15. Mycobacteria Flashcards
how do we know TB is very old?
we have found it in the spines of egyptian mummies
why are mortality rate for TB higher today then in the past?
as we have a much larger population
why are cases of TB declining?
less poverty
better public health
better sanitation
antibiotics and TB treatments
how did the WHO help with TB?
gave funding and infrastructure that sat above countries and improved cases
Why were TB cases increasing again?
resurgence of disease due to lack of funding
break down in local infrastructure
rise of HIV caused rise of TB
why are there fewer deaths in HIV patients with TB?
Due to improved retroviral treatments for HIV
why do TB cases appear to be declining?
larger population so cases per 100,000 are declining but overall cases are increasing
why does having TB make you more susceptible to HIV?
TB activates NF-kB which drives HIV replication making a higher viral load
TB recruits CCR5 cells which is a target for HIV viruses
why are you more likely to catch HIV when you have gonorrhoea?
more active T cells at mucosal surface for HIV virions to infect
why is MDR TB more prevalent in HIV patients?
no immune system so the selection pressure only comes from the drug
less fitness cost as no immune system to fight
what is a worrying burden for TB?
> 500 cases per 100,000
mycobacterium tuberculosis info
obligate aerobe
bacillus - straight or curved rods
non-motile and non spore forming
what’s abnormal about TB cell wall?
gram + but appear gram -
mycolic acid waxy outer layer gives the impression of a second membrane and can trap the stains so appearing gram -
waxy layer can exclude all dyes
what is the reservoir for TB?
only humans
so its a perfect candidate for eradication
what is the doubling time for TB?
12-24hours
what do TB colonies look like?
compact, crenellated yellow
what media does TB need to grow?
use Lowenstein-jensen solid medium
high in fatty acids
why is the slow onset of TB a problem?
problem for diagnosis so cannot detect disease
why was TB called consumption?
die of lack of oxygen function
not enough oxygen
fashionable to loose weight in victoria era
what does TB do to lungs?
granuloma formation
can spread to other organs
what is primary TB infection?
onset is gradual
infection is established before patients become aware
often mild
90% cases are asymptomatic
what is secondary latent infection of TB?
reactivation of dormant infection
happens usually when you become immunocompromised
pathology of TB
tubercle granuloma looks epithelial but not epithelial
B, T cells and fibroblasts surround the tubercle
causes caseous necrosis
TB is not restricted to the lungs so where can it disseminate?
lymph nodes
meninges
pericardial
bone and spine
renal
all form tubercles
where does initial TB infection take place?
in macrophages in the lungs
overcome phagosome
cause fusion of the macrophages to form multinucleate giant cells
what are the later steps of TB infection?
attract T cell to try stimulate the macrophage
release of pro inflammatory cytokines
attract fibroblasts which form tubercle
could disseminate to another area in the lungs
what are the important features of granulomas?
prevent dissemination of the mycobacteria
contain macrophages, T cells, B cells and fibroblasts
if the bacteria is not eliminated in the granuloma the infection will become latent
how long can latent TB survive in granulomas?
for years but includes subclinical disease as well as controlled disease
how does TB escape the phagosome?
proteins
PknG - serine kinase
SapM - phosphatase
when was TB genome sequenced?
1998
how was the BCG vaccine made?
Cattle TB subcultured repeatedly to make an attenuated strain. with each subculture it loses pathogenicity
innert
cross protection - worked okay
how can the BCG vaccine be improved with genomics?
shows the differences between vaccine strain and human strain
why is the BCG not as effective as it could be?
it targets highly conserved antigens but missed the active virulence factors that would be the more effective target
what is the role of the region of difference?
encodes a type 7 secretion system and other proteins that aid phagosome survival
ESAT-6
CFP-10
why is TB diagnosis hard?
slow onset and slow growth time
lack highly sensitive and rapid testing
tuberculin sensitivity test
prick with purified protein from tuberculin and shows if there is an immune response suggesting a previous infection
ways to better diagnosis
smear microscopy $1 but only about 50% sensitivity
Point of care tests - dipstick urine test (best for immunocompromised, $3.50) Automated machine testing - very expensive and limited testing
why don’t antibiotics work well for TB?
antibiotics target active processes like replication but all TB processes are so slow that antibiotic treatment lasts 6 months minimum
high resistance
what is directly observed treatment, short course?
still 6 months
have to be observed taking it every
working
what is the biggest downfall of BCG vaccine?
doesn’t work very well for the most common lung TB
containment level 3 so not many facilities do the research
why is it hard to run TB vaccine clinical trials?
so many people had BCG vaccine there are not many naive people left
only young people
