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tuberculosis AND treatment

Pooja Gopal, Michelle Yee, Jickky Sarathy, Jian Liang Low, Jansy P Sarathy, Firat Kaya, Véronique Dartois, Martin Gengenbacher, Thomas Dick
Pyrazinamide (PZA) is a critical component of first- and second-line treatments of tuberculosis (TB), yet its mechanism of action largely remains an enigma. We carried out a genetic screen to isolate Mycobacterium bovis BCG mutants resistant to pyrazinoic acid (POA), the bioactive derivative of PZA, followed by whole genome sequencing of 26 POA resistant strains. Rather than finding mutations in the proposed candidate targets fatty acid synthase I and ribosomal protein S1, we found resistance conferring mutations in two pathways: missense mutations in aspartate decarboxylase panD, involved in the synthesis of the essential acyl carrier coenzyme A (CoA), and frameshift mutations in the vitro nonessential polyketide synthase genes mas and ppsA-E, involved in the synthesis of the virulence factor phthiocerol dimycocerosate (PDIM)...
September 9, 2016: ACS Infectious Diseases
Fatemeh Nooshabadi, Hee-Jeong Yang, Yunfeng Cheng, Madeleine S Durkee, Hexin Xie, Jianghong Rao, Jeffrey D Cirillo, Kristen C Maitland
Tuberculosis is a pulmonary disease with an especially high mortality rate in immuno-compromised populations, specifically children and HIV positive individuals. The causative agent, Mycobacterium tuberculosis (Mtb), is a very slow growing and difficult organism to work with, making both diagnosis and development of effective treatments cumbersome. We utilize a fiber-optic fluorescence microendoscope integrated with a whole-body imaging system for in vivo Mtb detection. The system exploits an endogenous enzyme of Mtb (β-lactamase, or BlaC) using a BlaC-specific NIR fluorogenic substrate...
October 18, 2016: Journal of Biophotonics
P Mencarini, R Bellagamba, A Oliva, P Ghirga, M L Giancola, A Corpolongo, T Ascoli Bartoli, P De Nardo, A Baiocchini, F Del Nonno, P Narciso, E Nicastri
The diagnosis of sarcoidosis in a patient living with HIV infection is an uncommon event and a challenge for clinicians. Clinical manifestations are variable and fluctuating depending to adherence to ARV therapy and to the level of CD4 count. We analyze here one chronic case in which sarcoidosis appeared clinically two years after pulmonary tuberculosis. The course of the disease was influenced and prolonged by frequent interruptions of antiretroviral therapy. Moreover the diagnosis and the decision to treat have been delayed by the need of exclusion of other pathologies, principally tuberculosis reactivation/reinfection, other mycobacterial diseases, hematologic malignancies...
2016: Respiratory Medicine Case Reports
Prasan K Panda, Siddharth Jain, Rita Sood, Rajni Yadav, Naval K Vikram
Histoplasmosis is caused by a dimorphic fungus Histoplasma capsulatum in endemic areas, mainly America, Africa, and Asia. In India, it is being reported from most states; however, it is endemic along the Ganges belt. We report a case of an apparently immunocompetent male who presented with 3-month history of fever, cough, and weight loss with recent onset odynophagia and had hepatosplenomegaly and mucocutaneous lesions over the face. The differential diagnosis of leishmaniasis, tuberculosis, leprosy, fungal infection, lymphoproliferative malignancy, and other granulomatous disorders was considered, but he succumbed to his illness...
2016: Case Reports in Infectious Diseases
Simon Mutembo, Jane N Mutanga, Kebby Musokotwane, Lutangu Alisheke, Christopher C Whalen
BACKGROUND: Co-infection with Mycobacterium tuberculosis remains a leading cause of morbidity and mortality among HIV infected individuals especially in developing countries. Early initiation of cART in these patients when CD4+ T cell count is less than 200cells/mm(3) has reduced disease progression and mortality. However for patients with higher CD4+ T cell counts greater than 350cells/mm(3) evidence is conflicting. In this study we seek to evaluate the effectiveness of cART in reducing mortality among TB-HIV co-infected patients with CD4 + T cells above 350cells/mm(3) at the time of TB diagnosis...
October 17, 2016: BMC Infectious Diseases
Jiangan Xie, Christopher Codd, Kevin Mo, Yongqun He
M. bovis strain Bacillus Calmette-Guérin (BCG) has been the only licensed live attenuated vaccine against tuberculosis (TB) for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs) have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine...
2016: PloS One
Jesús E Ospina, Àngels Orcau, Joan-Pau Millet, Miriam Ros, Sonia Gil, Joan A Caylà
BACKGROUND: The increase in immigration in Barcelona between 2000 and 2008 forced a reorganization of the control of tuberculosis (TB). TB clinical units (TBCU) were created and community health workers (CHW) were gradually included. OBJECTIVE: To understand trends in the incidence of TB among immigrants, their main characteristics and treatment compliance during the period 1991-2013. DESIGN: We conducted a cross-sectional population-based study of cases detected among immigrants by the Tuberculosis Program in Barcelona, Spain...
2016: PloS One
Carmelo Guerrero-Laleona, Joan Calzada-Hernández, Matilde Bustillo-Alonso, Jorge Gil-Albarova, Marta Medrano-San Ildefonso, Estibaliz Iglesias-Jiménez, Antoni Noguera-Julian
Treatment with tumor necrosis factor-α inhibitors is a risk factor for tuberculosis. Despite previous treatment with isoniazid for latent tuberculosis, a 9-year-old girl with juvenile idiopathic arthritis developed disseminated tuberculosis after changing therapy with etanercept to adalimumab and after new contact with a smear-positive relative. Genotyping strain matches and susceptibility to isoniazid make reinfection more likely than reactivation in our patient.
October 3, 2016: Pediatric Infectious Disease Journal
Amanda K Debes, Robert H Gilman, Carolyne Onyango-Makumbi, Andrea Ruff, Richard Oberhelman, David W Dowdy
BACKGROUND: The objective of this analysis was to assess the cost-effectiveness of TB diagnosis using Microscopic Observation Drug Susceptibility (MODS), Xpert MTB/RIF (Xpert), and empiric treatment for all patients, in addition to current clinical diagnostic practices in children less than 5 years of age in a national tuberculosis (TB) referral hospital in Uganda. METHODS: A decision analysis was conducted from the healthcare perspective, with a primary outcome of incremental cost effectiveness expressed as cost per year of life gained (YLG)...
October 3, 2016: Pediatric Infectious Disease Journal
Ietza Bojorquez, Irais Salazar, Richard S Garfein, Paris Cerecer, Timothy C Rodwell
Directly observed therapy (DOT) is a cornerstone of tuberculosis (TB) control. DOT has been criticised as paternalistic, but it has also been argued that the interaction with healthcare workers (HWs) can be a source of support for patients. We explored the experience of patients in antituberculosis treatment, with the aim of understanding the balance between surveillance and support from the recipient's point of view. We interviewed 27 patients in Tijuana, Mexico, employing narrative analysis to understand how participants made sense of their illness and their experience of DOT...
October 16, 2016: Global Public Health
Marie-Odile Husson, Delphine Ley, Céline Portal, Madeleine Gottrand, Thomas Hueso, Jean-Luc Desseyn, Frédéric Gottrand
OBJECTIVES: Although n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) are used widely in the treatment of chronic inflammatory diseases, their effect in infectious disease requires a particular attention. METHODS: The present article discusses their anti-inflammatory and immune properties involved in the host defence and presents a systematic review of the effects of their oral administration on the prevention and outcome of experimental and clinical infections...
October 13, 2016: Journal of Infection
Na Yi, Bock-Gie Jung, Xisheng Wang, RamaKrishna Vankayalapati, Buka Samten
Abnormalities in hematopoiesis are common in tuberculosis patients and highly prevalent in AIDS patients with tuberculosis coinfection. To explore the potential role of the early secreted antigenic target of 6-kD (ESAT-6) of Mycobacterium tuberculosis (Mtb) in abnormal hematopoiesis in tuberculosis, we studied the effect of ESAT-6 on proliferation and differentiation of in vitro-expanded CD34(+) cells isolated from the peripheral blood of the healthy donors. ESAT-6 but not control protein antigen 85A (Ag85A) of Mtb inhibited the proliferation of CD34(+) cell derived peripheral blood stem/progenitor cells (PBSPC) in a dose dependent manner when determined by MTT-assay...
September 28, 2016: Tuberculosis
Devyani Deshpande, Shashikant Srivastava, Eric Nuermberger, Jotam G Pasipanodya, Soumya Swaminathan, Tawanda Gumbo
BACKGROUND:  The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model of pediatric intracellular tuberculosis. However, its kill rate was slower than the standard 3-drug regimen of isoniazid, rifampin, and pyrazinamide. We wanted to examine the effect of adding a third oral agent, faropenem, to this dual combination. METHODS:  We performed a series of studies in the hollow fiber system model of intracellular Mycobacterium tuberculosis, by mimicking pediatric pharmacokinetics of each antibiotic...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Devyani Deshpande, Shashikant Srivastava, Eric Nuermberger, Jotam G Pasipanodya, Soumya Swaminathan, Tawanda Gumbo
BACKGROUND:  No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need. METHODS:  We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Shashikant Srivastava, Devyani Deshpande, Jotam G Pasipanodya, Tania Thomas, Soumya Swaminathan, Eric Nuermberger, Tawanda Gumbo
Children with tuberculosis are treated with drug regimens copied from adults despite significant differences in antibiotic pharmacokinetics, pathology, and the microbial burden between childhood and adult tuberculosis. We sought to develop a new and effective oral treatment regimen specific to children of different ages. We investigated and validated the concept that target drug concentrations associated with therapy failure and death in children are different from those of adults. On that basis, we proposed a 4-step program to rapidly develop treatment regimens for children...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Soumya Swaminathan, Jotam G Pasipanodya, Geetha Ramachandran, A K Hemanth Kumar, Shashikant Srivastava, Devyani Deshpande, Eric Nuermberger, Tawanda Gumbo
BACKGROUND:  The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown. METHODS:  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
James A Seddon, Mamodikoe K Makhene
No abstract text is available yet for this article.
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Cynthia Wong, Ngan P Ha, Michal E Pawlowski, Edward A Graviss, Tomasz S Tkaczyk
While there have been research efforts to find faster and more efficient diagnostic techniques for tuberculosis (TB), it is equally important to monitor a patient's response to treatment over time, especially with the increasing prevalence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) TB. Between sputum smear microscopy, culture, and GeneXpert, only culture can verify viability of mycobacteria. However, it may take up to six weeks to grow Mycobacterium tuberculosis (Mtb), during which time the patient may have responded to treatment or the mycobacteria are still viable because the patient has MDR or XDR TB...
September 28, 2016: Tuberculosis
Robert W Aldridge, Dominik Zenner, Peter J White, Elizabeth J Williamson, Morris C Muzyamba, Poonam Dhavan, Davide Mosca, H Lucy Thomas, Maeve K Lalor, Ibrahim Abubakar, Andrew C Hayward
BACKGROUND: Tuberculosis elimination in countries with a low incidence of the disease necessitates multiple interventions, including innovations in migrant screening. We examined a cohort of migrants screened for tuberculosis before entry to England, Wales, and Northern Ireland and tracked the development of disease in this group after arrival. METHODS: As part of a pilot pre-entry screening programme for tuberculosis in 15 countries with a high incidence of the disease, the International Organization for Migration screened all applicants for UK visas aged 11 years or older who intended to stay for more than 6 months...
October 10, 2016: Lancet
Ajay Gupta, Siddhartha Baxi, Christopher Hoyne
INTRODUCTION: Comprehensive oncology services have recently been introduced in the Northern Territory (NT) enabling delivery of concurrent chemo-radiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LAHNSC). The purpose of this study is to assess feasibility, compliance and toxicity of CCRT in remote Australia. METHODS: Chart review was conducted for all patients >18 years, with biopsy-proven LAHNSC, receiving curative intent CCRT between January 2010 and September 2012...
July 1, 2016: Journal of Medical Radiation Sciences
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