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Axelsson-Robertson R Magalhaes I Parida SK Zumla A Maeurer M 《The Journal of infectious diseases》2012,205(Z2):S301-S315
Aerosols containing Mycobacterium tuberculosis (MTB) generated from the cough of patients with active pulmonary tuberculosis are the source of MTB infection. About 70% of individuals exposed to infected aerosols do not get infected, depending on the intensity and duration of MTB exposure. Only 40% of the rest of the individuals (about 10% of those originally exposed) develop primary tuberculosis, whereas the remaining 60% contain the infection with generation of a robust immune response leading to latent tuberculosis, which is regarded as a spectrum rather than a single entity. The mechanisms involved in this natural protection are not yet well understood. There is an increasing need to integrate all disparate observations into a coherent systems biology approach for a comprehensive understanding: we need to decipher the nature of success and failure in MTB infection in humans. New advances in cellular immunology will aid in achieving that goal. We review here the nature of MTB peptide generation, antigen presentation, and detection of major histocompatibility complex class I and II-presented T-cell epitopes. Cross-sectional thinking from lessons learned in the context of the major efforts to develop vaccines will help to dissect biologically relevant mechanisms that need to be translated into the clinical context of MTB infection with the aim to (1) better understand clinically relevant T-cell responses in individuals protected from tuberculosis disease and develop markers of immune protection and vaccine take, (2) characterize the nature of the immune response in individuals who are not able to contain MTB infection, and ultimately (3) characterize markers to gauge response to therapy. 相似文献
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Phillips PP Gillespie SH Boeree M Heinrich N Aarnoutse R McHugh T Pletschette M Lienhardt C Hafner R Mgone C Zumla A Nunn AJ Hoelscher M 《The Journal of infectious diseases》2012,205(Z2):S250-S257
A growing number of new drugs for the treatment of tuberculosis are in clinical development. Confirmatory phase 3 trials are expensive and time-consuming and the question of whether one particular drug combination can be used to treat tuberculosis is less important from a public health perspective than the question of which are the shortest, simplest, most effective, and safest regimens. While preclinical and phase 1 studies provide some guidance in the selection of combinations for clinical evaluation, a large number of combinations will require phase 2 testing to ensure that only the best regimens advance to phase 3. The multi-arm multi-stage trial design is an example of a treatment selection-adaptive design where multiple experimental arms are each simultaneously compared with a common control and interim analyses allow for poor performing arms to be dropped early. Such designs, if designed and implemented correctly, require fewer patients, can be completed in a shorter time frame, and answer more relevant questions without any loss in statistical validity or scientific integrity. There are, however, practical issues that must be considered in applying this in tuberculosis treatment trials. More innovative trials designs should be considered to speed drug and regimen development for the treatment of tuberculosis. 相似文献
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Traditionally, intravenous immunoglobulin (IVIg) has been used as replacement therapy for patients with primary or secondary immunoglobulin deficiencies. Increasingly, IVIg is being used (in doses higher than for replacement therapy) in certain bacterial or viral infectious diseases. A variety of modes of action have been attributed to the beneficial effects of IVIg, including its interaction with T-cell function, antigen-presenting cell maturation/presentation, combined with a general "tune down" effect on inflammatory reactions. More often, IVIg is being evaluated in clinical trials for the treatment of refractory and difficult-to-treat chronic infections. The evidence, molecular mechanisms, and rationale for the use of adjunct IVIg therapy in infectious diseases are reviewed, and its potential use in the adjunct treatment of difficult-to-treat drug-resistant tuberculosis discussed. 相似文献
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The term tropical diseases encompasses all diseases that occur principally in the tropics. This term covers all communicable and noncommunicable diseases, genetic disorders, and disease caused by nutritional deficiencies or environmental conditions (such as heat, humidity, and altitude) that are encountered in areas that lie between, and alongside, the Tropic of Cancer and Tropic of Capricorn belts. In tropical countries, apart from noncommunicable diseases, a severe burden of disease is caused by an array of different microorganisms, parasites, land and sea animals, and arthropods. 相似文献