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Infections Caused by Mycobacterium tuberculosis in Recipients of Hematopoietic Stem Cell Transplantation

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      Abstract

      Mycobacterium tuberculosis ( M. tuberculosis) infections are uncommon in recipients of hematopoietic stem cell transplantation. These infections are 10–40 times commoner in recipients of stem cell transplantation than in the general population but they are 10 times less in stem cell transplantation recipients compared to solid organ transplant recipients. The incidence of M. tuberculosis infections in recipients of allogeneic stem cell transplantation ranges between <1 and 16% and varies considerably according to the type of transplant and the geographical location. Approximately 80% of M. tuberculosis infections in stem cell transplant recipients have been reported in patients receiving allografts. Several risk factors predispose to M. tuberculosis infections in recipients of hematopoietic stem cell transplantation and these are related to the underlying medical condition and its treatment, the pre-transplant conditioning therapies in addition to the transplant procedure and its own complications. These infections can develop as early as day 11 and as late as day 3337 post-transplant. The course may become rapidly progressive and the patient may develop life-threatening complications. The diagnosis of M. tuberculosis infections in stem cell transplant recipients is usually made on clinical grounds, cultures obtained from clinical specimens, tissues biopsies in addition to serology and molecular tests. Unfortunately, a definitive diagnosis of M. tuberculosis infections in these patients may occasionally be difficult to be established. However, M. tuberculosis infections in transplant recipients usually respond well to treatment with anti-tuberculosis agents provided the diagnosis is made early. A high index of suspicion should be maintained in recipients of stem cell transplantation living in endemic areas and presenting with compatible clinical and radiological manifestations. High mortality rates are associated with infections caused by multidrug-resistant strains, miliary or disseminated infections, and delayed initiation of therapy. In recipients of hematopoietic stem cell transplantation, isoniazid prophylaxis has specific indications and bacillus Calmette-Guerin vaccination is contraindicated as it may lead to disseminated infection. The finding that M. tuberculosis may maintain long-term intracellular viability in human bone marrow-derived mesenchymal stem cells complicates the development of effective vaccines and strategies to eliminate tuberculosis. However, the introduction of linezolid, cellular immunotherapy, and immunomodulation in addition to autologous mesenchymal stem cell transplantation will ultimately have a positive impact on the overall management of infections caused by M. tuberculosis.

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      Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective.

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        The challenge of new drug discovery for tuberculosis.

        Tuberculosis (TB) is more prevalent in the world today than at any other time in human history. Mycobacterium tuberculosis, the pathogen responsible for TB, uses diverse strategies to survive in a variety of host lesions and to evade immune surveillance. A key question is how robust are our approaches to discovering new TB drugs, and what measures could be taken to reduce the long and protracted clinical development of new drugs. The emergence of multi-drug-resistant strains of M. tuberculosis makes the discovery of new molecular scaffolds a priority, and the current situation even necessitates the re-engineering and repositioning of some old drug families to achieve effective control. Whatever the strategy used, success will depend largely on our proper understanding of the complex interactions between the pathogen and its human host. In this review, we discuss innovations in TB drug discovery and evolving strategies to bring newer agents more quickly to patients.
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          Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?

          In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB.
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            Author and article information

            Affiliations
            1Section of Adult Hematology and Oncology, Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University , Riyadh, Saudi Arabia
            2Central Regional Laboratory, Ministry of Health , Riyadh, Saudi Arabia
            Author notes

            Edited by: Partow Kebriaei, The University of Texas MD Anderson Cancer Center, USA

            Reviewed by: Partow Kebriaei, The University of Texas MD Anderson Cancer Center, USA; Amir Hamdi, The University of Texas MD Anderson Cancer Center, USA

            *Correspondence: Khalid Ahmed Al-Anazi, College of Medicine, King Khalid University Hospital, King Saud University, P.O. Box: 2925, Riyadh, Central Province, Saudi Arabia e-mail: kaa_alanazi@ 123456yahoo.com

            This article was submitted to Hematology Oncology, a section of the journal Frontiers in Oncology.

            Contributors
            URI : http://frontiersin.org/people/u/56474
            URI : http://frontiersin.org/people/u/117405
            Journal
            Front Oncol
            Front Oncol
            Front. Oncol.
            Frontiers in Oncology
            Frontiers Media S.A.
            2234-943X
            26 August 2014
            2014
            : 4
            4144006 10.3389/fonc.2014.00231
            Copyright © 2014 Al-Anazi, Al-Jasser and Alsaleh.

            This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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            Figures: 0, Tables: 5, Equations: 0, References: 99, Pages: 11, Words: 10380
            Categories
            Oncology
            Review Article

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