Microbiology TB

Question 1

Classification

Answer 1

• M. tuberculosis (MTB) complex (Typical)

* MOTT (mycobacteria other than TB) (Atypical or Non-tuberculous mycobacterium (NTM)) – more difficult to manage.

Question 2

MTB Complex

Answer 2

• M. tuberculosis
• M. bovis (inc. BCG)
• M. africanum
• M. microti
• M. canetti
• M. caprae
• M. pimmipedii

Question 3

Non-cultivatable mycobacterium

Answer 3

• M leprae

Question 4

Runyon Classification (1959) MOTT

Answer 4

Atypical mycobacterium
• I Photochromogens → Yellow pigment formed after exposure to light when colonies grown in the dark and take more than 7 days
• II scotochromogens → Yellow or orange pigment formed when colonies grown in the dark and take more than 7 days
• III Nonphotochromogens → Colonies are non-pigmented regardless of whether grown in the dark or light and take more than 7 days
• IV Rapid growers → colonis (pigmented or non- pigmented) that take less than 7 days

Question 5

Rapid growers

Answer 5

Non Chromogens →
Chromogens
See page 110

Question 6

1

Answer 6

Number of tubercle bacilli required to establish infection

Question 7

10

Answer 7

Average number of people that get infected by a single case of pulmonary TB

Question 8

15

Answer 8

Number of years for which the incidence of TB has been progressively increasing in the UK

Question 9

20

Answer 9

Time in hours for M. tuberculosis, a slow growing mycobacterium, to replicate

Question 10

130

Answer 10

Hours of exposure to a case of infections pulmonary TB needed to be sure of contracting TB infection

Question 11

6,669

Answer 11

Number of cases of TB in the UK in 2001

Question 12

2,500,000

Answer 12

Annual number of deaths due to TB globally

Question 13

Mycobacterium Tuberculosis → Description

Answer 13

Human pathogen

Question 14

Mycobacterium Tuberculosis →Transmitted by

Answer 14

Respiratory droplet (infectious dose: 1-10 bacilli)

Question 15

Mycobacterium Tuberculosis →Adapted to

Answer 15

Intracellular survival within the human macrophage
• Latency/dormant/non-replicating persistence
• Allows lifelong infection

Question 16

Mycobacterium Tuberculosis →Factors that promote progression to active disease

Answer 16

HIV
•	At all CD4 counts
•	More extrapulmonary disease
Immunosuppressive drugs (iatrogenic)
•	High dose steroids
•	Infliximab (anti-TNF w/ latent TB due to T-cells)
Age: very young; very old
Poor nutrition
Homelessness/alcohol/ IVDA/ poverty

Question 17

Patients with active disease

Answer 17

Treat especially with infectious pulmonary tuberculosis

Question 18

Vaccination

Answer 18

Limited and variable efficacy (UK vs India; prevents dissemination)
Age 12-14, or at birth if parents are from high-risk groups.

Question 19

Diagnose people with latent tuberculosis infection and give preventative therapy

Answer 19

1 infections case infects 10 other people, of whom 1 will develop TB
Tuberculin skin test (Heaf): cross-reactivity of PPD with BCG
Contact tracing
New arrivals from high prevalence areas
Child contacts

Question 20

Diagnosis →

Answer 20

Specimens
Procedures
Culture
Histology

Question 21

Specimens

Answer 21

Sputum, gastric washings, bronchoalveolar lavage
Early morning urines
Biopsies

Question 22

Procedures

Answer 22

Microscopy (result within 24 h; not all AFBs are TB)
• Ziehl-Neelson
• Auramine

Question 23

Culture

Answer 23

Crucially important, but often negative)
Solid phase: Lowenstein-Jensen medium
Liquid phase: uptake and release of radiolabelled carbon
Drug sensitivities

Question 24

Histology

Answer 24

Granulomata with central caseous necrosis

Question 25

Drawbacks of Tuberculin Skin Test →

Answer 25

Poor specificity Poor sensitivity Operational drawbacks

Question 26

Tuberculin Skin Test Poor specificity

Answer 26

Antigenic cross-reactivity of PPD with BCG and environmental mycobacteria

Question 27

Tuberculin Skin Test Poor sensitivity

Answer 27

75-90% in active disease (lower in disseminated TB and HIV infection, unknown for latent infection.

Question 28

Tuberculin Skin Test Operational drawbacks

Answer 28

Need for return visit Operator variability (inoculation and reading) Standardisation of reagent Painful inflammation and scarring

Question 29

In-vitro and in-vivo diagnostic tests

Answer 29

APC presenting mycobacterial antigens to memory T-cells | See diagram page 112

Question 30

ELISPOT principle of test

Answer 30

RD1 contains the genes for ESAT6 (early secretory antigen target 6) and CFP10 (culture filtrate protein 16) → doesn’t give a false +ve w/ BCG as the genes aren’t in BCG bt +ve result = low risk popn → Can’t be –ve in patients w/ active disease

Question 31

Definition resistant TB

Answer 31

MDR-TB (Multidrug Resistant TB) describes strains of tuberculosis that are resistant to at least the two main first-like TB drugs – isoniazid and rifampicin.

Question 32

XDR-TB or Extensive Drug resistant TB (also referred to as Extreme Drug resistance)

Answer 32

Is MDR – TB that is also resistant to three or more of the six classes of second-line drugs.

Question 33

MDR-TB

Answer 33

Resistance to anti-TB drugs in populations is a phenomenon that occurs primarily due to poorly managed TB care. Problems include incorrect drug prescribing practices by providers, poor quality drugs or erratic supply of drugs, and also patient non-adherence.

Question 34

Risk assessment for MDR-TB

Answer 34

1. History of prior TB drug treatment, prior TB treatment failure 2. Contact with a known case of durg-resistant TB 3. Birth in a foreign country, particularly high-nicidence countries 4. HIV infection 5. Residence in London 6. Age profile, with highest rates between ages 25 and 44 7. Male gender

Question 35

XDR-TB

Answer 35

1. First described in 2006 2. During 2000-20004, of 17, 690 TB isolates referred to international network of TB laboratories, 20% were MDR nd 2% were XDR 3. In addition, population-based data on drug susceptibility of TB isolates were obtained from the United States (for 1993-2004), Latvia (for 2000-2002), and South Korea (for 2004), where 4%, 19% and 15% of MDR TB cases, respectively, were VDR

Question 36

Resistant TB →

Answer 36

A tuberculous cavity contains 107 to 109 bacilli. If mutations causing resistance to INH occurs in 1 in 106, and mutations causing RIF resistance occur in about 1 in 108, the probability of spontaneous MDR is 1 in 1014.

Question 37

Treatment of resistant TB (non-MDR)→

Answer 37

)→ resistant to 1 or 2 → streptomycin. Depends on site = initiation phase (4 drugs for 2 months), (2 drugs for 4 months). 4 drugs used: 1. Rifamapicin 2. Ioniaziad 3. Perizonamide 4. Ethanbutol