Tuberculosis

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The Evolution of Tuberculosis
Before the 20th century, there was little hope of survival for patients diagnosed with tuberculosis. The disease was considered impossible to fight and the only course of remedy was staying healthy by managing a healthy diet and getting plenty of rest (Goldberg et al., 2012). In 1921, advancements in scientific research led to the development of the first vaccine, known as Mycobacterium bovis bacillus Calmette-Guerin (BCG) (Lienhardt et al., 2012). The discovery of streptomycin (SM) along with paraaminosalicylic acid (PAS) led to a major breakthrough in tuberculosis control known as combination therapy (Goldberg et al., 2012). By combining the medicinal affects of both drugs, tuberculosis finally had an effective method of recovery. Isoniazid was added to the multi-therapy approach after it was discovered in 1951 and together the three drugs cured infected patients within 18-24 months (Lienhardt et al., 2012). Over the years this therapy was altered with the addition and deletion of various drugs and ultimately became the cardinal method of TB control (Goldberg et al., 2012). PAS was replaced with ethambutol in the 1960s, rifampicin was added in the 1970s, and streptomycin was substituted by pyrazinamide in the 1980s (Lienhardt et al., 2012). Today this serious infection is treated with a method known as DOTS- directly observed therapy short course (Weltman et al., 2012). “DOTS includes finding as many highly infected patients with TB as possible, initiating effective treatment, directly observing drug ingestion to ensure adherence, and standardized monitoring, evaluation, and reporting” (Weltman et al., 2012). The drugs utilized in tuberculosis control have brought researchers and doctors closer to diminishing the deaths caused by this endemic. Anti-tubercular drugs work together as a complex of medicine to treat this active and dangerous disease. Treatment requires a four-drug regime that is administered over a course of several months, while MDR strains, which are resistant to at least RIF and INH, are treated with up to six different drugs (Rattan et al., 1998). The regime includes two months of rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) or streptomycin (SM), followed by four months of only RIF and INH to eliminate persisting tubercle bacilli (Rattan et al., 1998). INH works by interfering with the mycolic acids comprising the Mtb cell wall by targeting InhA (Goldberg et al., 2012). Isoniazid (INH) restricts the biosynthesis of cell wall mycolic acids when the enzymes are inhibited, exposing it to oxygen radicals and other various environmental factors that ultimately kill the mycobacteria (Rattan et al., 1998). “RIF, along with INH, forms the backbone of short course chemotherapy” (Rattan et al., 1998). RIF interferes with the transcription process and inhibits RNA synthesis by binding to the beta subunit of bacterial DNA dependent RNA polymerase (Rattan et al., 1998). This drug is thought to target the mycobacterium RNA polymerase, killing the organism because of the disruption in the transcription process (Rattan et al., 1998). Another anti-tubercular drug, known as EMB, obstructs the formation of the cell wall due to increased permeability, leading to an increase in drug uptake and inhibition of arabinogalactan synthesis (Rattan et al., 1998). This bacteriostatic drug inhibits the mycobacterial arabinosyl transferases, prohibiting polymerization of arabinoglycans and halting mycobacterial growth (Rattan et al., 1998). Streptomycin, the very first anti-tubercular drug, works by targeting bacterial protein synthesis (Goldberg et al., 2012). This drug works by “disrupting the decoding of aminoacyl-tRNA and thus inhibits mRNA translation or causes inefficient translation” (Rattan et al., 1998). The medicinal effects of these drugs are altered in many cases in which mutations in the Mycobacterium tuberculosis genome express...
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