -Curable (6 months of combination therapy) -Mycobacterium tuberculosis
Contagious -If affecting the lungs (pulmonary) -Transmission via airborne particles
What happens when you get TB?
- Nothing
- Inhalation of TB organisms
Granuloma formation
- Macrophages engulf TB (“epithelioid histiocytes”)
- Fuse to form Giant Cells with central necrosis
- “Ghon Focus” (Lung)
- “Ghon Complex” (+LN)
How is latent TB screened?
Latent TB Screening
- Has this person been exposed to TB?
a) Tuberculin Skin Test (TST)
b) Interferon Gamma Release Assay (IGRA) i. QuantiFERON ii. T-Spot (used for those with immunocompromise) - Positive - check if they have active TB by seeing if they have symptoms of it
- Negative - check BCG scar (only effective for 60% of cases)
What is epidemiology of TB?
- ¼ of the worlds population is infected with TB (latent) – Globally 10 million people had TB (2017) (1%) – 1.4 million deaths (2017)
- TB as a cause of death – Number 1 amongst curable infectious diseases – One of the top 10 globally
- Associated with – poor sanitation – overcrowding – poverty
- Common in big cities such as Birmingham and London and South of England
Symptoms and signs of TB
Long history (slow growing organisms) – Fever Infection – Weight Loss & Fatigue Prolonged inflammatory state – Night Sweats TNF alpha
“Consumption”
• Cough / Haemoptysis / Abdominal Pain / Headache / Back Pain etc
X ray and TB
Upper lobe consolidation, destruction of lung and millet seed pattern
What are differential diagnosis of
Fever, Weight Loss, Night Sweats
What are differential diagnosis of granulomas?
Cancer (Lymphoma, Leukaemia, Lung, Bowel, Metastasis)
Infection (Bacterial / Fungal)
Granulomas:
Sarcoidosis Crohns Disease Granulomatosis with Polyangiitis (GPA) Infection (Fungal / Parasitic)
What is the treatment for TB?
– 6 months
- 2 months RIPE (Rifampicin, Isoniazid, Pyrazinamide & Ethambutol)
- 4 months Rifampicin & Isoniazid
What is the treatment for drug resistance TB?
Drug resistant TB
– Longer (9-24 months) depending on the resistance pattern
- Mono/Poly resistance
- Multi-drug resistant (MDR) - (Rifampicin & Isoniazid)
- Extensively drug resistant (XDR) (MDR + Quinolones & Injectables)
How do you diagnose TB
Think TB
Send sample to microbiology by doing any of the following:
– Sputum x 3 – Broncho-Alveolar Lavage (BAL) – Gastric Lavage – Blood – CSF – Tissue
Mycobacterium tuberculosis (ACID FAST BACILLI) Slow growing (15 – 20 hours to double)
“Acid Fast” Neither gram positive or negative oHigh lipid content (Mycolic Acid) o Poor dye absorption but high retention
- Auramine Stain (Auramine phenol) fluorescent a) “smear positive” – highly infectious b) initial screening of sputum (done on same day)
- Ziehl Neelson Stain (Carbol Fuchsin) red on blue
a) confirmation of Mycobacteria (takes a while)
b) Can comment on morphology (TB vs NTM) -> if it is branching it is NTM rather than TB
Growing the organism
Conventional - takes 8 weeks grown yellow colonies check picture - after growing u use ZN stain
Liquid media - faster - 4 weeks - white snow flakes
Then do drug susceptibility to see which antibiotic to use.
Microbiology behind
Mycobacterium
o Aerobic bacilli/rods (upper lobes) o >85 species
a) Mycobacterium Tuberculosis Complex (genetically linked) o Tuberculosis – human hosts o Bovis – cows and human hosts. Unpasteurized milk o Africanum, BCG
b) Mycobacterium leprae
c) Non-Tuberculos Mycobacteria (NTM)
o Environmental o Cause disease in immune-compromised patients o M avium-intracellulare (MAI)(HIV), M kansasii(bronchioectasis), M chimera(patients with heart bypass - water infected), M abscessus
How do you test drug sensitivity?
Growt in different tubes and see which tube is reacting to it. As you see below it is not effective with isoniazid
What is the limit of detection of ZN stain, auramine stain, Xpert MTB/RF, MGIT (liquid culture), solid culture
Considering Limits Of Detection and specimen volumes:
Xpert MTB/RIF might be 25-250 times less sensitive than MGIT culture
What rapid test can you do to detect TB complex?
Whole Genome Sequencing (WGS) - really sensitive and specific
•WGS detects single nucleotide variations (polymorphism) (SNPs) 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
It allows you to network as well. It is used in Birmingham diagnostically but not other places in Uk apart from London
Rapid test for TB
New technique:
. TB PCR (GeneXpert / Xpert MTB Rif / Cepheid)
– Straight from sputum
– Detects MTB complex (TB, Bovine, BCG etc)
– Can predict resistance to Rifampicin
- Do on high risk patients
