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Tuberculosis children

Anagha Loharikar, Laure Dumolard, Susan Chu, Terri Hyde, Tracey Goodman, Carsten Mantel
Since the global Expanded Program on Immunization (EPI) was launched in 1974, vaccination against six diseases (tuberculosis, polio, diphtheria, tetanus, pertussis, and measles) has prevented millions of deaths and disabilities (1). Significant advances have been made in the development and introduction of vaccines, and licensed vaccines are now available to prevent 25 diseases (2,3). Historically, new vaccines only became available in low-income and middle-income countries decades after being introduced in high-income countries...
October 21, 2016: MMWR. Morbidity and Mortality Weekly Report
Mary Norval, Anna K Coussens, Robert J Wilkinson, Liza Bornman, Robyn M Lucas, Caradee Y Wright
In this review, reports were retrieved in which vitamin D status, as assessed by serum 25-hydroxyvitamin D [25(OH)D] levels, was measured in South African population groups with varied skin colours and ethnicities. Healthy children and adults were generally vitamin D-sufficient [25(OH)D level >50 nmol/L] but the majority of those aged above 65 years were deficient. A major role for exposure to solar ultraviolet radiation (UVR) in determining 25(OH)D levels was apparent, with the dietary contribution being minor...
October 18, 2016: International Journal of Environmental Research and Public Health
Madhukar Pai, Mark P Nicol, Catharina C Boehme
Rapid and accurate diagnosis is critical for timely initiation of anti-tuberculosis (TB) treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and rollout of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development, and many tests have been reviewed by WHO for policy endorsement...
October 2016: Microbiology Spectrum
Zeynep Maraş Özdemir, Ayşegül Sağır Kahraman, Cemile Ayşe Görmeli, Reşit Sevimli, Nusret Akpolat
BACKGROUND: Langerhans cell histiocytosis (LCH), typically found in children, is a rare single or multisystem disorder with a wide range of clinical and radiological manifestations. Unusual presentations of LCH are occasionally encountered and it may be difficult to distinguish LCH from an infection or a benign or malignant tumor. RESULTS: A 35-year-old female presented with pain in her back and left buttock, malaise, and weight loss, with a duration of several months...
September 2016: Balkan Medical Journal
Keertan Dheda, Kwok Chiu Chang, Lorenzo Guglielmetti, Jennifer Furin, H Simon Schaaf, Dumitru Chesov, Aliasgar Esmail, Christoph Lange
Globally there is a burgeoning epidemic of drug mono-resistant tuberculosis (TB), multi-drug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Almost 20% of all TB strains worldwide are resistant to at least 1 major TB drug including isoniazid. In several parts of the world there is an increasing incidence of MDR-TB, and alarmingly almost a third of MDR-TB cases globally are resistant to either a fluoroquinolone or aminoglycocide. This trend cannot be ignored because DR-TB is associated with greater morbidity compared to drug-sensitive TB, it accounts for almost 25% of global TB mortality, is extremely costly to treat, consuming substantial portions of budgets allocated to national TB programmes in TB endemic countries, and is a major threat to healthcare workers who are already in short supply in resource-poor settings...
October 15, 2016: Clinical Microbiology and Infection
Isabelle Viel-Thériault, Roseline Thibeault, Francois D Boucher, Jean-Philippe Drolet
Paradoxical immune reconstitution inflammatory syndrome is a well-described entity even in immunocompetent children, principally in association with Mycobacterium tuberculosis infections. Central nervous system involvement is a potential life-threatening form, sometimes refractory to standard treatment. We report the case of an HIV-negative refugee teenager, who presented with brain tuberculomas and pseudoabscesses responsive only to thalidomide.
November 2016: Pediatric Infectious Disease Journal
Begoña Santiago-García, Daniel Blázquez-Gamero, Fernando Baquero-Artigao, Jesús Ruíz-Contreras, Jose M Bellón, Maria A Muñoz-Fernández, María J Mellado-Peña
BACKGROUND: Children are at higher risk of tuberculosis (TB) dissemination and extrapulmonary disease, contributing greatly to TB-associated morbidity and long-term sequelae. However, there are very few studies that assess the impact and clinical spectrum of pediatric extrapulmonary TB (EPTB) in low-prevalence regions. METHODS: Children <18 years of age diagnosed with TB in Madrid region (2005-2013) were reviewed. We compared the epidemiology, clinical characteristics and the performance of diagnostic tests in childhood extrapulmonary and pulmonary disease...
November 2016: Pediatric Infectious Disease Journal
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
Roberta Petrucci, Giulia Lombardi, Ilaria Corsini, Maria Letizia Bacchi Reggiani, Francesca Visciotti, Filippo Bernardi, Maria Paola Landini, Salvatore Cazzato, Paola Dal Monte
BACKGROUND: The diagnostic accuracy of Quantiferon-TB Gold In-Tube (QFT-IT) is uncertain in the pediatric population, while tuberculin skin test (TST) is still conventionally used despite its limitations. The aim of this study was to compare the performance of QFT-IT with TST in a large cohort of children screened for TB infection because of contact tracing, suspected TB, arrival from endemic country or immunosuppressive therapy. METHODS: A retrospective analysis was conducted on 517 children 0-14 years of age evaluated at the pediatric unit of the S...
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
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
Shashikant Srivastava, Devyani Deshpande, Jotam Pasipanodya, Eric Nuermberger, Soumya Swaminathan, Tawanda Gumbo
BACKGROUND:  When treated with the same antibiotic dose, children achieve different 0- to 24-hour area under the concentration-time curves (AUC0-24) because of maturation and between-child physiological variability on drug clearance. Children are also infected by Mycobacterium tuberculosis isolates with different antibiotic minimum inhibitory concentrations (MICs). Thus, each child will achieve different AUC0-24/MIC ratios when treated with the same dose. METHODS:  We used 10 000-subject Monte Carlo experiments to identify the oral doses of linezolid, moxifloxacin, and faropenem that would achieve optimal target exposures associated with optimal efficacy in children with disseminated tuberculosis...
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
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Stephen J Bush, Eric Nuermberger, Soumya Swaminathan, Tawanda Gumbo
BACKGROUND:  Infants and toddlers often present with disseminated and lymph node tuberculosis, in which Mycobacterium tuberculosis (Mtb) is predominantly intracellular. Linezolid, used to treat tuberculosis in adults, has not been formally studied in infants. Infants clear linezolid 5 times faster than adults and achieve lower 0- to 24-hour area under the concentration-time curves (AUC0-24). METHODS:  To mimic intracellular disease, we infected human-derived THP-1 macrophages with Mtb and inoculated hollow fiber systems...
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
Vijay G Mammen, Ziyaad Dangor, David P Moore, Alane Izu, Natalie Beylis, Shabir A Madhi
BACKGROUND: Children hospitalized with culture-confirmed pulmonary tuberculosis (PTB) frequently present with acute symptoms, possibly because of superimposed pneumococcal pneumonia. We undertook a time-series analysis to determine whether routine immunization of children with pneumococcal conjugate vaccine (PCV) was temporally associated with changes in the incidence of hospitalization for PTB in South African children. METHODS: PCV was introduced in the South African public immunization program in April 2009, with coverage for the third dose of PCV of 10%, 64% and 89% in 2009, 2010 and 2011, respectively...
October 12, 2016: Pediatric Infectious Disease Journal
Rutger Bennet, Margareta Eriksson
AIM: This study described the epidemiology and clinical features of childhood tuberculosis (TB) in Stockholm over a 45-year period, when there was a resurge of tuberculosis concomitant with increased immigration. METHODS: We describe 220 children up to the age of 16 years with active TB, seen at the Astrid Lindgren Children's Hospital from 1971-2015. The study period was divided into three 15-year periods. RESULTS: Cases increased from 10 children in 1971-1985 to 76 in 1986-2000 and 134 in 2001-2015, with overall incidence increasing from <1 to four per 100,000...
October 14, 2016: Acta Paediatrica
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