TUBERCULOSIS- An update of diagnostic methods in current practice.

What is Tuberculosis

Tuberculosis (TB) is an infectious disease that most often affects the lungs and is caused by a type of bacteria; Mycobacterium tuberculosis. It spreads through the air when infected people cough, sneeze or spit. TB can manifest as latent infection or active disease.

What are types of tuberculosis

The two types of clinical manifestation of tuberculosis (TB) are -

Pulmonary TB (PTB) and

Extrapulmonary TB (EPTB).

The pulmonary TB is most common form of tuberculosis. EPTB refers to TB involving organs other than the lungs (e.g., pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, or meninges).

What are the symptoms of tuberculosis

People with latent TB infection don’t feel sick and aren’t contagious. Only a small proportion of people who get infected with TB will get TB disease and symptoms. Babies and children are at higher risk. The symptoms also depend on the site involved by tuberculosis. Certain conditions can increase a person’s risk for tuberculosis disease such as-

• diabetes (high blood sugar)

• weakened immune system (for example, HIV or AIDS)

• being malnourished

• tobacco use.
  

Common symptoms of TB:

• prolonged cough (sometimes with blood)

• chest pain

• weakness

• fatigue

• weight loss

• Fever

• night sweats

What are the diagnostic modalities available for tuberculosis

The Mantoux tuberculin skin test (TST) or the TB blood test can be used to test for M. tuberculosis infection. Additional tests are required to confirm TB disease.

The Mantoux tuberculin skin test -is performed by injecting a small amount of fluid called tuberculin into the skin in the lower part of the arm. The test is read within 48 to 72 hours by a trained health care worker, who looks for a reaction (induration) on the arm.

Interferon-Gamma Release Assays (IGRAs) are whole-blood tests that can aid in diagnosing Mycobacterium tuberculosis infection. IGRA are also known as TB Gold/TB Platinum tests. IGRAs measure a person’s immune reactivity to M. tuberculosis. White blood cells from most persons that have been infected with M. tuberculosis will release interferon-gamma (IFN-g) when mixed with antigens (substances that can produce an immune response) derived from M. Tuberculosis. They do not help differentiate latent tuberculosis infection (LTBI) from tuberculosis disease.

Detection of acid-fast bacilli (AFB) by sputum smear supports treatment decisions with pulmonary tuberculosis (TB), but smear sensitivity for Mycobacterium tuberculosis is only approximately 45 to 75%. If AFB smear is positive, it means one probably have TB or other infection, but an AFB culture is needed confirm the diagnosis.

Culture remains the gold standard for laboratory confirmation of TB disease, and growing bacteria are required to perform drug-susceptibility testing and genotyping. The results of a tuberculosis culture can take many weeks. Rapid culture tests give results within 36 to 48 hours.

Drug Resistance

For all patients, the initial M. tuberculosis isolate should be tested for drug resistance. It is crucial to identify drug resistance as early as possible to ensure effective treatment.

Drug susceptibility patterns should be repeated for patients who do not respond adequately to treatment or who have positive culture results despite 3 months of therapy.

Chest Radiograph

A posterior-anterior chest radiograph is used to detect chest abnormalities. Lesions may appear anywhere in the lungs and may differ in size, shape, density, and cavitation. These abnormalities may suggest TB but cannot be used to definitively diagnose TB.

However, a chest radiograph may be used to rule out the possibility of pulmonary TB in a person who has had a positive reaction to a TST or TB blood test and no symptoms of disease.

In cases of extrapulmonary TB- site specific samples can be obtained for cytological and histopathological evaluation and confirmation of tuberculosis using ZN stain or other fluorescent stains Auramine-Rhodamine specific for TB.

Rapid molecular diagnostic tests

WHO recommends the use of rapid molecular diagnostic tests as the initial diagnostic test in all persons with signs and symptoms of TB.

Rapid tests recommended by WHO include the Gene-Xpert and Truenat assays. These tests have high diagnostic accuracy and will lead to major improvements in the early detection of TB and drug-resistant TB.

Line probe assay is also a rapid PCR test developed in India for detection of tuberculosis and drug resistant TB

Gene-Xpert, a CBNAAT (cartridge based nucleic acid amplification test) is a widely accepted diagnostic test for Tuberculosis. This test is a rapid diagnostic test for Tuberculosis detection as well as Rifampicin resistance in direct smear negative cases. GeneXpert has a higher sensitivity than AFB smear microscopy in respiratory samples. GeneXpert can be a useful tool for early diagnosis of patients with high clinical suspicion of pulmonary tuberculosis.

The Truenat assays utilize chip-based real-time micro-polymerase chain reaction (PCR) for detection of TB and RIF-resistance from Deoxyribonucleic Acid (DNA) that is extracted from sputum sample within an hour.

LPA (Line probe assay) is a rapid technique based on polymerase chain reaction (PCR) that is used to detect Mycobacterium tuberculosis (MTB) complex as well as drug sensitivity to rifampicin (RPM) and isoniazid (INH) through the Revised National Tuberculosis Control Programme (RNTCP) of India.

Prevention

Follow these steps to help prevent tuberculosis infection and spread:

• Seek medical attention if a person has symptoms like prolonged cough, fever and unexplained weight loss as early treatment for TB can help stop the spread of disease and improve chances of recovery.

• Get tested for TB infection if a person is at increased risk, such as if he/she has HIV or is in contact with people who have TB in their household or workplace.

• If one has TB, practice good hygiene when coughing, including avoiding contact with other people and wearing a mask, covering your mouth and nose when coughing or sneezing, and disposing of sputum and used tissues properly.

• Special measures like respirators and ventilation are important to reduce infection in healthcare and other institutions.

FAST FACTS-

• Culture still remains the gold standard test for diagnosis of Tuberculosis.

• CBNAAT tests like Gene-Xpert, Line probe assay and Truenat tests can be utilized as promising molecular tests for detecting Mycobacterium tuberculosis.

• Specimens that can be sent for testing with CBNAAT include respiratory specimens such as sputum, bronchial or tracheal aspirates, broncho-alveolar lavage and gastric lavage as well as extra pulmonary specimens like tissue biopsy including lymph node, pus from abscess, CSF, ascitic and pericardial fluid, pleural fluid.

• Tests like TST (Mantoux test) or IGRA based tests (TB Gold/ QuantiFERON / TB Platinum) cannot differentiate between latent infection and active disease.

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Blog by Dr. Aditi Kumar