Tuberculosis Flashcards
How is M. tuberculosis transmitted?
Airborne transmission
Enters lower airways
- No infection if consumed by macrophage
- Cellular immunity triggered by replication in lungs -> asymptomatic (latent) or symptomatic (active)
What are the risk factors for latent and active TB?
Latent and active:
- Residents of prisons, homeless shelters, nursing homes
- Close contact with pulmonary tuberculosis patients
- Co-infection with HIV
What are the risk factors for active TB only?
- Children <2y
- Elderly >65y
- Malnutrition
- Immunosuppression
- Co-infection with HIV
List 6 signs and symptoms for pulmonary tuberculosis.
- Productive cough
- Hemoptysis: cough blood
- Fever
- Fatigue
- Night sweats
- Weight loss
How can TB be differentiated from pneumonia?
Duration of symptoms
TB: gradual onset over weeks to months
Pneumonia: acute onset over hours to days
What are some radiological findings that assist in diagnosing TB?
Infiltrates in apical region (obligate anaerobe)
Cavitary lesions
Indications for latent TB infection (LTBI) screening
High risk + intent to treat if positive
- Children with recent TB contact
- HIV-infected individuals
- Considered for tumor necrosis factor antagonist therapy (immunosuppressive therapy)
- Transplant patients
- Dialysis (frequent healthcare encounters)
Tests for LTBI
Test if there is past exposure to TB
- Tuberculin skin test (tuberculin purified protein derivative test)
- inject 0.1ml of PPD intradermally -> read after 48-72h by trained reader -> read diameter of induration not redness
- positive is >10mm since most SG people have received BCG - Interferon-gamma release assay
- blood collection into special tubes -> measure interferon-gamma released by WBC in response to incubation with M. tuberculosis specific antigens
What are the advantages and limitations of tuberculin skin test and interferon-gamma release assay?
- Tuberculin
(+) Low cost, no need for blood samples
(-) false negative (immunosuppressed), false positive (environmental contact, BCG vaccination), intra-reader variability - Interferon-gamma
(+) no false positive in BCG-vaccination, minimal cross-reactivity with non TB mycobacterium, few hours
(-) false negative (immunosuppressed), cost, blood samples
Diagnosis of active TB
Clinical suspicion:
- History
- Risk factors (Immune status (HIV, diabetes), cramped living conditions, nutritional status, age, travel history)
- Clinical presentation
- Physical exam findings
- Chest X ray findings
Initiate treatment if sputum obtained for Ziehl Neelsen stain for acid fast bacilli (AFB) is positive
What are some infection control considerations for active TB patients?
Hospitals: airborne precautions
- negative pressure room & PPE
- Stop airborne precautions after 2 weeks of effective treatment
Community: take TB medications, practice cough etiquette, ventilate home
- No need to avoid household members (low risk of transmission on effective treatment)
Benefits & considerations for treating LTBI
Reduce lifetime risk of progression to active TB to 1%
Monotherapy is sufficient
Prior to initiation:
- exclude active TB
- weigh risk vs benefit (side fx for underlying liver disease -> choose not to treat LTBI)
Treatment of LTBI
- PO isoniazid 5mg/kg OD (max 300mg)
- x6mo or 9mo (HIV)
- Preferred in pregnancy, lactation, HIV
- Coadminister with pyridoxine (>10mg/d) to minimise neuropathy - PO rifampicin 10mg/kg OD (max 600mg)
- x4 mo
- Alternative if cannot tolerate isoniazid - PO isoniazid + rifapentine 900mg weekly
- 12 weeks (not recommended for HIV)
- given under DOT (directly observed therapy)
Who keeps track of TB in Singapore?
National Tuberculosis Registry: mandatory reporting by healthcare professionals
Singapore TB Elimination Programme (STEP):
- Promote DOT (compliance, best treatment outcomes)
- National Treatment Surveillance Registry
- Contact investigations (LTBI and treatment)
What are the benefits of treating active TB?
Patient: - reduce number of replicating and persisting bacteria - durable cure and prevent relapse - prevent resistance Public health: minimise transmission
What tests can be used to confirm diagnosis of active TB?
Culture: gold standard
- For confirmation of TB: 4-8wk
- For drug susceptibility tests: 4-6 wk
What are the 6-month and 9-month treatment schedules?
6-month:
- intensive phase (2mo): daily RIF + INH + PZA + EMB/STM
- continuation phase (4mo): daily or 3x/week RIF + INH
9-month (unlikely to tolerate PZA - elderly, liver disease):
- intensive phase (2mo): daily RIF + INH + EMB
- continuation phase (7mo): daily or 3x/week RIF + INH
* only switch to continuation phase after confirmed susceptibility to RIF and INH OR culture negative pulmonary TB
What are the doses of RIF and INH for the continuation phase?
PO rifampicin 10mg/kg 3x/week, max 600mg
- 100mg, 300mg tabs
PO isoniazid 15mg/kg 3x/week, max 900mg
- 150mg, 300mg tabs
1st line treatment for active TB
All OD at same time: concentration-dependent killing PO rifampicin 10mg/kg OD, max 600mg - 100mg, 300mg tabs PO isoniazid 5mg/kg OD, max 300mg - 150mg, 300mg tabs PO pyrazinamide 15-30mg/kg OD, max 2g - 500mg tabs PO ethambutol 15-25mg/kg OD, max 1600mg - 100mg, 400mg tabs IM streptomycin 10-15mg/kg OD, max 1g - 1g vial
Which 1st line anti-TB drugs require renal dosage adjustment?
Pyrazinamide
Ethambutol
Streptomycin
DDIs with TB medications
INH inhibits CYP2C19, 3A4, 2D6, 2E1
RIF induces CYP1A2, 2C9, 2C19, 3A4, pgp
How can we resolve nausea and vomiting during DOT?
take rifampicin & isoniazid earlier
pyrazinamide, ethambutol, pyridoxine later
What are the risk factors for hepatotoxicity in TB treatment?
Drugs: RIF, INH, PZA Risk factors: - age >35 y - female - underlying liver disease - concurrent alcohol use - HIV
How can we educate patients on hepatotoxicity for both latent and active TB treatment?
Symptoms: nausea, vomiting, unexplained fatigue, abdominal discomfort/pain
Stop treatment and see a doctor immediately if you experience any symptoms
Monitoring for LFTs
No risk factor: only monitor LFT if there are symptoms of hepatotoxicity (during treatment)
>1 risk factor: check baseline LFT before treatment
- check LFT every 2-4 weeks during treatment
Hepatotoxicity: ALT > 3x upper limit of normal [ULN] with symptoms; OR ALT > 5x ULN without symptoms
How should we manage treatment if there is hepatotoxicity?
- Stop treatment & monitor LFT 1-2x a week
- LBTI: re-challenge INH when ALT <2x ULN otherwise switch to RIF x4mo (if can’t tolerate INH)
- Active TB: re-challenge sequentially when LFT normalise + symptoms resolve (RIF, INH etc) -> failure req non-hepatotoxic regimen (EMB + FQ + STM)
Monitoring for visual acuity
Rationale: EMB causes visual toxicity (reduce visual acuity + red-green color discrimination)
Monitor visual acuity + color discrimination tests:
- Baseline for all patients
- Monthly: taking EMB >2mo or renal insufficiency (CKD)
Educate patient to stop treatment and see doctor immediately if they experience vision changes
