Tuberculosis Flashcards
Describe the structure of mycobacterium tuberculosis?
- areobic non spore forming bacteria
- Cell wall: high lipid content - acid fast bacilli
- Generation time is slow - 12 hours
How is TB transmitted?
airborne transmission - droplets from a cough
What is primary TB?
Initial TB infection which may lead to clinical disease (leading to hematogenous spread)
What is latent TB?
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
Tests for latent TB?
- tine test
- Igra tests
What is post-primary TB?
TB Infection which has progressed to a disease
1. pulmonary disease
2. extra-pulmonary disease
Treatment of TB?
RHZE
1. Rifampicin (R)
2. Isoniazid (INH) (H)
3. Pyrazinamide (Z)
4. Ethambutol (E)
Side effects of rifampicin?
- nausea
- skin
- AHA
- cholestase
Side effects of Isoniazid?
- PNP (Vit B6)
- hepatitis
Side effects of pyrazinamide?
- arthralgia
- gout
- hepatitis
Underlying principle for TB treatment?
- 2 months RHZE and 4 months RH
- 2 months RHZE and 1 month RHZE and 5 month RHE
Why do you need 3 active drugs?
- 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!
What are the most potent TB drugs?
Rifampicin and INH are still the most potent drugs we have against TB
What is multi drug resistant TB?
- 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
Clinical symptoms of TB in HIV?
- cough >2 weeks
- loss of weight
- night sweats
Problems with diagnosis of TB in HIV patients?
- HIV co-infected patients often have a lower bacterial load in sputum => Acid fast staining or Auramine stain not a good strategy
- They have more bacteria in the tissue but less in the bronchi (less cavities for example)
Diagnosis of TB in HIV patients on an X-ray?
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
Typical post primary TB pattern on an x-ray?
- infiltrate - 85% upper
- cavitation commonly seen
- adenopathy was uncommon
- effusion may be present
Atypical primary TB patter on an X-ray?
- infiltrate - 60% upper and 40% lower (usually upper in children)
- cavitation is uncommon
- adenopathy is 30% unilateral>bilateral (coomon in chilfren)
- effusion may be present
Examination of the lung?
- Auscultation and percussion are as traditionally the initial exams
- respiratory rate and the oxygen saturation - estimate effectiveness of gas-exchange
- chest X-ray (CXR)
PCP symtoms?
- Progressive dyspnoea is the hallmark of PCP - may be associated with cough (usually non-productive)
- fever (usually mild)
- 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
Chest x-ray findings in PCP?
bilateral, diffuse, symmetrical, ground-glass infiltration, pronounced in the central regions
Treatment of PCP?
- high-dose cotrimoxazole
- Adults ≤ 60kg 1920mg tds for 21 days - 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
Examination of Kaposi sarcoma?
In HIV patients with respiratory distress a KS screening is part of the examination – look at palate and groins
Treatment of Kaposi Sarcoma?
In case of suspected disseminated KS refer for chemotherapy – Paclitaxel is the first treatment of choice!
What is extra-pulmonary TB?
TB involving organs other than the lungs
e.g. pleura, lymph nodes, abdomen, GIT, skin, joints and bones, meninges
Commonest forms of extrapulmonary TB?
- lymph node
- especially in the neck or under the arms - pleural
- usually one-sided pleural effusion and disseminated tuberculosis (esp. in HIV+) - Pericardial, meningeal and spine tuberculosis are less frequent
- CNS
- meningitis - disseminated
- miliary tuberculosis - bones and joints of spine
- Potts’s disease - genito-urinary
- urogenital tuberculosis
Symptoms of extra pulmonary TB?
- Loss of weight
- night sweats
- anemia
- Cough for > 2 weeks may be present if the lung is involved as well => send sputum
- Systemic symptoms may be missing e.g. in bone TB
Clinical features of pericardial TB?
Cardiomegaly on CXR and pericardial effusion is suggestive of TB
Note: rule out KS
Treatment for pericardial TB?
- Presumptive treatment is the standard 2RHZE/4RH
- Steroids may be added if the patient is instable (e.g. prednisolone 80 mg od tapered over 1 month)
- 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
Clinical features of pleural TB?
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
Clinical symptoms of TB meningitis?
- headache
- confusion
- photophobia
- seizures
- confusion
- Cranial nerve palsies are suggestive of basal TB meningitis e.g. paresis of facial or abducens nerves
Mycobacterial meningitis CSF results?
- mildy increased polymorphs
- increased lymphocytes
- increased protein
- decreased glucose
- negative cryptoAg
Investigations in TB meningitis?
- CSF can be sent for GeneXpert to confirm the diagnosis (although negative result do not rule it out)
- CT can show basal enhancement of the meninges and hydrocephalus
Treatment of TB meningitis?
- Treatment duration is up to 12 months (2 RHZE and 10 RH)
- Addition of Prednisolon/or Dexamethson
- ART should be started only after 4-6 weeks of TB treatment, as the risk of IRIS in meningitis is high
Complications of TB meningitis?
The increase in inflammation (IRIS) can lead to increased intracranial pressure and hydrocephalus
Clinical Features of spine TB?
- The most common sign is spastic paralysis of the legs and back pain, possibly with a gibbus
- Spinal TB should be considered especially in upper motor neuron disease (=> X-ray spine). Presumptive TB treatment has to be started
Exogenous skin TB?
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)
Endogenous skin TB?
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)
What is a urine LAM test?
- 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
When to do the urine LAM?
- 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
What is IRIS?
immune reconstitution inflammatory syndrome
- potential complication of using ARTs
Types of IRIS?
- paradoxical IRIS
- unmasking IRIS
What is paradoxical IRIS?
symptoms and signs associated with a known opportunistic infection (OI) that has already been treated recur or become acutely worse after initiating ART
What is unmasking IRIS?
a previously unknown OI presents following ART initiation.
TB-IRIS and sequencing of drugs?
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
When to start ART treatment in cases of TB meningitis?
In cases of TB meningitis it is prudent to delay ART for 4-8 weeks as IRIS can lead to raised intracranial pressure
Drug-drug interactions in both HIV and TB treatment?
- 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
- RIF lowers the PI concentration to possibly sub-inhibitory concentration which allow the HIV virus to develop resistance
How to deal with the drug-drug interactions in HIV and TB treatment?
Switch patient from ATZ/r to lopinavir/r and use double dose (4 tbls bd.)
– this is acceptable but still not an ideal solution!
What is TB preventative treatment?
- TPT can protect people with HIV from developing active TB – which is clearly an advantage
- Efficacy between 50-90%
Problems with TB preventative treatment?
- side effects (hepatitis, PNP and neurological problems)
- possibility of resistance development when given in active TB cases
- costs to procure and implement IPT are a further problem
Who should receive TB preventative treatment?
- Adults and adolescents and children infected with HIV as part of their comprehensive care package
- Those previously treated for active TB (timeframe not given!!)
- Preventive treatment is not dependant on screening for latent TB in the developing world
What is isoniazid metabolic toxicity?
INH also interferes with the role of Vit B6 in the metabolism of Vit B3 (=niacin = nicotinamid)
Isoniazid side effects symptoms?
INH associated pellagra (D-D-D)
1. Dermatitis, especially photo dermatitis
2. Diarrhea
3. Dementia
