tuberculosis and leprosy Flashcards
what does mycobacteria tuberculosis (m. tuberculosis) cause?
causative agent of Tuberculosis in humans (often called “TB” for tubercle bacilli)
develop lesions in lungs
what does mycobacteria bovis (m. bovis) cause?
causes TB in cows, rarely in humans
humans can be infected by consumption of unpasteurized milk
leads to extrapulmonary tuberculosis in humans – which can be treated with the BCG vaccine made of m. bovis
what does mycobacteria avium (m. avium) cause?
causes tuberculosis-like illness in humans, particularly in AIDS patients
what does mycobacteria leprae (m. leprae) cause?
causative agent of Leprosy in humans
systemic infection in armadillos
approximately how many people have have latent tuberculosis? how many of those will develop active TB in their lifetime?
2 billion; 1/4 of the world’s population
about 10% of ^^ will develop active TB in their lifetime
how many people die from tuberculosis each year?
about 1.6 million people die from TB each year
what is the number 1 infectious agent?
tuberculosis….
how is tuberculosis spread?
contagious and spread through the air by people with active TB
what is meant by latent infection
harbours organism in lungs; no symptoms & can’t transmit disease
but do develop some immune response
what is multi-drug resistant TB (MDR-TB)?
being resistant to the two most effective first-line therapeutic drugs, isoniazid and rifampin
what is extensively drug resistant TB (XDR-TB)?
resistant to first line therapeutic drugs (rifampin and isoniazid) AND resistant to the most effective second-line therapeutic drugs used commonly to treat MDR-TB
XDR-TB has been found in all regions of the world
— but strains are virtually untreatable
where can mycobacteria tuberculosis be found when in humans?
lives within macrophages
(an intracellular pathogen)
what’s the generation time of mycobacterium tuberculosis? what does this mean?
greater than 15 hours (slow generation time)
makes studying it & creating antibiotics very difficult
if grown on the lab in specialized media, how long does mycobacterium tuberculosis take to get small colonies?
4 - 6 weeks
describe mycobacterium tuberculosis’s cell envelope
unusual cell envelope with high concentrations of mycolic acid (it’s lipid-rich aka hydrophobic) – making it “waxy”
due to its mycolic acid, it’s impermeable to stains and dyes – like other mycobacteria, it’s gram+ acid fast
its cell envelope is associated with resistance to:
—– some antibiotics
—– osmotic lysis via complement deposition
—– lethal oxidative stress promoting survival inside of macrophages
how is acid fast stain conducted for mycobacterium tuberculosis?
stain w/ carbol-fuchsin dye with slow heating (to melt waxy cell envelope) on slide
wash with EtOH and HCl
counter-stain w/ methylene blue
result:
acid-fast organisms = red
non-acid fast organisms = blue
what are the 4 stages in the spread and progression of tuberculosis?
stage 1: transmission
stage 2: survival in macrophage (key virulence property)
stage 3: formation of granulomas and killing by T-cell activated macrophages
stage 4: route of transmission and cavitation
describe how tuberculosis is transmitted (stage 1 of the spread and progression of tuberculosis)
inhalation of droplets from an infected host, usually by coughing or sneezing
coughing/sneezing can generate 3000 droplet nuclei, each of which can contain up 10 bacteria
small droplets can stay airborne for extended periods of time and these droplets can be inhaled directly into the lungs
—– a single bacteria can cause lesions in the lungs
describe tuberculosis survival in phagocytes (stage 2 of the spread and progression of tuberculosis) and what do TB cells do once in the macrophage?
lung (alveolar) macrophages phagocytose TB cells
TB blocks acidification of the phagosome
TB inhibits the fusion of the lysosome to the phagosome
TB delays dendritic cell migration to lymph nodes
TB multiplies in macrophages. the macrophages then lyse and release TB cells to infect more macrophages
describe the formation of granulomas and killing by T cell activated macrophages (stage 3 of the spread and progression of tuberculosis)
infected macrophages many form granulomas
TB granulomas are “tubercles” of immune cells that try to destroy invading pathogens (typically formed by macrophages)
the granulomas represent a “balance” between the pathogen and the host – the latent infection
—- TB can’t escape but the immune system can’t kill them all – stalemate: can have this for your whole life!
T cell activated macrophages can kill TB cells
— activated T cells can secrete cytokines (IFN-gamma) to activate the macrophages
— macrophages at the center of the granuloma remain hard to be activated by T cells which leads chronic inflammation causes “cheese-like” necrosis – aka caseous necrosis (cell death in which tissue maintains cheese-like appearance)
what is caseous necrosis?
cell death in which tissue maintains cheese-like appearance
seen during stage 3 of the spread and progression of tuberculosis: the formation of granulomas and killing by T-cell activated macrophages
describe the route of transmission and cavitation (stage 4 of the spread and progression of tuberculosis)
some macrophages remain
unactivated and infected
the tubercle grows
granuloma erodes into
the airway provides the route of transmission
deterioration of host immunity can result in active tuberculosis, a life threatening infection – most likely due to break down in T cell repsonses
the caseous center can liquefy leading to cavitation, essentially a granuloma post-mortem
what’s extrapulmonary tuberculosis? who is it more likely to occur in?
infection outside the lungs
can infect multiple organ systems (bone, joints, liver, spleen, gastrointestinal tract and brain)
more likely to occur in immunocompromised (e.g. HIV infected patients) individuals and young children
what is miliary tuberculosis?
a type of extrapulmonary tuberculosis that is more widespread
almost always fatal
what are ESX secretion systems? how many are there? what functions do they have?
5 ESX systems exist in mycobacteria tuberculsos
they enable the transport of select bacterial molecules across the thick cell envelope of mycobacteria tuberculsos
they also help damage the membrane of phagosomes in macrophages and also inhibit the immune responses
how is tuberculosis tested and diagnosed for?
tuberculin test = PPD or purified protein derivative from mycobacteria tuberculosis
— causes a T-cell mediated response
— if positive, will see red swollen circle at 48 hours
— a person is considered infected if they convert from negative to positive on a TB skin test
——- essentially, we look for if they have T cells that recognize TB antigens!
what does a positive result on TB testing mean?
latent or active TB
BCG vaccinated
previously infected and have been treated
what does a negative result on TB testing mean?
not infected
immunocompromised (e.g. AIDS)
not infected long enough
what do we look for on TB testing to see if someone is infected?
if they convert from negative to positive on TB skin test
if a TB test turns out positive, what must be done?
must collect careful history and chest x-ray
with an x ray, you’ll typically see upper lobe “shadowing” aka lesions – the x ray can also show calcified granulomas
can also conduct staining of sputum for acid fast bacilli and culturing AND interferon-gamma response assay
what is the treatment for tuberculosis?
six months of antibiotics for short treatment
– slow growth means long treatments
generally, multiple types of antibiotics are used:
– Rifampin (inhibits RNA polymerase)
– Isoniazid (inhibits mycolic acid synthesis)
– others…
multiple antibiotics are used to minimize chance of developing resistance (multiple strains surviving) – so e.g. if a cell develops resistance to rifampin, isoniazid will kill it
— don’t use antibiotics if you have the BCG vaccine!
if untreated, how many people could active tuberculosis kill?
active TB can kill approximately 2 out of 3 people if untreated
as an antibiotic used for TB, what does rifampin inhibit?
RNA polymerase
as an antibiotic used for TB, what does isoniazid inhibit?
mycolic acid synthesis
describe the BCG vaccine
bacille calmette guerin
live, reduced vaccine prepared from cultured M. bovis – grown in the lab many times, losing its virulence properties (lacks the ESX-1 secretion system)
BCG has shared antigenicity with TB
effective against miliary TB BUT has variable efficacy (0-80%) for pulmonary TB - thus controversial
—– can also leave large scars
recommended for individuals with high risk to exposure
NOT USED IN CANADA – we use a less effective vaccine to minimize scarring
describe the relationship between tuberculosis and HIV/aids (give stats)
those infected with HIV are more likely to develop active TB
—- 1/3 people with HIV are co-infected with TB
TB is leading cause of death in HIV-positive people
— Massive problem! the two are now intersecting
what is leprosy sometimes called?
hansen’s disease
how long is the incubation period of leprosy?
approximately 5 years
very slow progession
describe the permanent damages caused by leprosy?
can cause permanent damage to skin, nerves, limbs, and eyes
approximately 2 million people are permanently disabled by leprosy, mainly in tropical developing countries (this may be a low estimate due to low ragtes of reports because it’s a stigmatized disease)
——- but note it’s very rare in developed countries
where can mycobacterium leprae be found when in humans?
macrophages of skin
schwann cells in nerves
— schwann cells are normally wrapped around peripheral nerves and helps with action potential
why has mycobacterium leprae not been studied well?
cannot be cultivated in vitro
— it’s less well studied than mycobacterium tuberculosis
why, compared to tuberculosis, victims of leprosy are ostracized?
lesions in leprosy are visible but lesions in tb are hidden
weird, cause leprosy is much LESS infectious than TB!
what are the 2 major forms of leprosy?
tuberculoid leprosy
lepromatous leprosy
describe tuberculoid leprosy
cell-mediated immunity present
—- macrophage can contain
the bacteria
light coloured lesions with
“anesthetic” (no sense of feeling) areas
—- sometimes loss of hair and
pigmentation
patients become tuberculin positive (active T cell-mediated responses)
—- bacterial cells are generally not recoverable from lesions
tuberculoid Leprosy can be
self-limiting
—- immune system wins out and kills the organism
describe lepromatous leprosy
cell-mediated immune responses are absent
—- macrophages are not activated
M. leprae survives and multiples in macrophages and schwann cells
—- schwann cells provide myelin to peripheral nerves
nerve damage and loss of sensation leads to inadvertent traumatic lesions on the face and extremities
—- can cause loss of eyebrows, thickening and enlarged nares (nostrils), ears
and cheeks – a “lion like” appearance
lesions can become secondarily infected, eventually resulting in bone resorption, disfigurements and mutilation
how is leprosy transmitted?
most likely due to close/direct contact for extended periods of time
describe the treatment for leprosy?
also multiple drug therapy but with rifampin, dapsone, clofazimine
—- used for 6 months to 1 year for a full course of treatment
patients no longer transmit the disease after 1 dose of multiple drug therapy (MDT)
— can eventually eradicate this disease if everyone with leprosy takes drugs properly
