Tuberculosis (TB): Symptoms, Diagnosis and the 6-Month Regimen

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. It spreads through the air when a person with active lung TB coughs or sneezes. TB remains one of the world's leading infectious killers. Pakistan and other South Asian countries carry a high burden, so every doctor working there must be able to recognise and manage it.

Latent versus active TB

• Latent TB infection — the person is infected but has no symptoms and is not infectious. Some will develop active disease later, especially if their immunity falls.
• Active TB disease — symptomatic, and infectious when it affects the lungs.

Risk factors for active disease

• HIV infection.
• Malnutrition.
• Diabetes.
• Smoking and alcohol use.
• Close contact with an infectious case.
• Crowded living conditions.
• Immunosuppressive drugs (including anti-TNF therapy and steroids).
• Silicosis.
• Kidney failure.

Clinical features

Pulmonary TB:

• cough lasting more than 2 weeks, sometimes with blood (haemoptysis)
• fever, especially in the evening
• night sweats
• weight loss and loss of appetite

Extrapulmonary TB can affect almost any organ:

• lymph nodes (the most common site, often in the neck)
• pleura
• abdomen
• spine (Pott's disease)
• meninges
• genitourinary tract
• pericardium

Investigations

• Sputum tests: rapid molecular tests such as Xpert MTB/RIF (WHO-recommended initial test; also detects rifampicin resistance), smear microscopy for acid-fast bacilli, and culture (the gold standard, which also allows full drug-susceptibility testing).
• Chest X-ray: upper-lobe infiltrates, cavitation, hilar lymphadenopathy, effusion or a miliary pattern.
• For extrapulmonary TB: tissue or fluid samples for histology (caseating granulomas), molecular testing and culture.
• HIV test for all patients with TB.
• Latent TB: tuberculin skin test or interferon-gamma release assay.

Treatment of drug-susceptible TB

The standard regimen lasts 6 months: an intensive phase of 2 months with four drugs, isoniazid, rifampicin, pyrazinamide and ethambutol (2HRZE), followed by a continuation phase of 4 months with isoniazid and rifampicin (4HR). Some forms, such as TB meningitis and spinal TB, need longer treatment and sometimes corticosteroids. Follow your national TB programme guidelines, which may include newer, shorter regimens for eligible patients.

Key side effects

• Isoniazid: peripheral neuropathy (prevented with pyridoxine), hepatitis.
• Rifampicin: orange-red body fluids, hepatitis, and many drug interactions (it is an enzyme inducer, so it reduces the effect of oral contraceptives, warfarin and others).
• Pyrazinamide: hepatitis, raised uric acid and gout, joint pain.
• Ethambutol: optic neuritis (reduced visual acuity and red-green colour vision). Check vision before and during treatment.

Adherence and drug resistance

Incomplete treatment leads to drug resistance. Multidrug-resistant TB (resistance to at least isoniazid and rifampicin) needs specialist regimens. Directly observed or supported treatment, patient education and free supply through national programmes help patients complete therapy.

Prevention

• Early diagnosis and treatment of active cases.
• Contact tracing.
• BCG vaccination in infancy (protects mainly against severe childhood TB).
• Preventive treatment for eligible people with latent infection.
• Infection control in health facilities.

Exam pearls

• A cough for more than 2 weeks in a high-burden country means test for TB.
• Ethambutol affects the eyes; isoniazid affects the nerves (give pyridoxine).
• Rifampicin reduces the effectiveness of hormonal contraception.

For more, see Exam Night Notes 1.0: Pulmonology and the infectious diseases part of the Medicine Companion.

Test yourself

5 exam-style single-best-answer questions. Choose your answer, then tap “Show answer”.

1. Which test is recommended by WHO as an initial test for pulmonary TB and detects rifampicin resistance?

   1. Xpert MTB/RIF
   2. Tuberculin skin test
   3. ESR
   4. Widal test
   5. Chest X-ray alone
   Show answer

   Answer: A. Xpert MTB/RIF
   Xpert MTB/RIF is a rapid molecular test that detects M. tuberculosis and rifampicin resistance.

2. A patient on TB treatment develops numbness of the feet. Which drug, and what prevents it?

   1. Streptomycin; iron
   2. Ethambutol; folic acid
   3. Isoniazid; pyridoxine
   4. Pyrazinamide; calcium
   5. Rifampicin; vitamin C
   Show answer

   Answer: C. Isoniazid; pyridoxine
   Isoniazid causes peripheral neuropathy, prevented by pyridoxine (vitamin B6).

3. Which TB drug causes optic neuritis?

   1. Pyrazinamide
   2. None
   3. Ethambutol
   4. Isoniazid
   5. Rifampicin
   Show answer

   Answer: C. Ethambutol
   Ethambutol can cause optic neuritis with reduced acuity and red-green colour vision.

4. A woman on the combined pill starts TB treatment. Which advice is important?

   1. Pyrazinamide increases fertility
   2. No change needed
   3. Double the pill dose without advice
   4. Rifampicin reduces the effectiveness of hormonal contraception; use another method
   5. Stop TB drugs
   Show answer

   Answer: D. Rifampicin reduces the effectiveness of hormonal contraception; use another method
   Rifampicin is a potent enzyme inducer and reduces the effect of hormonal contraceptives.

5. What is the standard regimen for drug-susceptible pulmonary TB?

   1. 6 months of isoniazid alone
   2. 2 weeks of rifampicin
   3. 12 months HRZE
   4. 2HR/4HRZE
   5. 2HRZE/4HR
   Show answer

   Answer: E. 2HRZE/4HR
   Two months of isoniazid, rifampicin, pyrazinamide and ethambutol, then four months of isoniazid and rifampicin.

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Disclaimer

For education and exam preparation only. This is not medical advice and must not be used to diagnose or treat patients. Always follow current clinical guidelines and the advice of qualified senior colleagues.