Tuberculosis (Marta Martins lecture 4)

which bacterium causes tuberculosis?

mycobacterium tuberculosis

which 3 contries have the most cases of TB?

india, indonesia and china

are women or men more affected by tuberculosis?

men

The … vaccine is effective at preventing … tuberculosis and … … in … and …, but does not confer protection in …

Protection wanes over time, usually lasting about …

BCG, severe tuberculosis, tuberculous meningitis, infants, children, adults

5-15 years

what does XDR TB stand for?

extensively drug resistant TB

… tuberculosis is a severe, often life-threatening infection that spreads from the … to multiple organs via the … or … system

disseminated, lungs, bloodstream, lymph

3 clinical stages of tuberculosis

1. primary

2. secondary

3. disseminated

what does MDR TB stand for?

multidrug resistant TB

Primary MDR TB occurs when there is an infection with a strain of M. tuberculosis that is …

Secondary MDR TB occurs when there is an infection with a strain of M. tuberculosis that … due to … or … treatment

already resistant to one or more drugs

becomes drug resistant due to inappropriate or inadequate treatment

probability of transmission and infection depends on:

1. …

2. type of …

3. length of …

1. infectiousness

2. type of environment

3. length of exposure

TB spreads through … particles that contain M. tuberculosis called … …

Transmission occurs primarily when an infectious person … or …

… contact is needed for transmission

airborne particles, droplet nuclei

coughs or sneezes

prolonged

In … TB the infection is situated in the lungs

In … TB the infection speads to other parts of the body such as …

In … TB tubercle bacilli enter the … and are carried to all parts of the body

pulmonary

extrapulmonary, larynx, lymph nodes, brain and spine, bones and joints and kidneys

disseminated, bloodstream

in a latent TB infection, … form which are small granulomas, often featuring central … … lesions which heal by …

tubercules, caseous necrosis, calcification

Tuberculosis can be tested for by performing a … … test where a dermal injection of …/… is given and the diameter of the swollen area is measured

The test is considered positive if the diameter of the swollen area is bigger than …

tuberculin skin test, tuberculin/PPD

5mm

Chronic tuberculosis occurs when … filled with bacteria expand and drain into … tubes and the … … …

Symptoms include …

tubercules, bronchial tubes and the upper respiratory tract

productive prolonged cough, chest pain, hemoptysis, fever and night sweats

extrapulmonary TB is more common in … patients and in …

immunosuppressed, children

3 types of granulomas

1. caseous

2. non necrotising

3. fibrotic

people at a higher risk of developing or progressing to the active TB disease

1. HIV infected people

2. people taking TNF alpha antagonists

3. malnourished people

4. injection drug users

the four antibiotics used to treat TB and their functions

1. isoniazid inhibits mycolic acid synthesis

2. rifampicin targets RNA polymerase

3. pyrazinamide disrupts energy metabolism

4. ethambutol disrupts cell wall synthesis

what does DOT stand for?

directly observed therapy

what type of resistance does a M. tuberculosis bacterium have if it is resistant to at least the first line drugs isoniazid and rifampicin?

MDR TB

what type of drug resistance does M. tuberculosis have if it is resistant to the first line drugs isoniazid and rifampicin and to specific second line drugs?

XDR TB

what type of drug resistance does M. tuberculosis have if it is resistant to a wider range of drugs that strains classified XDR TB?

TDR TB

which type of resistance can be overcome and treated with second-line drugs?

MDR TB

is M. tuberculosis gram positive or negative?

neither

… … … are bacteria with …, … rich cell walls (with … acid) that resist decolorization by … … during staining

acid fast bacilli, waxy, lipid, mycolic, acid alcohol

… … is a … virulence factor located on the surface of M. tuberculosis cell walls. It causes bacteria to grow in characteristic …

cord factor, glycolipid

chains

3 glycolipids which act as virulence factors in MT cell wall

1. cord factor

2. lipoarabinomannan

3. phosphatidylinositol mannosides

which proteins are major components of the antibiotic resistance mechanism in Mtb?

efflux pumps

Mtb specific antigens such as … and … are encoded by genes in … which is not present in … … or the majority of other … → they induce production of … and they serve as … … for idntification of Mtb

ESAT6, CFP10, RD1, BCG vaccine, mycobacteria, INF gamma, specific markers

Mtb can enter a … … state under stress, forming … cells that are hard to kill with antibiotics

dormant latent, persister

Persister cells of Mtb are not … mutants, rather they are … … of the bacterial population

They are usually … growing, they arise by … and are tolerant to bactericidal …

genetic mutants, phenotypic variants

non or slow, chance, antibiotics

3 examples of evasion strategies by Mtb

1. pH changes - it interferes with normal acidification of the phagolysosome

2. inhibition of oxidative burst - it reduces the production of ROS that would normally kill it

3. inhibition of phagosome lysosome fusion

Primary TB is the disease during … infection

Secondary TB is the … of the disease or a … disease

initial

reactivation, post primary