TB is endemic worldwide, but high-endemic countries are in Southeast Asia, the Pacific, and Africa. Italy is considered a low-incidence country, where about 4,000 new cases are reported each year (ISS Epicenter).
Today, tuberculosis represents one of the top 10 leading causes of death worldwide. It causes about 2 million deaths each year, particularly concentrated in developing countries. An estimated one-third of the world's population is infected with TB.
The bacillus does not necessarily result in disease. In fact, most infected people show no symptoms, but mycobacteria can survive in the infected patient in a state called latency. The condition in which the bacteria remain inactive is called latent tuberculosis infection (LTBI). People who suffer from LTBI may become ill years later (altogether about 5-10% of those who do not receive treatment for LTBI), when for various reasons their immune system is maturing, as in childhood, or when it loses competence as in the case of the elderly, or when it is weakened by infectious diseases (as typically can occur in HIV disease, but not only), neoplasms of various kinds, endocrine diseases, autoimmune diseases, diabetes, and other chronic conditions.
The World Health Organization (WHO) estimates that about ¼ of the world's population is affected by latent TB infection.
In 10% of cases, TB evolves into the active form, which presents with symptoms such as productive cough (sometimes even with blood trails) for 3 or more weeks, chest pain, weakness, weight loss, fever, and night sweats.
If left untreated, the mortality rate is 50%.
Trying to simplify, we can state that generally this lung disease can cause symptoms such as:
Productive cough (sometimes even with blood trails) for 3 or more weeks, chest pain, weakness, weight loss, fever, night sweats.
Symptoms of latent tuberculous infection
People with latent tuberculosis infection:
- Have no symptoms
- Cannot transmit the tubercle bacillus
- Generally test positive for tuberculous bacillus
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The diagnosis of tuberculosis is subject to multiple evaluations and considerations.
Generally, clinical picture, chest X-ray examination, microbiological and sputum culture examination are evaluated to diagnose this lung disease.
The diagnosis of latent tuberculous infection is made after evidence of positivity to one (or both) of the screening tests and after confirmation of exclusion of active disease, usually by chest X-ray examination. In fact, the presence of any specific symptoms and the results of positive microscopic or culture tests for TB mycobacterium, significant radiographic findings indicate the presence of the active form.
Screening tests for latent tubercular infection
Over the course of a lifetime, we may be required to perform a screening test for latent tuberculous infection for several reasons:
- Close contact with a person with active tbc infection;
- Initiation of immunosuppressive therapies;
- Beginning a new job considered "at risk," such as working in the health care or international arena.
To date, the screening test is recommended in two different modalities:
- Mantoux Test (Tubercolin Skin Test or Purified Protein Derivative Test).
- Quantiferon Head (IGRA)
Mantoux's Test
The Mantoux test or Intradermal Tuberculin Skin Test, is a medical diagnostic test that is performed through an intradermal injection of 5 IU of PPD-S (purified protein derivative of tuberculin) into the patient's forearm. After 48-72 hours, the patient will be re-evaluated for determination of the test result. The test is considered positive when there is evidence of characteristic swelling with a diameter greater than the threshold value, which may be 5, 10 or 15 mm depending on the patient's risk. The test is generally considered negative when the induration and swelling is less than 5 mm in diameter.
A positive test does not in itself prove the presence of active tuberculous disease, but since it is a measure of the immune response, it only recognizes that the patient had contact in the more or less distant past with the tbc bacillus.
Quantiferon test
The Quantiferon test is a diagnostic test that is performed through blood sampling, carried out exclusively in a specialized laboratory, aimed at the detection of Interferon Gamma by enzyme immunoassay. This research identifies the response associated with Mycobacterium Tuberculosis infection, without interfering with nontuberculous mycobacteria or BGC vaccine.
Appropriate and timely treatment for pulmonary tuberculosis is critical for a good clinical course and public health safety.
The disease can be eradicated through multi-drug treatment over a long period of 6 to 9 months. Currently, the Food and Drug Administration (FDA) has approved ten drugs.
In choosing the most effective antitubercular treatment, it is essential to rely on the examination of mycobacterial drug sensitivity and resistance.
First-line treatment involves the administration of:
- isoniazid
- rifampicin
- ethambutol
- pyrazinamide
Treatment of multidrug-resistant tuberculosis
The bacteria that cause tuberculosis can develop resistance to antimicrobial drugs used to treat the disease. Multidrug-resistant TB (MDR-TB) shows resistance to at least two drugs: isoniazid and rifampin.
The reasons why multiple drug resistance continues to emerge and spread are:
- Inadequate management of TB treatment
- Person-to-person transmission of the multidrug-resistant bacillus
Most people with TB recover when placed on a drug regimen of four drugs (called first-line) lasting 6-9 months, performed strictly with support and supervision. Inappropriate or incorrect use of antimicrobial drugs or use of ineffective drug formulations (such as use of single drugs, poor quality drugs or poor storage conditions) and premature discontinuation of treatment can cause drug resistance, which can subsequently be transmitted.
Treating multidrug-resistant tuberculosis is increasingly difficult. Treatment options are limited and expensive, recommended drugs are not always available in all countries, and patients often experience many adverse effects.
The challenge does not end there. There is an even more resistant version, called extensively drug-resistant tuberculosis (XDR-TB). XDR-TB is a form of tuberculosis that is resistant to every fluoroquinolone and at least one of three second-line injectable drugs (capreomycin, kanamycin, and amikacin), as well as isoniazid and rifampin.
Drug resistance can be detected using special laboratory tests that test the sensitivity of bacteria to drugs or detect patterns of resistance. These tests can be molecular (such as Xpert MTB / RIF) and provide results within hours, or culture-based.
Solutions suggested by WHO to control drug-resistant tuberculosis are:
- Adequately and effectively treat the disease in its first appearance
- Provide access to diagnosis
- Ensure adequate infection control in facilities where patients are treated
- Ensuring appropriate use of recommended second-line drugs
Globally, half a million people had MDR-TB in 2019, of whom only 38 percent had access to treatment. In Italy, according to 2017 ECDC-WHO data, the proportion of multidrug-resistant TB cases was 2.5 percent of notified cases - of the 56 MDR-TB cases, 8.9 percent were extremely resistant (XDR-TB).
Treatment of latent tuberculosis
The medical specialist will decide whether or not to undertake treatment eradicating latent tuberculosis infection by evaluating several factors.
The recommended treatment schedule in countries with low incidence of the disease is:
- 6 or 9 months of Isoniazid monotherapy; or
- 3 or 4 months of combination therapy with Rifampin and Isoniazid; or
- 4 months of monotherapy with Rifampicin.
Vaccination is the main tool for tuberculosis prevention and is mandatory in many countries.
Currently, the only vaccine available is BCG (bacillus of Calmette Guérin), with an efficacy of around 80 percent in preventing severe childhood forms. This efficacy is highest in those living in highly endemic areas, while it decreases moving to regions where tuberculosis is rarer. It is also less effective in adults.