Understanding Tuberculosis: Causes, Symptoms, and Treatment

 

What is Tuberculosis?

Tuberculosis (TB) is a serious infectious disease that affects the lungs and other parts of the body. It is caused by a bacterium called Mycobacterium tuberculosis and spreads through the air when an infected person coughs, sneezes or talks. Despite being curable and preventable, tuberculosis remains a significant global health problem, with millions of new cases and deaths reported every year. Understanding tuberculosis is crucial for effective prevention, diagnosis, and treatment.

Symptoms of TB

The symptoms of tuberculosis vary depending on the part of the body affected. The most common form of TB is pulmonary tuberculosis, which affects the lungs. The symptoms of pulmonary TB include:

• A persistent cough that lasts for more than three weeks
• Coughing up blood or sputum
• Chest pain or discomfort
• Fatigue
• Loss of appetite and weight loss
• Night sweats
• Fever and chills

It can also affect other parts of the body, such as the lymph nodes, bones, joints, and kidneys. 

Symptoms may include swelling, pain, and fever.

Definition of Tuberculosis:

Definition: Tuberculosis is a Chronic necrotizing disease caused by Mycobacterium tuberculosis complex. It usually affects the lungs but almost all organs can be affected. 

Classification:

Thus it is classified into:

• Pulmonary TB (PTB): accounts for 80% of all TB cases.

    a. Primary pulmonary tuberculosis

    b. Post-primary pulmonary tuberculosis (adult type, reactivation or secondary         tuberculosis)

• Extra-pulmonary TB (EPTB): accounts for 20% of all TB cases.

What causes Tb?

Causative organism: It is caused by bacteria belonging to Mycobacterium tuberculosis complex.

• The most common agent of human disease is M. tuberculosis.

• M. bovis, an important cause of infection in those who consume unpasteurized milk, is now uncommon.

How is Tuberculosis transmitted?

Transmission:

• Most commonly the infection is transmitted from infected patients to other persons through droplet nuclei released by coughing, sneezing or speaking.

• Other rare routes of transmission are ingestion, through skin and transplacental.

Risk factors: 

The risk of acquiring infection is increased by factors like poverty and overcrowding.

1. diabetes, silicosis, alcoholism or immunocompromised states
2. Health workers are also at increased risk as they may be exposed to TB Patients.
3. HIV-positive patients
4. Healthcare workers
5. Close contacts of someone with TB
6. Glucocorticoid use
7. Hematologic malignancy
8. Injection drug users

Pathophysiology

a. Primary TB

1. Bacilli are inhaled and deposited into the lung, then ingested by alveolar macrophages.
2. Surviving organisms multiply and disseminate via lymphatics and the bloodstream.
3. Granulomas form and “wall off” the mycobacteria.
4. The granulomas in oxygen-rich areas, such as the lungs, allow these organisms to remain viable (they are aerobes).
5. After the resolution of the primary infection, the organism remains dormant within the granuloma.
6. An insult to the immune system may activate the TB at any time

Only 5% to 10% of individuals with primary TB will develop active disease in their lifetime.

b. Secondary TB (reactivation)

1. Occurs when the host’s immunity is weakened (e.g., HIV infection, malignancy, immunosuppressants, substance abuse, poor nutrition)
2. Usually manifests in the most oxygenated portions of the lungs—the apical/ posterior segments produces clinical manifestations of TB.
3. Can be complicated by hematogenous or lymphatic spread, resulting in military TB

Clinical features:

Primary Pulmonary Tuberculosis

The bacilli enter the lung parenchyma and cause a peripheral parenchymal lesion. The bacilli eventually travel to the mediastinal lymph nodes. This is known as primary complex.

• It usually affects children and remains asymptomatic in most.

• Middle and lower lobes of the lung are usually involved.

• In most (80-90%), the primary complex heals within 4- 6 weeks. The healed calcified peripheral parenchymal lesion is known as Ghon’s lesion .

However, in some, particularly in immunocompromised individuals, the disease may progress in the following forms:

• The parenchymal lesion may enlarge and cavitate (progressive primary tuberculosis).
• The disease may involve pleura and result into pleural effusion.
• Enlarged lymph node may compress bronchi and result in collapse (epituberculosis).
• Hematogenous dissemination is common and generally asymptomatic. However, occasionally it may lead to meningitis or miliary tuberculosis.
• Manifestations due to hypersensitivity reaction may occur in form of erythema nodosum or phlyctenular conjunctivitis

Post-primary Pulmonary Tuberculosis

• This is also known as adult-type, reactivation or secondary tuberculosis.
• Parenchymal involvement may be in the form of small infiltrates, pneumonia, collapse, extensive cavitatory lesions or miliary lesions.
• The lesion may remit spontaneously or in some, it may progress to chronic fibrosis.
• The patients initially present with symptoms like cough, malaise, loss of appetite, loss of weight, low grade fever with evening rise, night sweats and hemoptysis.
• Cough progresses from dry cough to purulent sputum. Hemoptysis suggests advanced TB.

How is Latent Tuberculosis Infection different from TB disease?

Diagnosis

Physical examination:

1. It may reveal a chronically sick patient with pallor and clubbing.
2. The chest examination may be normal or may reveal inspiratory crackles, particularly after cough, and bronchial breathing over large cavities.
3. Other uncommon presentations may be in the form of pleural effusion, spontaneous pneumothorax and pyrexia of unknown origin (PUO).

Lab diagnosis:

Chest xray

a. Classic findings are upper lobe infiltrates with cavitations

b. Other possible findings

• Pleural effusion(s)

• Ghon complex and Ranke complex: evidence of healed primary TB

• Atypical findings common in immunocompromised patients

Demonstration of AFB: 

• The diagnosis of tuberculosis is based on the demonstration of AFB in the smear of the sputum or in other specimens such as tissue biopsy materials or body fluids. Ziehl-Neelsen or Auramine fluorescence staining is usually done for this purpose.
• If the patient is not passing sputum, nebulization with hypertonic saline can be used to induce sputum expectoration.
• Samples can also be obtained by gastric lavage (in children), bronchoalveolar lavage or transbronchial biopsy.

Culture methods: The culture provides confirmation of the diagnosis by the isolation and identification of M. tuberculosis from the specimen.

a. Definitive diagnosis is made by sputum culture—growth of M. tuberculosis

b. Obtain three morning sputum specimens—culture takes 4 to 8 weeks

c. The growth on solid media (Löwenstein- Jensen media) is slow and may take 4-8 weeks. However, the time required for culture confirmation is shorter (2-3 weeks) when liquid media (BACTEC) is used

Tuberculin skin test (PPD test)

Purified protein derivative (PPD) skin test (using Montoux method or Heaf method) is positive 

• in persons infected with M. tuberculosis
• in persons sensitized by non-tuberculous mycobacteria
• In those who have received BCG vaccination.

Important points to  note:

1. A positive skin test does not tell about the active disease.
2. A positive test in those who have not received BCG may suggest the diagnosis of tuberculosis.
3. The test may be negative in miliary tuberculosis and in immunocompromised patients with tuberculosis.

• After Injecting PPD into the volar aspect of forearm. Measure the amount of induration 48 to 72 hours later. Positive result is interpreted as follows:
• The result is positive if induration ≥15 mm in patients with no risk factors
• In certain high-risk 10 mm of induration is considered positive.
• For patients with HIV, steroid users, organ transplant recipients, close contacts of those with ACTIVE TB, or those with radiographic evidence of primary TB, induration of 5 mm is positive.
• If a patient has never had a PPD test before, repeat the test in 1 to 2 weeks if the first test is negative (first test may be false negative). The results of the second test (whether positive or negative) are used for management

Histopathological tests: The FNAC (fine needle aspiration cytology) or biopsy specimens from the involved tissue may typically reveal caseous granuloma. AFB can be demonstrated in tissue specimens.


hematological findings: anemia, raised ESR and C reactive protein.


Liver biopsy and bone marrow biopsy specimens may also be examined for the evidence of granuloma and AFB.


Treatment

The main aims of treatment of tuberculosis are:

1. To cure the patients of tuberculosis

2. To decrease transmission of tuberculosis to others

3. To prevent relapse

4. To prevent morbidity and mortality from active tuberculosis

5. To prevent late effects of tuberculosis

• Patients with active TB must be isolated until sputum is negative for AFB.

The treatment consists of the initial phase and the continuation phase. 

The schedule is daily or intermittent (twice or thrice weekly).

The response to therapy is monitored through clinical improvement, X-ray chest and culture or smear examination.

Initial phase: The aim is to rapidly kill the bacilli, resolve symptoms and bring out sputum conversion (AFB negative) so that the patient becomes non-infectious. Generally, a combination of 3-4 drugs is used for 2-3 months.


Continuation phase: The purpose is to eliminate the remaining bacilli from the lesion (sterilizing effect) so that relapse may not occur. This is generally given for 4-6 Months.


First line drugs

1. Isoniazid (H) 4. Ethambutol (E)

2. Rifampin (R) 5. Streptomycin (S)

3. Pyrazinamide (Z)


Second line drugs

1. Thiacetazone (Tzn)

2. Para-aminosalicylic acid (PAS)

3. Ethionamide (Etm)

4. Cycloserine (Cys)

5. Kanamycin (Kmc)

6. Amikacin (Am

7. Capreomycin (Cpr)


Vaccination

Most countries recommend the use of Bacillus Calmette Guérin (BCG) vaccination. This contains attenuated strain of M. bovis.

• Intradermal route is recommended for the administration of the vaccine at the lower deltoid area.
• In India, it is recommended to be administered to infants after birth or at the first contact of the infant with the health worker.
• The BCG vaccination is contraindicated in children with symptomatic HIV disease.
• Ulceration at injection site and regional lymphadenopathy may occur in 1-10 % of vaccinated persons.
• The vaccination does not prevent infection or reactivation. However, it leads to inhibition of lymphohematogenous spread of bacilli..

Chemoprophylaxis :

This is indicated in:

1. Contacts of open cases who show recent Mantoux conversion.
2. Children with positive Mantoux and a TB patient in the family.
3. Neonate of tubercular mother.
4. Patients of leukaemia, diabetes, silicosis, or those who are HIV positive and show a positive Mantoux.

The standard drug for chemoprophylaxis of TB is H 300 mg (10 mg/kg in children) daily for 6–12 months.


Now because of high incidence of H resistance, a combination of H (5 mg/kg)
and R (10 mg/kg) given daily for 6 months is preferred.


Management of tuberculosis under dots : 

The ‘directly observed treatment short course’ (DOTS) was recommended by the WHO in 1995.

Treatment of TB is categorized into 4 categories by site and severity of disease, sputum smear positivity/negativity and history of previous treatment.


Category I: This category includes:

• New (untreated) smear positive pulmonaryTB.

• New smear negative pulmonary TB with extensive parenchymal involvement.

• New cases of severe forms of extrapulmonary TB


Initial phase :Four drugs HRZ + E or S are given daily or thrice weekly for 2 months.

Continuation phase :Two drugs HR for 4 months or HE for 6 months are given. Under the RNTCP, thrice weekly treatment with H and R is given for 4 months. This phase is extended to 6–7 months (total duration 8–9 months) for TB meningitis, miliary and spinal disease.


Category II :These are smear positive failure, relapse and interrupted treatment cases.

Initial phase :All 5 first line drugs are given for 2 months followed by 4 drugs (HRZE) for another month.

Continuation phase is started if sputum is negative, but 4 drug treatment is
 continued for another month if sputum is positive at 3 months.

---Three drugs (HRE) are given for 5 months either daily or thrice weekly
(only thrice weekly under the RNTCP).


Category III:These are new cases of smear negative pulmonary TB with limited parenchymal involvement or less severe forms of extrapulmonary TB

Initial phase: Three drugs (HRE) given for 2 months

Continuation phase :4 months daily/thrice weekly HR or 6 months daily HE therapy.


Category IV: These are chronic cases who have remained or have become smear positive after completing fully supervised retreatment (Category II) regimen. 

These are most likely MDR cases.

Choice of therapy depends on drugs used in the earlier regimen, dosage and regularity with which they were taken, presence of associated disease

In conclusion, tuberculosis is a serious infectious disease that can affect anyone. Early diagnosis and treatment are crucial for preventing the spread of the disease and achieving a complete cure.

 By understanding the risk factors, symptoms, and prevention strategies, individuals can take steps to protect themselves and their communities from TB.