mycobacteria Flashcards
more than 70 species identified in mycobacteria:
1-Tuberculosis:
* M. tuberculosis complex: Seven closely-relatedspecies, including – pathogens: M.tuberculosis, M. bovis, M. africanum
2-Non-tuberculous mycobacteria (NTM)
* Also known as “ – mycobacteria”, or mycobacteria other than tuberculosis (MOTT)
* Includes: M. kansasii, M. xenopi, M. avium-intracellulare complex (MAC), M. chelonae, M.
leprae, M. chimerae
human
atypical
characteristics of the genus:
* — , – forming, – rods ( – )
* Cell wall has high – content (— acid)
– — to stain with commonly used dyes in laboratory e.g. Gram stain
– Require specialised stains e.g. Ziehl-Neelsen (ZN) or auramine stain
– Resist decolorisation by – , hence ‘– bacilli’ or AFB
aerobic
non spore forming
nonmotile
bacilli
lipid
mycolic acid
difficult
acid
acid fast
growth:
* Do not grow on conventional agar plates such as– ; need – media
* Most species are – growers and take 3-6 weeks to grow in the lab; dividing time is 12-24h, e.g. M.tuberculosis, requires – incubation
blood
special media
slow growers
3-8 weeks
- M. Tuberculosis (M. bovis
and M. africanum less often) - — – disease
- Divided into:
– TB — ( – TB)
– TB – (—): - –
- Development of disease linked to — response
notifiable infectious
tb infection ( latent)
disease ( active) which can be primary or secondary
immune response
TB — ( —TB) is defined as infection with mycobacteria of the M. tuberculosis complex, where mycobacteria are multiplying and causing symptoms and signs of disease.
* TB infection (latent TB infection-LTBI) where mycobacteria are – but are – and not causing – of disease.
* However, if these bacteria become active and multiply, ( – ) TB – can develop into TB– ( — ).
disease
active
present
not active
not causing symptoms
latent tb infection can become tb disease through reactivation
transmission is — and it can occur by:
* Expelled when person with infectious TB coughs, sneezes, speaks (respiratory TB) – aka –
* Close contacts at – risk of becoming infected
* Transmission occurs from person with respiratory — not —
respiratory
airborne
highest risk
tb disease and not latent tb infection
TB pathogensis:
* Most droplets will be stopped from entering the body by the – barriers found in the upper respiratory tract, those that are less than – µm in size are able to bypass these barriers and reach the — and – .
* M. tuberculosis evades – and – immune responses
* Replicates in alveolar – – prevents – . In turn, – presentation of bacterial antigens
* Masks antigenic areas with – so not ‘recognized’ by host – immune system
physical barrier
1-2
lower respiratory tract
lungs
innate and adaptive
macrophages
phagosome-lysosome fusion
delaying
lipids
innate
( check slide 13)
1-conditions that increase risk that tb infection will progress into tb disease:
2- common sites of tb disease:
- —- which is 70% cases in Ireland
- — potentially everywhere as:
✓ Pleura
✓ Central nervous system
✓ Lymphatic system
✓ Genitourinary
✓ GIT (M. bovis ingested in contaminated milk)
✓ Bones & joints
✓ Disseminated (miliary TB) - rare, u
- Age < 5 years
- HIV (10% progress in one year versus 10% lifetime
risk in non-HIV) - Immunosuppression e.g. chemotherapy, prolonged
steroid use, haematological malignancy - Diabetes mellitus
- Excessive alcohol intake
- Chronic kidney disease or haemodialysis
- Injecting drug use
- Gastrectomy/jejunal bypass
- Silicosis
- pulmonary
- extra pulmonary
clinical features:
* TB – ( aka – ) -> asymptomatic, no signs of disease
* TB – -> signs and symptoms will depend on system involved -> wide variability leads to difficulty recognising
* Symptoms subacute/chronic:
– – symptoms: Fevers, night sweats, weight loss,
anorexia
– Respiratory: – (>3 weeks), —
– – at site of infection
– Can present with just – – sometimes get classified as ‘fever of unknown origin’
– No response to ‘ – ’ antibiotics e.g. pneumonia
infection aka latent
disease
systemic
chronic cough and haemoptysis
pain
fever
typical
1-epidemiology:
2- tb in ireland:
* 224 cases in 2023
* TB rates higher in –
* 66% of patients born outside Ireland
* 8 drug resistant cases – 3 MDR, 1 XDR
- Mortality reducing but remains 10th most common cause of death
globally - Multi-drug resistant (MDR) TB infection an increasing problem
- Poverty, overcrowding, malnutrition/famine, &
HIV are all major contributory factors
males
diagnosis of tb:
1. CLINICAL SUSPICION
* specific symptoms, e.g. –
* — symptoms, e.g. weight
loss, night sweats over weeks & not
days
* No response to —
* Fever (pyrexia) of – origin –PUO
* Epidemiological risk factors
2- TB screening for latent tb :
1. – tests. i.e. Mantoux, Heaf
2. — release assay (IGRA) e.g.
QuantiFERON blood test
-Use the body’s – response to TB antigens to determine if a person has been infected with TB previously
NB: don’t distinguish between infection and disease
haemoptysis
systemic
antibiotic
unknown
tuberculin skin test
interferon gamma release assay
immune response
skin test ie. Mantoux , heaf
- – injection of – derivative of –
* – cell mediated hypersensitivity – usually develops 3-9 wks after infection
Positive = TB infection or BCG vaccination
Negative = excludes diagnosis, unless
* very early primary infection, or
* disseminated/immunosuppressed
intradermal
protein
tuberculin
delayed
interferone gamma release assay ( IGARA): uantiFERON– trade name
* Whole blood assay that detects release of interferon gamma by sensitised – incubated with M. tuberculosis peptides or proteins
* Not affected by –
* Some – immunocompromised
or some patients with – infection
T cells
BCG vaccines
false -ve
active
diagnosis of tb
3. MICROBIOLOGICAL DIAGNOSIS
Specimens:
- — TB Sputum samples/ BAL
- —- TB – Site specific specimens: Early morning urine (EMU), CSF, pus, tissue
A: — :
ZN stain or auramine (see fluorescent bacteria) if +ve, presumptive diagnosis
B: – - PCR NAAT:
Quick provisional diagnosis/rifampicin resistance.
Confirm identity/resistance genes diagnosis of microscopy –ve
C: —
Automated liquid culture or Lowenstein-Jensen (LJ)
slopes – take weeks
pulmonary tb
extra pulmonary tb
microscopy
molecular
culture
diagnosis of tb : histology & radiology
4. Radiology
* –
– Consolidation
– Cavitation (esp. apices)
– Ghon lesion (calcified granuloma)
– Miliary
5. – - histology
* Caseating granulomata seen
* ZN stain positive on tissue
* Molecular testing
CXR
biopsy
tb treatment:
* – therapy (usually – agents)
* – not – of antibiotics
* Most agents used are not “ – ”
antibiotics (though some are)
* Drugs that penetrate – (TB
likes to live in macrophages)
combination
4
months not days
conventional
penetrates intracellularly
- Rifampicin
- Isoniazid
- Pyrazinamide
- Ethambutol
are all — drugs
potential toxicity: - — & hepatitis/peripheral
neuropathy* - – &
hepatitis/discolours
bodily fluids - — & optic
neuritis - — (Vitamn B6) often
prescribed concomitantly as
reduces risk of peripheral
neuropathy
first line drugs
isoniazid
rifmipcin
ethambutol
pyrodxine
- Regimen governed by susceptibility results
- Treatment at least – depending on – of infection and –
1-Susceptible – TB - Initially start on 4 drugs x 2/12 & then rationalised, based on susceptibility results to 2 agents x 4/12
2- Treatment of – - Isoniazid x 6/12 or isoniazid & rifampicin x 3/12
6 months
site and suspecpitlity
pulmonary tb
latent tb
- Drug-resistant TB transmitted in the same way as drug-susceptible TB
- Drug resistance is divided into two types:
- – resistance in a patient initially
infected with resistant organisms - – resistance (acquired resistance)
develops during TB therapy - risk factors for drug resistant tb:
- Previous – to TB drugs
- Contact of someone with –
- From an area with – rates of drug
resistance - – treatment regimen (if >than 2
weeks) - Non-compliance with –
primary
secondary
exposure
drug resistant tb
high
inadequent
medication
MULTI-DRUG RESISTANT TB (MDR-TB)
‘Resistance to – and –
+/- other drugs’
* Number of outbreaks abroad
* 3-6% of strains in UK
* Non-compliance
* Delays in laboratory confirmation &
susceptibility testing
- — :
RESISTANT TO ISONIAZID, RIFAMPICIN, FLUOROQUINOLONES, & AT LEAST ONE
OF THE INJECTABLE PREPARATIONS OF
CAPREOMYCIN/KANAMYCIN/AMIKACIN
isoniazid and rifampicin
extensively drug resistant XDR-TB
prevention of tb:
1- – conditions
– improved housing
– better nutrition, address poverty and social inequalities
2- Patient – and – tracing
– In hospitals, isolate infectious cases with – precautions, — room
– screen contacts, i.e. family members and
friends
social
patient isolation
contact
airborne
negative pressure rooms
BACILLE-CALMETTE-GUÉRIN (BCG)
VACCINATION
* – attenuated strain of –
–Produces a delayed-type hypersensitivity reaction similar to that of – infection
* Contraindicated in – patients &
those who are skin test –
* Efficacy variable:
– Most effective in – with no previous exposure to TB
– Protection from severe forms of childhood TB e.g. TB
meningitis, miliary TB (80% efficacy)
– Little evidence of efficacy in older persons
* No longer part of routine immunization schedule in
Ireland (low incidence TB country)
live
M.bovis
natural
immunosuppressed and skin test +ve
infant and young children
1-non-tuberculous mycobacteria:
* – pathogenic, often in –
* Prevalence – due to more
awareness & other factors e.g. AIDS, cystic fibrosis (M. abscessus), solid
organ transplantation
* Some resemble – in presentation, e.g. M. kansasii
2- M. avium-intracellulare complex (MAC)
* – source ( – / – )
* Presents as – infection, typically in – patients especially in terminal stages
* Occasionally damaged – e.g. CF patients
* Large numbers of organisms disseminated in
blood, marrow, GIT
* – to treat
less
environment
increasing
tb
environmental water/soil
primary
aids
lungs
difficult
leprosy:
* Mycobacterium leprae
* Previously known as – disease
* Historically, associated with – & led to –
* – culture not possible
* Do not – as strongly as M. tuberculosis & found in macrophages
* — the primary target leading to
anaesthesia & paralysis with granulomata
* Skin lesions with or without pigmentation, disability,
nasal destruction & eye lesions
* Diagnosis by – for — & –
treatment:
prevention:
Hansens
disfigurement
ostracism
in vitro
stain
shwann cells
tissue smears for acid fast bacilli and histopathology
Treatment
Dapsone, rifampicin & clofazimine for ≥6-12 months
Surgery to correct deformities
Prevention
Early detection & treatment
BCG may have some role
summary:
* Mycobacterial disease is of major global
importance & still seen in Ireland & elsewhere
* Variable clinical presentation & often missed
* Diagnosis depends on clinical suspicion & a
variety of investigations
* Drug-resistant TB a major global challenge
* Other mycobacteria increasingly seen in
specific patient populations
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