Lecture 11 - Tuberculosis Flashcards
what type of disease is tuberculosis?
a lung disease, but can sometimes become disseminated throughout the body
what causes tuberculosis?
caused by closely related strains of bacteria called the mycobacterium tuberculosis complex (some genetic differences)
describe the structure of M.tuberculosis
- complex lipid-rich cell wall
- acid fast bacilli
- unique, flaky scab looking arrangement
describe the features of m. tuberculosis
- grows very slowly (doubles in 24h)
- resistant to common antibiotics
- they live inside macrophages (oh noooo)
why is m. tuberculosis resistant to common antibiotics?
due to the complex cell wall and their slow growth
how is m. tuberculosis transmitted?
via the air
- bacilli released in droplets by infectious person.
- droplets survive for hours in the air
- settle in alveoli of lungs
what is the infectious dose of m. tuberculosis?
approximately 5 bacilli, very very low.
- probably a small clump worth
how does m. tuberculosis infect macrophages?
- bacilli are engulfed by alveolar macrophages and do not die
what are granulomas?
bacteria cause more macrophages and other immune cells to be recruited to the site of infection, which collect together to form an organised structure
- infected cells are contained/protected
what is the reason that bacteria create granulomas?
it gives them a protected space to grow, because they grow slowly
what happens when granulomas fail
- weaker immune system cause bacteria release into alveoli, which causes TB disease.
what is the containment phase of TB?
been exposed, innate and adaptive immunity has kicked in, granulomas form, then bacterial growth stops.
- the carrier is asymptomatic and not infectious
what percentage of people get infected from the inital TB exposure?
- 10% get the primary disease quartet
this depends on strain of TB and host immunity
what are the classic TB symptoms?
Quartet of symptoms:
- weight loss
- night sweats
- fever
- malaise
what symptoms do you get if TB is left untreated?
- chest pains and bloody cough due to lung damage
- patient is infectious
- if left longer then death
what is the untreated death rate of TB?
50%
does a person always stay in containment?
no, immunity breakdown can cause disease. approx 10% chance per year
- leads to reactivation disease and worsening symptoms
why is TB less common nowadays?
discovery of the fact it was an infectious disease, not a hereditary in 1882 caused drop in cases.
development of drugs reduced TB dramatically
when was the first antibiotic for TB produced?
in 1947
when was the first vaccine for TB produced?
in 1954
what caused the recent increase of TB cases in South africa?
due to the HIV epidemic in south africa
why do fatality rates differ in different places for TB?
access to drugs and care
name three historical interventions to prevent TB
- artificial pneumothorax
- milk pasteurisation
- streptomycin (first AB)
describe the incidence of TB in NZ
increased during WWII but dropped to very low ever since
what intervention reduced the TB in NZ even further from 2004?
Screening for TB in international students staying over 6 months
- should have treatment to allow no further transmission, dont just send those sorry suckers back home you prick
approximately how many people worldwide have TB?
2 billion (most wont know they are infected)
what was significant about the 8.2 million people being diagnosed with TB in 2023?
because this is an increase of TB after the pandemic which hasn’t happened for ages since the focus on trying to reduce it.
TB was the leading infectious disease killer until _____ , then ______ overtook it from _____ to ______, but now?
2020, covid, 2020-2022, but now TB is back to the leading infectious disease killer
who gets TB?
men tend to get more
- cases in every age bracket, most in 15-39 age bracket
what is the leading killer of people with HIV?
TB
160,000 deaths estimated in 2023
if you have HIV and contract TB, you are then classified as?
AIDS positive
most cases of HIV/TB are?
in africa, mostly south africa
what is the major treatment for those with HIV/TB
ART (antiretroviral therapy) for HIV
how many cases of TB were there in NZ in 2020?
311 total
254 from visit to GP
how many cases of TB were there in NZ in 2023?
more than 2020, 349 cases
what proportion of TB patients are admitted to hospital?
majority, it is a serious disease
what are the major TB risk factors in NZ?
- born outside NZ
- current or recent residence with someone outside NZ
- contact with confirmed case (little)
pete was diagnosed with TB. He moved to NZ from south africa 25 years ago and hasn’t been outside of NZ since. What statement about TB epidemiology does this prove?
the significance of the containment phase. Pete has had TB for at least 25 years and never shown symptoms
what is the vaccine we have for TB?
M. bovis bacille Calmette Geurin
aka BCG, derived from virulent isolate of bovine TB
how was the TB vaccine discovered?
TB from bovine was kept for 13 years on glycerinated potato medium containing beef bile, and by 1921 it has lost lots of virulence factors and it was shown to protect against M. Tuberculosis.
(wouldn’t be approved nowadays)
how many people have been given the TB vaccine and how is the efficacy?
more than 3 billion people, but efficacy varies, between 0-80% in trials, most effective in childhood
why does the efficacy of the TB vaccine vary?
because people may have been exposed to other mycobacterium prior to receiving the vaccine.
who is at risk when recieving the TB vaccine?
children that are HIV positive
how do we diagnose TB? (she usually asks a question about it)
- chest x-ray
- stain
- PCR
- Interferon testing
why is diagnosis of TB difficult?
because most people are asymptomatic
how can we use a chest x ray to diagnose TB?
shows evidence of a previous infection through pulmonary infiltrate and a ‘caving formation’
what do we do when someone suspected to have TB is coughing up sputum?
zeihl neelson stain - cheap solution
Gene Xpert - PCR based machine
Hains test - PCR based but cheaper
what is the acid fast test?
the ziehl neelson stain
how does Gene Xpert work?
expensive solution
very specifically amplifies M. tuberculosis complex DNA and amplifies DNA related to antibody resistance genes
- takes a few hours
how does the haines test work
DNA is extracted, then PCR is done, then compare to a list to see if M. Tuberculosis is present and if it is a stran that is resistant to rifampicin or isoniazid
- detects selected antibiotic resistance markers
- takes a day or so
what is interferon testing for tuberculosis?
done when patient may have been exposed to TB but not symptomatic (latent TB) as it can’t distinguish disease from a latent infection
- detects release of interferon by lymphocytes in response to mycobacterial antigens
what is the quantiferon gold test?
incubation of patients venous blood in a tube containing an M. Tuberculosis specific antigen. lymphoytes previously exposed to the disease will release interferon
- type of interferon test so can’t distinguish disease from asymptomatic
- fairly simple, no machines
what is the mantoux test?
0.1mL of tuberculin injected under the skin, if lymphocytes have been exposed to that antigen in the past, they will cause swelling in that area and release of interferon
- measure swell’s diameter at 2-3 days.
what is tuberculin?
a purified protein derivative extracted form the cell wall of mycobacterium tuberculosis, but is also found in other mycobacterial species such as M. bovis.
what is a flaw with the mantoux test?
since it can’t distinguish between a latent infection and can’t distinguish between types of mycobacteria
- blood test is specific for TB.
what is a positive result of the mantoux test?
a swelling formed with >5mm diameter
why do vaccinated people show a positive result on the mantoux test?
because the vaccine is from M. bovis, and the mantoux test can’t differentiate between types of myobacteria
what is the easiest treatment for TB?
directly observed short course (DOTS), which is a multidrug regimens taken for 6 months to try and stop resistance emerging
what are the phases of DOTS treatment for TB?
- two month intensive phase with isoniazid, rifampicin, pyrazinamide and ethambutol
- four month continuation phase with isoniazid and rifampicin
how many deaths were prevented with the DOTS treatment for TB?
53 million between 2000 - 2016
what are the side effects of DOTS?
- abdominal pain
- nausea
- joint pain
- burning feet
- rifampicin can make your urine red
what are the cons of DOTS treatment?
- promotes resistance
- long list of unpleasant side effects
what are MDR strains of TB resistant to?
rifampicin and isoniazid
what are pre-XDR and XDR-TB?
XDR = extremely drug resistant
pre-XDR = resistant to rifampicin and any fluroquinolone
XDR-TB = resistant to rifampicin, any fluroquinolone and bedaquiline or linezolid
which fluroquinolones are XDR strains resistant to?
levofloxacin and mexofloxacin
how many drug resistant TB cases were there in 2023 and how many deaths?
400,000 cases and 150,000 deaths
what is the trend we are observing with treatment success as time goes on?
more treatment success and less treatment failure
do we have drug resistant TB strains in NZ?
no
what happened to the one case of XDR-TB in NZ?
immigrant had it, was difficult because very specific drugs were required that we didn’t have in NZ. the person survived yayyyyyy
how can we prevent/control TB?
- eliminate pverty
- control animal TB
- isolation of infected patients
- better diagnosis
- faster and more tolerable drug treatment (main focus)
what is a major concern with TB for the future?
trump cut the funding for TB drugs, so we are anticipating up to 10,000,000 cases in the next 5 years
