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Tuberculosis

Tuberculosis (TB) is a contagious infectious disease caused by the Mycobacterium tuberculosis bacteria, commonly known as Koch's bacillus, after the German doctor who discovered it in 1882.

The bacteria usually affects the lungs (pulmonary tuberculosis), but can also affect other organs or systems, such as lymph nodes, pleura, kidneys, brain, and spine (extrapulmonary tuberculosis). Extrapulmonary tuberculosis is not transmitted by affected individuals.

CAUSES

Tuberculosis is caused by Mycobacterium tuberculosis, an aerobic, Gram-positive, rod-shaped bacterium that is able to survive mild disinfectants and live in a dehydrated state for weeks. It can be cultured in vitro, but it normally only reproduces within the cells of human beings, which are the bacteria’s only natural reservoir.

TRANSMISSION

Transmission of the disease is airborne and is spread via infectious microscopic droplets of saliva expelled when an infected person coughs or speaks. In order for an infected individual to actually be able to transmit and infect another, they must have the so-called active form of tuberculosis, i.e., the form of the disease with radiologically evident lesions and a high concentration of mycobacteria in the lungs.

A person is no longer considered infectious if they have been on current antibiotic treatment for at least 15 days, or have been under the supervision of a specialist centre for 6 months. Usually infection occurs in enclosed spaces where there is very little air exchange, following exposure a sufficiently long period (>8 hours).

GEOGRAPHICAL DISTRIBUTION

TB is endemic all over the world, but the countries with a high rate of endemicity are in South-East Asia, the Pacific, and Africa. Italy is considered a low incidence country, reporting approximately 4000 new cases a year (ISS EpiCentro).

Today, tuberculosis is one of the top 10 leading causes of death worldwide. In fact the disease causes approximately 2 million deaths per year, which are mainly concentrated in developing countries. It is estimated that one-third of the world's population is infected with TB.

SYMPTOMS

The bacillus does not necessarily lead to the onset of the disease. In fact, not all infected people get tuberculosis, but mycobacteria can survive in the infected patient in a state known as 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 approx. 5-10% of people who do not receive treatment for LTBI). This can occur for various reasons, such as when the immune system is maturing (e.g. in childhood); when it becomes less effective (e.g. in the elderly); when it is weakened by infectious diseases (as often occurs in HIV and other diseases); neoplasms of various kinds, endocrine diseases; autoimmune diseases; diabetes, and other chronic conditions.

The World Health Organization (WHO) estimates that approximately ¼ of the world's population is affected by latent tuberculosis infection.

In 10% of cases, TB evolves into the active form, which presents with symptoms, such as a productive cough (sometimes with traces of blood) that lasts for 3 or more weeks, chest pain, weakness, weight loss, fever, and night sweats.

If untreated, the mortality rate is 50%.

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DIAGNOSIS

Diagnosis of tuberculosis involves multiple assessments and considerations.

Generally, the patient’s clinical history, chest X-ray, microbiological and sputum culture tests are evaluated to diagnose this form of lung disease.

Diagnosis of latent tuberculous infection is made after the patient tests positive for one (or both) of the screening tests and after excluding active disease, which is usually assessed by chest X-ray. In fact, the presence of any specific symptoms, a positive microscopic or culture tests for TB mycobacterium, and significant radiographical findings, indicate the presence of the active form.

During our lives, we may need to be screened for latent tuberculosis infection for several reasons, including:

  • Close contact with an active TB patient;
  • When starting immunosuppressive therapies;
  • Starting a new job that is considered "at risk," such as working in health care or an international setting.

To date, there are two main screening tests for TB:

The Mantoux test (or Tuberculin Intradermal Reaction) is a medical diagnostic test that is performed via the intradermal injection of 5 IU of PPD-S (purified protein derivative of tuberculin) into the patient's forearm. After 48-72 hours, the patient is re-assessed to determine the test result. The test is considered positive when there is evidence of a characteristic inflammation (reaction), with a diameter that is greater than the threshold value, which could be 5, 10, or 15 mm depending on the patient's risk. The examination is generally considered negative when the reaction and swelling is less than 5 mm in diameter.

A positive test does not in itself prove the presence of active tuberculous disease, but it is a good way gauging if the immune response “remembers” coming into contact with the TB bacillus in the patient's more or less distant past.

The QuantiFERON test is a diagnostic test that is carried out on a sample of the patient’s blood. It is performed exclusively in a specialised laboratory, and is used to detect Interferon Gamma using an enzyme immunoassay test. This method identifies the response associated with Mycobacterium Tuberculosis infection, without interfering with nontuberculous mycobacteria, or the BGC vaccine.

TREATMENT

Appropriate and timely treatment for pulmonary tuberculosis is critical for a good clinical outcome and public health safety.

The disease can be eradicated using a multi-drug treatment programme, over a long period of 6 to 9 months. Currently, the Food and Drug Administration (FDA) has approved ten TB drugs. In choosing the most effective antitubercular treatment, it is essential to perform mycobacterial drug sensitivity and resistance tests.

First-line treatment involves the administration of:

  • isoniazid
  • rifampicin
  • ethambutol
  • pyrazinamide

However, the bacteria that causes tuberculosis can become resistant to the antimicrobial drugs used to treat the disease. Multidrug-resistant TB (MDR-TB) shows resistance to at least two drugs: isoniazid and rifampicin.

The reasons why multiple drug resistance continues to emerge and spread are:

  • An inadequate management of TB treatment.
  • Person-to-person transmission of the multidrug-resistant bacillus

Most people with tuberculosis recover when put on a regimen of four, first line medications for a period of 6-9 months, carried out under the strict guidance and supervision of a doctor. Inappropriate or incorrect use of antimicrobial drugs or the use of ineffective drug formulations (e.g. the 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 becoming increasingly difficult. Treatment options are limited and expensive, the recommended drugs are not always available in all of the countries, and patients often experience adverse effects.

But the challenge does not end there. There is an even more resistant version of the disease, called extensively drug-resistant tuberculosis (XDR-TB). XDR-TB is a form of tuberculosis resistant to all fluoroquinolone-based drugs and at least one of the three second-line injectable drugs (capreomycin, kanamycin, and amikacin), as well as isoniazid and rifampicin.

Drug resistance can be detected using special laboratory tests that test the bacteria’s sensitivity to drugs or detect models of resistance. These tests can be molecular (such as Xpert MTB / RIF), which can provide results in a matter of hours, or culture-based.

Solutions suggested by WHO to control drug-resistant tuberculosis include:

  • Adequately and effectively treat the disease the first time it appears;
  • Provide access to diagnosis
  • Ensure adequate infection control in facilities where patients are treated
  • Ensure the appropriate use of the recommended second-line medications

Globally, half a million people had a MDR-TB in 2019, of whom only 38% had access to treatment. In Italy, according to 2017 ECDC-WHO data, multidrug-resistant tuberculosis cases involved 2.5% of the notified cases - out of the 56 MDR-TB cases, 8.9% were extremely resistant (XDR-TB).

PREVENTION

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), which is approximately 80% effective in preventing severe childhood forms of the disease. The effectiveness is greatest among people who live in highly endemic areas, whereas effectiveness decreases as you move towards regions where tuberculosis is rarer. It is also less effective in adults.

Source: CDC

 

The information presented is general in nature, is published for informational purposes for a general public and does not replace the relationship between patient and doctor.
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