Microbiology TB Flashcards
Classification
- M. tuberculosis (MTB) complex (Typical)
* MOTT (mycobacteria other than TB) (Atypical or Non-tuberculous mycobacterium (NTM)) – more difficult to manage.
MTB Complex
- M. tuberculosis
- M. bovis (inc. BCG)
- M. africanum
- M. microti
- M. canetti
- M. caprae
- M. pimmipedii
Non-cultivatable mycobacterium
• M leprae
Runyon Classification (1959) MOTT
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
Rapid growers
Non Chromogens →
Chromogens
See page 110
1
Number of tubercle bacilli required to establish infection
10
Average number of people that get infected by a single case of pulmonary TB
15
Number of years for which the incidence of TB has been progressively increasing in the UK
20
Time in hours for M. tuberculosis, a slow growing mycobacterium, to replicate
130
Hours of exposure to a case of infections pulmonary TB needed to be sure of contracting TB infection
6,669
Number of cases of TB in the UK in 2001
2,500,000
Annual number of deaths due to TB globally
Mycobacterium Tuberculosis → Description
Human pathogen
Mycobacterium Tuberculosis →Transmitted by
Respiratory droplet (infectious dose: 1-10 bacilli)
Mycobacterium Tuberculosis →Adapted to
Intracellular survival within the human macrophage
• Latency/dormant/non-replicating persistence
• Allows lifelong infection
Mycobacterium Tuberculosis →Factors that promote progression to active disease
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
Patients with active disease
Treat especially with infectious pulmonary tuberculosis
Vaccination
Limited and variable efficacy (UK vs India; prevents dissemination)
Age 12-14, or at birth if parents are from high-risk groups.
Diagnose people with latent tuberculosis infection and give preventative therapy
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
Diagnosis →
Specimens
Procedures
Culture
Histology
Specimens
Sputum, gastric washings, bronchoalveolar lavage
Early morning urines
Biopsies
Procedures
Microscopy (result within 24 h; not all AFBs are TB)
• Ziehl-Neelson
• Auramine
Culture
Crucially important, but often negative)
Solid phase: Lowenstein-Jensen medium
Liquid phase: uptake and release of radiolabelled carbon
Drug sensitivities
Histology
Granulomata with central caseous necrosis
Drawbacks of Tuberculin Skin Test →
Poor specificity
Poor sensitivity
Operational drawbacks
Tuberculin Skin Test Poor specificity
Antigenic cross-reactivity of PPD with BCG and environmental mycobacteria
Tuberculin Skin Test Poor sensitivity
75-90% in active disease (lower in disseminated TB and HIV infection, unknown for latent infection.
Tuberculin Skin Test Operational drawbacks
Need for return visit
Operator variability (inoculation and reading)
Standardisation of reagent
Painful inflammation and scarring
In-vitro and in-vivo diagnostic tests
APC presenting mycobacterial antigens to memory T-cells
See diagram page 112
ELISPOT principle of test
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
Definition resistant TB
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.
XDR-TB or Extensive Drug resistant TB (also referred to as Extreme Drug resistance)
Is MDR – TB that is also resistant to three or more of the six classes of second-line drugs.
MDR-TB
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.
Risk assessment for MDR-TB
- History of prior TB drug treatment, prior TB treatment failure
- Contact with a known case of durg-resistant TB
- Birth in a foreign country, particularly high-nicidence countries
- HIV infection
- Residence in London
- Age profile, with highest rates between ages 25 and 44
- Male gender
XDR-TB
- First described in 2006
- During 2000-20004, of 17, 690 TB isolates referred to international network of TB laboratories, 20% were MDR nd 2% were XDR
- 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
Resistant TB →
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.
Treatment of resistant TB (non-MDR)→
)→ resistant to 1 or 2 → streptomycin.
Depends on site = initiation phase (4 drugs for 2 months), (2 drugs for 4 months).
4 drugs used:
- Rifamapicin
- Ioniaziad
- Perizonamide
- Ethanbutol
