Tuberculosis — Written Clinical Reasoning

SAQ 1 — Integrated Management (25 marks, 35 minutes)

Prompt: Outline your integrated management plan for this patient, addressing the problem list, infection control, the standard anti-tuberculous regimen and its modifications, the anticipated drug interactions, the management of comorbidities, public health responsibilities, and the surveillance plan. Justify each decision with reference to evidence and guidelines. [1]

Model Answer

Problem list (3 marks):

1. Smear-positive drug-susceptible pulmonary tuberculosis with cavitary disease — high infectivity.
2. Hepatitis B co-infection — high baseline risk of drug-induced hepatotoxicity.
3. Type 2 diabetes with poor control — worsens TB outcomes and is itself worsened by TB and rifampicin.
4. Stage 4 chronic kidney disease (eGFR 22) — requires dose adjustment of ethambutol and pyrazinamide.
5. Atrial fibrillation on warfarin — clinically significant rifampicin-warfarin interaction anticipated.
6. Smoker (35 pack-years) and cachexia — malnutrition, smoking cessation, and aspiration of supratherapeutic anticoagulation (haemoptysis).
7. Household and community contacts at risk — public health notification and contact tracing. [1]

Immediate infection control (3 marks):

• Place the patient in airborne isolation in a negative-pressure ventilation room (6 to 12 air changes per hour) with the door closed; healthcare workers and visitors wear a fit-tested N95 or P2 particulate respirator, not a surgical mask (droplet nuclei are smaller than 5 micrometres and pass through a surgical mask).
• Notify the TB service, microbiology, public health unit and infection control immediately.
• Airborne precautions continue until the patient is on effective therapy, clinically improving, and has three consecutive negative sputum smears on separate days (including one early morning) — typically 2 to 3 weeks for drug-susceptible disease (Lewinsohn et al, 2017, PMID 28052967). [1]

Confirming the diagnosis and resistance pattern (2 marks):

• The GeneXpert-positive sputum with no rifampicin resistance is sufficient to start standard therapy, but mycobacterial culture and full phenotypic drug susceptibility testing are still required because Xpert detects only the commonest rpoB mutations and does not test isoniazid, pyrazinamide or ethambutol. Liquid culture (MGIT) plus solid (LJ) in parallel; susceptibilities expected in 4 to 8 weeks.
• Line-probe assay (GenoType MTBdrplus) on smear-positive sputum can also rapidly detect isoniazid resistance and is performed in parallel. [1]

Standard anti-tuberculous regimen (3 marks): The patient has drug-susceptible pulmonary TB and starts the standard RIPE regimen (Nahid et al, 2016, PMID 27516382):

• Intensive phase (8 weeks): rifampicin 600 mg orally daily, isoniazid 300 mg orally daily (with pyridoxine 25 mg daily because of the diabetic/CKD/hepatitis B risk of neuropathy), pyrazinamide (renal-dose adjusted, see below), ethambutol (renal-dose adjusted, see below).
• Continuation phase (16 weeks): rifampicin 600 mg daily plus isoniazid 300 mg daily with pyridoxine.
• Total duration 6 months. Because he has cavitary disease, the 2-month sputum culture must be checked; if positive at 2 months the continuation phase is extended to 7 months for a total of 9 months. [1]

Renal dose adjustment (2 marks): With eGFR 22 mL per min per 1.73 m squared:

• Ethambutol is renally cleared and requires dose reduction (typically 15 mg/kg three times weekly after the first 2 weeks) with monthly visual acuity and colour vision monitoring; baseline Ishihara plates are essential and the patient must be educated to stop immediately and report any visual change.
• Pyrazinamide is hepatically metabolised but its metabolites are renally cleared; the daily dose is generally maintained but some guidelines reduce to 25 mg/kg three times weekly in advanced CKD.
• Rifampicin and isoniazid do not require dose adjustment in CKD. [1]

Rifampicin-warfarin interaction (3 marks): Rifampicin is a potent inducer of hepatic CYP2C9 and will markedly accelerate warfarin metabolism. The INR is expected to fall within 1 to 2 weeks of starting therapy. Management options:

• Continue warfarin and substantially increase the dose (often double or triple) with INR monitored twice weekly during rifampicin therapy, or
• Switch to therapeutic-dose low-molecular-weight heparin (weight-based enoxaparin, reduced for eGFR) for the duration of TB therapy. In this patient, with stage 4 CKD and the complexity of dose adjustment, the preference in ANZ is usually to continue warfarin with intensive twice-weekly INR monitoring and close liaison with the anticoagulation clinic; LMWH in severe CKD accumulates and is harder to manage. The patient must be counselled that the OCP would also be ineffective (not relevant here) and that any concomitant drug (statin, beta-blocker, sulfonylurea, corticosteroid) may have reduced effect. [1]

Rifampicin-sulfonylurea and diabetes interaction (2 marks): Rifampicin induces metabolism of sulfonylureas (gliclazide) and may reduce their hypoglycaemic effect. More importantly, active TB worsens glycaemic control and rifampicin alters drug levels. In the acute phase, the patient is usually started on a sliding-scale insulin regimen in hospital with the diabetes team; oral hypoglycaemics can be re-introduced once TB therapy is established and glycaemia is stable. Target HbA1c is relaxed in the acute illness (under 64 mmol per mol is reasonable) to avoid hypoglycaemia in a cachectic patient with reduced intake. [1]

Hepatitis B co-infection and hepatotoxicity monitoring (2 marks): The shared hepatotoxicity of isoniazid, rifampicin and pyrazinamide is significantly amplified by chronic hepatitis B. Baseline LFTs are normal; check hepatitis B DNA and refer to hepatology. LFTs are monitored monthly and immediately for any symptoms of hepatitis (nausea, vomiting, abdominal pain, jaundice). The action threshold for stopping therapy is ALT greater than 3 times ULN with symptoms, or greater than 5 times ULN without symptoms. If drug-induced hepatitis develops, all four drugs are stopped, other causes excluded, and drugs reintroduced sequentially (rifampicin first, then isoniazid, then pyrazinamide) with LFTs at each step. Consider antiviral prophylaxis for hepatitis B (entecavir or tenofovir) if the patient is at high risk of HBV reactivation during immunosuppression or chemotherapy; this is discussed with hepatology. [1]

Public health and contact tracing (2 marks):

• Notify the case to the public health unit under the relevant Public Health Act (mandatory in all ANZ jurisdictions).
• Initiate a concentric (stone-on-stone) contact investigation: highest priority to the household (wife and two adult children), who are screened with a symptom screen, IGRA or TST (8 to 10 weeks after last exposure), and chest radiograph. Close social and workplace contacts are screened next.
• The patient is educated about cough hygiene, the importance of adherence, and the support available (social work, transport, language interpreter). [1]

Surveillance and follow-up (3 marks):

• Monthly clinical review: weight, symptoms, adherence, side effects (especially visual symptoms on ethambutol and hepatitis symptoms).
• LFTs monthly (hepatitis B risk) and PRN; renal function monthly; INR twice weekly during rifampicin titration then weekly.
• Visual acuity and colour vision monthly while on ethambutol.
• Sputum smear and culture at 2, 5, and 6 months; if the 2-month culture is positive in cavitary disease, extend to 9 months.
• Chest radiograph at end of therapy for documentation (does not in itself determine cure; culture negativity does).
• Smoking cessation, nutritional support, pneumococcal and influenza vaccination (defer BCG-related workups; the patient is an adult with established infection).
• Hepatology follow-up for hepatitis B; endocrinology/diabetes team for glycaemic stabilisation. [1]

SAQ 2 — Latent TB Management Before Biologic Therapy (10 marks, 15 minutes)

Prompt: A 32-year-old woman with severe plaque psoriasis and psoriatic arthritis is referred to you for assessment before starting secukinumab (an interleukin-17 inhibitor). She was born in Australia and has never travelled to a high-burden country. She received a BCG vaccination at birth. Her grandmother was treated for pulmonary tuberculosis 20 years ago but the patient has no recollection of prolonged exposure. Tuberculin skin test shows 12 mm of induration at 72 hours. Interferon-gamma release assay (QuantiFERON-TB Gold Plus) is positive. Chest radiograph is normal. She is HIV-negative. Outline your approach to her latent tuberculosis infection, including the diagnostic interpretation, the recommended treatment regimen, the rationale for drug choice, and the counselling points. [1]

Model Answer

Diagnostic interpretation (2 marks): This patient has latent tuberculosis infection (LTBI). The positive IGRA is the decisive result: it uses M. tuberculosis-specific antigens (ESAT-6, CFP-10, TB7.7) that are absent from BCG and most environmental mycobacteria, so the prior BCG does NOT explain it. The TST of 12 mm is supportive (in the 10 mm threshold for people with possible exposure through her grandmother), but the IGRA is the basis of the diagnosis. The normal chest radiograph and the absence of symptoms (no chronic cough, no weight loss, no night sweats, no haemoptysis) exclude active TB. [1]

Rationale for treatment (2 marks): All international guidelines recommend treating LTBI before or concurrent with significant biologic immunosuppression, because the risk of reactivation rises several-fold with IL-17, IL-12/23, JAK, and most potently anti-TNF inhibitors. The UK PREDICT TB cohort (Abubakar et al, 2018, PMID 30154639) confirms that a positive IGRA has a small but real prognostic value for progression, justifying treatment in a patient about to be immunosuppressed. [1]

Recommended regimen (3 marks): In an adult with normal renal function and no contraindications, the preferred regimen is rifampicin 600 mg daily for 4 months. This is supported by the Menzies RCT (PMID 30067931), which demonstrated non-inferior efficacy to 9 months of isoniazid with significantly less hepatotoxicity and higher completion rates. Alternative regimens include:

• Isoniazid plus rifapentine weekly for 3 months (3HP) — 12 doses; equally effective with a shorter course; the main toxicity is a flu-like reaction and hepatotoxicity is less than isoniazid alone.
• Isoniazid 300 mg daily for 6 to 9 months — effective but longer, with higher hepatotoxicity and neuropathy risk; pyridoxine 25 mg daily is co-administered. [1]

Before starting, repeat a symptom screen and confirm the chest radiograph is normal to exclude active TB; treating LTBI with a single drug in a patient with active TB risks resistance. [1]

Counselling and follow-up (3 marks):

• Explain that LTBI is not infectious, that the positive test reflects dormant infection, and that treatment reduces the small risk of progression to active disease.
• Discuss the choice of regimen and its rationale (shorter course, less hepatotoxicity, higher completion).
• Warn about rifampicin's effect on secretions (orange-red urine, sweat, tears — benign but startling) and its drug interactions (OCP requires additional barrier contraception; warfarin/DOACs/stevens-johnson-type interactions with certain anticonvulsants).
• Educate about symptoms of hepatitis (nausea, vomiting, abdominal pain, jaundice) and instruct to stop and report immediately.
• Arrange monthly clinical review with LFTs (especially for isoniazid-based regimens).
• The biologic (secukinumab) should be deferred until the LTBI regimen is completed or, in some protocols, at least 1 month into LTBI therapy to confirm tolerability.
• Document the result and the management plan in writing to the dermatologist/rheumatologist. [1]