TUBERCULOSIS

By: Adriel Alves Borges e Daniela de Luna Martins

Tuberculosis (TB) is a serious infectious disease caused by a bacteria called

Mycobacterium tuberculosis (M. tuberculosis), also known as Koch's bacillus. This name was given in honor of Heinrich Hermann Robert Koch (Figure 1), the German bacteriologist who discovered this microorganism in the 19th century. [1] Nonetheless, the infection can also be caused by Mycobacterium bovis, M. africanum, and M. microti. [2] Tuberculosis primarily affects the lungs, but can also affect other organs of the body such as the kidneys, meninges, and bones. According to the World Health Organization (WHO), about 10 million people in the world are affected by TB, and approximately 1.5 million people die each year, with the majority of registered cases occurring in underdeveloped countries or in poor regions of developing countries. [3]

Figure 1 - Robert Koch (1841-1910) e M. tuberculosis

The main symptoms of pulmonary TB are persistent cough for more than two weeks, which may contain blood (haemoptysis) or sputum, night sweats, fever, unexplained weight loss, fatigue, feeling short of breath and chest pain when coughing. Depending on the affected organ, there will also be variation in symptoms. Notwithstanding, malaise, fever and weight loss are common in other cases. [4] When TB affects the kidneys, for example, the patient may experience low back pain, and blood may appear in the urine. When it reaches the central nervous system (CNS), meningitis, headaches and mental confusion can occur. [5] The BCG vaccine, which is within the Brazilian National Immunization Program (PNI), prevents cases of meningitis caused by TB. In bones, in turn, TB causes nerve compression. Exclusively non-pulmonary forms are not susceptible to transmission. [5]

Most people infected with the causative agent of tuberculosis do not develop symptoms because mycobacteria survive inactively in the body. However, with the weakening of the immune system, there may be activation of the mycobacteria. It is estimated that about 10% of those infected develop the active and contagious form at some point in their lives. [6] There are groups of people with latent tuberculosis, that is, who do not develop the disease. There are, however, people more likely to develop active tuberculosis: those infected by the HIV virus (Human Immunodeficiency Virus – which causes AIDS or Acquired Immunodeficiency Syndrome), due to the drug interaction that exists between the drugs employed to treat tuberculosis and HIV. [7] Also, infants and young children, the elderly, people with diseases that weaken the immune system, people who have not properly treated TB in the past, people who have been infected with Koch's bacillus in the past 2 years, transplant recipients, diabetics, malnourished people, among others, are also more likely to develop tuberculosis. [6]

Recent studies have shown that patients with concomitant tuberculosis and COVID-19 are more likely to have negative clinical outcomes and 25% less chance of recovering from COVID-19. Furthermore, the risk of death increases more than twice in these cases of coinfection than in patients with COVID-19 without associated tuberculosis. It has also been shown that individuals with pulmonary sequelae caused by COVID-19 may be at increased risk of developing tuberculosis in the future. [8,9] Environments with direct light incidence and good air circulation contribute to reduce transmission, as the bacillus is sensitive to sunlight and air circulation facilitates the dispersion of particles containing the transmitting agents. As the patient is treated, their ability to contaminate others decreases. However, it is very important that he is aware and helps to reduce contamination, putting his arm or a handkerchief in his mouth when coughing, talking or sneezing, in addition, it is important to promote the entry of natural light as well as the ventilation of the rooms. [10] In Brazil, cases of tuberculosis need to be notified and treatment is accessible through the Unified Health System (Sistema Único de Saúde - SUS). The Ministry of Health recommends that people with persistent cough for three weeks or more have an investigation for tuberculosis, looking for the nearest health facility. And, if the result is positive, the treatment must be followed disciplined until the end and must be started as soon as possible. Tuberculosis is curable, but for that, discipline with the treatment is necessary. Otherwise, the patient may develop resistance to therapy. In a later article, we will explain the issue of resistance in more detail, as it is a very complicating factor. [10] Treatment for TB lasts at least six months. The first-line drugs (Figure 2) used in the initial treatment are rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB). In cases of resistance to first-line drugs or in the treatment of people who do not tolerate them, so-called second-line drugs can be used, which are aminoglycosides, such as streptomycin, amikacin and kanamycin, and fluoroquinolones, such as levofloxacin and moxifloxacin, in addition to other drugs such as 4-aminosalicylic acid, thiacetazone and cycloserine (Figure 3). [11]

Figure 2 - Chemical structures of the firs-line drugs used for TB treatment

Figure 3 - Chemical structures of some second-line drugs used for TB treatment

References

[1] Site of the Secretary of Health of the Government of the State of Paraná (Brazil). Available: https://www.saude.pr.gov.br/Pagina/Tuberculose. Accessed: July 9, 2021.

[2] Sítio da Fundação Oswaldo Cruz. Tuberculose. Disponível em: https://portal.fiocruz.br/taxonomia-geral-doencas-relacionadas/tubercuolse. Acesso: 09 julho 2021.

[3] World Health Organization site. "Tuberculosis." Available: https://www.who.int/health-topics/tuberculosis. Accessed: July 9, 2021.

[4] Doctors Without Borders site. "Tuberculosis". Available: https://www.msf.org.br/o-que-fazemos/atividades-medicas/tuberculose?utm_source=adw ords_msf&utm_medium=&utm_campaign=doencas_geral_comunicacao&utm_content=_ex

clusao-saude_brasil_39923&gclid=CjwKCAjwqcKFBhAhEiwAfEr7zWnUfdia8R2PKRj-7JsiJp-Bm vZ-00MPZ3uhnjOI3qZZuF823T8QIhoCV5sQAvD_BwE. Accessed: July 9, 2021.

[5] MSD MAnuals site. "Tuberculose extrapulmonar (TB)." Available: https://www.msdmanuals.com/pt-br/profissional/doen%C3%A7as-infecciosas/micobact%C3%A9rias/tuberculose-extrapulmonar-tb. Accessed: July 9, 2021.

[6] Centers for Disease Control and Prevention site. "Hystory of World TB Day." Available: https://www.cdc.gov/tb/worldtbday/history.htm#:~:text=On%20March%2024%2C%201882 %2C%20Dr,the%20United%20States%20and%20 Europe. Accessed: July 9, 2021.

[7] Ministry of Health Virtual Health Library Site. "Recomendações para o manejo da coinfecção TB-HIV em serviços de atenção especializada a pessoas vivendo com HIV/AIDS." Available: https://bvsms.saude.gov.br/bvs/publicacoes/recomendacoes_manejo_coinfeccao_tb_hiv.pdf. Accessed: July 9, 2021.

[8] K. T. L. Sy, N. J. L. Haw, J. Uy, Previous and active tuberculosis increases risk of death and prolongs recovery in patients with COVID-19. Infect. Dis. 2020, 52, 902. Disponível em: https://doi.org/10.1080/23744235. 2020.1806353.

[9] A. Boulle, M. A. Davies, H. Hussey, M. Ismail, E. Morden, Z. Vundle, et al. Risk factors for COVID-19 death in a population cohort study from the Western Cape Province, South Africa [published online ahead of print, 2020 Aug 29]. Clin. Infect. Dis. 2020, ciaa1198. Available: https://doi.org/10.1101/2020.07.02.20145185.

[10] Brazilian Health Ministry Site. "Tuberculose: o que é, causas, sintomas, tratamento, diagnóstico e prevenção." Available: http://antigo.saude.gov.br/saude-de-a-z/tuberculose. Accessed: July 9, 2021.

[11] MSD Manuals site. "Medicamentos utilizados para tratar a tuberculose." Available: https://www.msdmanuals.com/pt/casa/multimedia/table/v21853024_pt#:~:text=Medicamentos%20de%20segunda%20linha%20s%C3%A3o,dos%20medicamentos%20de%20primeira%20linha. Accessed: July 9, 2021.

Créditos/Links to figures used:

* Woman coughing - https://pixabay.com/images/id-4392163/

* Robert Koch - https://educationalresearchtechniques.com/2021/03/19/robert-koch-proving-germ-theory/

* Micobacterium tuberculosis - https://www.microbiologyresearch.org/content/mycobacterium-tuberculosis/w