tuberculosis

how many people are estimated to have latent TB worldwide?

1.7 billion - 1 in 4

how many cases of active TB were there in 2019?

10 million

what are the risk factors for TB?

- immunosuppression

- homelessness

- birth in an endemic country

which countries to WHO list as the most endemic to TB?

- India

- China

- Indonesia

- The Philippines

- Pakistan

- Nigeria

- Bangladesh

- South Africa

what is given to babies who were born or whose parents were born abroad?

BCG vaccine

what are the 2 phases of tuberculosis?

- latent

- active

what is latent TB?

individuals who are infected with TB but have no active disease, no symptoms and are not infectious

what is active TB?

individuals who are symptomatic and have the progressive disease

what bacterium causes tuberculosis?

mycobacterium tuberculosis

what type of bacterium is mycobacterium tuberculosis?

gram positive bacillus

what happens when doing a gram stain with mycobacterium tuberculosis?

does not the hold stain well - acid-fast bacilli (afb)

what property do acid fast bacilli (AFB) have?

resistance to decolourisation of staining by acid

which stain should be used instead?

Ziehl-Neelsen stain

what colour will the Ziehl-Neelsen stain in the presence of TB?

bright red

what are the 4 types of mycobacterium are capable of causing TB in humans?

- mycobacterium tuberculosis - only humans can host

- mycobacterium bovis - cattle and other mammals

- mycobacterium africanum - seen in west Africa

- mycobacterium microti - other mammals

what are these 4 mycobacterium called?

mycobacterium complex (MTc)

do mycobacterium requre oxygen to grow?

yes

what is the technical name of requiring oxygen to grow?

obligate aerobes

where can mycobacterium grow?

can grow extracellularly, but advantageous to grow intracellularly - facultative intracellular

what can happen after the initial inhalation of mycobacterium tuberculosis?

- infection cleared straight away (breathed back out)

or

- primary TB

what is primary TB?

- infection present but suppressed by immune system

- asymptomatic

what can primary TB lead to ?

- progressive-primary TB

- latent TB

what is progressive-primary TB? (2)

- primary infection is not suppressed

- prolonged infection occurs

what can progress from latent TB?

post-primary TB

what is post-primary TB?

- also called reactivation

- usually due to immunocompromisation

what drug can cause post-primary TB?

infliximab - for rheumatoid arthritis and IBD

what happens when mycobacterium tuberculosis is inhaled at a microscopic level? (3)

- it can evade the mucociliary escalator

- through bronchioles and into alveoli

- usually into the middle and lower lobes first

what happens to the TB in the alveoli? (3)

- usually would be engulfed by alveolar macrophages (dust cells) and then digested by lysozymes

- but TB inhibits lysozymes and proliferates

- causing primary TB

what happens once a critical mass of TB is created in the lungs?

triggers cell-mediated immune response

what molecules on TB stimulated the macrophages?

CORD factor

is TB an exogenous or endogenous pathogen?

exogenous

which class of major histocompatibility complex (MHC) proteins will be activated?

class II

which type of cells will be activated from class II MHCs?

CD4+ cells

what will CD4+ cells release?

interferon gamma

what does interferon gamma do?

stimulates macrophages to secrete (tissue/tumour necrosis factor) TNF-alpha

what do the macrophages then do? (4)

- encircle a group of TB

- the inside dies and becomes necrotic

- the outside stays alive

= small caseating granuloma

what is a small caseating granuloma also called?

Ghon focus

what does a Ghon focus look like?

cheese :D

what can happen if the TB spreads into the lymphatic system?

a network of ghon foci develops in the lungs and lymphatics = Ghon's complex

what is it called when the Ghon's complex gets calcified?

Ranke complex

what happens if the infected persons immune system is compromised?

TB can be reactivated, the ranke complexes can no longer be maintained

where can the TB go first?

upper lobes of the lungs

why does the TB go to the upper lobes first?

most oxygen concentrated

what does this cause in the upper lobes?

lesions

what are the 3 ways that TB can spread?

- bronchogenic

- lymphatic

- circulatory

what can bronchogenic spread cause?

bronchopneumonia

what can lymphatic spread cause?

swelling in cervical nodes = scrofula

what does miliary tuberculosis mean?

tuberculosis spreads through the blood

what can you see on x-ray with miliary TB?

millet seeds

where are the 5 places that TB mainly spreads to via the blood?

- kidneys

- meninges

- lumbar vertebrae

- liver

- adrenal glands

what problems does TB cause for the kidneys? (3)

sterile pyuria:

- elevated WBC in urine

- cannot grow on culture (hence sterile)

what problems does TB cause for the meninges?

meningitis

what problems does TB cause for the lumbar vertebrae? (4)

Pott's disease:

- lower back pain

- microfractures

- inflammation

what problems does TB cause for the liver?

hepatitis

what problems does TB cause for the adrenal glands?

Addisons disease:

- effects sex steroids, catecholamines, mineralocorticoids

what are the symptoms of pulmonary tuberculosis? (4)

- fever

- nightsweats

- haemoptysis

- unplanned weight loss

- could have SOB

how would you diagnose TB?

1) skin or blood test

2) chest X-ray

what is the main skin test used?

mantoux test

what does the mantoux test involve?

- intradermal injection of tuberculin (protein derivative of mycobacterium TB)

- if patient has had TB they will have a type 4 hypersensitivity reaction

what can interfere with the mantoux test?

- previous BCG vaccination (for TB)

- mantoux test should be used prior to BCG vaccination

what is the blood test used?

interferon-gamma release assay (IGRA)

what does IGRA test for?

- the bodies cellular immune response to TB

- so tests whether person currently has TB

what is taken along with a chest X-ray?

sputum samples

what would they be looking for in a chest X-ray?

lesions

what is the treatment for latent TB?

isoniazid for 9 months

what must someone do if they have active TB?

quarantine for 2-3 weeks

what is the mneumonic for the drugs used in active TB?

R

I

P

E

what does RIPE stand for?

Rifampicin

Isoniazid (+ pyridoxine)

Pyrazinamide

Ethambutol

what does rifampicin do?

inhibits RNA polymerase and hence bacterial RNA synthesis

what does isoniazid do?

inhibits mycolic acid synthesis

what are the side effects of isonaizid?

peripheral neuropathy (pin and needles)

what is taken along side isonaizid to prevent peripheral neuropathy?

pyridoxine

what does pyrazinamide do?

inhibits cell wall synthesis

what is a side effect of ethambutol?

red-green colour blindness

why do we give all these drugs at once?

giving just one of the drugs increases the chance of TB becoming resistant

what is the difference in diagnosing a typical from an atypical pneumonia?

typical - can give co-amoxiclav

atypical - by a pathogen that cannot be gram stained

what is the first line treatment for active TB?

- RIPE for 2 months

- RI for further 4 months

(4 for 2, 2 for 4)

what is the first line treatment for latent TB?

- isoniazide for 6 months

OR

- isoniazide + rifampicin for 3 months