Respiratory System Conditions
Subtopic:
Tuberculosis (TB)
Tuberculosis
Tuberculosis (TB), often called “consumption” in the past, is a common and potentially fatal infectious disease caused by various strains of bacteria called mycobacteria. The bacterium most commonly associated with TB is Mycobacterium tuberculosis.
Global Impact: TB is a widespread global health problem. It’s estimated that approximately one-third of the world’s population – that is, roughly 1 in 3 people – is infected with TB bacteria. However, most of these individuals have latent TB infection and do not have active TB disease.
Lung Predominance: TB most frequently affects the lungs (pulmonary tuberculosis).
Extrapulmonary TB: TB can also affect other parts of the body beyond the lungs. This is known as extrapulmonary tuberculosis and can involve organs such as:
Pleura (lining of the lungs)
Lymph nodes
Bones and joints
Brain and meninges (membranes surrounding the brain and spinal cord)
Kidneys
Pericardium (sac around the heart)
Abdomen
Genitourinary system
Skin (rare)
HIV/AIDS and TB Risk: Individuals with Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) are at a significantly higher risk of developing active tuberculosis disease once infected with TB bacteria. HIV weakens the immune system, making it harder to control TB infection.
Aetiology (Cause):
Causative Agent: TB is caused by the bacterium Mycobacterium tuberculosis.
Bacterial Characteristics: Mycobacterium tuberculosis is described as:
Small in size
Aerobic (requires oxygen to live)
Non-motile (cannot move on its own)
Bacillus-shaped (rod-shaped bacteria)
Mode of Spread (Transmission):
TB primarily spreads through airborne transmission:
Airborne Droplets: TB bacteria are released into the air when a person with active pulmonary TB disease:
Coughs
Sneezes
Speaks
Sings
… or otherwise expels respiratory fluids (droplets) containing the bacteria.
Inhalation: Other individuals can become infected by inhaling these airborne droplets containing Mycobacterium tuberculosis.
Haematogenous Spread (Less Common): In less frequent cases, TB can also spread through the bloodstream. This is known as haematogenous spread and can occur when TB bacteria disseminate from the lungs to other parts of the body via the blood. This type of spread is more likely to lead to extrapulmonary TB.
Types of Tuberculosis (TB)
TB is broadly categorized into:
Pulmonary Tuberculosis (PTB): TB infection primarily affecting the lungs. This is the most common form of TB.
Extrapulmonary Tuberculosis (EPTB): TB infection occurring in organs outside of the lungs. EPTB can affect various parts of the body.
Primary Tuberculosis: The initial TB infection in a person who has never been infected with TB bacteria before.
Secondary Tuberculosis (Reactivation TB): TB disease that develops later in life, typically due to reactivation of a latent TB infection.
Clinical Features (Signs and Symptoms):
Pulmonary TB (PTB) Symptoms:
Systemic Symptoms:
Fever and chills
Night sweats (profuse sweating during sleep)
Loss of appetite (anorexia)
Unintentional weight loss
Easy fatigability (persistent tiredness and weakness)
Respiratory Symptoms:
Persistent cough: A cough lasting for 3 weeks or longer is a hallmark symptom.
Haemoptysis: Coughing up blood (may or may not be present).
Chest pain (may be pleuritic, worsening with breathing).
Productive cough: Cough producing sputum (phlegm), or non-productive dry cough (more common in smear-negative TB).
Lymphadenopathy: Swollen lymph nodes, often in the neck (cervical lymph nodes).
Other Signs:
Significant finger clubbing: Abnormal widening and rounding of the fingertips, indicating chronic lung disease and oxygen deprivation.
Extrapulmonary TB (EPTB) Symptoms:
Prevalence: EPTB occurs in approximately 15-20% of active TB cases.
Higher Risk Groups: More common in individuals with:
Weakened immune systems (e.g., HIV infection)
Young children
HIV Co-infection: In people with HIV, EPTB is significantly more frequent, occurring in over 50% of TB cases.
Common Extrapulmonary Sites and Manifestations:
Pleura (Tuberculous Pleurisy): Inflammation of the lining around the lungs, causing chest pain and fluid buildup.
Central Nervous System (Tuberculous Meningitis): Infection of the brain and meninges, leading to severe headache, stiff neck, fever, altered mental status, seizures, and neurological deficits.
Lymphatic System (TB Lymphadenitis): Infection of lymph nodes, commonly in the neck, causing painless swelling (TB lymph nodes).
Genitourinary System (Urogenital Tuberculosis): TB affecting the kidneys, bladder, and reproductive organs, causing urinary symptoms, flank pain, and infertility.
Bones and Joints (Skeletal Tuberculosis/Pott’s Disease): TB infection of bones, especially the spine (Pott’s disease), causing back pain, spinal deformity, and neurological complications. Osseous tuberculosis is a form of osteomyelitis (bone infection).
Skin (Tuberculous Ulcers): In rare cases, TB can cause skin ulcers. Tubercular abscesses (collections of pus) may rupture through the skin, forming tuberculous ulcers, which are typically painless.
Disseminated TB (Miliary Tuberculosis): A severe, widespread form of TB where bacteria spread throughout the body via the bloodstream. Miliary TB accounts for about 10% of EPTB cases and can affect multiple organs.
Risk Factors for Tuberculosis:
Several factors increase an individual’s risk of TB infection and progression to active TB disease:
HIV Infection: HIV is the most significant global risk factor for TB, contributing to an estimated 13% of all TB cases worldwide. HIV weakens the immune system, making individuals highly susceptible to TB.
Overcrowding and Malnutrition: TB is strongly linked to conditions of overcrowding and malnutrition, making it more prevalent in impoverished communities and areas with poor living conditions.
Congregate Settings: Living or working in settings where vulnerable populations gather increases TB risk. Examples include:
Prisons
Homeless shelters
Medically Underserved and High-Risk Populations: Limited access to healthcare, resource scarcity, and belonging to high-risk ethnic minority groups increase susceptibility.
Child Contact with High-Risk Individuals: Children who are in close contact with adults who have active TB are at higher risk of infection.
Healthcare Workers (TB Care Settings): Healthcare providers who work directly with TB patients have an occupational risk of TB exposure and infection.
Chronic Lung Disease: Pre-existing chronic lung conditions increase TB susceptibility.
Smoking: Cigarette smokers have nearly twice the risk of developing TB compared to non-smokers. Smoking damages the lungs and weakens immune defenses.
Other Medical Conditions: Certain conditions can elevate TB risk, including:
Alcoholism (weakens immune system, associated with poor nutrition and living conditions)
Diabetes mellitus (compromises immune function)
Silicosis
Kidney disease (end-stage renal disease)
Certain cancers and cancer treatments
Immunosuppressive medications (e.g., corticosteroids, TNF-alpha inhibitors, post-transplant drugs)
Epidemiology (Global and Regional Distribution):
Global Burden: Approximately one-third of the world’s population is latently infected with Mycobacterium tuberculosis.
Adult Mortality: TB is a major cause of preventable deaths in adults, accounting for 25% of preventable adult deaths globally.
Productive Age Group: A disproportionate number (three-fourths) of individuals affected by TB are in their economically productive age groups (15-54 years old), impacting families and economies.
Regional Burden:
South-East Asia: Region with the highest number of TB cases globally.
Africa: Continent with the highest TB incidence rate in the world, with an estimated annual incidence of 345 cases per 100,000 population.
Sex Disparity: TB infection rates and disease burden are generally higher in men than in women in most regions.
Primary Tuberculosis Infection:
Initial Exposure: Primary TB occurs in individuals who are newly infected with Mycobacterium tuberculosis and have not been previously exposed to the bacteria.
Inhalation and Lung Entry: Mycobacterium tuberculosis bacteria are inhaled and reach the lungs, where they begin to multiply.
Lymphatic and Blood Spread: From the lungs, the bacteria can spread through the lymphatic system to the regional lymph nodes in the lung hilum (hilar lymph nodes). They can also disseminate via the bloodstream (hematogenous spread) to other parts of the body.
Immune Response (6 Weeks): Approximately six weeks after the initial infection, the body’s immune system mounts a cell-mediated immune response. This immune response is usually effective in controlling further multiplication of the TB bacteria and preventing progression to active disease in most people.
Ghon Focus Formation: As part of the immune response, some TB bacteria are killed, while others are contained and walled off by immune cells called epithelioid cells and macrophages. This localized collection of bacteria and immune cells forms a characteristic lesion known as a Ghon focus (or Ghon lesion) in the lung tissue.
Latent TB: The Ghon focus represents a site of primary infection. The bacteria within the Ghon focus may become dormant or latent. The Ghon focus can persist in the lungs for years, representing latent TB infection.
Primary Complex: The combination of the Ghon focus in the lung parenchyma and associated hilar lymphadenopathy (enlargement of lymph nodes at the lung hilum) is termed the primary complex (or Ghon complex) in primary tuberculosis.
Progression to Active Disease: Importantly, only a minority of individuals (approximately 10%) with primary TB infection will go on to develop active tuberculosis disease in their lifetime. The remaining 90% develop latent TB infection, where the bacteria are contained but not eradicated, and the person is not contagious and does not have active symptoms. However, latent TB infection can reactivate and progress to active disease later, especially if the immune system becomes weakened.
Secondary Tuberculosis (Reactivation TB)
Secondary tuberculosis, also known as reactivation TB or post-primary TB, can arise through two main pathways:
Reactivation of Latent TB: It can develop from the reactivation of dormant Mycobacterium tuberculosis bacteria that have been present in the body since a previous primary TB infection. In these cases, the initial primary infection was contained by the immune system, resulting in latent TB infection, but the bacteria later reactivate and cause active disease, often when the immune system weakens.
Reinfection: Secondary TB can also occur due to reinfection with Mycobacterium tuberculosis in a person who has been previously infected with TB bacteria. This means an individual who has had TB in the past (either primary or secondary) can become infected again upon new exposure to TB bacteria.
Pathogenesis (Disease Development):
Initial Infection: TB infection begins when Mycobacterium tuberculosis bacteria reach the alveoli (air sacs) in the lungs.
Alveolar Invasion and Replication: Once in the alveoli, the bacteria invade and start to multiply within alveolar macrophages (immune cells in the lungs).
Spread Beyond Lungs: In addition to the lungs, Mycobacterium tuberculosis can spread via the bloodstream (hematogenous dissemination) to other parts of the body, leading to infection in distant organs and tissues, including:
Peripheral lymph nodes
Kidneys
Brain
Bones
Granuloma Formation: The body’s immune response to TB infection triggers an inflammatory reaction. This response leads to the formation of granulomas, which are characteristic microscopic structures in TB. Granulomas are organized collections of immune cells, including:
Activated macrophages (immune cells that engulf pathogens)
T lymphocytes (immune cells that coordinate immune responses)
B lymphocytes (immune cells that produce antibodies)
Fibroblasts (cells involved in tissue repair and scar formation)
Ghon Focus Formation: Within the granuloma, TB bacteria are surrounded and contained by lymphocytes, forming a peripheral rim around a central core. This structure is known as a Ghon focus (or Ghon lesion), representing the primary site of infection containment.
Latent Infection and Dormancy: Inside the granulomas, TB bacteria can become dormant or inactive, leading to latent TB infection. In latent TB, the bacteria are alive but not actively multiplying, and the person is not contagious and has no symptoms.
Caseation Necrosis: A characteristic feature of TB granulomas is caseation necrosis. This is a type of abnormal cell death that occurs in the center of the tubercles (granulomas). Caseation necrosis results in a cheese-like, necrotic (dead tissue) material within the granuloma core.
Miliary TB (Disseminated TB): In severe cases, particularly when the immune system is weakened (e.g., in young children or individuals with HIV), TB bacteria can escape the granulomas and enter the bloodstream in large numbers from damaged lung tissue. This widespread bloodstream dissemination leads to miliary tuberculosis (or disseminated TB). Miliary TB is characterized by the development of numerous, tiny foci (sites) of TB infection throughout the body’s tissues and organs. These foci appear as small, white, seed-like tubercles (granulomas), resembling millet seeds (hence “miliary”).
Tissue Damage, Necrosis, and Healing: The course of TB infection involves a dynamic balance between:
Tissue destruction and necrosis (cell death) caused by the bacteria and immune response.
Healing processes and fibrosis (scar tissue formation) as the body attempts to contain the infection.
Scarring and Cavities: Affected lung tissue can be replaced by scar tissue and cavities (open spaces) filled with caseous necrotic material. These cavities are a hallmark of active pulmonary TB and can harbor large numbers of actively multiplying bacteria, making the person highly contagious.
Diagnosis (Investigations and Tests for TB):
When TB is suspected based on clinical presentation and risk factors, several diagnostic investigations are used to confirm the diagnosis:
Clinical Suspicion: TB is suspected in individuals presenting with:
Signs and symptoms of lung disease (e.g., persistent cough, chest pain, hemoptysis).
Constitutional symptoms (e.g., fever, night sweats, weight loss, fatigue) lasting for more than two weeks.
Chest X-ray (CXR): Chest radiography is a crucial initial diagnostic tool. CXR imaging can reveal characteristic abnormalities in the lungs suggestive of TB, including:
Infiltrates (shadowy areas of inflammation in the lung tissue)
Cavities (air-filled spaces within the lungs, typically in active TB)
Nodules (small, rounded lesions)
Pleural effusion (fluid buildup in the pleural space)
Ghon complex (in primary TB)
Fibrosis and scarring (in chronic TB)
Miliary pattern (in disseminated TB)
Hilar lymphadenopathy (enlarged lymph nodes at the lung hilum)
Sputum Microscopy for Acid-Fast Bacilli (AFB Smear): Sputum samples (phlegm coughed up from the lungs) are examined under a microscope using a special stain (Ziehl-Neelsen stain) to detect the presence of acid-fast bacilli (AFB), which are characteristic of Mycobacterium tuberculosis.
Multiple Sputum Samples: To increase the sensitivity of sputum microscopy, multiple sputum samples are collected, typically:
Spot sputum sample (collected at the clinic or lab during the visit)
Early morning sputum sample (collected first thing in the morning, as sputum tends to pool overnight)
Smear-Positive TB: If AFB are seen on sputum smear microscopy, the person is considered to have smear-positive TB, which is highly contagious.
Smear-Negative TB: If AFB are not seen on sputum smear, but TB is still suspected clinically, the person is classified as having smear-negative TB. Further tests are needed to confirm or exclude TB in smear-negative cases.
Sputum Culture for Mycobacterium tuberculosis: Sputum samples are cultured in specialized laboratory media to grow Mycobacterium tuberculosis bacteria.
Gold Standard: Sputum culture is considered the gold standard for TB diagnosis because it can confirm the presence of Mycobacterium tuberculosis and allows for drug susceptibility testing (DST) to determine if the bacteria are resistant to anti-TB drugs.
Time to Result: Sputum culture takes several weeks (typically 4-8 weeks) to yield results due to the slow growth of Mycobacterium tuberculosis.
Tuberculin Skin Test (TST) / Mantoux Test: The tuberculin skin test (TST), also known as the Mantoux test or Heaf test, is used to detect latent TB infection.
Procedure: A small amount of tuberculin purified protein derivative (PPD) is injected intradermally (under the skin) on the forearm.
Reading and Interpretation: After 48-72 hours, the injection site is examined for induration (a raised, hardened area). The size of the induration is measured in millimeters and interpreted based on risk factors (e.g., HIV status, contact with TB cases).
Positive TST: A positive TST indicates that the person has been infected with Mycobacterium tuberculosis at some point in their life. It does not distinguish between latent TB infection and active TB disease.
Limitations: TST can have false-positive results (e.g., due to BCG vaccination or non-tuberculous mycobacteria) and false-negative results (e.g., in immunocompromised individuals).
Interferon-Gamma Release Assays (IGRAs): Blood tests that measure the immune system’s response to Mycobacterium tuberculosis. Examples include QuantiFERON-TB Gold and T-SPOT.TB tests.
Advantages over TST: IGRAs are more specific than TST, less affected by BCG vaccination, and require only one patient visit.
Detection of Latent TB: IGRAs, like TST, primarily detect latent TB infection.
Nucleic Acid Amplification Tests (NAATs): Rapid molecular tests that detect Mycobacterium tuberculosis DNA or RNA in sputum or other samples. Examples include Xpert MTB/RIF assay.
Rapid Diagnosis: NAATs provide rapid results (within hours), allowing for faster diagnosis and treatment initiation.
Rifampicin Resistance Detection: Some NAATs, like Xpert MTB/RIF, can also detect resistance to rifampicin, a key anti-TB drug, simultaneously with TB detection.
WHO Recommendation: Xpert MTB/RIF is recommended by the World Health Organization (WHO) as the initial diagnostic test for TB in adults and children suspected of having pulmonary TB and HIV-associated TB.
Haematological Tests (Blood Tests): Blood tests are not specific for TB but may provide supportive evidence of infection or inflammation.
Full Blood Count (FBC) / Complete Blood Count (CBC): May show abnormalities such as:
Leukocytosis (increased white blood cell count, indicating infection)
Lymphopenia (decreased lymphocyte count, may be seen in severe TB or HIV co-infection)
Anemia (low red blood cell count, common in chronic TB)
Thrombocytopenia or thrombocytosis (abnormal platelet counts)
Erythrocyte Sedimentation Rate (ESR): ESR is a non-specific marker of inflammation. An elevated ESR can raise suspicion for TB, as it indicates inflammation in the body, but it is not specific to TB and can be elevated in many other conditions.
Tissue Biopsy and Histopathology: In cases of suspected extrapulmonary TB or when other tests are inconclusive, a biopsy (small tissue sample) may be taken from the affected organ or tissue (e.g., lymph node, pleura, bone marrow).
Microscopic Examination: The biopsy tissue is examined under a microscope for characteristic features of TB, such as granulomas and caseation necrosis.
AFB Stain and Culture: The biopsy sample can also be stained for AFB and cultured for Mycobacterium tuberculosis to confirm the diagnosis.
Relationship Between HIV and TB:
TB and HIV form a dangerous “dual epidemic” due to their synergistic interaction:
Effects of HIV on TB:
Increased Risk of Active TB: HIV significantly weakens the immune system, dramatically increasing the risk of latent TB infection progressing to active TB disease. People with HIV are much more likely to develop active TB if infected with Mycobacterium tuberculosis.
Higher Risk of Reinfection: HIV-positive individuals are more susceptible to reinfection with TB. Even if they have been treated for TB in the past, their weakened immune system makes them more vulnerable to getting TB again if re-exposed to TB bacteria.
Increased TB Incidence: The HIV epidemic has driven a significant increase in the overall incidence of tuberculosis globally, particularly in sub-Saharan Africa and other regions with high HIV prevalence. HIV fuels the TB epidemic.
Altered TB Presentation: TB in HIV-positive individuals may present with atypical clinical and bacteriological features, making diagnosis more challenging:
Non-productive cough: Less likely to have a sputum-producing cough.
Absence of hemoptysis: Less likely to cough up blood.
Miliary pattern on imaging: Chest X-ray may show a disseminated miliary pattern more frequently instead of classic lung cavities seen in TB in HIV-negative individuals.
Smear-negative TB: More likely to have smear-negative pulmonary TB (TB in the lungs that is negative on sputum smear microscopy), making diagnosis by sputum smear less reliable.
Extrapulmonary TB: Higher proportion of cases present with extrapulmonary TB.
Accelerated TB Complications: HIV infection accelerates the progression of TB disease and increases the risk of developing severe TB complications, such as:
TB meningitis
Disseminated TB
Death
Effects of TB on HIV:
Increased HIV Replication: Active TB infection can stimulate the immune system, paradoxically leading to increased HIV viral replication and a higher HIV viral load. This accelerates HIV disease progression.
Common Opportunistic Infection: TB is one of the most common opportunistic infections in people living with HIV/AIDS. It is a leading cause of illness and death in this population, especially in resource-limited settings.
ARV Treatment Interference: Certain anti-TB medications, particularly rifampicin, can interact with and reduce the effectiveness of some antiretroviral drugs (ARVs) used to treat HIV. Rifampicin can lower blood levels of certain ARVs, such as:
Nevirapine (NVP)
Protease inhibitors (PIs)
This drug-drug interaction can complicate the management of HIV/TB co-infection and may necessitate adjustments in ARV regimens or using alternative ARVs that have fewer interactions with rifampicin.
Consequences of Dual HIV and TB Infection (HIV/TB Co-infection):
The combination of HIV and TB infection has severe consequences:
Increased Morbidity and Mortality: People with HIV/TB co-infection have significantly higher rates of illness and death compared to those with either infection alone. TB accelerates HIV progression, and HIV worsens TB outcomes.
Higher TB Recurrence: Even after successful TB treatment, individuals with HIV have a higher risk of TB recurrence (TB coming back) due to their weakened immune system.
Drug Resistance: HIV/TB co-infection is associated with an increased risk of developing drug-resistant TB, including:
Multidrug-resistant TB (MDR-TB): Resistant to at least isoniazid and rifampicin, the two most important first-line anti-TB drugs.
Extensively drug-resistant TB (XDR-TB): MDR-TB with additional resistance to fluoroquinolones and at least one second-line injectable anti-TB drug.
Drug-resistant TB forms are much harder and more expensive to treat and have poorer outcomes.
Treatment Non-Adherence: Managing both HIV and TB often involves complex and overlapping medication regimens. The burden of taking multiple pills for both conditions can lead to higher rates of treatment non-adherence, which can result in treatment failure, drug resistance, and poorer outcomes.
Increased Drug Toxicity: The combined use of anti-TB drugs and ARVs increases the risk of drug-related toxicities and side effects due to overlapping toxicities or drug interactions.
Management of HIV and TB Co-infection:
Managing HIV/TB co-infection requires a coordinated and integrated approach:
Prioritize TB Treatment: In general, TB treatment should be started first in patients with HIV/TB co-infection. Treating TB is often prioritized because active TB is immediately life-threatening.
Initiate ARVs Based on CD4 Count: The timing of starting antiretroviral therapy (ARVs) for HIV depends on the patient’s CD4 count (a measure of immune system strength):
CD4 Count < 350 cells/mm³: If the CD4 count is below 350 cells/mm³, ARVs should be started, either:
After completion of the intensive phase of TB treatment (initial 2 months of multi-drug TB therapy).
During the intensive phase of TB treatment, depending on the clinical situation and patient stability. Earlier ARV initiation may be considered in patients with very low CD4 counts to improve survival.
CD4 Count > 350 cells/mm³: If the CD4 count is above 350 cells/mm³, ARV initiation may be deferred until after the intensive phase of TB treatment or later, depending on clinical assessment and guidelines.
Address Drug Interactions: Carefully consider potential drug interactions between anti-TB drugs and ARVs when selecting medications for both regimens.
Rifampicin Interactions: Be aware of rifampicin’s interactions with certain ARVs (e.g., nevirapine, protease inhibitors).
Regimen Adjustments: ARV regimens may need to be adjusted, or alternative ARVs with fewer interactions with rifampicin may be used.
Directly Observed Therapy (DOT): Directly observed therapy (DOT) is strongly recommended for TB treatment in HIV/TB co-infection. DOT involves a healthcare worker directly observing the patient taking each dose of TB medication to ensure adherence and treatment completion.
Close Monitoring: Closely monitor patients for drug toxicity, side effects, and treatment adherence due to the complexity of managing multiple medications and potential drug interactions.
Prophylaxis for Opportunistic Infections: Administer prophylaxis (preventive treatment) for other opportunistic infections (besides TB) as indicated, based on CD4 count and risk assessment, to prevent other infections common in HIV-infected individuals.
Complications of Tuberculosis:
Untreated or poorly managed tuberculosis can lead to a range of serious complications:
Pleural Effusion: Fluid buildup in the pleural space (between the lung and chest wall), causing chest pain and shortness of breath.
Pericardial Effusion: Fluid accumulation around the heart (in the pericardial sac), potentially leading to cardiac tamponade (compression of the heart) and heart failure.
Empyema: Collection of pus within the pleural space, often requiring drainage.
Pneumothorax: Lung collapse due to air leaking into the pleural space, causing sudden chest pain and breathing difficulty.
Lung Fibrosis: Permanent scarring and thickening of lung tissue (pulmonary fibrosis), leading to chronic respiratory impairment and reduced lung function.
Lung Collapse (Atelectasis): Collapse of a lung lobe or entire lung due to bronchial obstruction or compression, impairing oxygenation.
Extrapulmonary TB Complications: Complications specific to extrapulmonary TB depend on the organ system affected. For example:
TB Meningitis: Can cause permanent neurological damage, hydrocephalus (fluid buildup in the brain), stroke, and death.
Skeletal TB (Pott’s Disease): Can lead to spinal deformity (kyphosis), paralysis, and chronic pain.
Urogenital TB: Can cause kidney damage, bladder dysfunction, and infertility.
Treatment of Tuberculosis (TB)
Aims of TB Treatment:
The primary goals of TB treatment are:
Cure: To completely eradicate the Mycobacterium tuberculosis infection from the patient’s body and achieve a lasting cure.
Prevent Complications and Death: To prevent the development of serious complications of TB disease and reduce TB-related mortality.
Reduce Transmission: To interrupt the chain of TB transmission in the community by rendering individuals with active TB non-infectious through effective treatment, thereby protecting others from infection.
Case Definitions in TB Management:
To standardize TB management and reporting, specific case definitions are used:
New Case: A person newly diagnosed with TB who:
Has never received TB treatment before, or
Has taken anti-TB drugs for four weeks or less.
Relapse: A patient who:
Was previously diagnosed with TB and completed a full course of anti-TB treatment.
Was declared cured of TB based on treatment completion and negative bacteriological tests.
Now presents with recurrent active TB disease, evidenced by becoming sputum smear-positive again for AFB (acid-fast bacilli).
Failure: A patient whose TB treatment is considered to have failed if they meet any of the following criteria:
Remains sputum smear-positive for AFB at five months or later of anti-TB treatment, despite having taken anti-TB drugs adequately as prescribed.
Was initially sputum smear-negative at the start of treatment but becomes smear-positive for AFB again at two months or later of treatment.
Defaulter (Treatment Interruption): A patient who:
Started taking anti-TB drugs and has been on treatment for more than four weeks.
Interrupts treatment (stops taking anti-TB drugs) for a period of four consecutive weeks (or more).
Drugs Used in TB Treatment (First-Line Anti-TB Drugs):
The cornerstone of TB treatment is a combination of several anti-TB drugs, typically given for a duration of 6-9 months or longer. The main first-line drugs used in standard TB regimens are:
Rifampicin (R): A bactericidal drug that is highly effective against Mycobacterium tuberculosis. It is a key component of all standard TB regimens.
Isoniazid (H or INH): Another potent bactericidal drug and a cornerstone of TB treatment, particularly for latent TB infection and in combination regimens for active TB.
Ethambutol (E): A bacteriostatic drug (inhibits bacterial growth) that is included in initial TB regimens to prevent or delay the emergence of drug resistance, especially in areas with higher rates of isoniazid resistance.
Pyrazinamide (Z): A bactericidal drug that is particularly effective in killing TB bacteria in acidic environments within macrophages and granulomas. Pyrazinamide is used in the intensive phase of short-course TB treatment to shorten the overall duration of therapy.
Streptomycin (S): An injectable aminoglycoside antibiotic that is bactericidal against Mycobacterium tuberculosis. Streptomycin was historically one of the first effective anti-TB drugs. In current standard regimens, it is primarily used as a first-line drug in the retreatment regimen for previously treated TB cases (Category II regimen) for the initial intensive phase.
Standard TB Treatment Regimen (Drug-Sensitive TB):
The World Health Organization (WHO) recommends a standard six-month short-course treatment regimen as the first-line treatment for drug-sensitive TB (TB that is not resistant to first-line drugs). This regimen is highly effective in curing TB when taken correctly.
The standard regimen consists of two phases:
Intensive Phase (Initial 2 Months): During the first two months of treatment, patients receive a combination of four anti-TB drugs daily:
Rifampicin (R)
Isoniazid (H)
Pyrazinamide (Z)
Ethambutol (E)
This 2-month intensive phase aims to rapidly kill the majority of actively multiplying TB bacteria, reduce infectiousness, and prevent drug resistance. The combination of four drugs is crucial in this phase to maximize efficacy and minimize resistance risk. The abbreviation for this intensive phase is 2HRZE.
Continuation Phase (Next 4 Months): Following the intensive phase, patients transition to a continuation phase for the next four months (or longer in some cases). The drug combination used in the continuation phase may vary depending on:
The patient’s response to treatment during the intensive phase.
Results of drug susceptibility testing (DST) to confirm drug sensitivity.
Local treatment guidelines.
Typically, the continuation phase regimen involves two drugs given daily or intermittently (e.g., 3 times per week):
Isoniazid (H)
Rifampicin (R)
The 4-month continuation phase aims to eliminate any remaining dormant or slowly multiplying TB bacteria and prevent relapse. The abbreviation for a common continuation phase is 4HR.
The standard 6-month regimen is therefore often written as 2HRZE/4HR.
Importance of Directly Observed Therapy (DOTS):
TB treatment must be taken consistently and completely for the full duration (usually 6 months) to be effective and prevent drug resistance. To ensure adherence, the WHO recommends Directly Observed Therapy (DOTS) whenever possible for TB treatment administration.
Treatment Regimens for Different Categories of TB:
TB treatment regimens are tailored to different categories of patients based on their TB history and drug susceptibility:
| Patient Category (Type of TB) | Initial Phase | Continuation Phase |
| 1. New Smear-Positive PTB | 2EHRZ (2 months of Ethambutol, Isoniazid, Rifampicin, Pyrazinamide) | 6EH (6 months of Ethambutol, Isoniazid) |
| 2. New Smear-Negative PTB | 2EHRZ | 6EH |
| 3. Severe Extrapulmonary TB (EPTB) | 2EHRZ | 6EH |
| 4. Previously Treated Smear-Positive TB: | ||
| – Relapse | ||
| – Treatment Failure | 2SEHRZ/1EHRZ (2 months of Streptomycin, Ethambutol, Isoniazid, Rifampicin, Pyrazinamide, followed by 1 month of Ethambutol, Isoniazid, Rifampicin, Pyrazinamide) | 5EHR (5 months of Ethambutol, Isoniazid, Rifampicin) |
| – Return After Interruption (Default/Treatment After Loss to Follow-up) | 2SEHRZ/1EHRZ | 5EHR |
| 5. Any Form of TB in Children | 2HRZ (2 months of Isoniazid, Rifampicin, Pyrazinamide) | 4HR (4 months of Isoniazid, Rifampicin) |
| 6. Adult Non-Severe Extrapulmonary TB | 2HRZ | 4HR |
Non-Anti-TB Drugs Used in TB Management:
In addition to the core anti-TB drugs, other medications are used in TB management, primarily to address side effects or specific clinical situations:
Pyridoxine (Vitamin B₆):
Purpose: Administered to prevent or treat peripheral neuropathy, a potential nerve damage side effect of Isoniazid (H). Isoniazid can interfere with vitamin B₆ metabolism, leading to nerve damage.
Mechanism: Pyridoxine supplementation helps to counteract this effect and prevent or alleviate isoniazid-induced peripheral neuropathy (numbness, tingling, pain in hands and feet).
Steroids (Corticosteroids):
Purpose: Used as adjunct therapy (in addition to anti-TB drugs) in specific, severe forms of TB to reduce inflammation and improve clinical outcomes. Steroids are not routinely used for all TB cases but are reserved for specific situations where excessive inflammation is harmful.
Common Indications: Steroids are commonly used in the treatment of:
TB Meningitis: To reduce inflammation in the brain and meninges, which can decrease neurological damage and improve survival.
TB Pericarditis: To reduce inflammation of the pericardium (sac around the heart) and prevent constrictive pericarditis (scarring and stiffening of the pericardium).
TB of Adrenals (Addison’s Disease due to TB): In cases of adrenal TB causing adrenal insufficiency (Addison’s disease), steroids (hydrocortisone) are used as hormone replacement therapy to compensate for the adrenal gland’s reduced function.
DOTS (Directly Observed Therapy, Short-Course) – Explained:
How DOTS Works:
Community-Based Care: DOTS is a patient-centered, community-based approach to TB care that has been adopted globally to improve TB treatment success rates.
Treatment Supporters: DOTS relies on trained individuals called treatment supporters (or DOT providers), who are often community health workers, nurses, volunteers, or family members.
Direct Observation: Treatment supporters are responsible for directly observing patients as they take each dose of their prescribed anti-TB medications, typically on a daily basis during the intensive phase and often during the continuation phase as well.
Treatment Recording: The treatment supporter records each observed dose administration on the patient’s TB treatment card (a record-keeping tool).
Standard of Care: DOTS is considered the standard of care for all TB cases and TB suspects worldwide, as recommended by the WHO.
Benefits of DOTS:
Improved Adherence: DOTS is highly effective in improving patient adherence to the lengthy TB treatment regimen, ensuring patients take their medications regularly and completely.
Reduced Relapse: By ensuring treatment completion, DOTS helps to decrease TB relapse rates (TB coming back after treatment).
Lower Default Rates: DOTS reduces default rates (patients interrupting or stopping treatment prematurely) by providing ongoing support and monitoring.
Prevention of Drug Resistance: DOTS is crucial in preventing the development of acquired drug resistance in TB. Inconsistent or incomplete treatment is a major driver of drug-resistant TB.
Treatment Success: DOTS, when combined with other components of TB control programs, significantly promotes TB treatment success and cure rates.
DOTS Implementation in Practice (Example Workflow):
TB Diagnosis and Registration: After a patient is diagnosed with TB at a diagnostic center (e.g., clinic, hospital), and anti-TB treatment is initiated, the diagnostic center records the patient’s information in the health unit’s TB register (a confidential record of all TB cases managed at the facility).
Sub-County Health Worker Notification: The health unit staff then notifies the sub-county health worker (a public health official responsible for TB control in a defined geographical area) about the new TB case. The sub-county health worker records this information in their own sub-county health worker register.
Treatment Supporter Identification: The sub-county health worker, in collaboration with the patient and local community resources, identifies a suitable treatment supporter who lives in the patient’s village or community. The treatment supporter should be someone who is trusted by the patient, accessible, and willing to be trained and take on this role.
Treatment Supporter Training: The sub-county health worker trains the identified treatment supporter on their responsibilities, which include:
Observing the patient taking their daily doses of anti-TB medication.
Recording each observed dose on the patient’s TB treatment card.
Safeguarding and storing the patient’s TB medications securely.
Reminding the patient about scheduled follow-up appointments and assessments at the health unit at key intervals (e.g., 2 months, 5 months, 8 months).
Medication Supply: The sub-county health worker collects the necessary supply of anti-TB medications from the central health unit or TB clinic.
Medication Delivery to Supporter: The sub-county health worker then delivers the medications to the trained treatment supporter in the patient’s village.
DOT Implementation: The treatment supporter then implements DOT in the patient’s home or a convenient location, ensuring daily observed treatment and accurate recording on the TB card.
Follow-up and Monitoring: The sub-county health worker and health unit staff monitor the patient’s progress through the TB card records, scheduled follow-up assessments at the health unit, and regular communication with the treatment supporter.
Prevention of Tuberculosis (TB):
Effective TB prevention strategies are crucial to reduce the global burden of TB. Key preventive measures include:
Early Detection and Prompt Treatment: Early identification of TB cases through active case finding (screening) and prompt initiation of effective anti-TB treatment are essential to:
Cure individuals with TB.
Reduce the duration of infectiousness, thereby limiting TB transmission in the community.
Health Education and Awareness: Public health campaigns and health education programs are vital to:
Raise community awareness about TB, its transmission, symptoms, and the importance of early diagnosis and treatment.
Promote knowledge about TB prevention strategies, such as respiratory hygiene (cough etiquette) and ventilation.
Training Healthcare Workers: Comprehensive training for all healthcare workers is essential to:
Improve their ability to recognize early signs and symptoms of TB in patients.
Ensure they are proficient in TB diagnosis, treatment, and management guidelines.
Strengthen TB infection control practices in healthcare settings.
BCG Vaccination: Vaccination of infants and young children with the Bacille Calmette-Guérin (BCG) vaccine is recommended in many countries with high TB burden. BCG vaccine:
Protects against severe forms of TB in childhood, such as TB meningitis and disseminated TB.
Has limited effectiveness in preventing pulmonary TB in adults.
Isoniazid Preventive Therapy (IPT): Prophylactic treatment with isoniazid (IPT) is recommended for individuals at high risk of developing active TB, including:
People with latent TB infection (positive TST or IGRA, but no active TB disease) to prevent reactivation.
People living with HIV (PLHIV), regardless of TST or IGRA status, to prevent both primary TB infection and progression from latent infection to active disease.
Child contacts of TB cases.
Prevention and Management of HIV/AIDS: Addressing the HIV epidemic is critical for TB prevention, as HIV is the strongest risk factor for TB. Effective HIV prevention strategies and comprehensive HIV care and treatment, including antiretroviral therapy (ART), are essential to reduce HIV-associated TB.
Implementation of DOTS Program: Widespread and effective implementation of the DOTS strategy is a cornerstone of TB prevention and control. DOTS ensures high TB treatment success rates, reduces drug resistance, and limits TB transmission at the community level.