Tuberculosis — Written Clinical Reasoning

Model answer — Part A: the anti-TNF candidate with a positive IGRA

Frame the problem. This is the highest-stakes latent-TB scenario in adult medicine: TNF blockade in a sensitised host reactivates TB rapidly and often in disseminated form — the signal was clear within infliximab's first years of use [1]. The consultation has two sequential questions: does he have active disease now, and if not, how do I prevent reactivation while his Crohn's is treated [2].

Assessment. Take a symptom history actively rather than passively — cough, fevers, night sweats, weight loss, haemoptysis — and a risk history: BCG status, prior TB contact, prior treatment, and other immunosuppression. Examine for lymphadenopathy and chest signs. His imaging is the pivot: fibronodular apical scarring stable over 3 years favours old, contained disease, but stability on a plain film does not exclude low-grade activity [2].

Distinguishing latent from active is the discriminator the examiner is scoring. Neither IGRA nor TST can do it — both measure immune memory, not bacilli, and their positive predictive value for progression is only a few per cent even in high-risk cohorts [4]. The exclusion of active disease is therefore clinical plus microbiological: in an asymptomatic man with stable imaging, obtain sputum for smear, NAAT and culture if there is any symptom, any new radiological change, or any doubt — and accept that a well patient with stable films and no organisms is latently infected [7].

Management. Treat latent infection before the biologic: 4 months of daily rifampicin is the preferred regimen — non-inferior to 9 months of isoniazid, with better completion and less hepatotoxicity [3]. Reconcile rifampicin's interactions with his other drugs. Infliximab can start after at least a month of preventive therapy is on board when the Crohn's cannot wait; document baseline LFTs and counsel about orange urine from rifampicin. State clearly what you will NOT do: start infliximab with untreated latent TB, or give preventive monotherapy while active disease remains unexcluded [1] [2].

Model answer — Part B: subacute meningitis with HIV

Diagnosis. A subacute meningitis — 10 days of headache and fever progressing to drowsiness and a sixth-nerve palsy — with a lymphocytic CSF, very high protein and low glucose is tuberculous meningitis until proven otherwise, and advanced HIV makes it more likely and more dangerous. Send a large CSF volume for NAAT and mycobacterial culture, image the brain for hydrocephalus and basal exudates, and look for disease elsewhere — chest imaging and sputum, because pulmonary TB coexists and changes isolation and contact-tracing decisions [7]. Crucially, do not let a negative early NAAT stop treatment in a compatible syndrome — yield is imperfect and delay is lethal [5].

Immediate management is two parallel actions: start four-drug antituberculous therapy (isoniazid, rifampicin, pyrazinamide, ethambutol — with pyridoxine) empirically, AND start dexamethasone tapered over 6–8 weeks, which reduced mortality in the landmark randomised trial in adolescents and adults with TBM [5]. Manage the complications actively: sodium disturbances, seizures, hydrocephalus — with a low threshold for repeat imaging and neurosurgical input if consciousness falls [5].

ART timing is the exam hinge. For most HIV-TB co-infection with CD4 below 50, ART starts within 2 weeks of TB therapy — integrated therapy reduced mortality in SAPiT [9]. TB meningitis is the explicit exception: immediate ART in HIV-associated TBM produced more severe adverse events without survival benefit in a randomised trial, so ART is deferred to around 8 weeks [6]. When ART does start, counsel about paradoxical TB-IRIS — worsening inflammation as immunity recovers — managed by continuing both therapies, with prednisone for moderate-to-severe cases on trial evidence [8].

Close the loop: notify the case, isolate if pulmonary disease coexists, and refer partner notification and HIV care linkage as part of the same plan [7].