24a Mycobacterium TB from Lecture then Leprosy Flashcards
What are the four types of Mycobacterial classifications?
Mycobacterium leprae (leprosy) Mycobacterium tuberculosis (human TB) Mycobacterium bovis (bovine and human TB) Non-tuberculous mycobacteria (some human pathogens)
What M. tuberculosis Complex (5)?
These are different than, but overlapping the “types” of TB.
Essentially, it is a mix of Mycobacterium that are sometimes found together in a diseased patient.
M. tuberculosis M. africanum M. bovis M. bovis-BCG vaccine strain M. cannetti
What are the general properties of mycobacteria? Gram status? Shape? Capsule status? Motility? Spore status? O2 status? Intra or Extra cellular status? Ease of producing culture?
Gram + non-encapsulated rod
Not motile
Non-spore forming
Obligate aerobe (except one species: M. bovis)
Intracellular
Fastidious (needs special medium to grow) and grows very slowly
What is the only Mycobacterium that is NOT and OBLIGATE AEROBE?
M. bovis
Describe the significance of “Acid-Fast”?
Code word: Acid fast usually = mycobacterium
Red phenol dye (arylmethane) complexes with MYCOLIC ACIDS and cannot be washed out with acid alcohol
Note: other species are also weakly acid fast
In addition to Mycobacterium, what other bacteria are also acid fast?
Nocardia (respiratory)
Actinomycoses (respiratory)
Cryptosporidium parvum (GI)
Isospora (GI)
Cyclospora cysts
Sarcocystis (GI)
However, if it is a board question that says “acid fast” think Mycobacterium TB
What are the two stains that use acid fast?
Ziehl-Neelsen stain
Kinyoun stain
What parasites are acid fast?
Mycobacterium are strongly acid fast with a thick wall of MYCOLIC ACID
Nocardia, Actinomycoses, Cryptosporidium parvum, Isospora, Cyclospora cysts, Sarcocystis are weakly acid fast with a thinner wall of MYCOLIC ACID
What is a short cut to acid fast observation?
Flourscent dye makes Mycobacteria glow and is easier to see.
What is unique about Mycobacterial cell walls?
Very thick layer containing mycolic acid (binds to red phenol dye in acid fast test)
The cell wall is so thick Mycobacterium are described as “wax ball” enclosing DNA
What is the “cord factor” of Mycobacterium tuberculosis?
Two MYCOLIC ACIDS attached to TREHALOSE
Virulence factor
What is “cording” with regard to Mycobacterium?
Phenomenon of culture growth.
Mycobacterium grow in a frayed cord-like picture.
This is due to the thick cell wall of Mycolic acids and Trehalose.
Describe the slow growth of Mycobacterium?
Very thick wall leads to slow growth
eg Generation time is 20 hours
Which Mycobacterium cannot be grown on artificial medium?
M. Leprae (leprosy)
Detail: Why should we be wary of assuming TB if we see granulomas in the lungs?
Granulomas can also be due to:
Infections: mycobacteria, histoplasmosis, cat scratch, cryptococcosis, coccidio, blasto
Non-infectious: sarcoid, Crohn’s, berylliosis, Wegener’s granulomatosis, Churg-Strauss, rheumatoid, particulates
What is the significance and uniqueness of respiratory transmission of TB?
“One droplet nuclei”
A single organism can cause disease
Organisms can live in a air-floating respiratory droplet for up to 8 hours.
Droplets are very small and can pass through surgical mask. Need a special mask.
Very expensive to filter air of hospital patients.
30% infection rate in close contact!
Detail: Mycobacterium leprae
Prevalence in US: 1000 cases per year, mostly imported
Prevalence in world: 20 million!
Detail:
Prevalence in US: 1000 cases per year, mostly imported
Prevalence in world: 20 million!
What are the 4 possible outcomes when a patient inhales TB?
These are four terms to know.
Eliminated
Multiply and cause disease = primary TB
Become dormant = latent TB infection (LTBI) ASYMPTOMATIC
LTBI converts to active TB = reactivation TB disease
What are the symptoms of pulmonary TB?
Cough
Weightloss
Drenching night sweats
What is a Ghon focus?
What is a Ghon complex?
What is a Ranke complex?
Ghon focus: granulomatous inflammation of healed primary TB in lung parenchyma
Ghon complex: Ghon focus with lymph node
Ranke complex: calcified Ghon complex
What is Caseous Necrosis vs Caseous Granuloma?
Macro veiw vs histological view
What is Rasmussen’s Aneurysm?
a pulmonary artery aneurysm adjacent or within a tuberculous cavity. It occurs in up to 5% of patients with such lesions. It may lead to rupture and haemorrhage. Patients may cough up blood till death.
Distinguishing infection from diesease…
What are the risks of a patient with LTBI developing TB?
Lifetime?
Per year?
What if they have HIV also?
Persons with LTBI have high risk of progressing to TB disease, esp in first 2 years
Lifetime risk of LTBI to disease is 10%
TB and HIV synergistic: annual risk of disease 10%
What symptoms occur with Latent TB?
Is LTBI infectious?
NONE. Trick question.
NOT infectious if there are no symptoms. The infection is LATENT and cannot be spread.
What are steps to Dx TB?
1) See it: microscopy with acid fast or fluorescent stain
2) Grow it: solid or liquid culture
3) Find bits of its: Mycolic acids (e.g., LAM urine test) and/or Genetic material (e.g., PCR)
4) Demonstrate host response to it:
Typical pathology: Chest Xray? Granulomas?
Immune response to PPD or IGRAs
What determines the decision to intiate treatment for TB?
Epidemiology Signs compatible with TB AFB smear status Seriously ill (e.g., miliary TB) High risk of transmission
Most of the world just uses AFB smear.
What is M. bovis?
What is BCG?
M. bovis is a species. They tried to use it as a vaccine. Total Fail. People were infected with M. bovis.
BCG is live attenuated M. bovis that is a modestly successful vaccine.
Who is the BCG vaccine used for?
Who does it not protect?
BCG is effective at preventing fatal pediatric TB
Not effective at preventing adult pulmonary TB.
Note: most of the world has had this vaccine.
What are the hosts for Mycobacterium leprae?
Humans and armadillos
Note: M. leprae is an obligate pathogen. Cannot survive without host.
What is the prefered temperature for Mycobacterium leprae?
On what tissues do they normally grow?
27 to 33 C (cooler)
Skin, nose, mucous membranes of upper respiratory tract
Epidemiology of Mycobacterium leprae... Transmission? What age is susceptible? Incubation period? How infectious?
Respiratory transmission nasal secretions (snot), but possibly skin to skin
Children are more susceptible than adults
2-5 years incubation period!
VERY LOW INFECTIOUS LEVEL: only 5% of people can be infected. Each infected person is rended non-infectious within a few days of treatment.
What is the official name for Leprosy?
Hansen’s Disease (HD)
What are tissues affected by Mycobacterium leprae?
Skin
Amyloidosis can occur in kidney, liver, and spleen
What are the three forms of Mycobacterium leprae?
Lepromatous (bad) aka MULTIBACILLARY
Intermediate
Tuberculoid (better) aka PAUCIBACILLARY
What is the genesis of these forms of Mycobacterium leprae…
Lepromatous
Tuberculoid
L: Macrophage or histiocyte takes up bacilli
T: Similar to TB; chronic granulomatous lesions form as a proliferative reaction to bacilli; epithelioid and giant cells are present without caseation
Detail for Mycobacterium leprae…
L forms a “lepra” cell, which is a macrophage stuffed with bacilli
T forms a microscopic tubercules
.
What are the skin lesions like for these forms of Mycobacterium leprae…
Lepramatous?
Tuberculoid?
L: PAPULE, raised brown wheal-like mosiquito bite; thickening of the skin; ulceration is possible.
T: MACULE, may be hypo-pigmented or erythematous; Anaesthesia due to nerve toxicity; confluent lesions give rise to plaques
What are the number of Mycobacterium leprae found in…
Lepramotous infections?
Tuberculoid infections?
L: LOTS per gram of infected skin
T: FEW towards the center of the lesion
What are the effects of the LEPROMIN SKIN TEST in Mycobacterium leprae…
Lepramotous?
Tuberculoid?
L: lepromin skin test NEGATIVE
T: lepromin skin test POSTITIVE
What about the immune response in general for lepramotous vs tuberculoid Mycobacterium leprae?
Ability to mobilize T cells?
What type of T cells?
IgG response
L: LOW IMMUNE RESPONSE, LOW ability to mobilize T cells, SUPRESSOR T CELLS present, HIGH POLYCLONAL IgG levels
T: GOOD IMMUNE RESPONSE, GOOD delayed hypersensitivity is intact, helper T cells present, NORMAL IgG levels
Note: in both cases, there is a lack of host killing intracellular bacteria
What are some physical Dx features of Leprosy aka Hensen’s disease?
Loss of eyebrows
Nostrils deformed
Ear lobe thick
“Lion face”
Note: Hensen’s disease can can infect nerves and make them swollen and insensitive.
.
What is Erythema Nodosum Leprosum (ENL)?
Which form of Mycobacterium leprae causes this?
IgGs form immune complexes that deposit AMYLOID in the kidneys, liver, and spleen.
Lepramotous causes
Complication of the hyper polyclongal IgGs
What is the Tx for Erythema Nodosum Leprosum (ENL)?
Immunosuppression
What is the Dx of Mycobacterium leprae?
Difficult.
Based on gross appearance and location of lesions, histology, Acid-fast stains from lesions
That is the Tx for Mycobacterium leprae?
Multi-Drug Treatment MDT
Dapsone (sulfonamide-like)
Rifampin (cidal)
Clofazimine (can cause blue skin)
ENL complication? Tx with immune suppression
Control measures and prevention for Mycobacterium leprae?
List of household contacts for 5 years!
BCG aka a TB vaccine offers some protection
