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tuberculosis AND treatment

Malcolm Spain, Joseph K-H Wong, Gayathri Nagalingam, James M Batten, Elinor Hortle, Stefan Oehlers, Xiao Fan Jiang, Hasini E Murage, Jack T Orford, Patrick Crisologo, James A Triccas, Peter J Rutledge, Matthew H Todd
We recently reported the discovery of non-toxic cyclam-derived compounds that are active against drug-resistant Mycobacterium tuberculosis. In this paper we report exploration of the structure-activity relationship for this class of compounds, identifying several simpler compounds with comparable activity. The most promising compound identified, possessing significantly improved water solubility, displayed high levels of bacterial clearance in an in vivo zebrafish embryo model, suggesting this compound series has promise for in vivo treatment of tuberculosis...
March 20, 2018: Journal of Medicinal Chemistry
Basant Kumar, Vijai Dutta Upadhyaya, Sandeep Kumar Rahul, Laxmi Kant Bharti, Ram Nawal Rao, Sheo Kumar
Background: To analyse our experience with acute presentations of abdominal tuberculosis (TB) in children for early diagnosis and management. Materials and Methods: From December 2010 to April 2016, available electronic and operation theatre (OT) records of 17 patients with confirmed diagnosis of abdominal TB were analysed retrospectively. Parameters reviewed were age, sex, presentations, diagnostic investigations, surgery/intervention performed, final outcome and follow-up...
July 2017: African Journal of Paediatric Surgery: AJPS
J M Carrascosa, E Del-Alcazar
Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy...
March 20, 2018: Expert Review of Clinical Immunology
Xue-Juan Bai, Hong-Min Li, You-Rong Yang, Jun-Xian Zhang, Yan Liang, Xue-Qiong Wu
Relapse of pulmonary tuberculosis (PTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis. Severe immunodeficiency or immune disorders may be the main reason for TB recurrence. This study aimed to quantify serum inflammatory cytokine and soluble adhesion molecule levels in Re-treated smear-positive PTB patients before and after re-anti-TB drug therapy. Serum samples were collected from 30 healthy controls and 215 Treated active PTB patients at baseline and 2, 4, and 6 months post-re-treatment...
March 16, 2018: Cytokine
David W Dowdy, Grant Theron, Jeffrey A Tornheim, Robin Warren, Emily A Kendall
A novel, shorter-course regimen for treating multidrug-resistant (MDR) tuberculosis was recently recommended by the World Health Organization. However, the most appropriate use of drug susceptibility testing (DST) to support this regimen is less clear. Implementing countries must therefore often choose between using a standardized regimen despite high levels of underlying drug resistance or require more stringent DST prior to treatment initiation. The former carries a high likelihood of exposing patients to de facto monotherapy with a critical drug class (fluoroquinolones), whereas the latter could exclude large groups of patients from their most effective treatment option...
October 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Setegn Eshetie, Mucheye Gizachew, Animut Alebel, Dick van Soolingen
BACKGROUND: Knowledge of tuberculosis (TB) treatment outcomes is substantially needed to assess the performance of national TB controls programs (NTPs). To date, the overall estimates of treatment outcomes have not been determined in Ethiopia. Therefore, this meta-analysis was undertaken to produce pooled estimates of TB treatment outcomes and to analyze the impact of prior anti-TB drug exposure and HIV co-infection. METHODS: Potentially relevant studies were retrieved from PubMed, EMBASE, and MEDLINE online databases...
2018: PloS One
Mitchell E Menezes, Praveen Bhoopathi, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B Fisher
Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24)...
2018: Advances in Cancer Research
Jana Amlerova, Ibrahim Bitar, Jaroslav Hrabak
Tuberculosis (TB) is considered one of the most serious infectious diseases worldwide. Effective control of tuberculosis infection involves multiple steps, such as reliable detection, treatment, an epidemiological control as a part of case management, and further surveillance and monitoring of TB spread in the human population. Due to the accelerating advances in molecular biology, especially in DNA sequencing, in the past decade, the application of these methods has become crucial for TB evolution studies, differentiation of Mycobacterium tuberculosis genotypes, and their distribution...
March 17, 2018: Folia Microbiologica
Helen Cox, Jennifer Hughes, John Black, Mark P Nicol
Treatment for drug-resistant tuberculosis is largely delivered through standardised, empirical combination regimens in low-resource, high-burden settings. However, individualised treatment, guided by detailed drug susceptibility testing, probably results in improved individual outcomes and is the standard of care in well-resourced settings. Driven by the urgent need to scale up treatment provision, new tuberculosis drugs, incorporated into standardised regimens, are being tested. Although standardised regimens are expected to improve access to treatment in high-burden settings, they are also likely to contribute to the emergence of resistance, even with good clinical management...
March 13, 2018: Lancet Infectious Diseases
María Ángeles Jiménez-Fuentes, Celia Milà Augé, Jordi Solsona Peiró, María Luiza de Souza-Galvão
No abstract text is available yet for this article.
March 13, 2018: Archivos de Bronconeumología
Andrew McDowell, Neeraj Raizada, Sunil D Khaparde, Raghuram Rao, Sanjay Sarin, Aakshi Kalra, Virender Singh Salhotra, Sreenivas Achuthan Nair, Catharina Boehme, Claudia M Denkinger
BACKGROUND: Diagnosing tuberculosis (TB) in children presents considerable challenges. Upfront testing on Xpert® MTB/RIF ('Xpert')-a rapid molecular assay with high sensitivity and specificity-for pediatric presumptive TB patients, as recommended by India's Revised National Tuberculosis Control Program (RNTCP), can pave the way for early TB diagnosis. As part of an ongoing project implemented by Foundation for Innovative New Diagnostics (FIND) dedicated to providing upfront free-of-cost (FOC) Xpert testing to children seeking care in the public and private sectors, a qualitative assessment was designed to understand how national guidelines on TB diagnosis and Xpert technology have been integrated into the pediatric TB care practices of different health providers...
2018: PloS One
Ana Trapero, Angela Pacitto, Vinayak Singh, Mohamad Sabbah, Anthony G Coyne, Valerie Mizrahi, Tom L Blundell, David B Ascher, Chris Abell
Tuberculosis (TB) remains a major cause of mortality worldwide, and improved treatments are needed to combat emergence of drug resistance. Inosine 5´-monophosphate dehydrogenase (IMPDH), a crucial enzyme required for de novo synthesis of guanine nucleotides, is an attractive TB drug target. Herein, we describe the identification of potent IMPDH inhibitors using fragment-based screening and structure-based design techniques. Screening of a fragment library for Mycobacterium thermoresistible (Mth) IMPDH(ΔCBS) inhibitors identified a low affinity phenylimidazole derivative...
March 16, 2018: Journal of Medicinal Chemistry
Noemia Teixeira de Siqueira-Filha, Maria de Fatima Militao de Albuquerque, Laura Cunha Rodrigues, Rosa Legood, Andreia Costa Santos
OBJECTIVE: The objective of this study was to measure the costs of people living with HIV (PLHIV) as well as active tuberculosis (TB/HIV), latent tuberculosis infection (LTBI/HIV) or without TB (HIV/AIDS). METHODS: We analysed the costs through the entire pathway of care during the prediagnosis and treatment periods from the Brazilian public health system perspective. We applied a combination of bottom-up and top-down approaches to capture and estimate direct medical and non-medical costs...
March 15, 2018: Sexually Transmitted Infections
André Grenho, Joana Arcângelo, Pedro Jordão, Catarina Gouveia
We present a 10-year-old boy with 2-month duration non-traumatic wrist pain and inflammatory signs. Due to elevated inflammatory markers on blood tests, with an increase in radiocarpal and intercarpal joints synovial fluid and no bony lesions, the patient was submitted to wrist arthrocentesis for the suspicion of septic arthritis. The patient did not improve on conventional treatment, however. An MRI showed synovitis around the carpus and a lytic lesion of the capitate bone due to osteomyelitis. A biopsy was able to identify the causative agent as Mycobacterium tuberculosis , and the patient was treated with antibiotics...
March 15, 2018: BMJ Case Reports
Seema Shetty, Shashikiran Umakanth, Bhawani Manandhar, Pankaj Bahadur Nepali
Leprosy and tuberculosis (TB) are endemic to India, however, their coinfection is not frequently encountered in clinical practice. Here, we report a 32-year-old female patient who presented with a history of high-grade intermittent fever, cough and painless skin lesions since a month, along with bilateral claw hand (on examination). The haematological profile was suggestive of anaemia of chronic disease, chest radiograph showed consolidation, sputum smears were positive for Mycobacterium tuberculosis, and skin slit smear confirmed leprosy...
March 15, 2018: BMJ Case Reports
Alain Bruno Tagne Nouemssi
Tuberculosis (TB) continues to represent an important public health challenge in the world and the USA, especially given its association with HIV infection and population migration. Cervical tuberculous lymphadenitis represents the most common extrapulmonary presentation of TB in the USA. Considerations for other causes of neck mass often contribute to delay in diagnosis. In this report, we describe the case of a 41-year-old man who presented with painful swelling of the neck and was diagnosed with tuberculous lymphadenitis, complicated by HIV therapy-associated immune reconstitution syndrome...
March 15, 2018: BMJ Case Reports
Cheon Tae Kim, Tae-Ok Kim, Hong-Joon Shin, Young Chun Ko, Yeong Hun Choe, Hak-Ryul Kim, Yong-Soo Kwon
Relatively little is known about the efficacy and safety of the programmatic use of bedaquiline and delamanid in multidrug-resistant tuberculosis (MDR-TB) treatment. This study evaluated 61 patients with MDR-TB treated with bedaquiline (n=39), delamanid (n=11), or both, either sequentially (n=10) or in co-administration (n=1), for more than 1 month, combined with a World Health Organization-recommended regimen. Of these, 49 (80.3%) were men and 12 (19.7%) were women. The median age was 53 years (interquartile range [IQR]=38...
March 15, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Yi-Lei Fan, Xiao-Hong Jin, Zhong-Ping Huang, Hai-Feng Yu, Zhi-Gang Zeng, Tao Gao, Lian-Shun Feng
Tuberculosis still remains one of the most common, communicable, and leading deadliest diseases known to mankind throughout the world. Drug-resistance in Mycobacterium tuberculosis which threatens to worsen the global tuberculosis epidemic has caused great concern in recent years. To overcome the resistance, the development of new drugs with novel mechanisms of actions is of great importance. Imidazole-containing derivatives endow with various biological properties, and some of them demonstrated excellent anti-tubercular activity...
March 7, 2018: European Journal of Medicinal Chemistry
Djalma A Alves da Silva, Marcos V da Silva, Cleyson C Oliveira Barros, Patrícia B Dias Alexandre, Rodolfo P Timóteo, Jonatas S Catarino, Helioswilton Sales-Campos, Juliana R Machado, Denise B R Rodrigues, Carlo J Oliveira, Virmondes Rodrigues
Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients...
2018: PloS One
Ahmed A Aljohaney
OBJECTIVES: To determine the mortality rates and predictors among patients hospitalized with active tuberculosis (TB) at King Abdulaziz University Hospital (KAUH) in Jeddah. METHODS: A retrospective study was performed on 291 active TB patients hospitalized in KAUH, Jeddah, Saudi Arabia from December 2011 to December 2016. Medical records were collected and evaluated using a dedicated data extraction sheet. The records included demographics, clinical, radiological, laboratory, and drug resistance data...
March 2018: Saudi Medical Journal
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