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Modeling AND tuberculosis

Azizeh Jabbari, Carlos Castillo-Chavez, Fereshteh Nazari, Baojun Song, Hossein Kheiri
A two-strain tuberculosis (TB) transmission model incorporating antibiotic-generated TB resistant strains and long and variable waiting periods within the latently infected class is introduced. The mathematical analysis is carried out when the waiting periods are modeled via parametrically friendly gamma distributions, a reasonable alternative to the use of exponential distributed waiting periods or to integral equations involving ``arbitrary'' distributions. The model supports a globally-asymptotically stable disease-free equilibrium when the reproduction number is less than one and an endemic equilibriums, shown to be locally asymptotically stable, or l...
August 1, 2016: Mathematical Biosciences and Engineering: MBE
Pierre Santucci, Feriel Bouzid, Nabil Smichi, Isabelle Poncin, Laurent Kremer, Chantal De Chastellier, Michel Drancourt, Stéphane Canaan
Despite a slight decline since 2014, tuberculosis (TB) remains the major deadly infectious disease worldwide with about 1.5 million deaths each year and with about one-third of the population being latently infected with Mycobacterium tuberculosis, the etiologic agent of TB. During primo-infection, the recruitment of immune cells leads to the formation of highly organized granulomas. Among the different cells, one outstanding subpopulation is the foamy macrophage (FM), characterized by the abundance of triacylglycerol-rich lipid bodies (LB)...
2016: Frontiers in Cellular and Infection Microbiology
Namrita Lall, Vivek Kumar, Debra Meyer, Nomasomi Gasa, Chris Hamilton, Motlalepula Matsabisa, Carel Oosthuizen
ETHNOPHARMACOLOGICAL RELEVANCE: The Natal gwarri or Natal ebony (Euclea natalensis A.DC.) is a deciduous tree found widespread throughout southern Africa, especially in Kwazulu-Natal and the southern cost. It has been widely used by indigenous communities such as the Zulus, Tsongas and Vendas for symptoms related to tuberculosis (TB). The decoctions made from the plant parts are administered for chest diseases to treat complications such as chest pains, bronchitis, pleurisy and asthma...
October 20, 2016: Journal of Ethnopharmacology
Juan José Palacios, Yurena Navarro, Beatriz Romero, Ana Penedo, Ángela Menéndez González, M Dolores Pérez Hernández, Ana Fernández-Verdugo, Francisca Copano, Aurora Torreblanca, Emilio Bouza, Lucas Domínguez, Lucía de Juan, Darío García-de-Viedma
Human Mycobacterium bovis infections are considered to be due to reactivations, when involve elderly people, or to recent transmissions, when exposure is occupational. We determined the cause of M. bovis infections by genotyping M. bovis isolates in a population-based study integrating human and animal databases. Among the 1,586 tuberculosis (TB) cases in Asturias, Northern Spain (1,080,000 inhabitants), 1,567 corresponded to M. tuberculosis and 19 to M. bovis. The number of human isolates sharing genotype with cattle isolates was higher than expected (47%) for a setting with low prevalence of bovine TB and efficient control programs in cattle...
November 15, 2016: Veterinary Microbiology
Fernando Vargas-Romero, Guillermo Mendoza-Hernández, Francisco Suarez-Güemes, Rogelio Hernández-Pando, Mauricio Castañón-Arreola
Mycobacterium bovis is the causative agent of tuberculosis in farms, wildlife and causes sporadic disease in humans. Despite the high similitude in genome sequence between M. bovis strains, some strains like the wild boar 04-303 isolate show a highly virulent phenotype in animal models. Comparative studies will contribute to link protein expression with the virulence phenotype. In vitro, the 04-303 strain was more phagocytized by J774A.1 macrophages in comparison with 444 strain (a cow isolate with the same genotype) and BCG...
October 18, 2016: Microbial Pathogenesis
Stéphane Verguet, Solomon Tessema Memirie, Ole Frithjof Norheim
BACKGROUND: Out-of-pocket (OOP) medical expenses often lead to catastrophic expenditure and impoverishment in low- and middle-income countries. Yet, there has been no systematic examination of which specific diseases and conditions (e.g., tuberculosis, cardiovascular disease) drive medical impoverishment, defined as OOP direct medical costs pushing households into poverty. METHODS: We used a cost and epidemiological model to propose an assessment of the burden of medical impoverishment in Ethiopia, i...
October 21, 2016: BMC Medicine
Bini Mathew, Judith Varady Hobrath, Larry Ross, Michele C Connelly, Hava Lofton, Malini Rajagopalan, R Kiplin Guy, Robert C Reynolds
A variety of commercial analogs and a newer series of Sulindac derivatives were screened for inhibition of M. tuberculosis (Mtb) in vitro and specifically as inhibitors of the essential mycobacterial tubulin homolog, FtsZ. Due to the ease of preparing diverse analogs and a favorable in vivo pharmacokinetic and toxicity profile of a representative analog, the Sulindac scaffold may be useful for further development against Mtb with respect to in vitro bacterial growth inhibition and selective activity for Mtb FtsZ versus mammalian tubulin...
2016: PloS One
Y-M Chiu, C-H Tang, S-T Hung, Y-W Yang, C-H Fang, H-Y Lin
OBJECTIVES: Few studies on tumour necrosis factor (TNF) inhibitor-associated tuberculosis (TB) and hepatic events have been performed in regions where these risks are elevated. This study aimed to provide a direct comparison between adalimumab and etanercept in a high-risk population and to address the implications for physicians working with patients in such an environment. METHOD: Data collected from the National Health Insurance Research Database (NHIRD) in Taiwan between 2007 and 2011 were analysed retrospectively for incidences of eight adverse events associated with TNF-α inhibitors...
October 21, 2016: Scandinavian Journal of Rheumatology
S I Watson, E B Wroe, E L Dunbar, J Mukherjee, S B Squire, L Nazimera, L Dullie, R J Lilford
BACKGROUND: User fees have generally fallen out of favor across Africa, and they have been associated with reductions in access to healthcare. We examined the effects of the introduction and removal of user fees on outpatient attendances and new diagnoses of HIV, malaria, and tuberculosis in Neno District, Malawi where user fees were re-instated at three of 13 health centres in 2013 and subsequently removed at one of these in 2015. METHODS: We conducted two analyses...
October 20, 2016: BMC Health Services Research
Michel de Jesús Aceves-Sánchez, Mario Alberto Flores-Valdez
No abstract text is available yet for this article.
October 20, 2016: Human Vaccines & Immunotherapeutics
Santram Lodhi, Avijeet Jain, Alok Pal Jain, Rajesh Singh Pawar, Abhay Kumar Singhai
OBJECTIVE: Martynia annua L. (M. annua), (Martyniaccae) has been traditionally used in the treatment of epilepsy, sore throat and inflammatory disorders. The leaf paste is used topically on Tuberculosis of the lymphatic glands and wounds of domestic animals. Tephrosia purpurea (T. purpurea), (Fabaceae) has been used traditionally as a remedy for asthma, gonorrhea, rheumatism and ulcers. This study aimed to evaluate the potential wound healing effects of different fractions ofethanol extract of M...
September 2016: Avicenna Journal of Phytomedicine
Mark R Cronan, Rebecca W Beerman, Allison F Rosenberg, Joseph W Saelens, Matthew G Johnson, Stefan H Oehlers, Dana M Sisk, Kristen L Jurcic Smith, Neil A Medvitz, Sara E Miller, Le A Trinh, Scott E Fraser, John F Madden, Joanne Turner, Jason E Stout, Sunhee Lee, David M Tobin
Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flattened appearance. Although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. Here, using the zebrafish-Mycobacterium marinum model, we found that mycobacterial granuloma formation is accompanied by macrophage induction of canonical epithelial molecules and structures...
October 18, 2016: Immunity
Carl Nathan
In tuberculosis, some macrophages in granulomas assume an epitheloid appearance. Using the Mycobacterium marinum-zebrafish model, Cronan et al. (2016) now show that granuloma macrophages undergo reprograming events involving E-cadherin-dependent formation of epithelial-like cell-cell junctions. Interference with the function of E-cadherin in macrophages disorganized the granulomas and protected the fish, introducing new ideas and questions about macrophage function and granulomatous diseases.
October 18, 2016: Immunity
J M Greene, P Dash, S Roy, C McMurtrey, W Awad, J S Reed, K B Hammond, S Abdulhaqq, H L Wu, B J Burwitz, B F Roth, D W Morrow, J C Ford, G Xu, J Y Bae, H Crank, A W Legasse, T H Dang, H Y Greenaway, M Kurniawan, M C Gold, M J Harriff, D A Lewinsohn, B S Park, M K Axthelm, J J Stanton, S G Hansen, L J Picker, V Venturi, W Hildebrand, P G Thomas, D M Lewinsohn, E J Adams, J B Sacha
Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts...
October 19, 2016: Mucosal Immunology
Stevens M B Kisaka, Elizeus Rutebemberwa, Simon Kasasa, Francis Ocen, Joan Nankya-Mutyoba
BACKGROUND: Most tuberculosis (TB) case management guidelines emphasize microbiological cure as treatment goal without highlighting quality of life outcomes. This study assessed health-related quality of life (HRQoL) and related factors in the pre-treatment, intensive and continuation phases of anti-TB therapy among sputum smear positive pulmonary TB patients in Mbale region, Eastern Uganda. METHODS: In this cross-sectional study, questionnaires and 36-Item Short-Form Health Survey Version 2...
October 18, 2016: BMC Research Notes
Lucie D Cluver, F Mark Orkin, Franziska Meinck, Mark E Boyes, Alexa R Yakubovich, Lorraine Sherr
BACKGROUND: The first policy action outlined in the Sustainable Development Goals (SDGs) is the implementation of national social protection systems. This study assesses whether social protection provision can impact 17 indicators of five key health-related SDG goals amongst adolescents in South Africa. METHODS: We conducted a longitudinal survey of adolescents (10-18 years) between 2009 and 2012. Census areas were randomly selected in two urban and two rural health districts in two South African provinces, including all homes with a resident adolescent...
2016: PloS One
Tawanda Gumbo, Mamodikoe K Makhene, James A Seddon
There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development...
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:  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
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