27: Tuberculosis Flashcards
originally called…
consumption because patients appeared as if being consumed from within
weight loss, gaunt appearance, etc.
symptoms
bloody cough
weight loss (wasting)
fever, nausea
progresses slowly but almost always leads to death if untreated
industrial revolution
causing disease for at leat 50,000 years but increased during the industrial revolution
responsible for 1/7 of deaths during the 19th century
cases and deaths in present day
10M new symptomatic (active) TB cases annually
~1.6M deaths annually
- more than any other infection disease until COVID
TB comparison with COVID
basically causing a COVID-scale pandemic annually for more than 200 years
where do TB deaths occur?
> 90% occur in the developing world
lethal synergy between HIV-AIDS and TB
co-infection with HIV is a huge problem
- of 1.6M deaths, 200K in HIV-infected people
AIDS characterised by a decrease in CD4 T cells which are critical to control TB
mycobacterium tuberculosis discovery
1882 by Robert Koch
second bacterium discovered and showed to cause an infectious disease
Koch’s postulates
scientific methodology to prove that it was caused by bacteria
- suspected microbe must be identified in infected patients, but not healthy individuals
- suspected microbe must be grown in pure culture
- when introduced in a healthy host, the suspected microbe must cause disease similar to human disease
- same microbe must be isolated from diseased host
characteristics of mycobacterium tuberculosis
non-motile
- no flagellum
humans are the only natural reservoir
- since coughing is the main way for transmission
stained and visualised with acid fast stain
intracellular bacterial pathogen
- can hide within host cells, allowing it to avoid extracellular immune defenses
thick waxy coat
- intrinsic resistance to immune responses/antibiotics
mycobacterium tuberculosis grows very slowly
divides every 20 hours
- very slow-growing
takes 2-3 weeks to form a colony
hard to work on/diagnose/perform rapid antibiotic susceptibility testing/treat
waxy coat of mtb
made up of mycolic acids and other lipids
normal bacteria only have the membrane and peptidoglycan which make up the cell wall
mtb is aerosol transmissible
after inhalation, replication in alveolar macrophages
- typically, when breathing in harmless bacteria, it goes into air sacs and macrophages kill it
infectious dose is very low
alveolar macrophages are unable to kill mtb
- waxy protective coat
- disruption of phagosome maturation
most bacteria engulfed by alveolar macrophages are killed in lysosomes
engulfed, goes into an early endosome (membrane-bond compartment), fusion with lysosomes which then degrade and destroy bacterium
killing of bacterium in lysosomes depends on acidification of the phagosome
mtb avoids being killed by stopping phagosome maturation
phagosome never fully acidifies because of the block, so pH stays neutral and not enough fusion with lysosomes
tuberculosis life cycle
breathed in, taken into lungs, get taken up by alveolar macrophages and bacteria starts to grow
bacteria continues to grow and forms granulomas
- then divergence in outcomes
if bacteria still grows, large lesions in lungs and patients develop symptoms
another outcome where bacteria aren’t killed but also don’t grow
- stalled stage and standoff between immune system and bacteria
active disease is associated with
uncontrolled lung inflammation in about 10% of infected individuals
granulomas
organised aggregates of immune cells and bacteria
immune response that helps contain but not eliminate mtb
- without elimination, always susceptible to reactivation
conversion from latent to active TB
normally, 5% chance of conversion within a year of being infected and total 5-15% chance in remaining lifetime
for someone with AIDS, 8% chance of conversion annually and 80% change within 10 years
patients on anti-TNF also have an increased risk of reactivation
diagnosis of active TB
chest x-rays
smear test
culture test
diagnosing active TB: chest x-ray
lots of abnormalities so not always super obvious
cloudiness and central cavitative park
diagnosing active TB: smear test
patients cough up sputum and bacteria can be visualised with acid-fast tain
inexpensive, rapid and specific (low rate of false positives)
but test is not sensitive enough (high rate of false negatives)
only gives positive if >10k bacilli/mm of sputum
- cannot detect latently infected patients
diagnosing active TB: culture test
more sensitive than sputum test, so gold standard
- but very very slow and more difficult
diagnosis of latent TB
tuberculin skin test
interferon gamma release assay (IGRA)
no method of diagnosis to detect viable bacteria so it is diagnosed indirectly by looking for the presence of an immune response
diagnosing latent TB: tuberculin skin test (TST) - mantoux test
purified protein derivative injected into skin
bump forms due to an immune response which indicates previous exposure to mtb
anyone given the BCG vaccine also gives a positive TST even without infection
diagnosing latent TB: interferon gamma release assay
detection of a cytokine called interferon gamma produced by T cells in response to mtb
detects antigens unique to mtb and not found in BCG so can be used to detect mtb in BCG-vaccinated individuals
antibiotic treatments for TB
in general, can cure someone with TB as long as the bacteria is susceptible to antibiotics
first-line antibiotics for simple cases
- isoniazid
- rifampin
second-line antibiotics
- fluoroquinolones
antibiotics for drug-sensitive TB
6 months of first-line treatment is standard
for multiple drug-resistant TB, often requires 1-2 years of treatment with second-line antibiotics
