TB

Question 1

who identiried the infectious nature of TB?

Answer 1

robert Koch- Kochs postulates

Question 2

what bacteria causes TB? what are its traits?

Answer 2

• Mycobacterium tuberculosis.
• Aerobic, gram positive, acid-fast bacilli.
• Highly unusual cell surface made up of
  lipids and mycolic acid.
• Intracellular - Able to survive inside
  macrophages.

Question 3

how is TB transmitted?

Answer 3

• Transmitted by aerosolised droplet from an
  infected patient
• Inhaled into the alveoli of a new host

Question 4

what are the outcomes of being infected with TB?

Answer 4

– Primary Tuberculosis (first infection)
– Complete clearance
– Post-primary Tuberculosis (re-infection)
– Active Tuberculosis
– Latent Tuberculosis

Question 5

how does primary TB occur?

Answer 5

Mostly affects lungs – Pulmonary
Tuberculosis
* Results in an area of granulomatous
inflammation– Seen as a shadow on an x-ray, in TB it is called a Ghon focus

Question 6

what is the result of 90% of primary TB?

Answer 6

90% of people will never develop active
disease due to a competent immune
response.

Question 7

what is latent TB?

Answer 7

the bacillus may continue to reside trapped inside the granuloma.

Question 8

how do you detect latent TB?

Answer 8

• A skin prick test - the tuberculin
  test. Is able to detect this hypersensitivity

Question 9

what can trigger reactivation to latent TB?

Answer 9

abnormalities in cell mediated immunity

Question 10

what is used to eradiacte latent TB?

Answer 10

• Extended antibiotic regimes used to
  eradicate latent TB

Question 11

what is active or post-primary active TB?

Answer 11

• Small percentage develop at first acquisition.
• More commonly reactivation of latent TB infection.
• May be induced if patient becomes immunocompromised
  – E.g. HIV, chemotherapy, high dose corticosteroids.
• Results in an aggressive immune reaction which leads to large granulomas with a “cheesy” contents called caseation.

Question 12

what does active TB look like on x-ray?

Answer 12

• In the lungs this material is coughed up which leads to large cavitating
  lesions (observed on x-ray)

Question 13

what is the 2-year mortality rate of untreated active TB ?

Answer 13

50%

Question 14

where does extrapulmonary TB cause disease?

Answer 14

at almost ant site in the body

Question 15

what usually causes extrapulmonary TB?

Answer 15

Usually caused by reactivation of latent infection

Question 16

what are the most common sites of extrapulmonary tb?

Answer 16

– Lymph nodes; pleura; gastrointestinal tract; bone and CNS

Question 17

what is disseminated disease?

Answer 17

(Miliary tuberculosis)
– Bacilli transported in blood or lymphatic system
– May develop as a primary infection or post primary reactivation.
– Can affect many organs and may cause diagnostic delay,
particularly if the lungs are not infected.
– More often presents in children and immunocompromised

Question 18

what is the clinical presentation of active TB?

Answer 18

– cough, weight loss, fever, night sweats, fatigue, dyspnoea, chest pain, haemoptysis.

Question 19

how do you diagnose active TB?

Answer 19

• Respiratory
  – Chest X ray
  – Acid fast bacilli test and (multiple) sputum cultures.
  – Rapid diagnostic nucleic acid amplification tests (NAAT) often
  this is a PCR test (polymerase chain reaction)
• Non respiratory
  – Biopsy / needle aspiration (culture)
  – Culture any surgical / radiological sample
  – MRI /CT / Ultrasound as appropriate
  – Chest X ray ( to confirm/exclude respiratory disease)

Question 20

how do you initially manage pulmonary TB in hospital?

Answer 20

• In hospital management – infection control measures required
  – Patient must be isolated (single room) if possible
  – Personal protective equipment (PPE), staff and visitors.
  – Negative pressure room if high risk of multi–drug resistant TB (MDR-TB)

Question 21

how do you initially manage pulmonary TB in community?

Answer 21

– Advise patient the disease is highly contagious (When active)
– Avoid work / school / crowded places
– Wear face mask in public during first 2 weeks of treatment

Question 22

what are the two phases of treatment of pulmonary TB?

Answer 22

– Intensive (Initial) phase treatment- normally lasting two months with 4 drugs
– Continuation phase- usually 4-7 months, with 2 drugs

Question 23

what is the standard treatment for pulmonary TB?

Answer 23

– Initial - rifampicin, isoniazid (with pyridoxine), pyrazinamide and ethambutol for 2 months
– Continuation - rifampicin, isoniazid (with pyridoxine) for a further 4 months.

Question 24

what is rifampicin? how does it work?

Answer 24

• Bactericidal, blocks RNA polymerase and therefore prevents protein formation.
• Important member of the initial phase treatment
• Kills slowly replicating bacteria throughout the whole course.
• More active than isoniazid in the anaerobic environment of the caseous lesion

Question 25

when is rifampicin absorption reduced?

Answer 25

* Readily absorbed from the gastrointestinal tract. * This is reduced if ingested with food.

Question 26

what are the adverse effects of rifampicin?

Answer 26

– Red orange discolouration of body fluid (stains contact lenses) – Liver damage * Common to see elevated liver enzymes, may reflect inflammatory response from disease or a reaction to treatment. * Enzymes at 4x Upper Limit of Normal (ULN) suggest stopping drug treatment. * Powerful enzyme inducer major possibility of drug interactions

Question 27

how does isonaizid work?

Answer 27

* Inhibits the synthesis of the mycolic acids required for the cell wall. * Bactericidal and very effective at killing rapidly multiplying mycobacteria. * Acts rapidly to reduce initial bacterial load.

Question 28

when is isoniazid given?

Answer 28

* Given throughout entire treatment phase to supplement rifampicin.

Question 29

where is isonaizid metabolised?

Answer 29

* Metabolised in the liver. * Acetylation - can be fast or slower. * This can effect the half life

Question 30

who is most likely to have more adverse effects from isonaizid? why?

Answer 30

* Slow acetylates and advance HIV more likely to have adverse effects.

Question 31

what are the adverse effects of isonaizid?

Answer 31

– Hepatotoxicity – Nausea and vomiting – Hypersensitivity reaction – Peripheral neuropathy (PN)

Question 32

how do we try and avoid peripherap neuropathy with isonaizid?

Answer 32

supplement with B6 (pyridoxine)

Question 33

what is pyrazinamide? where does it work?

Answer 33

* Bacteriostatic * Only works in acidic pH - which occurs inside macrophages in the tubercle

Question 34

why is pyrazinamide only effective for a short time?

Answer 34

* Only works in acidic pH - which occurs inside macrophages in the tubercle. * The number of these decrease later in therapy, explaining why this is no longer effective.

Question 35

what are the side effects of pyrazinamide?

Answer 35

– Hepatotoxicity – Rashes – Urticaria - gout

Question 36

what kind of drug is ethambutol?

Answer 36

Bacteriostatic

Question 37

what is the most signifigant side effect with ethambutol?

Answer 37

optic neuritis. * Manifests as visual alteration, particularly loss of redgreen colour discrimination, progressing to a loss of visual acuity

Question 38

what is the standard treatment for continuation phase?

Answer 38

Standard treatment is with rifampicin and isoniazid for a further four months after initiation.

Question 39

what is the risk of non-adherence with TB?

Answer 39

* previous non-adherence, previous treatment failure, history of homelessness, drug or alcohol misuse, in prison/detention centre, cognitive or psychological disorders, MDR-TB * Also offer if significantly unwell or the patient requests.

Question 40

what are ways of promoting adherence?

Answer 40

– Includes Directly Observed Therapy (DOT) * Medication provided in an appropriate form * Patient reminders for appointments * Extensive patient counselling + written information in appropriate language * Home visits * Random urine tests and other monitoring * Access to free TB treatment for everyone * Social and psychological support (including cultural case management and broader social support) * Incentives and enablers to help people follow their treatment regimen

Question 41

when would there be a treatment interruption?

Answer 41

At least 2 weeks missed or 20% of doses in initial phase = “treatment interruption” * Care needed to re-establish treatment

Question 42

what is multi-drug resistant TB?

Answer 42

– strains which are resistant to both rifampicin AND isoniazid

Question 43

what is extensive drug resistant TB?

Answer 43

– strains resistant to at least rifampicin and isoniazid, a fluoroquinolone and one or more of the three available second line injectable drugs: * kanamycin, amikacin, capreomycin

Question 44

who are at high risk of being resistant?

Answer 44

* Previous TB drug treatment, particularly with poor adherence * Contact with a known case of multidrug resistant TB * Birth or residence in “WHO Hot Spots”

Question 45

what are examples of novel therapies for multi and extensive drug resistant TB?

Answer 45

Bedaquiline Delamanid

Question 46

how does having HIV affect TB?

Answer 46

* The risk of developing TB is estimated to be between 26 and 31 times greater in people living with HIV

Question 47

how do you manage HIV-related TB disease?

Answer 47

– Drug Interactions * Rifampicin with antiretroviral agents (e.g. some of the protease inhibitors and non-nucleoside reverse transcriptase inhibitors).

Question 48

how do you diagnose latent TB?

Answer 48

* Mantoux test offered to: – Household contacts and non household close contacts of patients with active TB – people who are immunocompromised and at high risk of – new entrants from high incidence countries presenting for health care

Question 49

how do you treat latent TB?

Answer 49

3 months of isoniazid and rifampicin OR 6 months of isoniazid

Question 50

what is the vaccination against TB?

Answer 50

The Bacillus Calmette Guérin (BCG) vaccine

Question 51

who is BCG given to?

Answer 51

* National programme withdrawn in 2005. * Now selective neonatal vaccination and those at high risk, under the age of 35.