Pharmacology
What is the standard first-line drug regimen for tuberculosis?
Rifampicin, isoniazid, pyrazinamide, and ethambutol (RIPE)
Which type of TB has bacteria in the body but shows no symptoms and does not spread the disease?
Latent TB
What is bronchiectasis?
Permanent abnormal dilatation of the bronchi, which may be localised or generalised.
What triggers the release of BNP and NT-proBNP?
Ventricular wall stretch due to pressure or volume overload.
Differentiate between passive and active surveillance
Passive surveillance relies on routine reporting by healthcare workers, while active surveillance involves proactive case finding by health authorities.
What is the concern regarding rifampicin and drug interactions?
Rifampicin induces drug-metabolising enzymes and transporters, which reduces the concentration of other drugs to subtherapeutic levels.
A patient has no symptoms but has a positive sputum test for TB. Which stage is this most likely and why?
Asymptomatic TB — the patient has microbiological evidence of TB but has not yet developed symptoms.
What are the classic clinical features of bronchiectasis?
Excessive sputum production, foul breath (halitosis), and finger clubbing
What conditions are BNP and NT-proBNP mainly used to assess?
Heart failure
Give two reasons why disease notification is important.
A patient complains of difficulty distinguishing red and green colours after starting TB therapy. Which drug is responsible and why?
Ethambutol causes optic neuritis by disrupting mitochondrial function in the optic nerve. This leads to red-green colour blindness and reduced visual acuity
Differentiate between latent, asymptomatic, and active TB
What is the pathogenesis of bronchiectasis?
Initial bronchial epithelial damage leads to bacterial colonisation, impaired ciliary clearance, chronic infection and inflammation, creating a “vicious cycle” of airway destruction and bronchial wall weakening.
In abetalipoproteinaemia due to MTP deficiency, which lipoproteins fail to form and what pathways are affected?
Chylomicrons (exogenous pathway) and VLDL (endogenous pathway)
A doctor diagnoses cholera in South Africa. Explain the notification process, why it is necessary, and classify the disease.
Cholera is a Category 1 notifiable medical condition. It must be reported immediately using the fastest method (e.g., telephone), followed by formal written notification within 24 hours. This is necessary to enable outbreak detection, contact tracing, implementation of control measures, and prevention of disease spread.
TB patient develops jaundice and elevated liver enzymes during RIPE therapy. Which drug is most likely responsible and what is the mechanism?
Rifampicin (and also pyrazinamide) can cause hepatotoxicity. The mechanism involves dose-related hepatocellular injury due to toxic metabolites and enzyme induction–related metabolic stress on the liver.
Describe the pathogenesis of pulmonary tuberculosis from transmission to latent infection and reactivation.
Mycobacterium tuberculosis is transmitted via inhalation of droplet nuclei released when an infected person coughs, sneezes, speaks, or sings. These droplet nuclei are small, remain airborne for long periods, and require a very low infectious dose (about 1–10 bacilli). They are inhaled and reach the alveoli, where alveolar macrophages phagocytose the organisms. However, M. tuberculosis can survive within macrophages and triggers a cell-mediated immune response. In most individuals (about 90–95%), the immune response contains the infection within granulomas, resulting in latent TB infection, which is asymptomatic and non-infectious. In a smaller proportion (about 5–10%), containment fails, leading to primary progressive active tuberculosis. Latent infection may later reactivate if immunity declines, particularly in immunocompromised states, resulting in active disease.
What is the key pathological diagnostic feature that distinguishes primary pulmonary tuberculosis from secondary (post-primary) tuberculosis?
Primary TB is characterised by the presence of a Ghon complex (subpleural Ghon focus with associated hilar lymphadenopathy showing necrotising granulomatous inflammation), whereas secondary TB lacks a Ghon complex and instead shows apical, fibrocaseous cavitary disease with minimal lymph node involvement and extensive tissue destruction.
You are an intern in OPD. A 32-year-old woman with HIV is started on TB treatment including rifampicin. She is also on oral contraceptive pills and antiretrovirals. Two weeks later she returns with breakthrough bleeding and rising viral load. Explain what is happening pharmacologically and why.
Rifampicin is a potent inducer of hepatic cytochrome P450 enzymes and drug transporters. This increases the metabolism of drugs such as oral contraceptives and many antiretrovirals, reducing their plasma concentrations to subtherapeutic levels. This results in contraceptive failure (breakthrough bleeding/pregnancy risk) and reduced efficacy of ART leading to viral rebound.
What is the primary goal of randomisation in an RCT?
To evenly distribute known and unknown confounders between groups, reducing selection bias.
Which drug is given alongside RIPE, why is it given, and for how long?
Pyridoxine (vitamin B6) is given alongside isoniazid for 6 months because isoniazid depletes vitamin B6 and can cause peripheral neuropathy.
Suppose you are an intern at Groote Schuur Hospital and the attending doctor asks you to request laboratory investigations for suspected pulmonary TB. What is your diagnostic approach, and why?
My diagnostic approach would be to confirm Mycobacterium tuberculosis infection using rapid molecular testing first, followed by microbiological confirmation and drug susceptibility testing to guide treatment and detect resistance.
First-line testing in South Africa is the GeneXpert MTB/RIF Ultra (Xpert MTB/RIF Ultra), a cartridge-based real-time PCR assay widely implemented through the NHLS. It is used on all pulmonary samples and has largely replaced sputum microscopy. It detects MTB DNA and rifampicin resistance (rpoB gene mutations). It is preferred because it is more sensitive than acid-fast bacilli (AFB) smear microscopy, has a rapid turnaround time of under 2 hours, is a closed system reducing contamination risk, and allows early identification of rifampicin resistance. However, it is limited by cost and requires laboratory infrastructure despite decentralised availability.
In parallel, I would send sputum for acid-fast bacilli (AFB) smear microscopy, although it is now largely secondary because it is less sensitive and mainly detects patients with high bacterial loads.
For definitive diagnosis and full resistance profiling, I would request mycobacterial culture. This is the gold standard and confirms TB by demonstrating visible growth of Mycobacterium tuberculosis colonies on solid media. Additionally, culture can be performed using the BACTEC MGIT system, an automated liquid culture method where TB bacilli consume oxygen in the tube. This changes the fluorescence of an indicator at the bottom of the tube, and once a threshold change is detected, the system registers a positive result, allowing earlier detection than solid culture.
To further guide management in suspected or resistant cases, I would request line probe assays, which are highly technical molecular PCR tests used to detect resistance to rifampicin, isoniazid (INH), and fluoroquinolones. Other molecular platforms such as BD MAX and Roche systems may also be used depending on availability.
Overall, this stepwise approach ensures rapid diagnosis (GeneXpert), confirmation of active disease (culture/MGIT), and early detection of drug resistance (line probe assays), which is essential for appropriate treatment initiation and infection control.
A patient presents with chronic productive cough, foul-smelling sputum, and finger clubbing. What is the most likely diagnosis and underlying mechanism?
Bronchiectasis caused by chronic infection leading to a “vicious cycle” of inflammation, airway destruction, and permanent bronchial dilatation.
Imagine you are an intern on call in a district hospital. A 28-year-old HIV-positive patient presents with chronic cough, weight loss, night sweats, and now worsening shortness of breath. Chest X-ray shows upper lobe cavitary lesions, and sputum is GeneXpert-positive for Mycobacterium tuberculosis with rifampicin resistance. Over the next 48 hours, the patient develops haemoptysis and sudden respiratory deterioration. Explain the underlying pathogenesis of the disease process from primary infection to the current complications, and account for the haemoptysis.
The patient likely has secondary (post-primary) pulmonary tuberculosis, resulting from reactivation of dormant Mycobacterium tuberculosis bacilli that were previously contained within granulomas during primary infection. These bacilli persist in areas of high oxygen tension, particularly the lung apices, and may reactivate in the setting of immunosuppression such as HIV.
Reactivation leads to a robust hypersensitivity-driven immune response with caseating granulomatous inflammation and progressive tissue destruction. The caseous necrosis may liquefy and erode into a bronchus, forming a cavitary lesion. This cavity has a characteristic structure consisting of an inner zone of caseous necrosis, a middle layer of granulomatous inflammation, and an outer fibrotic wall.
As the cavity enlarges, it causes local destruction of lung parenchyma and blood vessels. In particular, chronic inflammation may lead to endarteritis obliterans, weakening and distortion of bronchial and pulmonary arteries. In some cases, focal dilation of these vessels forms a Rasmussen’s aneurysm within the cavity wall.
The patient’s acute haemoptysis is most likely due to rupture of these fragile, inflamed vessels or rupture of a Rasmussen’s aneurysm into the airway. This results in potentially life-threatening pulmonary haemorrhage. The respiratory deterioration reflects both loss of functional lung tissue from cavitation and flooding of airways with blood, causing impaired gas exchange.
In a study, risk in exposed group = 0.08 and unexposed group = 0.02. Calculate and interpret the attributable fraction in the exposed.
Different Q: An RCT has a 25% dropout rate (mostly in the intervention arm due to side effects), and researchers use per-protocol analysis. What are the two main methodological flaws?
Calculation: (0.08 − 0.02) ÷ 0.08 = 0.75
Interpretation: 75% of cases in the exposed group are attributable to the exposure.
Q2: