**1. Introduction**

*More than 100 years have been since the discovery of Mycobacterium tuberculosis (TB) and still continues to be* one of the world's leading causes of death by a single infectious organism. Despite extensive knowledge of its pathophysiology and its infectious characteristics, TB continues to cause great morbidity, and continue to be a significant diagnostic challenge. But far from making the diagnosis, the true odyssey occurs when many patients develop an infection with resistance to available therapy.

*Mycobacterium tuberculosis* is a bacillus shaped, aerobic, slow growing and acid-fast positive staining bacteria. The organism is mostly transmitted through out droplets of particles suspended in the air, and inhalation by the infected host. Deposition of the bacteria in the tissues, especially the lungs, cause the principal manifestations of the disease. Most of the infected people developed a natural immunity by phagocytes which engulf the mycobacteria and form granulomas causing no clinical symptoms. This is known as latent tuberculosis. Differently,

around 10% of exposed people develop active infection, characterized by cavitary and fibrotic lung disease [1]. Immunosuppression can cause that tuberculosis bacilli migrate from the initial lung infection to other sites, causing extra pulmonary disease, which is one of the most lethal sequelae of the infection. TB can virtually invade any organ system and mimic other noninfectious conditions, causing to be a significant source of morbidity and mortality [2]. Early identification and appropriate treatment are the clues to obtain a satisfactory outcome.

The diagnosis of TB is done by identification of the mycobacteria in the affected tissue by culture or polymerase chain reaction. Once the organism is identified, combination antimicrobial drug therapy is started, and continued according to drug sensitivity. Length of treatment is determined by the site of infection and the immunologic status of the host, as well as the drug sensitivity of the organism.

Before the end of the first half of the 20th century, antimicrobial medications for Tuberculosis were discovered, following by the use of combination drug therapy as its principal management [3]. Around 1970s, the use of medications as Isoniazid and Rifampin were established as the principal core of treatment that participates in addition to other drugs for treatment of tuberculosis. The combination with other drugs allowed to decrease length of therapy to around 6 months [3]. After more than 50 years, new drugs for tuberculosis have been approved in 2019. The assemblance of previous known drugs and new ones is the pivotal therapy for the infection, including those with resistance to one or more medications (**Figure 1**).

In between the amaze and current focus in the catastrophic pandemic of Covid-19, we tend to forget that a year before in 2018, *M. tuberculosis* infected more than 10 million people, with 1.5 million people dying from the disease [1]. Despite being TB a well-known disease, it is suspected that more than one third of the cases did not receive adequate treatment due to lack of diagnosis and lack of resources [1]. Besides the direct poor outcome in the individual patient, the absence of an appropriate treatment increase the risk of developing drug resistance, facilitates alterations in the genealogy, and favors poor outcomes in morbidity and mortality. Thus, drug resistance is considered a significant menace to populations of high prevalence of disease, and an important set back to eradicate the infection.

Genealogy is described as the study of the history of a specific descendance and how we can follow the different lineages of a family or group. Throughout exposure to drugs, TB has developed the capability of resist antimicrobial therapy, which have evolved in strains that survive beyond those which are sensitive to medications, creating those drug resistant populations of mycobacteria. Current technologies, allow the identification of TB strains with drug resistance using DNA tests which detect genetic mutations to different drugs is less than 48 hours [4]. Also, gene sequencing studies have allowed to follow the lineage of TB in different areas of Latin America. Using specific "gene markers" and mutations detected by


**57**

*Genealogy of Resistant Tuberculosis in Latin America and the Caribbean until 2020*

migration patterns from those regions, establishing familiar origins.

(**Figure 1**). These are the basic definitions of drug resistant TB:

drugs but not to both INH and Rifampicin simultaneously.

polymerase chain reactions, the populations of mycobacteria are identified and characterized in different territories [5]. Those genetically identified strains are compared to TB strains in Europa and other continents, and are studied along with

As mentioned above, the most common therapy for tuberculosis originated from

1970s, which consist in a combination of Isoniazid (INH) and Rifampin (RIF). Adding Ethambutol (EMB) and Pyrazinamide (PZA) can shorten the length of therapy. The first two drugs are considered as the firs line therapy for tuberculosis

• **Drug-resistant tuberculosis** is when TB remains unaffected to at least one

• **Mono drug resistance** refers to an infection with resistance to one of the first

• **Poly-drug resistant TB** occurs when there is resistance to two or more anti-TB

• **Multidrug-resistant tuberculosis (MDR-TB)** occurs when resistance occurs in more than one antimicrobial drug, or at least isoniazid (INH) and

• **Extensively drug resistance tuberculosis (XDR-TB)**: The extreme case of resistance, in which TB is resistant to at least one drug in each group in the second line therapy groups (see **Figure 1**, groups A to D), besides being resistant

• For the purpose of this chapter, we will refer and discuss mainly to the multi-

The development of drug resistance of tuberculosis seems to be secondary to a mutation process of a chromosome that can cause that a specific population of mycobacteria develops a "phenotypic resistance" to a certain drug. That mutation can be cause an alteration in the drug transport in the cell membrane of the mycobacteria, or the increase in production of an enzyme that metabolize and cause incapacity of the treatment drug. When those mycobacterias are exposed to either inappropriate antimicrobial therapy, inappropriate length of treatment, poor quality or low dose of medications, or lack of combination therapy, confers to the resistant bacteria a survival advantage that allows a "genetic" transformation which

The common use of more than one drug to treat TB resulted from initial studies that showed a progressive increased in mycobacterial populations with resistance in sputum cultures from patients treated only with streptomycin. Combining para-aminosalicylic acid with streptomycin in a clinical trial showed a more than 7 to 8 times decrease in the rate of resistance to streptomycin [7]. With the eventual

*DOI: http://dx.doi.org/10.5772/intechopen.96280*

**2. Definition of drug resistance and causes**

anti-tuberculosis drug.

line agents.

rifampin (RIF).

to first line therapy.

**3. Drug resistance**

drug resistant tuberculosis (MDR-TB).

is transmitted over other nonresistant strains [6].

**Figure 1.** *2016 WHO Drug Therapy Groups Tuberculosis.* *Genealogy of Resistant Tuberculosis in Latin America and the Caribbean until 2020 DOI: http://dx.doi.org/10.5772/intechopen.96280*

polymerase chain reactions, the populations of mycobacteria are identified and characterized in different territories [5]. Those genetically identified strains are compared to TB strains in Europa and other continents, and are studied along with migration patterns from those regions, establishing familiar origins.
