Tuberculosis Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mr Tran is a 58-year-old man born in Vietnam who arrived in Australia 12 years ago, presenting with six weeks of productive cough, eight kilograms of weight loss, drenching night sweats, and two episodes of streaky haemoptysis. [1]

His past history includes:

• Type 2 diabetes (HbA1c 78) on metformin and gliclazide
• Atrial fibrillation on warfarin, INR target 2.0 to 3.0
• Stage 4 chronic kidney disease (eGFR 22) presumed diabetic nephropathy
• Hepatitis B surface antigen positive
• He has smoked 20 cigarettes a day for 35 years [1]

His chest radiograph shows a 4 cm right upper lobe cavity with surrounding fibronodular infiltrate. Two of three sputa are strongly smear-positive for acid-fast bacilli, and GeneXpert MTB/RIF is positive for Mycobacterium tuberculosis complex with NO rifampicin resistance. HIV serology is negative. [1]

My problem list is:

1. Smear-positive, drug-susceptible cavitary pulmonary tuberculosis — highly infectious
2. Hepatitis B co-infection — high baseline hepatotoxicity risk
3. Type 2 diabetes with poor control — worsened by TB and by rifampicin
4. Stage 4 chronic kidney disease — requires ethambutol and pyrazinamide dose adjustment
5. Atrial fibrillation on warfarin — clinically significant rifampicin interaction
6. 35-pack-year smoking history and cachexia
7. Household contacts (wife and two adult children) at risk [1]

My immediate priorities are airborne isolation, notification, and starting the standard six-month RIPE regimen with renal-adjusted ethambutol and pyrazinamide, pyridoxine, intensive INR monitoring, and a public health contact investigation." [1]

Problem list and integrated management plan

Problem 1 — Smear-positive pulmonary TB [1]

The candidate is expected to articulate:

• Airborne isolation in a negative-pressure room with N95/P2 respirator protection; not droplet precautions and not a surgical mask.
• Three negative sputum smears on separate days (including one early morning) required before discontinuing isolation; typically 2 to 3 weeks for drug-susceptible disease.
• Standard six-month RIPE regimen: rifampicin 600 mg, isoniazid 300 mg with pyridoxine 25 mg, pyrazinamide (renal-adjusted), ethambutol (renal-adjusted) for 2 months; then rifampicin and isoniazid for 4 months (Nahid et al, 2016, PMID 27516382).
• Because of cavitary disease, the 2-month sputum culture must be checked; if positive, the continuation phase extends to 7 months (total 9 months). [1]

Problem 2 — Hepatitis B co-infection [1]

The candidate should state:

• Baseline LFTs are normal but the risk of drug-induced hepatitis is significantly amplified.
• LFTs monitored monthly and immediately for symptoms of hepatitis.
• Action threshold: stop all four drugs if ALT greater than 3 times ULN with symptoms, or greater than 5 times ULN without symptoms.
• Hepatitis B DNA testing and hepatology referral for consideration of antiviral prophylaxis.
• Sequential drug reintroduction protocol after drug-induced hepatitis. [1]

Problem 3 — Type 2 diabetes [1]

• TB worsens glycaemic control; rifampicin induces sulfonylurea metabolism.
• Acute phase: insulin sliding scale; oral agents reintroduced once stable.
• Target HbA1c relaxed in acute illness to avoid hypoglycaemia in a cachectic patient. [1]

Problem 4 — Stage 4 CKD [1]

• Ethambutol: reduce to 15 mg/kg three times weekly after the first two weeks; monthly visual acuity and colour vision (Ishihara plates).
• Pyrazinamide: maintain daily dose or reduce to three times weekly in advanced CKD.
• Rifampicin and isoniazid: no dose adjustment.
• Nephrology liaison; monthly renal function. [1]

Problem 5 — Atrial fibrillation on warfarin [1]

• Rifampicin is a potent CYP2C9 inducer; INR will fall markedly within 1 to 2 weeks.
• Either substantially increase warfarin dose (often double or triple) with twice-weekly INR monitoring, or switch to therapeutic-dose LMWH (with caution in CKD where LMWH accumulates).
• In this patient, ANZ preference is to continue warfarin with intensive INR monitoring. [1]

Problem 6 — Smoking and cachexia [1]

• Smoking cessation support.
• Nutritional supplementation; weigh weekly. [1]

Problem 7 — Contact tracing [1]

• Notify public health.
• Concentric contact investigation: household first (symptom screen, IGRA or TST at 8 to 10 weeks after last exposure, chest radiograph). [1]

Probing questions (model answers)

Examiner: "What is the mechanism by which rifampicin induces warfarin metabolism, and why does it take 1 to 2 weeks to peak?" [1]

Candidate: "Rifampicin binds to and activates the pregnane X receptor in hepatocytes, which upregulates transcription of multiple cytochrome P450 enzymes, especially CYP2C9 (the principal metaboliser of S-warfarin, the more potent enantiomer) and CYP3A4. Enzyme induction requires new protein synthesis, so the effect builds over 1 to 2 weeks as enzyme levels rise. The effect also persists for up to two weeks after rifampicin is stopped, because the induced enzyme takes that long to degrade. The practical consequence is that warfarin dose needs to be doubled or tripled during therapy and then rapidly reduced as rifampicin is withdrawn — a point where many patients are inadvertently over-anticoagulated." [1]

Examiner: "Your patient is HBsAg-positive. Does that change your hepatitis B management during TB therapy?" [1]

Candidate: "Yes. Chronic hepatitis B infection significantly increases the risk of drug-induced hepatotoxicity from isoniazid, rifampicin and pyrazinamide — three hepatotoxic drugs given together. The baseline LFTs are normal but I would check a hepatitis B DNA level and refer to hepatology. The decision to start antiviral prophylaxis (entecavir or tenofovir) depends on the HBV DNA level and the patient's overall fibrosis stage; patients with high HBV DNA or established fibrosis are at risk of HBV reactivation during significant illness or immunosuppression. I would monitor LFTs monthly and immediately for any symptoms of hepatitis, and I would have a low threshold to stop therapy if ALT exceeded 3 times ULN with symptoms or 5 times ULN without symptoms, with a planned sequential reintroduction." [1]

Examiner: "What is the role of corticosteroids in tuberculosis?" [1]

Candidate: "Corticosteroids are adjunctive therapy in three forms of TB. First, in tuberculous meningitis, the Thwaites et al trial (PMID 15496623) showed that dexamethasone improved survival across all BMRC severity stages; the WHO, CDC and ATS/IDSA recommend it for all patients with TBM. Second, in tuberculous pericarditis, corticosteroids are recommended by the WHO to reduce the risk of constrictive pericarditis, although the IMPI-1 trial did not show a clear mortality benefit. Third, in severe paradoxical reactions or immune reconstitution inflammatory syndrome (IRIS) in HIV-TB co-infection, corticosteroids are used for life-threatening manifestations such as worsening respiratory failure, enlarging lymph nodes causing airway compromise, or worsening neurological status in TBM. Corticosteroids are NOT routinely used in pulmonary TB and add an immunosuppressive burden." [1]

Examiner: "What is the BMRC staging of tuberculous meningitis and why does it matter?" [1]

Candidate: "The British Medical Research Council stages TBM into three grades. Stage I is a conscious patient with no focal neurological signs and no hydrocephalus — mortality under 10 per cent. Stage II is a confused or drowsy patient, or one with a focal neurological sign such as a cranial nerve palsy — mortality around 30 per cent. Stage III is a comatose patient or one with decerebrate or decorticate posturing or dense paraplegia — mortality over 50 per cent. Staging matters because it predicts outcome, it stratifies the urgency of adjunctive corticosteroids and neurosurgical CSF diversion, and it is the basis of prognostic counselling with the family." [1]

Examiner: "When would you suspect multidrug-resistant TB and what would you do?" [1]

Candidate: "I would suspect MDR-TB in several situations: a GeneXpert showing rifampicin resistance; a patient from a high-MDR-burden setting (Russia, parts of India, South Africa); prior TB treatment, especially incomplete or unsupervised; a contact of a known MDR-TB case; and treatment failure or non-response at 5 months. The immediate management is to place the patient in airborne isolation, refer urgently to a multidisciplinary drug-resistant TB service, and await full phenotypic and molecular susceptibility testing. I would NOT start standard RIPE therapy in a known rifampicin-resistant case because it is effectively three-drug therapy (rifampicin does not work) and amplifies resistance. The modern approach is an all-oral regimen, increasingly the BPaL or BPaLM regimen for eligible patients (Conradie et al, 2020, PMID 32130813)." [1]

Examiner: "How does HIV co-infection change TB management?" [1]

Candidate: "HIV changes TB in five ways. First, the clinical and radiographic presentation is atypical — more extrapulmonary and disseminated disease, lower lobe rather than upper lobe infiltrates, intrathoracic lymphadenopathy, and absence of cavitation in advanced immunosuppression. Second, every patient with TB is tested for HIV, and every patient with HIV is screened for TB. Third, the standard RIPE regimen is used but the ART regimen must be compatible — efavirenz-based ART with rifampicin, or rifabutin substituted for rifampicin if a protease inhibitor is required. Fourth, the timing of ART depends on the CD4 count — within 2 weeks for CD4 less than 50, by 8 weeks for higher CD4 — except for tuberculous meningitis, where ART is deferred for at least 4 weeks because of IRIS-related neurological deterioration. Fifth, immune reconstitution inflammatory syndrome (IRIS) can complicate ART initiation and presents as worsening fever, lymphadenopathy, or respiratory compromise; severe IRIS is treated with corticosteroids." [1]

Short Case Discussion

Instruction

"Examine this patient's respiratory system and cervical lymph nodes. Present your findings and discuss the diagnosis and management." [1]

Examination routine (what the candidate demonstrates)

1. Introduction, consent, exposure, position at 45 degrees.
2. End of bed — cachexia, breathlessness, accessory muscle use.
3. Hands — finger clubbing (chronic suppurative disease); no peripheral stigmata of endocarditis.
4. Face and neck — oral candidiasis (consider HIV); a 2 cm matted, non-tender mass in the right posterior triangle of the cervical chain consistent with scrofula; no overlying skin discolouration or discharging sinus.
5. Thorax — inspection (no scars); palpation (reduced right upper lobe chest expansion); percussion (dullness at right apex); auscultation (bronchial breath sounds and inspiratory crackles at the right apex, consistent with consolidation or cavity).
6. Back — no spinal tenderness (exclude Pott disease).
7. Abdomen — no hepatosplenomegaly (exclude miliary disease). [1]

Presentation template

"Mrs Lee is a cachectic 68-year-old woman with no respiratory distress. There is finger clubbing. In the right posterior triangle of the neck there is a 2 centimetre, matted, non-tender lymph node with no overlying skin change, consistent with scrofula. Examination of the chest reveals reduced right upper lobe expansion, dullness to percussion, and bronchial breath sounds with late inspiratory crackles at the right apex. The remainder of the examination, including the back and abdomen, is unremarkable. My differential diagnosis is pulmonary tuberculosis with associated tuberculous lymphadenitis; I would also consider lung malignancy (given the cachexia and clubbing), non-tuberculous mycobacterial disease, and fungal infection. My initial investigations are sputum for acid-fast bacillus smear, GeneXpert MTB/RIF and mycobacterial culture, a chest radiograph, and an HIV test." [1]

Discussion questions

Examiner: "How would you distinguish TB from non-tuberculous mycobacterial (NTM) disease?" [1]

Candidate: "Clinically and radiologically NTM disease can mimic TB — chronic cough, upper lobe cavities, or nodular bronchiectatic pattern in older women (Lady Windermere syndrome). The distinction rests on the laboratory. GeneXpert MTB/RIF detects only M. tuberculosis complex and is negative in NTM. Culture speciation with molecular probes (or line-probe assay) is the definitive test — M. avium complex, M. kansasii, M. abscessus each have distinct antibiotic susceptibility profiles. Treatment is entirely different: NTM requires long macrolide-based regimens, often with rifampicin and ethambutol for MAC, and surgical resection for localised disease. The key point is that I would not start standard RIPE therapy without speciation if NTM is a real possibility — RIPE is not the right regimen for most NTM infections and rifampicin induces macrolide metabolism." [1]

Examiner: "Why is the apical region preferentially involved in post-primary TB?" [1]

Candidate: "M. tuberculosis is an obligate aerobe and grows best in tissue with the highest oxygen tension. The apices of the upper lobes have the highest ventilation-perfusion ratio in the upright lung and therefore the highest alveolar oxygen tension. The organism also prefers the relatively poorly perfused, more acidic, caseous granuloma of the reactivating lesion. This is the pathophysiological basis of the radiographic 'upper lobe predominance' that is the single most useful chest radiograph discriminator for post-primary TB in a candidate." [1]

Examiner: "What is the role of the interferon-gamma release assay in active TB?" [1]

Candidate: "IGRA has no role in the diagnosis of active TB. It detects a cell-mediated immune response to M. tuberculosis antigens and therefore identifies infection (latent or active), not disease. In active pulmonary TB the sensitivity is around 80 per cent — meaning a negative IGRA does not exclude active TB — and a positive result does not distinguish latent from active disease. IGRA is a test for latent TB infection in a patient being screened (HIV, contacts, pre-biologic, migrants), supported by a normal chest radiograph and a negative symptom screen. Using IGRA in suspected active TB can mislead the clinician into treating LTBI with a single drug while active disease goes undertreated and acquires resistance." [1]