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Amber Kunkel, Forrest W Crawford, James Shepherd, Ted Cohen
OBJECTIVE: Extending the duration of isoniazid preventive therapy (IPT) among people living with HIV (PLHIV) may improve its effectiveness at both individual and population levels, but could also increase selective pressure in favor of isoniazid-resistant tuberculosis (TB) strains. The objective of this study was to determine the relative importance of these two effects. METHODS: Transmission dynamic model. DESIGN: We created a mathematical model of TB transmission incorporating HIV incidence and treatment, mixed strain latent TB infections, and four different phenotypes of TB drug resistance (pan-susceptible, isoniazid monoresistant, rifampicin monoresistant, and multidrug resistant)...
November 13, 2016: AIDS
Rein M G J Houben, Peter J Dodd
BACKGROUND: The existing estimate of the global burden of latent TB infection (LTBI) as "one-third" of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI. METHODS AND FINDINGS: We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014...
October 2016: PLoS Medicine
Nouha Souayed, Malek Chennoufi, Nadia Ben Frej, Amel Chaabane, Mossadok Ben-Attia, Karim Aouam, Alain Reinberg, Naceur A Boughattas
INTRODUCTION: This study is designed to investigate whether the pharmacokinetics of the antituberculous agent isoniazid (INH) varied according to the circadian dosing-time. METHODS: A total of 168 male mice aged 10 weeks and synchronized for 3 weeks to 12h light and 12h dark were used. A single INH (100mg/kg) dose was administered by intraperitonal (i.p.) route at either of the four different circadian stages (1, 7, 13 and 19h after light onset, HALO). At each circadian stage, blood samples were withdrawn at 0, 0...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Z Koné, G Coulibaly, A T J Daix, A S Bakayoko, K Samaké, D P Kouassi, K M S Domoua
INTRODUCTION: The National tuberculosis program (NTP) in Ivory Coast recommends that children under 5 years living in a family environment with contagious tuberculosis patients, should receive Prophylactic treatment with INH (PTI), whatever the result of the tuberculin skin test (positive or negative) and their BCG status (vaccinated or not), at a dose of 5mg/kg/day for 6 months. We conducted this study to check the implementation of this recommendation in three support services of tuberculosis in Abidjan, the economic capital...
October 21, 2016: Revue de Pneumologie Clinique
A L Lopez, J G Aldaba, C G Ama, P G Sylim, X D Geraldino, J N Sarol, A M Salonga
SETTING: Estimates of the tuberculosis (TB) burden in the Philippines are largely dependent on prevalence surveys. OBJECTIVE: To conduct a prospective community-based survey to generate epidemiological data on TB among patients seeking care in public health centres in a rural municipality in the Philippines. DESIGN: Prospective surveillance and follow-up of presumptive TB cases from May 2013 to July 2015. RESULTS: Of 1622 participants with presumptive TB, 468 (28...
November 2016: International Journal of Tuberculosis and Lung Disease
A J Garcia-Prats, L du Plessis, H R Draper, A Burger, J A Seddon, K Zimri, A C Hesseling, H S Schaaf
SETTING: Isoniazid-resistant rifampicin-susceptible (H(R)R(S)) tuberculosis (TB) is the most prevalent form of drug-resistant TB globally, and may be a risk factor for poor outcomes, but has been poorly described in children. OBJECTIVE: To characterise the clinical presentation, treatment, and clinical and microbiological outcomes among children with culture-confirmed H(R)R(S) TB. DESIGN: Retrospective hospital-based cohort study. RESULTS: Of the 72 children included in the study, the median age was 50...
November 2016: International Journal of Tuberculosis and Lung Disease
A T Cruz, A L Hersh, J R Starke, S E Beekmann, P M Polgreen, R Banerjee
OBJECTIVE: To evaluate the extent to which advancements in the diagnosis and treatment of latent tuberculous infection (LTBI) have been integrated into practice by pediatric infectious disease (PID) specialists. DESIGN: We conducted an online survey of the Infectious Diseases Society of America's Emerging Infections Network (EIN) membership. RESULTS: Of the 323 members, 197 (61%) responded: 7% cared for ⩾5 children with TB disease and 34% for ⩾5 children with LTBI annually...
November 2016: International Journal of Tuberculosis and Lung Disease
Tiffany Elizabeth Cho, Jack Uetrecht
Little is known with certainty about the mechanisms of idiosyncratic drug reactions (IDRs); however, there is substantive evidence that reactive metabolites are involved in most, but not all, IDRs. In addition, evidence also suggests that most IDRs are immune mediated. That raises the question of how reactive metabolites induce an immune response that can lead to an IDR. The dominant hypotheses are the hapten and danger hypotheses. These are complementary hypotheses: a reactive metabolite can act as a hapten to produce neoantigens, and it can also cause cell damage leading to the release of danger-associated molecular pattern molecules that activate antigen presenting cells...
October 24, 2016: Chemical Research in Toxicology
Bharathkumar Inturi, Gurubasavaraj V Pujar, Madhusudhan N Purohit
Mycobacterium tuberculosis enoyl-ACP reductase (InhA) has been validated as a promising target for antitubercular agents. Isoniazid (INH), the most prescribed drug to treat tuberculosis (TB), inhibits a NADH-dependent InhA that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. It is a pro-drug that needs activation to form the inhibitory INH-NAD adduct by KatG coding for catalase-peroxidase. The INH resistance of M. tuberculosis is caused by mutations in KatG, which may lead to multidrug-resistant TB (MDR-TB)...
October 24, 2016: Archiv der Pharmazie
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
K V Shur, M V Zaychikova, N E Mikheecheva, K M Klimina, O B Bekker, S N Zhdanova, O B Ogarkov, V N Danilenko
We report a draft genome sequence of Mycobacterium tuberculosis strain B9741 belonging to Beijing B0/W lineage isolated from a HIV patient from Siberia, Russia. This clinical isolate showed MDR phenotype and resistance to isoniazid, rifampin, streptomycin and pyrazinamide. We analyzed SNPs associated with virulence and resistance. The draft genome sequence and annotation have been deposited at GenBank under the accession NZ_LVJJ00000000.
December 2016: Genomics Data
Petar Duvnjak, Mario Laguna
The use of live attenuated intravesicular Bacillus Calmette-Guerin (BCG) therapy is a generally accepted safe and effective method for the treatment of superficial transitional cell carcinoma (TCC) of the bladder. Although rare, < 5% of patient's treated with intravesicular BCG therapy may develop potentially serious complications, including localized infections to the genitourinary tract, mycotic aneurysms and osteomyelitis. We present here a case of a 63-year-old male who developed left coronary and multiple peripheral M...
August 2016: Journal of Radiology Case Reports
Jyothi Padiadpu, Priyanka Baloni, Kushi Anand, MohamedHusen Munshi, Chandrani Thakur, Abhilash Mohan, Amit Singh, Nagasuma Chandra
The global mechanisms and associated molecular alterations that occur in drug-resistant mycobacteria are poorly understood. To address this, we obtain genomics data and then construct a genome-scale response network in isoniazid-resistant Mycobacterium smegmatis and apply a network-mining algorithm. Through this, we decipher global alterations in an unbiased manner and identify emergent vulnerabilities in resistant bacilli, of which redox response was prominent. Using phenotypic profiling, we find that resistant bacilli exhibit collateral sensitivity to several compounds that block antioxidant responses...
September 9, 2016: ACS Infectious Diseases
Aliya Yamin, Ethan Bornstein, Rachel Hensel, Omar Mohamed, Russell R Kempker
Background.  Despite the low and decreasing prevalence of tuberculosis (TB) in the United States, there remain certain high-risk groups with high incidence rates. The targeted screening and treatment of latent TB infection (LTBI) among these high-risk groups are needed to achieve TB elimination; however, by most accounts, LTBI treatment completion rates remain low. Methods.  We retrospectively studied all patients accepting treatment for LTBI at the Fulton County Health Department TB clinic over 2 years...
October 2016: Open Forum Infectious Diseases
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
Glennah Kerubo, Evans Amukoye, Stefan Niemann, Samuel Kariuki
BACKGROUND: Anti-tuberculosis drug resistance is an emerging health problem in Kenya and especially in slums. Slum environments create a conducive environment for the spread of tuberculosis (TB) due to high population density and lack of basic amenities such as decent housing, access to clean water, lack of drainage and basic sanitation. Furthermore, ineffective health services in crowded and poorer populations, poor patient compliance, a large pool of untreated cases, delayed diagnosis and inappropriate treatment regimens are likely to favour selection and spread of drug resistant Mycobacterium tuberculosis (Mtb) strains in such settings, however, precise data on this problem are only sparsely available...
October 19, 2016: BMC Infectious Diseases
Rahul Pal, Saif Hameed, Sharda Sharma, Zeeshan Fatima
Novel strategies to combat the ever increasing burden of drug resistance in Mycobacterium tuberculosis (MTB) causing tuberculosis (TB) remains a global concern. The ability of MTB to sense and adapt to restricted iron conditions in the hostile environment is essential for their survival and confers the basis of their success as dreadful pathogen. The striking and clinically relevant virulence trait of MTB is its ability to form biofilms and adhere to the host cells. The present study elucidated the effect of iron deprivation on biofilm formation and cell adherence of Mycobacterium smegmatis, a non-pathogenic surrogate of MTB...
October 15, 2016: Brazilian Journal of Infectious Diseases
Yu Huang, Qingqing Wu, Shuiyang Xu, Jieming Zhong, Songhua Chen, Jinghang Xu, Liping Zhu, Haibo He, Xiaomeng Wang
With 25% of the global burden, China has the highest incidence of drug-resistant tuberculosis (TB) in the world. However, surveillance data on extensively drug-resistant TB (XDR-TB) from China are scant. To estimate the prevalence of XDR-TB in Zhejiang, Eastern China, 30 of 90 TB treatment centers in Zhejiang were recruited. Patients with suspected TB who reported to the clinics for diagnosis were requested to undergo a smear sputum test. Positive sputum samples were tested for drug susceptibility. Data on anti-TB drug resistance from 1999 to 2008 were also collected to assess drug resistance trends...
October 18, 2016: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Zully M Puyén, Joshi Acosta, George Obregon, Edson Pacheco, Hada Ramirez, Alberto Mendoza, Diana Marín, Anthony D Harries
Objective To determine the use and performance of a line probe assay (LPA) compared with conventional culture and drug sensitivity testing (CDST) in patients registered with tuberculosis (TB) under routine program conditions in Peru in 2011-2013. Methods This was a descriptive, operational research, cross-sectional study of sputum specimens from patients with smear-positive pulmonary TB and mycobacterial cultures from patients with smear-negative or positive TB. Drug resistance to rifampicin and/or isoniazid detected by LPA was compared to CDST...
January 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
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
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