Summary of "Tuberculosis" Article. For decades, tuberculosis has been a problem in the world, especially in low-income and middle-income countries. There has been a lot of research and development of drugs for tuberculosis treatment, but there are still serious limits in treating and preventing tuberculosis due to the susceptibility of HIV-infected people in several regions of the world. HIV infection raises the risk for developing tuberculosis, and also affects "resource-poor health system of sub-Saharan Africa," (Maartens), a specific region with a high HIV-infection rate. In the article, the authors discuss the relationship between HIV-infection and tuberculosis treatment from examining all the main issues of tuberculosis, from epidemiology of the diseases through the HIV-infection association, the host-pathogen interaction in macrophage to maintain the pathogen in the host cell, the general origin of M tuberculosis, disadvantages of different diagnosis and treatment methods, serious limitations of vaccinations, and how to control HIV-associated tuberculosis in all the regions of the world.
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The first effect of HIV-infection to tuberculosis is that the epidemiology of HIV-infection increases tuberculosis incidence in both developed and developing countries. There has been a higher annual incident of about 30% of tuberculosis patients associated with HIV-infection in South Africa. HIV-infection can not only reactivate latent tuberculosis, but can also increase transmission of tuberculosis from adults to children. Another significant HIV-infection effect is the increased percentage of drug-resistant (XDR) to 24%, which makes tuberculosis essentially untreatable.
The discovery of how host cells and pathogens of tuberculosis interact lead to the understanding of the relationship between M tuberculosis in humans and M bovis in animals. The conclusion was made that M tuberculosis and M bovis "share a same common ancestor"; therefore, M tuberculosis did not arise from M bovis as originally theorized. In the history of M tuberculosis, there are six lineages that adapt to specific populations. One of the examples mentioned in the article is the W/Beijing family of strains from the Asian lineage, which is at a higher risk of virulence and hyper-mutable.
In comparison of the mice defense and human defense systems against tuberculosis, although the receptors of the mycobacterial cell wall, called Toll-like receptors ( TLRs), take an important role in the immune system of tuberculosis, the role of TLRs in the human system is still unclear. In the immune system, Vitamin D also helps prevent tuberculosis by inducing "antimicrobial peptides such as cathelicidin LL-37". Mice and human have two common genes encoding immunity-related GTPases, which are IRGC and IRGM. IRGM is reported to help the host defend against mycobacteria and help T-cells regconize tuberculosis antigens. Another study in the 1990s of the mutation of interleukin-12 and interferon-y-driven type-1 cytokine showed evidence of causing mycobacterial infections.
While investigating tuberculosis in mice, two important studies of microarray screening of mutated mycobacteria were done by Sasseti and Rubin, and Stewart and colleagues. Sassetti and Rubin muted non-essential genes and confirmed that 194 genes of M tuberculosis are needed for growth in mice. Using a similar technique, Stewart and colleagues examined the ability of the "early immune evasion in slow-growing mycobacteria" through the effect of random mutation in BCG. Both studies concluded the importance of membrane-associated proteins and small-molecule transporters in bacterial replication. In the early state of infection, mycobacteria utilize carbohydrates, but in latency they use lipids as energy sources.
In order to find a new method of tuberculosis diagnosis, TST etc., Lalvani and colleagues studied ESAT-6-based and CFP-10-based enzyme-linked immunospot (EKISpot analysis).This analysis gives better "exposure to a point source of infection and less compromised than the TST by the presence of HIV infection." The test lead to T-SPOT.TB, QuantiFERON TB Gold, and QuantiFERON TB Gold for tuberculosis infection examining. The results of these two tests are still needed to investigate for more accurate results.
In the treatment of tuberculosis, one of the international suggested strategies is directly observed treatment short course (DOTS). There are five elements in DOTS: "political will, case detection, standardized observed therapy, effective drug supply, and monitoring and evaluation." Although DOTS combines all approaches such as "new diagnostics, new drugs, new vaccines, reduction etc.", the failure of this theory happens when patients discontinue treatment when their symptoms get better. Another treatment method is rifapentine, but increasing rigapentine raises HIV-infection; however, new antitubercular drugs cost a lot of money to investigate. PA-284 and diarylquinoline R207910 are new antimycobacterial drugs that promise a good method of treatment. Steroids bring advantages for tuberculosis treatment but it increases the HIV viral load for patients. Treatment of latent tuberculosis infection is still not clear in treating tuberculosis patients with and without HIV-infection due to the hepatotoxicity effects. HIV-infected patients are reported to have more severe hepatotoxicity when using rifaampicin and pyrainamide rather than using rifampicin, pyrazinamide and isoniazid. The non HIV-infected tuberculosis patients have the opposite effects when using these two combinations of antitubercular drugs.
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Vaccinations from BCG or STOP-TB can provide some protection for patients against tuberculosis to prevent tuberculosis in children and prevent the latent infection. However, there are two bottlenecks occurring in vaccine research. The question is how to make the effect of vaccines last for a long time and how to provide a protective immune response.
The article gives detailed research about HIV-associated tuberculosis. In general, HIV-infection causes disadvantages of diagnosis, prevention, treatment and vaccinations for tuberculosis. For each issue, the author gives specific information of studies that confirm the effect of HIV-associated tuberculosis. Through this article, a distinguished approach for non HIV-associated tuberculosis and HIV-associated tuberculosis is examined during research. This shows the need for more research on the different treatment methods for HIV-associated tuberculosis. Obviously, the traditional method of treating tuberculosis cannot be applied for HIV-associated tuberculosis because, as mentioned above, they have opposite effects of causing hepatotoxicity from antitubercular drugs. Another important message that the article conveys is the failure of DOTS method when patients fail to complete the program. Tuberculosis treatment requires a well connected health system, more accurate results from research for stopping and preventing tuberculosis, and also political will of the entire world in the war against tuberculosis. HIV-associated tuberculosis also needs more research for better control in regions of high risk of HIV-infected people.
Maartens. G, "Tuberculosis."Â Lancet. 370.9604 (2007):2037-34. Print.