Mycobacteria Flashcards
Groups at high risk of TB
- People with HIV infection
- People who were infected in the last 2 years
- Babies and young children
- People who inject illegal drugs or abuse alcohol
- People sick with other diseases that weaken the immune system
- Medications such as corticosteroids, tumour necrosis factors alpha inhibiors, calcinerin inhibitors (which includes cyclosporine and tacrolimus) and xytocix chemotherapy.
- Elderly people
BCG vaccine
- Live attenuated vaccine
- Derived from strain of* M. bovis*
- High protective efficacy >70% against meningitis and miliary TB
- Variable efficiacy against TB in adults
- Adverse events:
- Local s/c abscess and ulcers
- Suppurative lymphadenitis
- Rarely disseminated disease
*Mycobacteria *microbiology
- Non-motile, nonspore-forming weakly gram positive rods; often appear slightly bent or beaded.
- Obligate aerobes; simple growth requirements
- Cell wall: 20 to 60 percent lipids.
- Generation time of 12 to 48 hours.
- Acid-fastness: form stable mycolate complexes with arylmethane dysed
- Particles 1-5um in diameter
- Aerobic
- Non-spore forming
- Nonmotile bacillus
- High cell wall content of high molecular weight lipids.
- Complete 4.4 MB circular genome sequence of the H37Rv strain
- Very large proportion MTB genes encode enzymes involved in lipogenesis and lipoysis
Acid fast bacilli (AFBs)
Retain basic dyes when treated with acidic solutions (most other ogrniams swill decolourise). Hence, they are ‘acid-fast’
Immunology and pathogenesis
- Spread by airborne droplets. Particles can remain airborne for minutes-hours.
- Inhaled and lodge in the alveoli.
- MTB taken up by alveolar macrophages.
- Activated T lymphocytes and macrophages form granulomas that limit further replication.
- Replicated slowly (15-20 hours) but continuously.
- Spread by lymphatic system to hilar lymph nodes.
TST
Uses cell mediated immunity
- Alveolar macrophages infected interacts with T lymphocytes
- Infected macrophage releases IL 12 and 18
- Stimulate T lymphocytes to release interferon gamma
- This stimulates phagocytosis of MTB in macrophage
- Interferon gamma stimulates macrophages to release tumour necrosis factor alpha
- T lymphocyte response is antigen specific
Intradermal administration of tuberculin
Delayed type hypersensitivity response to PPD (purified protein derivative)
- PPD = crude mixture of antigens
- Tuberculin positivity occurs 3-8 weeks after infection
Treatment of latent TB diagnosed on basis of TST reuslts = reduces risk of active disease by 60%.
TST cut-off points
A TST of >5mm of induration is interpreted as a positive result in the following groups:
- HIV infected persons
- Recent contacts of TB case
- Persos with fibrotic changes on CXR consistent with old, healed TB
- Patients with organ transplants and other immunosuppressed patients
TST cutoff is determined by diameter of induration
- 5mm = HIV
- 10mm = if from country where infection common
- 5mm = low risk and low prevalence
IGRAs
Newer IF gamma assays use a cocktail of MTB - specific region of difference 1 (RD1) antigens
- Early secretory antigenic target 6 (ESAT6)
- Culture filtrate protein 10 (CFP10)
Treatment of latent TB
In those suitable for chemoprophylaxis treat adults with 6-9 months of 300mg isoniazid and 25mg pyridoxine.
In theonly study comparing the efficacy of different durations:
- 6 months of treatment was 65 percent effective; and
- 12 months of treatment was 75 percent effective (not not statistically different from 6 months) in preventing TB
Diagnosis of active TB
May present with
- Fever
- Cough >3 weeks
- Chest pain
- Weight loss
- Fatigue
- Coughing up blood - haemoptysis
- Decreased appetite
Primary TB signs and symptoms
Usually asymptomatic.
If symptomatic
- Often fever alone
- Changes on CXR - midlung
- Hilar lymphadenopathy
- RML atelectasis
- Calficiations
- Pleural effusion
- Erythema nodosum
- Conjunctivitis
Children; AIDS = progressive pneumonia
Reactivation pulmonary TB
Symptoms
- Anorexia
- Fatigue
- Weight loss
- Chills
- Afternoon fever
- Night sweats
- Productive cough
- WHO: test for TB if unexplained 2 weeks productive cough
Reactivation TB Laboratory findings
Monos 10%, Increased Ca2+, decreases Na+ (addisons)
Reactivation TB CXR
Adolescents and adults
- Subapical posterior upperlobe > apex > lower lobe
- Cavity up to 50%
- Without adenopathy/calcification
- Often nondescript lower lobe pneumonia
- Elderly/paients with comorbidities
- Children
- HIV
What is the gold standard of diagnosis for TB?
**Culture. **There are three types of media
- Solid media: 3-8 weeks
- _Liquid broth: _1-3 weeks
- Bacter MGIT
Treatment of TB
The most effective way of stopping transmission
- Isolate
- Start treatment with anti-TB medicine
Active pulmonary TB
4 drugs for the first two months
- Isoniazid
- Rifampicin
- Pyrazinamide
- Ethambutol
2 drugs for additional months
- Isoniazid
- Rifampicin
Never forget to add pyridoxine to all persons treated with isoniazid to prevent peripheral neuropathy
TB medication
Isoniazid is the most effective bactericidal drug.
Rifampicin and pyrazinamide are the most important sterilising drugs.
- Thought to act by killing different populations of semi-formant organisms (persisters)
Isoniazid and rifampicin are the most effective drugs at preventing the emergence of resistance to other drugs.
Pyrazinamide has good activity against intracellular organisms and is most active in the first 2 months of treatment;
- it enables the total duration of treatment to be shortened to 6 months (for fully drug-sensitive infections).
Ethambutol is a bacteriostatic drug that is given to prevent the emergence of resistance.
MDR-TB definitin
Resistance to at least
- Isoniazid
- Rifampicin
Second line medications
- Relatively less effective (limited sterilising capacity)
- Poorly tolerated (significant potential for toxicity)
- Expensive
Treatment may need to be administered for up to 2 years in MDR-TB
Persons at increased risk fo MDR
- People already receiving TB treatment
- Those who have inadequate treatment for >2 weeks.
- Contacts of known drug resistance patients
- People born or living in areas wiht high prevalence of drug resistance TB
XDR-TB
MDR TB plus resistance to:
- Fluroquinolones
- Plus at least one of the 3 injectable second line drugs (capreomycin, kanamycin or amikacin)
What does successful management of TB require?
- Judicious use of drugs
- Supervised standardised treatment
- Focused clinical, radiologic and bacteriologic follow up
- Surgery when appropriate
- Contract tracing
Most common adverse drug reactions
- Hepatirus
- Gi disturbances
- Rash
- Weakness/fatigue
- Joint pain
What increases risk of ADR?
- Female sex
- Increased age
- Increased baseline AST
- Drug resistance
