Tuberculosis: An Old Disease That Refuses to Disappear
Tuberculosis (TB) is a communicable infectious disease caused primarily by Mycobacterium tuberculosis. Although TB can affect almost any organ, the lungs are the most commonly involved site.
Tuberculosis (TB) is a preventable and usually curable disease. Nonetheless, more than 10 million people continue to fall ill with TB every year and more than 1 million die from the disease, making it the world’s leading cause of death from a single infectious agent and among the top 10 causes of death worldwide.
What causes TB?
The principal causative organism is Mycobacterium tuberculosis, an aerobic, non-motile, acid-fast bacillus.
M. tuberculosis belongs to the Mycobacterium tuberculosis complex. Other members of this complex, including M. bovis and M. africanum, can also cause tuberculosis in humans.
How does TB Spread?
TB is primarily transmitted through airborne particles generated by individuals with infectious pulmonary or laryngeal disease. Transmission is facilitated by prolonged or repeated exposure, particularly in crowded or poorly ventilated environments.
Importantly, TB infection and TB disease are not synonymous. A person may become infected with M. tuberculosis without developing clinical disease.
Individuals with TB infection who do not have active disease generally have no symptoms and do not transmit TB. Approximately one quarter of the world's population is estimated to have been infected with TB bacteria, although only a proportion subsequently develop TB disease.
Classification of Tuberculosis
According to anatomical site
Pulmonary TB: Infection primarily involving the lungs.
Extrapulmonary TB: Infection involving organs outside the lungs, such as lymph nodes, pleura, bones and joints, kidneys, abdomen or the central nervous system.
According to disease state
TB infection: The individual is infected with M. tuberculosis but does not have clinical TB disease.
TB disease: Active disease is present, with clinical, microbiological and/or radiological evidence of tuberculosis.
According to drug susceptibility
Drug-susceptible TB: The infecting organism remains susceptible to the drugs used in the standard treatment regimen.
Drug-resistant TB: The organism has resistance to one or more anti-TB drugs. Important categories include rifampicin-resistant TB (RR-TB), multidrug-resistant TB (MDR-TB) and other forms of drug-resistant TB.
Important clinical forms
Miliary TB: A disseminated form of TB in which the infection spreads through the bloodstream and produces numerous small lesions in multiple organs.
Tuberculous meningitis: TB involving the meninges and central nervous system.
Disseminated TB: TB involving multiple non-contiguous organs or sites.
Who are at risk for TB?
Several conditions increase the likelihood of progression from TB infection to TB disease. Important risk factors include:
HIV infection and other forms of immunosuppression
Diabetes mellitus
Malnutrition
Tobacco use
Older age
Close or prolonged contact with a person with infectious TB
Living or working in crowded environments
Alcohol or substance use disorders
Previous or untreated TB infection
People with impaired immunity are at particularly high risk of developing TB disease after infection.
Clinical Features
The clinical presentation depends on the organ involved. Pulmonary TB commonly develops gradually, and symptoms may initially be mild.
Common symptoms of pulmonary TB
Persistent cough
Sputum production, occasionally with blood
Fever
Night sweats
Weight loss
Loss of appetite
Fatigue and weakness
Chest pain
Shortness of breath, particularly in advanced disease
Hemoptysis
A prolonged cough accompanied by constitutional symptoms should prompt evaluation for TB, particularly in individuals with relevant risk factors.
Extrapulmonary TB produces symptoms related to the affected organ. For example, tuberculous meningitis may present with headache, fever, altered mental status or neurological deficits, whereas skeletal TB may cause chronic pain and swelling.
Diagnosis
Diagnosis should be based on the clinical presentation together with appropriate microbiological, molecular and radiological investigations. WHO recommends rapid molecular diagnostic tests as initial diagnostic tests in people with signs and symptoms suggestive of TB.
1. Clinical assessment
A detailed history should assess:
Duration and nature of cough
Fever and night sweats
Weight loss and appetite
Hemoptysis
Previous TB treatment
Contact with a person with TB
HIV and other immunocompromising conditions
Diabetes and other relevant comorbidities
Previous exposure to anti-TB drugs
2. Sputum examination
Respiratory specimens can be examined for M. tuberculosis. Sputum smear microscopy can detect acid-fast bacilli, although microscopy has limitations in sensitivity and does not adequately determine drug resistance.
3. Rapid molecular diagnostic tests
Nucleic acid amplification tests, including WHO-recommended rapid molecular assays such as Xpert MTB/RIF or related technologies, can detect M. tuberculosis and provide information about rifampicin resistance.
4. Culture
Mycobacterial culture remains an important reference method for confirming infection and can be used for drug susceptibility testing. However, culture is slower than molecular diagnostic methods
5. Chest radiography
Chest X-ray can provide supportive evidence of pulmonary TB and may demonstrate abnormalities such as infiltrates, cavities or other patterns suggestive of TB. However, radiography alone cannot definitively establish microbiological diagnosis.
6. Tests for TB infection
The tuberculin skin test, commonly known as the Mantoux test, and interferon-gamma release assays can help identify TB infection. These tests do not by themselves distinguish TB infection from active TB disease and therefore should not be used as standalone tests for diagnosing active pulmonary TB.
7. Drug susceptibility testing
Drug susceptibility testing is essential when drug resistance is suspected or detected. Molecular testing can identify resistance-associated mutations, while culture-based methods can provide phenotypic susceptibility information.
Complications
Untreated or inadequately treated TB can result in significant morbidity and mortality. Pulmonary complications include:
Lung tissue destruction
Pulmonary fibrosis
Bronchiectasis
Cavitation
Hemoptysis
Respiratory failure
Secondary infections
Extrapulmonary disease may cause organ-specific complications, particularly when the central nervous system, bones or other critical organs are involved.
Pharmacological Treatment
The primary objectives of TB treatment are to:
Cure the patient and achieve durable microbiological clearance.
Prevent death and disease complications.
Prevent relapse.
Prevent transmission to others.
Prevent the emergence and spread of drug resistance.
Principles of anti-TB therapy
TB treatment requires the use of multiple effective drugs in combination. Combination therapy reduces the likelihood that naturally occurring resistant organisms will survive and multiply.
Treatment is generally administered in phases. For drug-susceptible pulmonary TB in adults, the conventional standard regimen consists of an intensive phase containing four drugs followed by a continuation phase containing two drugs.
First-line anti-TB drugs
The principal first-line agents used in drug-susceptible TB include:
Isoniazid (H): A bactericidal drug that inhibits synthesis of mycolic acids, important components of the mycobacterial cell wall.
Rifampicin (R): A potent bactericidal drug that inhibits bacterial DNA-dependent RNA polymerase. Rifampicin is a key component of standard TB treatment.
Pyrazinamide (Z): Particularly important during the initial phase of treatment because of its activity against susceptible bacilli in acidic environments.
Ethambutol (E): Inhibits arabinosyl transferases involved in mycobacterial cell-wall synthesis and is used primarily to protect against the development of resistance to the other core drugs during initial treatment.
The standard drug-susceptible TB regimen is commonly represented as:
Intensive phase: HRZE
Continuation phase: HR
The exact regimen, dose and duration should be determined according to the patient's age, body weight, disease site, drug susceptibility results, comorbidities and applicable national guidelines. WHO currently describes standard treatment for drug-susceptible TB as a six-month course of four antibiotics, while certain patients may qualify for alternative shorter regimens under specific guideline criteria.
Drug-resistant TB
Drug-resistant TB requires a different treatment approach. Therapy should be guided by rapid molecular resistance testing and, when appropriate, additional drug susceptibility testing.
The older classification of treatment into Category I, Category II, Category III, Category IV and Category V, including routine use of kanamycin, capreomycin and other older injectable agents, should not be presented as the current standard of care.
Modern drug-resistant TB management increasingly uses all-oral, shorter regimens incorporating newer and repurposed medicines such as bedaquiline, linezolid and fluoroquinolones when appropriate. The specific regimen depends on the resistance pattern, previous treatment exposure, patient characteristics and national or WHO recommendations. WHO has substantially updated its drug-resistant TB treatment guidance, and treatment should therefore be individualized according to current guidelines rather than older fixed categories.
Adverse Effects and Monitoring
Patients receiving anti-TB therapy should be monitored for adverse effects.
Important examples include:
Isoniazid: Hepatotoxicity and peripheral neuropathy
Rifampicin: Hepatotoxicity, drug interactions and orange-red discoloration of urine, sweat and tears
Pyrazinamide: Hepatotoxicity and hyperuricaemia
Ethambutol: Optic neuritis and changes in visual acuity or colour vision
Aminoglycosides: Ototoxicity and nephrotoxicity, where these agents are used
Fluoroquinolones: Tendinopathy, QT prolongation and other class-specific adverse effects
Linezolid: Myelosuppression and peripheral or optic neuropathy with prolonged exposure
The selection of baseline and follow-up monitoring should be individualized according to the regimen and patient-specific risk factors.
Non-Pharmacological Management and Infection Control
Drug therapy is the cornerstone of treatment, but supportive and public health measures are also important.
Infection-control measures
Patients with infectious pulmonary TB should follow local infection-control advice, particularly during the period when they may transmit infection. Measures can include:
Appropriate respiratory hygiene and cough etiquette
Adequate ventilation
Wearing an appropriate mask when advised
Avoiding unnecessary close contact during the infectious period
Adhering closely to the prescribed treatment regimen
Nutritional support
Patients with TB may experience anorexia, weight loss and nutritional deficiencies. A balanced diet with adequate energy and protein intake should be encouraged according to individual nutritional needs.
Smoking cessation
Tobacco use adversely affects respiratory health and is associated with increased risk of TB disease and poorer outcomes. Smoking cessation should therefore be encouraged.
Treatment support
Adherence support is essential. Treatment interruption can contribute to treatment failure, relapse and the development or amplification of drug resistance.
The historical term DOTS (Directly Observed Treatment, Short-course) described a public health strategy involving supervised treatment and programme-level TB control measures. Modern TB care is increasingly focused on patient-centred adherence support rather than assuming that direct observation of every dose is necessary for every patient.
Prevention
TB prevention involves identifying and treating TB infection in appropriate individuals, early diagnosis and effective treatment of active disease, infection-control measures and management of risk factors.
Preventive treatment can substantially reduce the risk of progression from TB infection to TB disease in eligible individuals. Current preventive treatment options include shorter regimens in appropriate patients.
Key Takeaways
TB is caused primarily by Mycobacterium tuberculosis and is transmitted mainly through the air.
TB infection does not necessarily progress to active TB disease.
Pulmonary TB commonly presents with prolonged cough, weight loss, fever and night sweats.
Rapid molecular tests are important tools for diagnosing TB and detecting drug resistance.
Drug-susceptible TB is generally treated with a multidrug regimen containing isoniazid, rifampicin, pyrazinamide and ethambutol during the initial phase, followed by isoniazid and rifampicin during the continuation phase.
Drug-resistant TB requires susceptibility-guided treatment using contemporary regimens.
Treatment adherence, adverse-effect monitoring, infection control and patient counselling are essential for successful outcomes.
References
Assessed and Endorsed by the MedReport Medical Review Board
