Mycobacterial Disease

Question 1

Which bacteria cause TB?

Answer 1

• M. tuberculosis
• M. bovis (1% of human cases) in cattle
• More rare sub-species

Question 2

What are the different stages of a TB infectiton?
Which ones are usually symptomatic?

Answer 2

Usually Reactivation of Latent TB with trigger (immunosuppression, idiopathic) becomes symptomatic

More rarely primary TB can also be symptomatic

Question 3

How is TB generally transmitted?

Answer 3

Human to Human Aerosole tranmission (with active pulmnoary/laryngeal TB - other forms of TB (e.g. bone obv, not infectious))

Question 4

Give an example of another Mycobacteria / Acid Fact Bacilli positive bacteria that does not cause TB?

Answer 4

• e.g. M. chelonae (skin infections)
• M. avium
• others

Question 5

What is Latent TB?

Answer 5

A TB infection, that only causes one acute infection period (2-3 weeks of B symptoms + cough), with no active TB afterwards

Question 6

What is the worldwide prevalence of Latent TB?

Answer 6

1/4 - 1/3 of population

Question 7

What is the progression rate of Latent TB into active TB?
When does this usually develop?

How does the likelihood change with active HIV infection?

Answer 7

10%
Usually incubation period 3-9 months, usually <2 years

With active HIV infection: 30-50%

Question 8

How is latent TB diagnosed?

Answer 8

Mantoux with PPD (purified protein derivate) –> shows exposure (positive in latent, active, BCG)

or gamma interferon release assays (IGRA) –> Shows Exposure (active or latent, negative in BCG)

Question 9

What is the current treatment Regime for drug-senstive TB?

Answer 9

Give 4 (RIPE) for 2 months, and then 2 of them for 4 months (depending on Culture and Sensitivity - usually P and E stopped due to bigger side-effect profile) (RIP available as combinations Rifater)

	○ Pyrazinamide and Ethambutol   - 2 months
	○ Rifampicin and Isoniazid - 6 months ("Rifinan") 

Depending on sensitivity results: may decrease down to 3 drugs

Question 10

With what 5 Methods can TB be diagnosed?

Answer 10

1. Microscopy ZN stain (30min)
2. Microscopic Auramine stain (20-30min)
3. Xpert MTTB/ RIF (PCR) (2h)
4. Liquid cultures (2 weeks)
5. Solid Cultures (4-6 weeks)

Question 11

What is Multi-drug resistant TB?

Answer 11

TB resistance to Rifampacin and Isaniazid

Question 12

How is Muldti drug resistance TB diagnosed?

Answer 12

Now with WGS (Whole genome sequencing) DNA sequencing of Culture TB to test for resistance gene (Rifampacin most important).

Future looking into WGS of sputum direcly

Question 13

How good is rapid TB diganostics compared to cultures

What is the gold-standard diagnosis of TB?

Answer 13

75% of microscopy negative cultures will be true positive on rapid diagnostic tests

Culture on Lowenstein-Jensen medium for 6wks (gold standard)→ acid fast bacilli seen + positive stain of Zhiel Nielson on sputum

Question 14

Which factors influcence likelihood of TB transmission?

Answer 14

• Infectiousness of person with TB disease
• Environment in which exposure occurred
• Length of exposure
• Virulence (strength) of the tubercle bacilli

Question 15

How is latent TB generally managed?

Answer 15

Overall aim: prevent active TB
1. Diagnosis
2. Chemoprophylaxis

Offer different drug regimes, depending on patient but usually

• 3 months of isoniazid (with pyridoxine) and rifampicin or
• 6 months of isoniazid (with pyridoxine)

Question 16

What is the epidemiology of Multi-drug resistant TB?

Answer 16

common, depending on country.
3 countries account for 50% of worldwide MDR/RR TB
1. India (24%)
2. China (13%)
3. Russia (10%)

(Most of UK/ EEA drug sensitive)

Question 17

What is the efficacy of the BCG vaccine?

What is a contraindication of giving the BCG vaccine?

Answer 17

About 70%

Immunosuppression is contra-indication, as it is a life-attenuated vaccine)

Question 18

The classical presentation of TB is pulmonary Tb with constitutional symptoms, cough (+/- haemoptysis) and upper lobe caviation.

Can you name 2 others?

Answer 18

Overall more common with immunosuppression

2. 1. Spinal (Pott’s disease): back pain, discitis, vertebral destruction, iliopsoas abscess
3. Milliary TB: disseminated haematogenous spread (seen on CXR)

+ Many more (can presen pretty much anywhere)

Question 19

What is the most common side-effects of each of the RIPE drugs?

Answer 19

1. Rifampacin - orange secretions
2. Isoniazid: peripheral neuropathy
3. Pyrazinamide: hepatotoxic
4. ethambutol – optic neuritis

Question 20

What pathogen is Leprosy caused by?
What is the current epidemiology?

Answer 20

Caused by Mycobacterium Leprae (non-tuberculous Mycobacterium)

Now only worldwide 150 new cases annually, most in US

Question 21

What is the clinical presentation of Leprosy?

Answer 21

Skin depigmentation
nodules, trophic ulcers

nerve thickening

Lifelong illness, most disability due to nerve damage

Question 22

What disease is caused by Mycobacterium Avium-Intracellulare complex?

What is the usual patien group involved?

Answer 22

Example of a non-tuberculous causing Mycobacterium

disseminated infection in immunocompromised; resembles TB if underlying lung disease

Question 23

A fish lover with 6 aqauriums is presenting with a slow-growing bump on his left hand. Biopsy of the lesion reveals positive Zhiel-Nielson stain. What is the mst likely diagnosis?

Answer 23

Infection with Mycobacerium Marinarum –> causing Fish-tank granuloma

(Non-tuberculosis causing Mycobacerium)