Classification of the Organism
Tuberculosis has been a significant global health concern for centuries. This disease is caused by Mycobacterium tuberculosis, which is a pathogenic bacteria belonging to the order Actinomycetales, family Mycobacteriaceae, and genus Mycobacterium (Bandaru et al., 2020). M. tuberculosis belongs to a group of obligate pathogens referred to as the Mycobacterium tuberculosis complex (MTBC). MTBC consists of Mycobacterium bovis, Mycobacterium pinnipedii, Mycobacterium microti, Mycobacterium africanum, Mycobacterium caprae, and Mycobacterium canetti. Scholars have reported that these organisms have distinct phenotypic characteristics and host range, with M. tuberculosis demonstrating less than a 0.05% difference from M. bovis (Kesharwani et al., 2020). However, M. bovis is known for causing cattle tuberculosis infection, but it can cause this illness in human beings.
Organism Morphology and Staining
A bacterial organism’s morphology helps in the initial identification of a microorganism in an isolate consisting of other microbes. Morphology is defined by an organism’s size, shape, arrangement, and cell structure. M. tuberculosis is characterized by a thin, curved, or rod shape, measuring approximately 0.2 to 0.6 µm by 1 to 10 µm (Lehman, 2020). Additionally, these organisms are nonmotile, non-spore-forming, consisting of thin peptidoglycan and a thick lipid layer. M. tuberculosis is a gram-negative and acid-fast bacillus, facilitated by the thick lipid layer, which does not allow staining with regular dyes. This layer provides this microorganism with its distinctive acid fastness. The dyes used for staining and identifying this bacteria are carbol fuchsin and methylene blue (Highsmith et al., 2019). The staining techniques used for the identification are the Ziehl-Neelsen and Kinyoun methods. The carbol fuchsin stains the thick lipid layer of mycolic acid into a pink color.
Pathogenicity
The pathogenicity of an organism is defined as the processes involved in the development and progression of a disease. All the members of MTBC cause tuberculosis, with M. tuberculosis classified as the significant pathogenic organism causing this infectious illness in human beings. This bacteria attacks the host’s immune system — macrophages or phagocytic cells —in the alveoli (Farver & Jagirdar, 2018; Kesharwani et al., 2020). This process enables it to prevent the host’s immune cells from recognizing its presence in the body. During an infection, the macrophages or phagocytic cells identify foreign particles and digest them, leading to the boy’s protection. However, with M. tuberculosis, the bacteria prevent these immune cells from attacking it or being recognized by defending the macrophages’ degrading mechanisms, making it reside unrecognized within the body’s immune system (Farver & Jagirdar, 2018; Kesharwani et al., 2020). As a result, M. tuberculosis can remain in the cells of these organs for more extended periods in a latent state.
The pathogenicity of M. tuberculosis arises from its cell wall structure. This organism is a gram-negative and acid-fast bacteria composed of a thin peptidoglycan layer and a thick lipid structure consisting of mycolic acid, cord factor, and WAX-D (Kesharwani et al., 2020). Mycolic acid forms a solid protective shell around the M. tuberculosis cell wall, which affects the permeability of a host’s immune cells. Additionally, this lipid structure enables the bacteria to evade the phagocytic process of lysozymes, and other immune destructive components, preventing the action of the complement system on foreign materials (Kesharwani et al., 2020). The cord factor allows the bacteria to assume a distinctly long and slender format, demonstrating its virulence in the hosts’ cells. Finally, WAX-D helps the bacteria to evade phagocytic cells or macrophages.
The transmission of tuberculosis occurs due to inhalation and deposition of M. tuberculosis bacteria nuclei droplets into the respiratory bronchioles or alveoli. The droplets pass from an individual with an active infection through coughing, talking, and sneezing (Highsmith et al., 2019). The alveolar macrophages engulf the bacteria in these droplets and initiate an immune response. However, the ability of this microorganism to evade the immune response makes the bacteria survive within these cells and proliferate intracellularly (Highsmith et al., 2019). Afterward, the bacteria move to hilar lymph nodes and spread to other body organs through the thoracic duct.
The host’s immune system responds depending on its cellular ability to fight foreign materials. In individuals with adequate cellular immunity, the macrophages secret interleukin 12 and tumor necrosis factor-alpha, which recruit T cells and natural killer cells resulting in an increased inflammatory reaction (Lehman, 2020). The latency of M. tuberculosis begins after the cellular-mediated immune response has contained the bacteria through the formation of granulomas two to 10 weeks after contagion. Differentiating T cells results in the formation of helper T-cells type 1, which releases gamma interferon (IFN-γ) (Lehman, 2020; Highsmith et al., 2019). In the infection site, the IFN-γ stimulates macrophages to destroy the microorganism. This process further results in regression and healing of the primary lesion.
Immunologists have reported that the pathologic features of tuberculosis are caused by the hypersensitivity reaction to the mycobacterial antigen. Minimal antigen with increased hypersensitivity reaction may form a granuloma, which may destroy M. tuberculosis (Lehman, 2020). Afterward, healing occurs, followed by calcification and scar formation. With increased antigen and hypersensitivity, tissue necrosis occurs because of the degeneration of enzymes from macrophages. Granulomas are protected from phagocytosis due to the protective covering of fibrin. However, caseous material may form at the primary lesion site as a result of the formation of a semi-solid amorphous material at the necrosis site (Lehman, 2020). The bacteria may not be completely eradicated after healing the primary infection. Consequently, it remains dormant in granulomas, which can be reactivated into an active state upon exposure to factors contributing to immunosuppression.
Disease Caused by the Organism
M. tuberculosis causes an infectious disease predominantly affecting the lungs known as tuberculosis. This malady progresses from the lungs to other body parts and is classified into latent and active states. The latent state is whereby the bacteria persist in an inactive form inside the body organs. The organism does not cause any symptoms or become contagious in this state (Kesharwani et al., 2020). However, it can become active at any moment, especially when an individual’s immune system is compromised. In the active state, M. tuberculosis causes symptoms and transmissions in its later stages of infection.
M. tuberculosis causes three types of tuberculosis — primary tuberculosis, reactivation tuberculosis, and extrapulmonary tuberculosis (EPTB). Diagnosis of primary tuberculosis is aided by using the positive purified protein derivative (PPD) skin test and assessing the prevailing signs and symptoms. The bacteriologic finding is that primary tuberculosis may be insufficient, with a 25-30% positivity rate when the sputum or bronchial washing is cultured (Lehman, 2020). A failed cellular immunity and bacilli multiplication might result in progressive active pulmonary tuberculosis development. Meningeal or military (disseminated) tuberculosis may occur in children or older adults with primary infection, immunodeficient individuals, or those with massive lymphohematogenous dissemination (Lehman, 2020). A small percentage of adults with this malady might experience progression into an active disease, which resembles reactivation tuberculosis in older adults. The difference between these illnesses can be seen determined using positive PPD skin test results in previously negative patients.
Reactivation tuberculosis occurs after latent M. tuberculosis is exposed to a weak immune system. A weakened immune system can be due to alteration or immunosuppression. The probability of occurrence of reactivation tuberculosis after initial diagnosis using the PPD skin test is about 3.3%. However, this illness has a 5-15% chance of happening in an immunocompromised patient’s lifetime (Lehman, 2020). The progression varies depending on the patient’s age, bacterial intensity, and exposure. Finally, the risk factors for this malady include malnutrition, alcoholism, low-socioeconomic status, immunosuppression, incarceration, and AIDS.
EPTB is less common than other types of tuberculosis infections. This disease is usually seen among patients diagnosed with HIV and pulmonary tuberculosis. EPTB is significantly contributed by risk factors such as HIV and aging occurs in almost all patients diagnosed with HIV (Farver & Jagirdar, 2018; Highsmith et al., 2019; Lehman, 2020). However, the association between EPTB and HIV is less understood compared to HIV to other types of tuberculosis. EPTB occurs in almost any organ in the body. Consequently, diagnosing this ailment is challenging since clinical sample collection is crucial due to insufficient bacteria and the inaccessibility of the affected organs (Highsmith et al., 2019; Lehman, 2020). The malady forms seen in EPTB are lymphadenitis, pleural, gastrointestinal, skeletal, meningeal, peritoneal, genitourinary illnesses, and military tuberculosis — rampant among children and individuals diagnosed with HIV. These maladies have varying signs and symptoms depending on the organ affected.
Signs and Symptoms of the Illness
The signs and symptoms of tuberculosis this illness depend on the type of the disease. Pulmonary tuberculosis is characterized by nonspecific early signs and symptoms such as nonproductive cough, fatigue, anorexia, shortness of breath among children, weight loss, night sweats, or a low-grade fever (Highsmith et al., 2019; Lehman, 2020; Prasanna & Niranjan, 2019). Additionally, the malady causes a cough that progresses into a more frequent mucoid or mucopurulent sputum. This progression might cause an advanced pulmonary tuberculosis infection associated with hemoptysis, chest pain, and sometimes dyspnea. Reactivation tuberculosis is composed of insidious symptoms similar to those of pulmonary tuberculosis. However, many patients diagnosed with reactivation tuberculosis exhibit a productive cough, chest pain, and fever, but about 20% may fail to show any signs and symptoms (Highsmith et al., 2019). Further, about 25% of all cases of reactivation tuberculosis are characterized by hemoptysis due to cavitation and necrosis. Therefore, the PPD test is slightly inaccurate when diagnosing reactivation tuberculosis. The reliable tests include sputum culture, gastric aspirates, or bronchoscopy specimens. Finally, EBPT signs and symptoms depend on the organ affected.
Treatment Methods
Tuberculosis is a significant global health and scholars have made significant efforts to eradicate it from humanity’s existence. This illness is commonly treated by administering more than one antimicrobial agent to prevent drug resistance for at least six months and nine months for HIV-infected patients (Highsmith et al., 2019; Prasanna & Niranjan, 2019). The common first-line drugs used are isoniazid, rifampin, ethambutol, and pyrazinamide. The second-line therapeutic agents — fluoroquinolones, streptomycin, capreomycin, amikacin, ethionamide, cycloserine, para-aminosalicylic acid, linezolid, and bedquiline — are administered if the bacteria are resistant to the first-line medications (Highsmith et al., 2019; Prasanna & Niranjan, 2019). However, these medications have less potency than first-line medicines and are difficult to administer due to severe, frequent side effects.
Laboratory technologists must conduct susceptibility testing before these drugs are administered to patients or the regimens are changed. In the first two months, four medications — isoniazid, rifampin, pyrazinamide, and ethambutol — are prescribed, which provides adequate protection for pulmonary, EPTB, and primary tuberculosis (Farver & Jagirdar, 2018; Highsmith et al., 2019; Prasanna & Niranjan, 2019). The duration of treatment depends on the sputum results, cavitation as evidenced in chest x-rays, and susceptibility of the bacteria.
References
Bandaru, R., Sahoo, D., Naik, R., Kesharwani, P., & Dandela, R. (2020). Pathogenesis, biology, and immunology of tuberculosis. In P. Kesharwani (Ed.), Nanotechnology-based approaches for tuberculosis treatment (pp. 1–25). Academic Press.
Farver, C. F., & Jagirdar, J. (2018). Mycobacterial diseases. In D. S. Zander & C. F. Farver (Eds.), pulmonary pathology (2nd ed., 201–216). Elsevier.
Highsmith, H. Y., Starke, J. R., & Mandalakas, A. M. (2019). Tuberculosis. In R. W. Wilmott et al (Eds.), Kendig’s disorders of the respiratory tract in children (9th ed., pp. 475–497.e5). Elsevier.
Lehman, D. (2020). Mycobacterium tuberculosis and nontuberculous Mycobacteria. In C. R. Mahon, & D. C. Lehman (Eds.), Textbook of diagnostic microbiology (6th ed., pp. 2-21). Elsevier Saunders.
Prasanna, A., & Niranjan, V. (2019). Classification of Mycobacterium tuberculosis DR, MDR, XDR isolates and identification of signature mutation pattern of drug resistance. Bioinformation, 15(4), 261–268.