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What are the goals of the Help Stop TB project?

The tuberculosis (TB) bacterium has an outer coat that protects it from treatments and a patient’s immune system. The Help Stop TB project is aimed at helping scientists to better understand that coat and its role in protecting the bacteria. This understanding can help us and other scientists to design better drugs against TB in the future.

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How are you going to meet those goals?

The outer protective coat of the TB bacteria contains a class of waxy or fatty molecules called mycolic acids. These are long, chain-like molecules of varying length and structure, and although they can be classified into three main groups, there are many variations within these groups that have not been modeled before.

By using World Community Grid to simulate the interactions of these molecules and their variations along with other molecules present in the coat, scientists will be able to understand for the first time how these variations affect molecule behavior. The simulation results will provide a realistic representation of the outer coat of the TB bacterium for the first time. The researchers will use these results to build a database of mycolic acid molecules that occur in the outer coat of the TB bacteria, allowing scientists to better understand how this outer coat protects the bacteria from drugs and the host immune system.

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What would be the long-term anticipated outcomes as a result of this research?

The results will provide a detailed understanding of the conformational behavior of mycolic acids, which can shed light into their biological role and how it is linked to their folding pattern. With these details, we will have a greater understanding of how mycolic acids help the TB bacterium to survive and spread.

Additionally, we will be able to create a database of structures that will be used to build a detailed model of the bacterium’s outer layer. This model will be used to investigate the bacterium's biological properties further, and to assess how this knowledge can aid in TB drug development.

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What is tuberculosis? How is it transmitted?

Tuberculosis is a disease caused by Mycobacterium tuberculosis (M. tb). The disease mostly affects the lungs, but if left untreated, can also spread to other organs and ultimately lead to death. TB is transmitted by small, airborne droplets resulting from coughing or sneezing from an infected person.

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Why is TB still a major global health problem?

One factor in the increase of TB infection is related to an increase in HIV infection. People with HIV/AIDS have a weakened immune system and are therefore more susceptible to TB. Once healthy people come into contact with the TB bacteria, the bacteria can usually be fought off effectively by their immune system without developing TB. However, a person with HIV is about 30 times more likely to develop TB disease, due to their weakened immune system. It is more difficult to detect and treat TB in an HIV-infected individual, and therefore those co-infected with TB and HIV often remain reservoirs of TB for extended times, with the potential of infecting more people.

Another factor in the increased TB infection is the TB bacteria becoming increasingly resistant to TB drugs. As drug resistance has increased, it has become more difficult to treat TB successfully, requiring much longer treatment times with combinations of drugs. Often, patients fail to continue treatments to the full term which can take up to two years. When treatment stops part-way, the bacteria evolve resistance to the drugs because it lets the bacteria that survived the initial portion of treatment live and infect others. This also results in people carrying TB for a longer time, potentially infecting more people with drug resistant strains of TB that are more difficult to treat. The World Health Organization recently ranked tuberculosis as nearly tied with HIV as the deadliest infectious disease in the world, mostly due to TB building its resistance to drugs.

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Is TB a serious problem compared to other diseases?

HIV, TB and malaria represent three major infectious diseases. TB is second only to HIV and the combination of HIV and TB is particularly serious since one infection promotes the other. TB and HIV each accounted for about 1.1 to 1.2 million deaths in 2014. Malaria accounted for over 500,000 deaths in 2013.

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Who does TB affect?

Most people who come into contact with TB do not become ill with the disease, but those who are malnourished or have weakened immune systems, such as HIV patients, are more susceptible to developing the disease once they have been exposed to the bacteria. In addition, poor living conditions and overcrowded places are the ideal conditions for TB to spread through coughing or sneezing of infected individuals.

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How can I help stop TB?

You can help stop TB by joining World Community Grid and donating your computer’s spare computing time to this project.

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What are the broader social and economic impacts of TB?

It is quite common for TB patients to suffer from discrimination. Fear of infection is the most common cause of TB stigma. TB stigma has serious socioeconomic consequences and it is thought to increase diagnostic delay and treatment noncompliance. The disease is also associated with factors that can themselves create stigma, such as poverty and HIV. TB patients who are discriminated against may be isolated socially, especially in small communities. TB also has a serious economic impact, especially in developing countries. The growing cost of TB medical care is a constant drain on health systems, rendering developing countries unable to provide proper medical care for their patients.

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