Question
A 45-year-old smoker comes to outpatient department with history of productive cough, evening rise of temperature and loss of weight. Microscopic examination of the sample revealed acid fast bacilli.
- (a) What is the most probable clinical diagnosis. 1 mark(s)
- (b) Name the causative agent. 1 mark(s)
- (c) Write the mode of transmission of the infective agent. 1 mark(s)
- (d) Discuss the pathogenesis of the disease. e) Describe in detail the laboratory diagnosis of the condition. f) Discuss the drug resistance seen in this organism and the treatment of the resistant forms. g) Name the national programme for this condition. 2 mark(s)
Answer
(a) Most probable clinical diagnosis: Pulmonary tuberculosis — a smoker with productive cough, evening rise of temperature, weight loss, and acid-fast bacilli on microscopy is the classical presentation.
(b) Causative agent: Mycobacterium tuberculosis.
(c) Mode of transmission: airborne, via inhalation of droplet nuclei produced by an infected (sputum-smear-positive) individual during coughing, sneezing, or talking.
(d) Pathogenesis: inhaled droplet nuclei reach the alveoli, where the bacilli are phagocytosed by alveolar macrophages; M. tuberculosis survives and multiplies within macrophages (facultative intracellular pathogen), forming the initial Ghon focus — a local lesion, usually in the mid-to-lower lung zones. Bacilli spread via lymphatics to hilar lymph nodes, and the combination of the Ghon focus and involved lymph nodes constitutes the primary (Ghon) complex. In most immunocompetent individuals, cell-mediated immunity (via Th1 response, activated macrophages, and granuloma formation with central caseous necrosis) contains the infection, which becomes latent (walled off, dormant bacilli persisting). Reactivation (post-primary/secondary TB) can occur later, particularly with waning immunity (ageing, immunosuppression, malnutrition, smoking — a relevant risk factor in this patient), typically in the apical/posterior segments of the upper lobes (higher oxygen tension favouring the aerobic organism), producing progressive cavitary disease with the classical chronic symptom complex.
(e) Laboratory diagnosis:
- Sputum smear microscopy — Ziehl-Neelsen (acid-fast) stain, demonstrating acid-fast bacilli; a rapid, low-cost, widely available initial test, though with limited sensitivity.
- CBNAAT/GeneXpert MTB/RIF — rapid molecular test detecting M. tuberculosis DNA and rifampicin-resistance mutations simultaneously; the current preferred initial diagnostic test in India’s National TB Elimination Programme.
- Culture — on Lowenstein-Jensen medium (solid, definitive but slow, 2–8 weeks) or liquid culture systems (e.g., BACTEC MGIT), faster (1–3 weeks); remains the gold standard, also allowing full phenotypic drug-susceptibility testing.
- Line Probe Assay (LPA) — for detailed drug-resistance profiling (first- and second-line).
- Chest X-ray — supportive, showing upper lobe infiltrates/cavitation, not diagnostic alone.
(f) Drug resistance and treatment of resistant forms:
- Multi-Drug Resistant TB (MDR-TB) — resistance to at least isoniazid and rifampicin, arising through spontaneous chromosomal mutations selected under inadequate/incomplete treatment.
- Extensively Drug-Resistant TB (XDR-TB) — MDR-TB with additional resistance to fluoroquinolones and at least one second-line injectable agent (or, per updated definitions, resistance to fluoroquinolones and bedaquiline/linezolid).
- Treatment of resistant forms: standard first-line ATT (isoniazid, rifampicin, ethambutol, pyrazinamide) is ineffective; MDR/XDR-TB requires a longer, individualized regimen using second-line drugs (e.g., fluoroquinolones, bedaquiline, linezolid, clofazimine), guided by drug-susceptibility testing, and treatment duration is substantially longer (many months to nearly 2 years for older regimens, though newer shorter all-oral regimens, e.g., BPaLM, have reduced this in many programmes).
(g) National programme: the National Tuberculosis Elimination Programme (NTEP) (formerly the Revised National Tuberculosis Control Programme, RNTCP), India’s national programme for TB control/elimination, providing free diagnosis and treatment (DOTS — Directly Observed Treatment, Short-course) with a target of TB elimination in India by 2025.