Question
A 50 year old male presented to medicine OPD with evening rise of temperature, weight loss and productive cough for the past two months. Microscopic examination of the sputum revealed acid fast bacilli.
- (a) What is the most probable clinical diagnosis 1 mark(s)
- (b) Name the etiological agent 1 mark(s)
- (c) Discuss the pathogenesis of this disease 2 mark(s)
- (d) Describe the laboratory diagnosis including newer methods of diagnosis e) Define multidrug resistance of this etiological agent 4 mark(s)
Answer
a) Most probable clinical diagnosis: Pulmonary tuberculosis — chronic evening rise of temperature, weight loss, and productive cough for two months, with sputum microscopy showing acid-fast bacilli, is classical.
b) Etiological agent: Mycobacterium tuberculosis.
c) 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. This forms the initial (Ghon) focus with spread to hilar lymph nodes (primary complex). Cell-mediated immunity typically contains the infection, producing a caseating granuloma with epithelioid cells and Langhans giant cells, usually healing by fibrosis/calcification and leaving dormant bacilli (latent infection). Reactivation (post-primary TB), as in this chronic presentation, occurs if immunity wanes, typically in the apical/posterior upper lobes, progressing to cavitation and caseous pneumonia.
d) Laboratory diagnosis including newer methods
- Sputum smear microscopy — Ziehl-Neelsen staining for acid-fast bacilli; 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.
- Newer molecular methods — CBNAAT/GeneXpert MTB-RIF — rapid, automated PCR-based test detecting M. tuberculosis DNA and rifampicin resistance within ~2 hours; line-probe assays for rapid drug-susceptibility testing against isoniazid and rifampicin; whole-genome sequencing in reference laboratories for comprehensive resistance profiling.
- Tuberculin skin test (Mantoux) and Interferon-Gamma Release Assays (IGRAs) — indicate infection/exposure; IGRAs are unaffected by BCG vaccination.
- Radiology — chest X-ray/CT showing apical infiltrates, cavitation, or fibrosis.
e) Multidrug resistance (MDR-TB): defined as resistance of M. tuberculosis to at least the two most potent first-line drugs, isoniazid and rifampicin — resistance arises predominantly from spontaneous chromosomal mutations (e.g., rpoB for rifampicin, katG/inhA for isoniazid), selected for and allowed to overgrow under inadequate/incomplete treatment; MDR-TB requires prolonged, more toxic, second-line drug regimens with poorer treatment outcomes than drug-susceptible disease.