Question
A 35 years old female patient was admitted to the hospital with low grade fever, loss of weight and appetite and chronic cough with expectoration for past 5 months. Microscopic examination of sputum revealed long, slender and beaded acid fast bacilli. What is your provisional diagnosis What is the probable etiological agent Describe the pathogenesis of this condition Discuss the laboratory diagnosis in detail Mention briefly about the drug resistance that can occur in this causative agent (1+1+3+3+2)
Answer
Provisional diagnosis: Pulmonary tuberculosis — chronic low-grade fever, weight loss, anorexia, and chronic productive cough for 5 months, with sputum microscopy showing acid-fast bacilli, is classical.
Probable etiological agent: Mycobacterium tuberculosis — the “long, slender, beaded” morphology described is characteristic of its appearance on Ziehl-Neelsen staining.
Pathogenesis Inhaled droplet nuclei reach the alveoli and are phagocytosed by alveolar macrophages; the organism’s mycolic-acid-rich cell wall resists intracellular killing, allowing it to survive and multiply within macrophages (facultative intracellular pathogen). This forms the initial (Ghon) focus, with spread to hilar lymph nodes constituting the primary complex. In most immunocompetent individuals, cell-mediated immunity (delayed-type hypersensitivity, detectable by tuberculin conversion in 4–6 weeks) contains the infection, producing a caseating granuloma with central caseation necrosis surrounded by epithelioid cells, Langhans giant cells, and a lymphocytic cuff — typically healing by fibrosis/calcification, leaving viable dormant bacilli (latent infection). Reactivation (post-primary/secondary TB), as seen in this chronic presentation, occurs later if immunity wanes, typically in the well-aerated apical/posterior segments of the upper lobes, progressing to cavitation and caseous pneumonia.
Laboratory diagnosis
- Sputum smear microscopy — Ziehl-Neelsen staining for acid-fast bacilli on at least two samples; fluorescence (auramine-rhodamine) microscopy is more sensitive for screening.
- Culture — Lowenstein-Jensen medium (gold standard, slow, 2–8 weeks); liquid culture (BACTEC MGIT) is faster and permits drug-susceptibility testing.
- Molecular tests — CBNAAT/GeneXpert MTB-RIF for rapid detection and rifampicin-resistance screening; line-probe assays.
- Tuberculin skin test (Mantoux) and Interferon-Gamma Release Assays (IGRAs) — indicate infection/exposure, the latter unaffected by BCG vaccination.
- Radiology — chest X-ray (apical infiltrates, cavitation, fibrosis).
- Histopathology — caseating granuloma with Langhans giant cells on biopsy, when tissue is available.
Drug resistance
- Multidrug-resistant TB (MDR-TB) — resistance to at least isoniazid and rifampicin, the two most potent first-line drugs.
- Extensively drug-resistant TB (XDR-TB) — MDR-TB plus additional resistance to a fluoroquinolone and at least one second-line injectable agent.
- Mechanism: resistance arises predominantly from spontaneous chromosomal mutations in genes encoding drug targets or drug-activating enzymes (e.g., rpoB mutation for rifampicin resistance, katG/inhA mutations for isoniazid resistance) — antibiotics select for and allow overgrowth of pre-existing resistant mutants, particularly under inadequate/incomplete treatment (poor compliance, inappropriate regimens), rather than the organism acquiring resistance via plasmids (unlike many other bacteria).
- Rapid molecular tests (CBNAAT, line-probe assays) allow early detection of rifampicin/isoniazid resistance, guiding appropriate second-line regimen selection.