15. Mycobacteria

Question 1

how do we know TB is very old?

Answer 1

we have found it in the spines of egyptian mummies

Question 2

why are mortality rate for TB higher today then in the past?

Answer 2

as we have a much larger population

Question 3

why are cases of TB declining?

Answer 3

less poverty
better public health
better sanitation
antibiotics and TB treatments

Question 4

how did the WHO help with TB?

Answer 4

gave funding and infrastructure that sat above countries and improved cases

Question 5

Why were TB cases increasing again?

Answer 5

resurgence of disease due to lack of funding
break down in local infrastructure
rise of HIV caused rise of TB

Question 6

why are there fewer deaths in HIV patients with TB?

Answer 6

Due to improved retroviral treatments for HIV

Question 7

why do TB cases appear to be declining?

Answer 7

larger population so cases per 100,000 are declining but overall cases are increasing

Question 8

why does having TB make you more susceptible to HIV?

Answer 8

TB activates NF-kB which drives HIV replication making a higher viral load
TB recruits CCR5 cells which is a target for HIV viruses

Question 9

why are you more likely to catch HIV when you have gonorrhoea?

Answer 9

more active T cells at mucosal surface for HIV virions to infect

Question 10

why is MDR TB more prevalent in HIV patients?

Answer 10

no immune system so the selection pressure only comes from the drug
less fitness cost as no immune system to fight

Question 12

what is a worrying burden for TB?

Answer 12

> 500 cases per 100,000

Question 13

mycobacterium tuberculosis info

Answer 13

obligate aerobe
bacillus - straight or curved rods
non-motile and non spore forming

Question 14

what’s abnormal about TB cell wall?

Answer 14

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

Question 15

what is the reservoir for TB?

Answer 15

only humans
so its a perfect candidate for eradication

Question 16

what is the doubling time for TB?

Answer 16

12-24hours

Question 17

what do TB colonies look like?

Answer 17

compact, crenellated yellow

Question 19

what media does TB need to grow?

Answer 19

use Lowenstein-jensen solid medium
high in fatty acids

Question 20

why is the slow onset of TB a problem?

Answer 20

problem for diagnosis so cannot detect disease

Question 21

why was TB called consumption?

Answer 21

die of lack of oxygen function
not enough oxygen
fashionable to loose weight in victoria era

Question 22

what does TB do to lungs?

Answer 22

granuloma formation
can spread to other organs

Question 23

what is primary TB infection?

Answer 23

onset is gradual
infection is established before patients become aware
often mild
90% cases are asymptomatic

Question 24

what is secondary latent infection of TB?

Answer 24

reactivation of dormant infection
happens usually when you become immunocompromised

Question 25

pathology of TB

Answer 25

tubercle granuloma looks epithelial but not epithelial
B, T cells and fibroblasts surround the tubercle
causes caseous necrosis

Question 26

TB is not restricted to the lungs so where can it disseminate?

Answer 26

lymph nodes
meninges
pericardial
bone and spine
renal
all form tubercles

Question 27

where does initial TB infection take place?

Answer 27

in macrophages in the lungs
overcome phagosome
cause fusion of the macrophages to form multinucleate giant cells

Question 28

what are the later steps of TB infection?

Answer 28

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

Question 29

what are the important features of granulomas?

Answer 29

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

Question 30

how long can latent TB survive in granulomas?

Answer 30

for years but includes subclinical disease as well as controlled disease

Question 31

how does TB escape the phagosome?

Answer 31

proteins
PknG - serine kinase
SapM - phosphatase

Question 32

when was TB genome sequenced?

Answer 32

1998

Question 33

how was the BCG vaccine made?

Answer 33

Cattle TB subcultured repeatedly to make an attenuated strain. with each subculture it loses pathogenicity
innert
cross protection - worked okay

Question 34

how can the BCG vaccine be improved with genomics?

Answer 34

shows the differences between vaccine strain and human strain

Question 35

why is the BCG not as effective as it could be?

Answer 35

it targets highly conserved antigens but missed the active virulence factors that would be the more effective target

Question 36

what is the role of the region of difference?

Answer 36

encodes a type 7 secretion system and other proteins that aid phagosome survival
ESAT-6
CFP-10

Question 37

why is TB diagnosis hard?

Answer 37

slow onset and slow growth time
lack highly sensitive and rapid testing

Question 38

tuberculin sensitivity test

Answer 38

prick with purified protein from tuberculin and shows if there is an immune response suggesting a previous infection

Question 39

ways to better diagnosis

Answer 39

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

Question 40

why don’t antibiotics work well for TB?

Answer 40

antibiotics target active processes like replication but all TB processes are so slow that antibiotic treatment lasts 6 months minimum
high resistance

Question 41

what is directly observed treatment, short course?

Answer 41

still 6 months
have to be observed taking it every
working

Question 42

what is the biggest downfall of BCG vaccine?

Answer 42

doesn’t work very well for the most common lung TB
containment level 3 so not many facilities do the research

Question 43

why is it hard to run TB vaccine clinical trials?

Answer 43

so many people had BCG vaccine there are not many naive people left
only young people