Medicine – Tuberculosis

Tuberculosis (TB) is a chronic infectious disease caused predominantly by Mycobacterium tuberculosis. It is transmitted mainly through inhalation of airborne particles from a person with infectious pulmonary or laryngeal TB. Although the lungs are the most commonly affected organs, TB can disseminate and involve almost any part of the body.

1. Groups at Increased Risk

The risk of TB is determined by both the likelihood of exposure to M. tuberculosis and the likelihood that latent infection will progress to active disease.

People who have migrated from countries where TB is highly prevalent have an increased risk, particularly during the first several years after migration.

HIV Infection and Immunosuppression

HIV infection is an especially important risk factor because impaired cell-mediated immunity greatly increases the probability that latent TB will reactivate and that newly acquired infection will progress rapidly.

Other forms of immunosuppression, including corticosteroids, transplantation, chemotherapy, and anti-TNF therapy, also increase the risk of active and disseminated TB.

Social Risk Factors

People experiencing homelessness, overcrowded living conditions, poverty, incarceration, or poor access to healthcare may have increased exposure and delayed diagnosis.

Alcohol dependence and substance-use disorders can also increase risk through associated socioeconomic factors, malnutrition, impaired immunity, and difficulty completing treatment.

Primary Tuberculosis

2. Initial Infection

Primary TB refers to infection occurring in an individual who has not previously developed specific immunity to M. tuberculosis.

Inhaled organisms reach the distal airways and alveoli, where they are taken up by macrophages. The infection may initially produce few or no symptoms.

3. Ghon Focus

The initial pulmonary lesion is traditionally called the Ghon focus.

It is usually a small area of granulomatous inflammation located in the peripheral lung, often in the lower part of an upper lobe or upper part of a lower lobe.

4. Lymphatic Spread

Mycobacteria can travel from the initial pulmonary focus through the lymphatic vessels to the regional hilar lymph nodes.

The combination of the pulmonary Ghon focus and involved regional lymph nodes is known as the Ghon complex.

5. Arrest of Primary Infection

In most immunocompetent individuals, an effective cell-mediated immune response develops and controls the infection.

The organisms may be contained within granulomas rather than completely eliminated. Viable bacilli can therefore remain dormant for many years, producing latent TB infection.

6. Development of an Immune Response

After infection, immune sensitisation to M. tuberculosis develops.

A tuberculin skin test (Mantoux test) may therefore become positive several weeks after infection. Interferon-gamma release assays (IGRAs) can also demonstrate immunological sensitisation to TB.

Importantly, these tests indicate TB infection or immune sensitisation but cannot by themselves distinguish latent infection from active TB disease.

7. Clinical Features of Primary TB

Primary infection is frequently asymptomatic.

When symptoms occur, they may include mild fever, cough, fatigue, and occasionally wheezing when enlarged hilar lymph nodes compress an airway.

Erythema nodosum can occur as an immunological reaction to primary TB, although it has many other possible causes.

Post-Primary Tuberculosis

8. Reactivation Disease

Post-primary, or secondary, TB commonly results from reactivation of previously dormant organisms, although reinfection can also occur.

Reactivation is particularly likely when cell-mediated immunity becomes impaired because of ageing, malnutrition, HIV infection, immunosuppressive therapy, or other illnesses.

9. Upper-Lobe Predominance

Post-primary pulmonary TB classically affects the apical and posterior regions of the upper lobes.

These regions have relatively high oxygen tension, which favours growth of M. tuberculosis, an obligate aerobe.

Tissue destruction can lead to caseation and cavitation, allowing large numbers of bacilli to enter the airways and increasing infectiousness.

Miliary Tuberculosis

10. Haematogenous Dissemination

Miliary TB occurs when M. tuberculosis spreads widely through the bloodstream.

This produces numerous tiny granulomatous lesions in multiple organs. The term miliary describes the characteristic appearance of innumerable small lesions resembling millet seeds.

11. Organ Involvement

Miliary TB may involve the lungs, liver, spleen, bone marrow, kidneys, meninges, and other organs.

It is particularly important in young children and immunocompromised individuals but can occur at any age.

Clinical Features

12. Constitutional Symptoms

Active TB commonly produces constitutional symptoms including fever, drenching night sweats, loss of appetite, fatigue, and unintentional weight loss.

The onset may be gradual, with symptoms developing over weeks or months.

13. Cough

Persistent cough is a common manifestation of pulmonary TB.

It may initially be dry but can become productive as pulmonary disease progresses.

14. Haemoptysis

Haemoptysis can occur when cavitating disease or chronic inflammation damages pulmonary or bronchial blood vessels.

Bleeding ranges from minor blood-streaking to potentially life-threatening haemoptysis.

15. Pleural Effusion

TB can involve the pleura and produce a tuberculous pleural effusion.

The fluid is usually an exudate with lymphocyte predominance. Pleural fluid glucose may be reduced, particularly in more intense or chronic disease.

16. Tuberculous Meningitis

Dissemination to the central nervous system can produce tuberculous meningitis, a severe form of extrapulmonary TB.

Patients may develop persistent headache, fever, vomiting, altered consciousness, cranial nerve abnormalities, and neurological deficits.

Early recognition and treatment are essential because neurological complications can be permanent.

Diagnosis

17. Chest Radiograph

In post-primary pulmonary TB, the chest radiograph may demonstrate upper-zone or apical opacification, volume loss, fibrosis, and cavitation.

Primary TB may instead show hilar lymphadenopathy, consolidation, or pleural effusion.

Miliary TB classically produces innumerable tiny bilateral pulmonary nodules.

18. Sputum Examination

Patients suspected of having pulmonary TB should have respiratory samples examined for acid-fast bacilli (AFB).

Traditionally this involved sputum smear microscopy followed by mycobacterial culture.

Modern diagnosis increasingly incorporates rapid molecular tests, which can detect M. tuberculosis DNA and, depending on the assay, identify important drug-resistance markers much faster than conventional culture.

19. Mycobacterial Culture

Mycobacterial culture remains important because it confirms viable organisms and allows detailed drug-susceptibility testing.

Traditional solid cultures may require several weeks, explaining the older teaching that cultures take at least six weeks. Modern liquid culture systems frequently produce results considerably sooner, although final negative cultures may still require prolonged incubation.

20. Urine Examination

Early-morning urine samples can be examined for mycobacteria when genitourinary TB is suspected.

Multiple specimens may be required because organisms are not continuously shed into the urine.

21. Tissue Biopsy

When extrapulmonary TB is suspected, tissue may be obtained from sites such as an enlarged lymph node, pleura, or other affected organ.

Histology may demonstrate caseating granulomatous inflammation, while the tissue can also undergo molecular testing and mycobacterial culture.

22. Bone Marrow Examination

Bone marrow aspiration or biopsy may occasionally be useful in suspected disseminated or miliary TB, particularly when patients have unexplained cytopenias or systemic illness.

It is not a routine investigation for uncomplicated pulmonary TB.

23. Bronchoscopy

Bronchoscopy with bronchial washing or bronchoalveolar lavage can provide diagnostic material when sputum cannot be obtained or remains negative despite strong suspicion of pulmonary TB.

Treatment

24. Standard Initial Therapy

For drug-susceptible active TB, standard treatment generally begins with four drugs, not three:

Rifampicin + isoniazid + pyrazinamide + ethambutol.

These are commonly abbreviated RIPE therapy.

25. Duration of Treatment

For uncomplicated drug-susceptible pulmonary TB, the traditional standard regimen consists of:

2 months: rifampicin + isoniazid + pyrazinamide + ethambutol.

Followed by 4 months: rifampicin + isoniazid.

This gives a total treatment duration of approximately 6 months, although treatment varies according to drug susceptibility, site of disease, response, comorbidities, and national guidelines.

TB meningitis and some other forms of extrapulmonary disease generally require modified and/or longer treatment.

26. Drug Resistance

The older approach of reserving ethambutol only for patients with HIV or people from areas with high resistance is no longer standard.

Four-drug initial therapy is generally used while drug susceptibility is being established, because isoniazid resistance may be present even without obvious risk factors.

Drug-resistant TB requires specialist treatment using regimens determined by molecular and culture-based susceptibility testing.

27. Importance of Adherence

Adherence to the complete treatment regimen is essential.

Poor adherence can result in treatment failure, relapse, continued transmission, and selection of drug-resistant M. tuberculosis.

Adverse Effects of Antituberculous Drugs

28. Rifampicin

Rifampicin can cause hepatotoxicity, gastrointestinal disturbance, rash, and orange-red discoloration of urine, sweat, saliva, and tears.

The discoloration of body fluids is harmless but patients should be warned about it.

Rifampicin is also a powerful hepatic enzyme inducer, producing clinically important interactions with numerous medications, including some anticoagulants, anticonvulsants, hormonal contraceptives, and antiretroviral drugs.

29. Isoniazid

Isoniazid can cause hepatotoxicity and peripheral neuropathy.

Neuropathy results partly from interference with vitamin B6 metabolism and can be prevented or reduced by giving pyridoxine (vitamin B6), particularly in patients at increased risk.

30. Pyrazinamide

Pyrazinamide can cause hepatotoxicity, gastrointestinal symptoms, rash, arthralgia, and hyperuricaemia.

The rise in uric acid may occasionally precipitate acute gout.

31. Ethambutol

The most important adverse effect of ethambutol is optic neuropathy, which can cause reduced visual acuity and impaired colour vision, classically affecting red-green discrimination.

Patients should have appropriate assessment of vision and be advised to report visual changes promptly.

Because ethambutol is largely eliminated through the kidneys, dose adjustment may be necessary in significant renal impairment. Renal dysfunction itself is not the classic toxicity of ethambutol.

Key Clinical Pattern

Think of pulmonary TB in a patient with persistent cough, weight loss, fever, night sweats and haemoptysis, particularly when imaging demonstrates upper-lobe disease with cavitation.

Remember the progression:

Primary infection → Ghon focus and regional lymph nodes → immune containment/latent TB → possible later reactivation as post-primary TB.

Miliary TB results from widespread haematogenous dissemination and can involve multiple organs.

For uncomplicated drug-susceptible pulmonary TB, remember RIPE for the initial 2 months, followed traditionally by rifampicin + isoniazid for another 4 months, with treatment adjusted according to susceptibility results and the clinical form of disease.