Tuberculosis

Question 1

Describe the structure of mycobacterium tuberculosis?

Answer 1

• areobic non spore forming bacteria
• Cell wall: high lipid content - acid fast bacilli
• Generation time is slow - 12 hours

Question 2

How is TB transmitted?

Answer 2

airborne transmission - droplets from a cough

Question 3

What is primary TB?

Answer 3

Initial TB infection which may lead to clinical disease (leading to hematogenous spread)

Question 4

What is latent TB?

Answer 4

Primary TB Infection contained by the immune system = No Disease = NOT SICK = NOT INFECTIOUS
Note: person has contact with M tuberculosis but has no signs of clinical disease

Question 5

Tests for latent TB?

Answer 5

1. tine test
2. Igra tests

Question 6

What is post-primary TB?

Answer 6

TB Infection which has progressed to a disease
1. pulmonary disease
2. extra-pulmonary disease

Question 7

Treatment of TB?

Answer 7

RHZE
1. Rifampicin (R)
2. Isoniazid (INH) (H)
3. Pyrazinamide (Z)
4. Ethambutol (E)

Question 8

Side effects of rifampicin?

Answer 8

1. nausea
2. skin
3. AHA
4. cholestase

Question 9

Side effects of Isoniazid?

Answer 9

1. PNP (Vit B6)
2. hepatitis

Question 10

Side effects of pyrazinamide?

Answer 10

1. arthralgia
2. gout
3. hepatitis

Question 11

Underlying principle for TB treatment?

Answer 11

1. 2 months RHZE and 4 months RH
2. 2 months RHZE and 1 month RHZE and 5 month RHE

Question 12

Why do you need 3 active drugs?

Answer 12

• You need at least 3 active drugs because of the slow growth of mycobacteria, some are actively replicating while others atre more or less dormant
• You need bactericidal and sterilizing drugs!

Question 13

What are the most potent TB drugs?

Answer 13

Rifampicin and INH are still the most potent drugs we have against TB

Question 14

What is multi drug resistant TB?

Answer 14

• These are strains that are Rifampicin and Isoniazid resistant
• Rifampicin and INH are the mainstay of our current regular TB regimen!
• We often use the Gene-Xpert result of Rifampicin resistance as proxy

Question 15

Clinical symptoms of TB in HIV?

Answer 15

1. cough >2 weeks
2. loss of weight
3. night sweats

Question 16

Problems with diagnosis of TB in HIV patients?

Answer 16

1. HIV co-infected patients often have a lower bacterial load in sputum => Acid fast staining or Auramine stain not a good strategy
2. They have more bacteria in the tissue but less in the bronchi (less cavities for example)

Question 17

Diagnosis of TB in HIV patients on an X-ray?

Answer 17

The pattern of involvement in the lung resembles more the “primary” pattern of TB with hilar lymphadenopathy and infiltrates in the lower lobes not the “typical” post-primary pattern with upper lobe infiltrates and cavities

Question 18

Typical post primary TB pattern on an x-ray?

Answer 18

1. infiltrate - 85% upper
2. cavitation commonly seen
3. adenopathy was uncommon
4. effusion may be present

Question 19

Atypical primary TB patter on an X-ray?

Answer 19

1. infiltrate - 60% upper and 40% lower (usually upper in children)
2. cavitation is uncommon
3. adenopathy is 30% unilateral>bilateral (coomon in chilfren)
4. effusion may be present

Question 20

Examination of the lung?

Answer 20

1. Auscultation and percussion are as traditionally the initial exams
2. respiratory rate and the oxygen saturation - estimate effectiveness of gas-exchange
3. chest X-ray (CXR)

Question 21

PCP symtoms?

Answer 21

1. Progressive dyspnoea is the hallmark of PCP - may be associated with cough (usually non-productive)
2. fever (usually mild)
3. CD4 usually <200 !!
   Note: PCP patients suffer from symptoms for an average of 3-4 weeks, while pneumonia patients usually seek attention in less than a week

Question 22

Chest x-ray findings in PCP?

Answer 22

bilateral, diffuse, symmetrical, ground-glass infiltration, pronounced in the central regions

Question 23

Treatment of PCP?

Answer 23

1. high-dose cotrimoxazole
   - Adults ≤ 60kg 1920mg tds for 21 days
2. Steroids are indicated in patients who are hypoxic
   > 60- 80 mg prednisone od daily for five days
   > 40 mg for five days
   > 20 mg for 10 days.
   Note: with effective treatment expect a response in 7 to 10 days

Question 24

Examination of Kaposi sarcoma?

Answer 24

In HIV patients with respiratory distress a KS screening is part of the examination – look at palate and groins

Question 25

Treatment of Kaposi Sarcoma?

Answer 25

In case of suspected disseminated KS refer for chemotherapy – Paclitaxel is the first treatment of choice!

Question 26

What is extra-pulmonary TB?

Answer 26

TB involving organs other than the lungs e.g. pleura, lymph nodes, abdomen, GIT, skin, joints and bones, meninges

Question 27

Commonest forms of extrapulmonary TB?

Answer 27

1. lymph node - especially in the neck or under the arms 2. pleural - usually one-sided pleural effusion and disseminated tuberculosis (esp. in HIV+) 3. Pericardial, meningeal and spine tuberculosis are less frequent 4. CNS - meningitis 5. disseminated - miliary tuberculosis 6. bones and joints of spine - Potts's disease 7. genito-urinary - urogenital tuberculosis

Question 28

Symptoms of extra pulmonary TB?

Answer 28

1. Loss of weight 2. night sweats 3. anemia 4. Cough for > 2 weeks may be present if the lung is involved as well => send sputum 5. Systemic symptoms may be missing e.g. in bone TB

Question 29

Clinical features of pericardial TB?

Answer 29

Cardiomegaly on CXR and pericardial effusion is suggestive of TB Note: rule out KS

Question 30

Treatment for pericardial TB?

Answer 30

1. Presumptive treatment is the standard 2RHZE/4RH 2. Steroids may be added if the patient is instable (e.g. prednisolone 80 mg od tapered over 1 month) 3. Only if there is tamponade, it is necessary to drain the fluid - Signs of cardiac tamponade could be low blood pressure, dilated jugular veins and rapid breathing

Question 31

Clinical features of pleural TB?

Answer 31

Pleural effusion 1. Effusion few month after primary infection (hypersensitivity reaction) 2. Effusion as a result of lung disease in older adults which might develop into purulent effusion (empyema) 3. Rupture of a cavity and escape of bacteria and air into the pleural - Empyema and pyo-pneumothorax may result 4. miliary TB can cause polyserositis

Question 32

Clinical symptoms of TB meningitis?

Answer 32

1. headache 2. confusion 3. photophobia 4. seizures 5. confusion 6. Cranial nerve palsies are suggestive of basal TB meningitis e.g. paresis of facial or abducens nerves

Question 33

Mycobacterial meningitis CSF results?

Answer 33

1. mildy increased polymorphs 2. increased lymphocytes 3. increased protein 4. decreased glucose 5. negative cryptoAg

Question 34

Investigations in TB meningitis?

Answer 34

1. CSF can be sent for GeneXpert to confirm the diagnosis (although negative result do not rule it out) 2. CT can show basal enhancement of the meninges and hydrocephalus

Question 35

Treatment of TB meningitis?

Answer 35

1. Treatment duration is up to 12 months (2 RHZE and 10 RH) 2. Addition of Prednisolon/or Dexamethson 3. ART should be started only after 4-6 weeks of TB treatment, as the risk of IRIS in meningitis is high

Question 36

Complications of TB meningitis?

Answer 36

The increase in inflammation (IRIS) can lead to increased intracranial pressure and hydrocephalus

Question 37

Clinical Features of spine TB?

Answer 37

1. The most common sign is spastic paralysis of the legs and back pain, possibly with a gibbus 2. Spinal TB should be considered especially in upper motor neuron disease (=> X-ray spine). Presumptive TB treatment has to be started

Question 38

Exogenous skin TB?

Answer 38

direct inoculation of tubercle into the skin of predisposed individuals 1. primary inoculation (Tb chancre) (sing) 2. tuberculosis verrucosis cutis (sing/mult) (hand and feet in children)

Question 39

Endogenous skin TB?

Answer 39

secondary to pre- existing primary focus resulting in either continuous or hematogenous spread 1. Lupus vulgaris (face) (sing) 2. Scrofuloderma (sing) (neck and scapula LN breaks through) 3. metaststatic TB abscess (sing/mult) (cold abscess, TB gumma) 4. acute miliary TB (mult) (minute maculo-papular lesions, itchy) 5. orificial TB (Ulcers: mouth, nose, anal)

Question 40

What is a urine LAM test?

Answer 40

- Alere Lam is an immunochromographic assay for the detection of LAM antigen of Mycobacteria* in Urine specimens - Good test to detect antigenuria - LAM is released from mycobacteria infecting the kidneys as part of disseminated systemic tuberculosis

Question 41

When to do the urine LAM?

Answer 41

- LAM may be used in the diagnosis of TB in HIV positive adult patients with signs and symptoms of TB who have a low CD4 cell counts - Studies showed the highest benefit in in-patients with CD4 counts less than or equal to 100 cells/μL

Question 42

What is IRIS?

Answer 42

immune reconstitution inflammatory syndrome - potential complication of using ARTs

Question 43

Types of IRIS?

Answer 43

1. paradoxical IRIS 2. unmasking IRIS

Question 44

What is paradoxical IRIS?

Answer 44

symptoms and signs associated with a known opportunistic infection (OI) that has already been treated recur or become acutely worse after initiating ART

Question 45

What is unmasking IRIS?

Answer 45

a previously unknown OI presents following ART initiation.

Question 46

TB-IRIS and sequencing of drugs?

Answer 46

For patients who need treatment for TB and ART – start with the TB treatment first Note: advisable to start ART after two weeks to see if the patients develop side effects to drugs especially when the CD4 count is <200cells/ml as the risk due to severe immunosuppression is high

Question 47

When to start ART treatment in cases of TB meningitis?

Answer 47

In cases of TB meningitis it is prudent to delay ART for 4-8 weeks as IRIS can lead to raised intracranial pressure

Question 48

Drug-drug interactions in both HIV and TB treatment?

Answer 48

1. Dolutegravir (DTG) => DTG needs to be doubled to 2x50 mg (so TDF/3TC/DTG in the morning and single drug DTG 50 mg in the evening 2. RIF lowers the PI concentration to possibly sub-inhibitory concentration which allow the HIV virus to develop resistance

Question 49

How to deal with the drug-drug interactions in HIV and TB treatment?

Answer 49

Switch patient from ATZ/r to lopinavir/r and use double dose (4 tbls bd.) – this is acceptable but still not an ideal solution!

Question 50

What is TB preventative treatment?

Answer 50

- TPT can protect people with HIV from developing active TB – which is clearly an advantage - Efficacy between 50-90%

Question 51

Problems with TB preventative treatment?

Answer 51

1. side effects (hepatitis, PNP and neurological problems) 2. possibility of resistance development when given in active TB cases 3. costs to procure and implement IPT are a further problem

Question 52

Who should receive TB preventative treatment?

Answer 52

1. Adults and adolescents and children infected with HIV as part of their comprehensive care package 2. Those previously treated for active TB (timeframe not given!!) 3. Preventive treatment is not dependant on screening for latent TB in the developing world

Question 53

What is isoniazid metabolic toxicity?

Answer 53

INH also interferes with the role of Vit B6 in the metabolism of Vit B3 (=niacin = nicotinamid)

Question 54

Isoniazid side effects symptoms?

Answer 54

INH associated pellagra (D-D-D) 1. Dermatitis, especially photo dermatitis 2. Diarrhea 3. Dementia