Tuberculosis, while mostly eradicated in developed nations, is still a major problem in the developing world. This article details why this is the case, and what problems are being encountered while attempting diagnosis and treatment, specifically in latent and multi-drug resistant strains. Large emphasis is also placed on the problems faced by the numerous people in at-risk areas, such as sub-saharan Africa, who also are hosts to HIV. The article then outlines upcoming vaccinations and treatments that show potential. The conclusion then briefly outlines what would be necessary to implement preventative measures in the developing world.
Synopsis of Data
The first topic of discussion is the epidemiology of Tuberculosis as it relates to HIV and drug resistance. The incidence in Africa, for instance, increases while the rest of the world decreases. The authors attribute this to the greater incidence of HIV there than in the rest of the world. They further state that 10-30% of HIV patients are also Tuberculin skin Test positive, indicating a much higher risk factor for those afflicted with HIV.
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Multidrug-resistance is defined by Maartens as resistance to at least rifampicin and isoniazid. Estimates show that 4% of patients with tuberculosis are multidrug-resistant, but this rises to 10% in Eastern Europe. There is also an extremely drug resistant category (XDR), and is defined by Maartens as follows; resistant to rifampicin, isoniazid, any quinolone, and a second-line agent. A certain incidence is reported in which 24% of Multidrug-resistant cases were XDRs resulting in the death of 52 of 53 patients.
The authors then mention that Tuberculosis, due to modern mycobacterial research methods, is a good model for bacterial genomic studies. Through various comparisons to other strains, such as M bovis, the history of M tuberculosis as it relates to humans was studied using genomic deletions as phylogenetic markers. Noted here is that different strains of M tuberculosis adapted to different populations with the exception of W/Beijing, which is successful in many diverse populations and is more virulent than other strains.
A short description of the immune reaction to Tuberculosis follows, focusing on the various TLRs that act upon ligation. Emphasis is put on TLR1 and TLR2 which activate vitamin D when ligated, which indicates that the vitamin may have some role in tuberculosis prevention. Also mentioned is that phagocytosis is a powerful way of combating the bacteria. The various members which induce and regulate the immune system against tuberculosis are then discussed, specifically referencing a study wherein mutation of certain interferon and interleukin driven pathways led to severe mycobacterial infection. This indicates that there may be some genetic component of susceptibility, and the results of several genomic tests on mycobacterial virulence were then presented.
Most modern methods of tuberculosis diagnosis result in a low yield. Those that give a better yield and are more sensitive are generally prohibitively expensive. These problems persist, but better techniques for drug resistance identification and diagnosis of latent tuberculosis have been developed. Among those discussed are nucleotide amplification, the TST test, T-SPOT.TB test, QFG, and QFGIT tests. Nucleotide amplification tests are determined to have limited sensitivity and to be overly expensive. TST tests are highly non-specific and can register a positive under many circumstances, which brought about the much more specific enzyme-linked immunospot assays. The main method for detection of drug resistance mentioned is the line probe assay to determine resistance of rifampicin. Also mentioned is the importance of case definitions to clinically diagnose those tuberculosis patients also afflicted with HIV.
Strategies for treatment of tuberculosis include the directly observed treatment (DOT) method. This involves observing each dose of drugs over the course of treatment, which can be as long as six months. Greater adherence to the schedule was observed when patients were allowed to administer the drugs at home rather than at the clinic.
The various drugs used in treatment include rifampicin, which, in the author's opinion, is underused in African clinics. However, drugs are needed to treat drug resistant tuberculosis. These drugs are overly difficult and expensive to produce, however, so little progress has been made. One promising drug family is the fluoroquinolones. These may be easier to resist and could have toxic side effects though, so they have not been approved for widespread use. Other promising drugs include nitroimidazopyran and diarylquinolone. There has also been research into the efficacy of steroids and inhaled interferons in tuberculosis treatment. There are also several drugs used in treatment of latent tuberculosis in those patients with HIV. Rifampicin is used, as is pyrazinimide and isoniazid. These are best used in combination.
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The most prevalent vaccine for tuberculosis in use now is the BCG vaccine. Although it has several shortcomings, it is effective in preventing severe infections in children. It's biggest problem, according to the authors, is that it cannot prevent transmission of the disease. It is currently being used as a standard against which to test upcoming vaccines. Vaccine research is difficult, however, because of the numbers of people needed for the study, and the long time needed to study them given the extensive time it may take for the disease to manifest.
Further attention is then turned to the growing HIV-related tuberculosis epidemic in sub-saharan Africa. Certain preventative measures have been taken, but the most effective seem to be anti-retrovirals, and other such HIV-preventative techniques. The best methods for stopping the epidemic seem to be treating tuberculosis, but this is a very expensive and time-consuming process, so using all available means to treat the disease is not reasonable. The authors argue that resources should be directed toward the greatest curative effects.
Other complications of tuberculosis treatment in HIV patients include the side effects of drugs such as rifampicin. Rifampicin may lower the efficacy of anti-retroviral drugs while in the system with them. Replacement drugs, such as rifabutin, have been suggested, but developing areas, such as Africa, cannot afford them. Research is being done to determine the best time to begin anti-retroviral therapy in patients being treated for Tuberculosis.
Treatment and prevention of Tuberculosis is a very important topic, especially when related to the developing world. The main purpose of this article was to do just that. All preventative measures were evaluated with high regard to the cost and other resources needed to procure them. Tuberculosis itself was evaluated with other high-risk diseases in mind, primarily HIV. This article conveyed the problems of sub-saharan Africa and other developing areas in relation to tuberculosis well. The article leaves the reader wondering if other diseases in these areas beside HIV cause similar complications. The article doesn't tell much about the author's desire to enact a worldwide plan to stop tuberculosis. Several possible routes of research are suggested, but actual methods and politics are omitted, perhaps purposefully. Overall, the authors did a very good job of elucidating a dangerous phenomenon, in the dangers of HIV in relation to tuberculosis. Moreover, the article was very informative regarding newer research projects going into treatment and prevention of the disease.