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                                                                                                            Introduction        “Stopping TB requires a government program that functions every day of the year, and that’s hard in certain parts of the world. And partly it’s because of who tuberculosis affects: it tends to affect the poor and disenfranchised most.” (Tom Frieden). Tuberculosis (TB) remains one of the deadliest diseases known to man. There are more cases of TB now than any other time in history, with over ten million cases of TB each year and deaths exceeding 2 million (Williams 2010 ).  One of every three people in the world are infected with TB (? of worlds population). TB is a deadly disease that is re-emerging because it has evolved resistance to the antibiotics used to treat it. Effective treatments and prevention strategies are needed to combat the global TB epidemic.    TB Pathogen    Tuberculosis is a major global health problem, causing more deaths than any other single infectious disease. Tuberculosis is an ancient disease dating back to the Neolithic in 5800 BCE and in the Egyptian mummies dating back to 2400 BCE (Boire 2013). However, humans are not the only victims of TB as other animals can be infected and the disease is thought to have originated in animals and was later passed to humans (Gagneux 2012). TB appears to have emerged in Africa and spread as humans migrated from Africa to other places.  TB expanded as humans populations increased and as humans traveled and colonized new continents along trade and exploration routes (Gagneux 2012). Furthermore, several animal-adapted members of MTBC exist, which affect a range of wild and domestic animal species. Some forms of TB affect cattle and can be transmitted to humans through the consumption of raw milk, but once a human is infected it is not easily transmitted from one human to another.  Once pastuerization technologies were used on milk this form of TB decreased considerably.TB Transmission    Although Tuberculosis is contagious, it is not easy to catch. Tuberculosis is transmitted from a tainted individual to a defenseless individual in airborne particles, called droplet nuclei. The nuclei is 1-5 microns in measurement. The irresistable droplet nuclei are microscopic water droplets with the bacteria that are discharged when people who have aspiratory or laryngeal tuberculosis hack, sniffle or potentially giggle. The droplet nuclei stay suspended noticeable all around for up to a few hours. Tuberculosis microscopic organisms, (Mycobacterium tuberculosis) are transmitted through the air, not by surface contact. This means, touching can’t spread the disease unless it is taken in. Transmission happens when a person breathes in droplet nuclei containing tuberculosis microorganisms. The droplet nuclei go by the mouth or nasal sections and move into the upper respiratory tract. From that point onward, they achieve the bronchi, the lungs and the alveoli (Jensen 2005). Individuals who are well on the way to transmit TB incorporate, people who will have certain highlights. The highlights incorporate, nearness of hack enduring three weeks or more, the individuals who neglect to cover their mouth and nose while hacking or wheezing and those on improper and inaqequate treatment of the disease Tuberculosis is less likely to spread to strangers than it is to people who you see often (co-workers, family, friends) (Jensen 2005)TB Symptoms    There are many symptoms of tuberculosis, ranging from mild to severe. On the off chance that you have the latent type of tuberculosis, you don’t show any symptoms and you can’t spread the sickness to others. In the event that you have the active type of tuberculosis, you do show symptoms and you can spread the disease to others. Which particular side effects you have rely upon whether your TB disease is in your lungs or in another part of your body (Pasipanodya 2015). Symptoms of active tuberculosis in the lungs start step by step and create over a time of weeks or months. You may have a couple gentle symptoms and not realize that you have the disease. Some regular symptoms include: Fever, chills, night sweats, weariness, shortcoming, loss of craving, unexplained weight reduction, shortness of breath and chest torment (Pasipanodya 2015). Indications of tuberculosis outside the lungs differ generally relying upon which territory of the body is contaminated. An example is, back agony can be a manifestation of TB in the spine, or your neck may get swollen when lymph nodes in the neck are infected.Drug Resistant TB    Drug resistant TB is caused by an organism that is resistant to at least isoniazid and rifampin, the two most powerful TB drugs. These drugs are used to treat all persons with TB disease. Patients should take all their TB medicine exactly as prescribed by the physician. Drug resistant TB can be prevented when health care providers quickly identify cases, follow the recommended treatment guidlines, observe the patients response to treatment, and ensure that medications are taken and completed as ordered. In the never ending battle between germ and host, natural selection usually weeds out any mutations that make bacteria less fit, but TB seems oddly immune to this kind of purifying selection. “As few as 1-10 bacterial cells are enough to initiate a new tuberculosis infection,” explains Sebastien Gagneux of the University of Basel, Switzerland, so each time the disease passes from one person to the next, the bacteria will experience an extreme population bottleneck (Levy 2012).  Mycobacterium tuberculosis may survive by turning the human immune response to its own advantage. Gagneux points out that the most contagious form of the disease, cavitary TB, is driven by immune responses that increases the lung damage and makes the infection more likely to spread to other people (Levy 2012)TB Treatment    Treatment to prevent active tuberculosis from developing in a person with a latent tuberculosis infection aims to kill walled up germs that are doing no damage right now but could break out years from now (Schiffman 2017). If you are going to be treated to prevent sickness, your doctor usually prescribes a daily dose of isoniazid, an inexpensive TB medicine. You will take isoniazid for up to a year, with periodic checkups to make sure you are taking it as prescribed and that it is not causing undesirable side effects. In some cases, intolerance or allergic response can mandate an alternative treatment that may go on for 2 years (Schiffman 2017). Treatment can also stop the spread of TB in large populations. The tuberculosis vaccine that is known as bacille Calmette Guerin may prevent the spread of TB and TB meningitis in children, but the vaccine does not necessarily protect against pulmonary tuberculosis. Health officials may recommend the vaccine in countries or communities where the rate of infection is greater than 1% per year. The BCG vaccine is not recommended for use in the United States because there is a very low risk of tuberculosis infection (Schiffman 2017).Antimicrobial Resistance in Tuberculosis    Multidrug-resistant tuberculosis (MDR-TB) is an example of Antimicrobial Resistance (AMR). It is a threat that appeared in the era of antimicrobial warfare because the TB bacterium’s unique characteristics give it vast potential for developing resistance to even the strongest antibiotics (Collins 2017). The use of poor quality TB drugs can result in the development of MDR-TB, a form of TB that is resistant to two of the most important first line drugs, and extensively drug resistant TB (XDR-TB), which is also resistant to some second line drugs (Collins 2017). In 2016, approximately 10.4 million new cases of TB, and about 600,000 cases of MDR-TB (including RR-TB) have emerged. MDR-TB took the lives of an estimated 240,000 people in 2016. When patients with MDR-TB are left untreated, they will transmit resistant forms of TB back into the community and can infect others. This will threaten the effective prevention and treatment of TB, making the disease more difficult and possibly impossible to treat (Collins 2017). Drugs to Combat TB    Multiple-drug therapy to treat tuberculosis means taking several different medicines at the same time. This is the first choice to treat the TB that is growing in your body (active TB disease) (Fitzgerald 2010). The American Thoracic Society, Centers for Disease Control and prevention, and the Infectious Diseases Society of America reccomend using one of several combinations of the first choice medicines to start treatment (Fitzgerald 2010). To treat the disease it’s required to take isoniazid, rifampin, ethambutol, and pyrazinamide for 2 months. Most of the medications are given as pills. The treatment is continued for at least 4 months with fewer medications. There are special treatment reccomendations for people with HIV and TB, people with drug-resistant TB, children with active TB, and pregnant women with active TB. Medicine combinations, such as Rifater, are usually used when there is a need for fewer numbers of pills. Combining antibiotics into a single pill makes it less likely that you will miss taking any of the doses. The drug, Streptomycin, is usually given to people who cannot take ethambutol (Fitzgerald 2010). Natural Selection Resistance To TB    Infections have long been thought to apply natural selection on humans. Infectious disease resistance is frequently invoked as a mechanism shaping human genetic diversity, but such hypotheses have rarely been quantitatively evaluated with direct measures of disease realted morality (Lipsitch 2002). Enhancement of genetically determined resistance to tuberculosis by natural selection has been proposed as a factor explaining the decline of tuberculosis in Europe and North America in the years of 1830-1950 and the apparently reduced susceptibility of Europeans and their descendants to tuberculosis infection and/or disease. Selection during the peak of the European TB epidemic could have substantially reduced the frequency of already rare alleles conferring increased susceptibility to PTB mortality, but only if the phenotypic effects of these alleles were very large (Lipsitch 2002). If resistant alleles were rare at the beginning of this period, 300 years would not have been long enough for such selection to increase their frequency to epidemiologically significant levels (Lipsitch 2002). Reductions in the frequency of rare susceptibility alleles could have played at most a small part in the decline of the epidemic in the century preceding 1950. Natural selection by PTB deaths during the European TB epidemic alone cannot account for the presently low level of TB disease observed among Europeans and their descendants just prior to the appearance of antibiotic treatment (Lipsitch 2002). Conclusion     Tuberculosis is a disease that you definitely don’t want. One third of the world’s population is infected with TB. Tuberculosis is less likely to spread to strangers than it is to the people that you see often. There are many symptoms of TB that range from mild to severe. Some patients that have the disease may be resistant to some of the drugs that they need to combat it, such as isoniazid and rifampin. Combating drug resistant TB requires a multistep approach, MDR-TB can be resistant to the strongest drugs (Antimicrobial Resistance). There are ways to treat the disease but, treating it will only minimize some of the symptoms. Natural selection played a big role in the decline of tuberculosis in Europe and North America from the 1800s to the 1900s.CitationsLipsitch, Marc. “Historical Intensity of Natural Selection for Resistance to Tuberculosis .” Ncbi, Aug. 2002.Fitzgerald. “Multiple-Drug Therapy for Tuberculosis (TB).” WebMD, 2010.Levy, Sharon. “Evolution of Tuberculosis: Genetic Analysis Offers New Insight on the Spread of an Ancient Disease | BioScience | Oxford Academic.” OUP Academic, Oxford University Press, 1 July 2012.The Editors of Encyclopædia Britannica. “Tuberculosis.” Encyclopædia Britannica, Encyclopædia Britannica, Inc., 3 Jan. 2018.Gagneux, Sebastien. “Host–Pathogen Coevolution in Human Tuberculosis.” Philosophical Transactions of the Royal Society B: Biological Sciences, The Royal Society, 19 Mar. 2012.Smith, Tasha, et al. “Molecular Biology of Drug Resistance in Mycobacterium Tuberculosis.”Current Topics in Microbiology and Immunology, U.S. National Library of Medicine, 2013.Ventola, C. Lee. “The Antibiotic Resistance Crisis: Part 1: Causes and Threats.” Pharmacy and Therapeutics, MediMedia USA, Inc., Apr. 2015.”Drug-Resistant Tuberculosis.” World Health Organization, World Health Organization.                        

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