week 5 Mycobacterial disease Flashcards
What shape are mycobacteria?
slender bacillus
What makes mycobacteria different to all other bacterial genera?
Unusual waxy cell wall:
High lipid content
Slow growing
Different media requirements
What is the staining character of mycobacteria?
They have poor take up with standard Gram’s stains.
They also retain certain stains without decolourisation by acid / alcohol because they are acid fast bacilli” (AFBs).
Stains used to identify them are:
Ziehl Neelsen (ZN)
Phenol auramine.
What type of pathogens are mycobacteria and waht type of infection do they cause?
They are Intra - cellular pathogens
They cause chronic infections with Latent phase of infection
What is the treatment of mycobacteria compared to other bacteria genera
They are treated with different antimicrobial agents compared to other bacteria.
The much longer courses of therapy.
Combination of agents to prevent resistance emergence
What mycobacteria causes Tuberculosis?
M. tuberculosis complex:
M. tuberculosis
M. bovis
What mcyobacteria caues leprosy?
M.leprae
Name 3 atypical mycobacteria that are assoicated with HIV and Fish tank granuloma?
M. avium complex
M. kansasii
M. marinum
In terms of M.tuberculosis what % of population is infected, deaths per year and what disase is a co infection with?
One third of world population infected
2 million deaths per year.
Co-infection with HIV: Sub-Saharan Africa
TB has become more common in the developed world because of what factors?
HIV infection
Breakdown of control programmes
Increased global migration from endemic areas
Increased travel
How does Tb spread?
Person to person - inhalation of infected respiratory droplets
What is the couse of the Tb infection?
1) Primary infection (usually pulmonary disease) - Some patients will be symptomatic (flu like) and some completely asymptomatic
2) Latent infection period
3) Reactivation of TB (does not occur in all people some people it will remain latent forever)
4) Dissemination (doesn’t disseminate to affect other organs in all people who get reactivation) NB. Primary infection may disseminate completely skipping the latent phase (this can happen in children)
What is the common site of primary Tb infection?
In the periphery of lung midzone
How does the body repond to Tb infection?
Tubercle formation (granuloma formation) via a cell mediated response
What is the structure, route and action of tubercles formed in TB?
There is a central area of epitheloid cells and giant cells. Have a surrounding lymphocytic cell infiltration, with central area caseous necrosis. Eventually getting fibrosis and calcification of lesions. The tubercles aim to contain the infection.
The bacilli slowly die or amy remain viable for 20 yeas.
What group of people are more likely to see a reactivation of tuberculosis?
Lowered immunity Western countries : over 50 year old, men Malnutrition Alcoholism Debilitating illness HIV infection
How can you test for Tb when there is absent or mild clinical symptoms
Chest X ray.
Tuberculin skin test conversion
What 3 diseases make it more likely for reactivation of tuberculosis to occur?
Silicosis, chronic renal failure, gastrectomy
Taking what drug can increase the chances of reactivation of tuberculosis and why?
Taking Anti TNFα blockade (e.g. infliximab)
This is because Role of TNF alpha is to maintain the granuloma
Where does TB usually residde and be reactivated? Explain why
In the Lung apices due there highest oxygen tension.
What is the consequence of reactivation on tubercles of Tb.
Tubercles coalesce and get caseous necrosis Can also get cavitation - leading to a higher organism load so greater risk of transmission
What are the symptoms of reactivation of TB?
Chronic productive cough Haemoptysis Weight loss Fever Night sweats.
What is the name for dissemianted TB? Who is susceptible?
Miliary tuberculosis.
Very young/old or those who are immunocompromised
What is the consequence of Miliary tuberculosis?
Causes erosion of necrotic tubercle into blood vessel in secondary diseases.
Get wide spread infection
What are common sites where miliary TB can spread too?
Pleura Lymph nodes Kidneys Epididymis Bone Intestines Brain / meninges Pericardium
What is Disseminated tuberculosis?
It is a contagious bacterial infection in which TB bacteria has spread from the lungs to other parts of the body through the blood or lymph system
What are the main signs of TB meningitis?
Often insidious onset Unidentified fever Personality change Focal neurological deficit Mild headache / meningism
May lack constitutional quartet
(fever, night sweats, anorexia, weight loss
How is TB diagnosed?
Radiology:Chest X - ray.
Histology
Skin testing
(Blood test: Interferon- γ release assay: IGRA)
When is the use of microbiology neccessary to diagnose TB? What type of sample is used?
Confirmation of diagnosis
Drug sensitivities.
Molecular typing profile: “MIRUs”.
The sample type need is: “Fresh” samples / tissue: i.e. NOT formalin fixed
What is the procedure in collecting the sputum needed for testing TB?
Sputum: 3 “Early Morning” specimens.
3 taken > 8 hours apart, with > one early morning
How is the sputum used to detect TB?
Direct microscopy for Acid fast bacilli (AFBs)> 5000 organisms per ml sputum: “smear positive”
Risk of transmission
What are the two ways in which TB can be cultured?
Lowenstein - Jensen solid media: 3 - 4 weeks
Broth culture: automated, usually
What processes are carried out if there is Positive AFB culture?
Referred to regional reference laboratory
Species identification
Sensitivities:
within two weeks
Strain typing
In who would there be potentially a lack of sputa to test for TB and how do you get around this problem?
This is common in children –> Induced sputa
Nnebulised saline.
Bronchial aspirates
Gastric aspirates
If you expect someone of having Renal TB what test do you do?
Early Morning Urines x3
If you suspect someone having TB meniningitis what te CSF analyses do you do?
Cell count, protein, glucose
Microscopy / culture.
“Adequate” volume: > 6mls - increased yield.
What is the advantage and disadvtange of uing TB nucleic acid amplification?
It is done by PCR. Adv --> rapid Dis--> Less sensitive than culture Expensive Not 100 % specific - false positives
How is Xpert MTB/RIF test used and in what settting would it be used in?
Direct to sputum which is clinically based and get result in two hours;
The Xpert MTB/RIF test is used in developing world where there is lack of access to cultures.
What are the disadvantages of the treatment for TB?
Lengthy
Combined tablets which can cause poor adherence
What is the standard treatment of TB?
2 months of Isoniazid, rifampicin, pyrazinamide ethambutol / (streptomycin)
4 months of: Isoniazid, rifampicin
What is the treatment if the TB is in other sites (except for meningeal)
Standard 6 month regimen.
Why is TB treatment involves multiple drugs?
To reduce the chance of drug resistance
What is the treatment for TB meningitis?
12 months therapy
What two types of TB will also increase initial treatment with corticosteroids?
TB meningitis and TB pericarditis
What is the second line of treatment for TB?
Amikacin
Ethionamide / prothionamide
Cycloserine
Fluoroquinolones: ciprofloxacin, moxifloxacin
What are common drugs that TB can become resistant to? MDRI
Isoniazid and rifampicin resistant.
What drugs are invovled in extensive drug resistant?
MDR + Fluoroquinolone + injectable (amikacin or capreomycin)
What new drugs are being developed for TB?
Bedaloquine
Delamanid
Pa-824
What are the advantages of shorter regime of treatment for TB?
Improve completion rates
What 5 factors are put in place to control TB?
Notifiable disease - Chest Clinics. Contact Tracing. Tuberculin skin test: Blood test: Interferon- γ release assay Chest X - Ray.
What are the 2 tuberculin skin test done to control TB?
Heaf test
Mantoux test.
How does Mantoux test work?
Inject purified protein derivative (MTB extract) subcutaneously Read at 48-72 hours observing skin reaction
You get a cell mediated immune reponse
What does Interferon gamma release assays measure?
Specific T-cells: IFN γ production.
TB specific antigens (ESAT6, CFP10)
DON’T cross-react with M bovis BCG.
When can interferon gamma release assays be used to identify TB?
Latent TB: New entrants, contacts, immuno-suppressed (incl HIV), HCWs
Also identify Active disease:
extra-pulmonary; paediatric
What does BCG vaccine contain?
Attenuated strain Mycobacteria bovis
Bacille Calmette Guerin
When is BCG vaccine given?
Either to neonatal or if there is occupational risk of being exposed to TB
What treatments of chemoprophylaxis is given to treat TB?
3 months Rifampicin / isoniazid; or 6 months isoniazid.
Can a atypical non tuberculous mycobacteria be transmitted between people?
It is a Environmental organisms
Lack of person to person transmission
What type of mycobacterium causes a HIV infected person to have a disseminated disease?
Mycobacterium avium Complex
What type of disease would a non HIV infected adult or young child get if they have Mycobacterium avium Complex?
In adults: Pulmonary: tuberculosis – like disease
Young children: cervical lymphadenitis.
How is mycobacterium avium diagnosed?
In a similar way, cultured, they are acid fast bacilli so can be stained in a similar way
What is the treatment of mycobacterium avium?
Combination
Prolonged
Macrolide – clarithromycin or azithromycin
What causes leprosy?
M. leprae
What are the two immune responses caused by M.leprae in leprosy?
Tuberculoid –
macules/plaques, can cluster around nerves (ulnar and common peroneal) - not severe
Lepromatous
Subcutaneous tissue accumulation (disfiguring lesions)
Ear lobes, face - leonine facies.
What is the treatment of leprosy?
Dapsone, rifampicin, clofazimine
How is leprosy identified?
Genomic analysis as non culturable in vitro
