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Wallstedt H.,Medicine och Lungmottagningen | Maeurer M.,Karolinska Institutet | Maeurer M.,Center for allogeneic stem cell transplantation
International Journal of Infectious Diseases | Year: 2015

We review the history of TB in Sweden beginning in 1800, when 25% of mortality in Sweden was associated with TB. The Royal Family was involved in establishing dedicated sanatoria in Sweden to offer better diagnostics and clinical care. TB has declined in Sweden steadily, with some recent increases due to local spread of TB and challenging international and national socio-economical structures. Improved research and clinical knowledge is needed to diagnose and manage drug-susceptible as well as drug-resistant TB. © 2015 The Authors.

Ahmed R.K.,Swedish Institute for Communicable Disease Control SMI | Rohava Z.,Republican Scientific and Practical Center for Pulmonology and Tuberculosis | Balaji K.N.,Indian Institute of Science | Hoffner S.E.,Swedish Institute for Communicable Disease Control SMI | And 6 more authors.
BMC Infectious Diseases | Year: 2012

Background: Tuberculosis (TB) is an enduring health problem worldwide and the emerging threat of multidrug resistant (MDR) TB and extensively drug resistant (XDR) TB is of particular concern. A better understanding of biomarkers associated with TB will aid to guide the development of better targets for TB diagnosis and for the development of improved TB vaccines.Methods: Recombinant proteins (n = 7) and peptide pools (n = 14) from M. tuberculosis (M.tb) antigens associated with M.tb pathogenicity, modification of cell lipids or cellular metabolism, were used to compare T cell immune responses defined by IFN-γ production using a whole blood assay (WBA) from i) patients with TB, ii) individuals recovered from TB and iii) individuals exposed to TB without evidence of clinical TB infection from Minsk, Belarus.Results: We identified differences in M.tb target peptide recognition between the test groups, i.e. a frequent recognition of antigens associated with lipid metabolism, e.g. cyclopropane fatty acyl phospholipid synthase. The pattern of peptide recognition was broader in blood from healthy individuals and those recovered from TB as compared to individuals suffering from pulmonary TB. Detection of biologically relevant M.tb targets was confirmed by staining for intracellular cytokines (IL-2, TNF-α and IFN-γ) in T cells from non-human primates (NHPs) after BCG vaccination.Conclusions: PBMCs from healthy individuals and those recovered from TB recognized a broader spectrum of M.tb antigens as compared to patients with TB. The nature of the pattern recognition of a broad panel of M.tb antigens will devise better strategies to identify improved diagnostics gauging previous exposure to M.tb; it may also guide the development of improved TB-vaccines. © 2012 Ahmed et al; licensee BioMed Central Ltd.

Zumla A.,University College London | Maeurer M.,Center for allogeneic stem cell transplantation
Nature Reviews Drug Discovery | Year: 2015

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies. © 2015 Macmillan Publishers Limited.

Madansein R.,University of KwaZulu - Natal | Parida S.,Karolinska Institutet | Padayatchi N.,MSC Durban Team | Padayatchi N.,University of KwaZulu - Natal | And 6 more authors.
International Journal of Infectious Diseases | Year: 2015

Surgery for drug-resistant tuberculosis has been shown to be safe and effective, with similar level of mortalities associated with surgical intervention observed with that for lung cancer. While surgery has been an option to treat TB in the pre-antibiotic era, it is now increasingly used to treat complications of pulmonary TB, particularly in patients with drug-resistant TB who do not respond to medical treatment. The two most frequent indications for lung resection in drug- resistant TB, are i) failed medical treatment with persistent sputum positivity or ii) patients who have had medical treatment and are sputum negative, but with persistent localized cavitary disease or bronchiectasis. Massive hemoptysis is a potentially life-threatening complication of TB. Lung resection is potentially curative in patients with massive hemoptysis and cavitary or bronchiectatic disease. Bronchial artery embolization in these patients has a high success rate but bears also the risk of recurrence. Lung resection can be safely undertaken in selected patients with HIV co-infection and pulmonary complications of TB. Ambulatory drainage is a novel, safe, affordable and effective method of draining a chronic TB associated empyema thoracis. We review here the current surgical treatment of the complications of pulmonary TB and discuss the experience from the Durban Cardiothoracic Surgery Unit for the surgical treatment of patients with complicated pulmonary TB. © 2015 The Authors.

Parida S.K.,Karolinska Institutet | Madansein R.,Inkosi Albert Luthuli Hospital | Madansein R.,University of KwaZulu - Natal | Singh N.,King DinuZulu Hospital | And 6 more authors.
International Journal of Infectious Diseases | Year: 2015

Cellular therapy now offer promise of potential adjunct therapeutic options for treatment of drug-resistant tuberculosis (TB). We review here the role of Mesenchymal stromal cells, (MSCs), as well as other immune effector cells in the therapy of infectious diseases with a focus on TB. MSCs represent a population of tissue-resident non-hematopoietic adult progenitor cells which home into injured tissues increase the proliferative potential of broncho-alveolar stem cells and restore lung epithelium. MSCs have been shown to be immune-modulatory and anti-inflammatory mediated via cell-cell contacts as well as soluble factors. We discuss the functional profile of MSCs and their potential use for adjunct cellular therapy of multi-drug resistant TB, with the aim of limiting tissue damage, and to convert unproductive inflammatory responses into effective anti-pathogen directed immune responses. Adjunct cellular therapy could potentially offer salvage therapy options for patients with drug-resistant TB, increase clinically relevant anti- M.tuberculosis directed immune responses and possibly shorten the duration of anti-TB therapy. © 2015 The Authors.

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