Publications by authors named "Martin Dedicoat"

63 Publications

Host Immune-Metabolic Adaptations Upon Mycobacterial Infections and Associated Co-Morbidities.

Front Immunol 2021 23;12:747387. Epub 2021 Sep 23.

Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

Mycobacterial diseases are a major public health challenge. Their causative agents include, in order of impact, members of the complex (causing tuberculosis), (causing leprosy), and non-tuberculous mycobacterial pathogens including Macrophages are mycobacterial targets and they play an essential role in the host immune response to mycobacteria. This review aims to provide a comprehensive understanding of the immune-metabolic adaptations of the macrophage to mycobacterial infections. This metabolic rewiring involves changes in glycolysis and oxidative metabolism, as well as in the use of fatty acids and that of metals such as iron, zinc and copper. The macrophage metabolic adaptations result in changes in intracellular metabolites, which can post-translationally modify proteins including histones, with potential for shaping the epigenetic landscape. This review will also cover how critical tuberculosis co-morbidities such as smoking, diabetes and HIV infection shape host metabolic responses and impact disease outcome. Finally, we will explore how the immune-metabolic knowledge gained in the last decades can be harnessed towards the design of novel diagnostic and therapeutic tools, as well as vaccines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.747387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495197PMC
September 2021

Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease.

Tuberculosis (Edinb) 2021 Sep 14;131:102127. Epub 2021 Sep 14.

Vaccine Discovery Division, La Jolla Institute for Immunology, La Jolla, CA, USA; Department of Medicine, University of California San Diego, CA, USA. Electronic address:

Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tube.2021.102127DOI Listing
September 2021

Phase I Trial Evaluating the Safety and Immunogenicity of Candidate TB Vaccine MVA85A, Delivered by Aerosol to Healthy -Infected Adults.

Vaccines (Basel) 2021 Apr 16;9(4). Epub 2021 Apr 16.

The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.

The immunogenicity of the candidate tuberculosis (TB) vaccine MVA85A may be enhanced by aerosol delivery. Intradermal administration was shown to be safe in adults with latent TB infection (LTBI), but data are lacking for aerosol-delivered candidate TB vaccines in this population. We carried out a Phase I trial to evaluate the safety and immunogenicity of MVA85A delivered by aerosol in UK adults with LTBI (NCT02532036). Two volunteers were recruited, and the vaccine was well-tolerated with no safety concerns. Aerosolised vaccination with MVA85A induced mycobacterium- and vector-specific IFN-γ in blood and mycobacterium-specific Th1 cytokines in bronchoalveolar lavage. We identified several important barriers that could hamper recruitment into clinical trials in this patient population. The trial did not show any safety concerns in the aerosol delivery of a candidate viral-vectored TB vaccine to two UK adults with ( infection. It also systemically and mucosally demonstrated inducible immune responses following aerosol vaccination. A further trial in a country with higher incidence of LTBI would confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/vaccines9040396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073411PMC
April 2021

Prosthetic hip joint infection by Bacillus Calmette-Guerin therapy following intravesical instillation for bladder cancer identified using whole-genome sequencing: a case report.

BMC Infect Dis 2021 Feb 5;21(1):151. Epub 2021 Feb 5.

Department of Infectious Diseases, Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Background: Joint replacement is an effective intervention and prosthetic joint infection (PJI) is one of the most serious complications of such surgery. Diagnosis of PJI is often complex and requires multiple modalities of investigation. We describe a rare cause of PJI which highlights these challenges and the role of whole-genome sequencing to achieve a rapid microbiological diagnosis to facilitate prompt and appropriate management.

Case Presentation: A 79-year-old man developed chronic hip pain associated with a soft-tissue mass, fluid collection and sinus adjacent to his eight-year-old hip prosthesis. His symptoms started after intravesical Bacillus Calmette-Guerin (BCG) therapy for bladder cancer. Synovasure™ and 16S polymerase chain reaction (PCR) tests were negative, but culture of the periarticular mass and genome sequencing diagnosed BCG infection. He underwent a two-stage joint revision and a prolonged duration of antibiotic therapy which was curative.

Conclusions: BCG PJI after therapeutic exposure can have serious consequences, and awareness of this potential complication, identified from patient history, is essential. In addition, requesting appropriate testing is required, together with recognition that traditional diagnostics may be negative in non-pyogenic PJI. Advanced molecular techniques have a role to enhance the timely management of these infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-021-05831-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866480PMC
February 2021

Encephalitis secondary to nitrous oxide and vitamin B deficiency.

BMJ Case Rep 2019 Dec 2;12(12). Epub 2019 Dec 2.

Department of Infectious Diseases and Tropical Medicine, Birmingham Heartlands Hospital, University Hospitals Birmingham, Birmingham, UK.

A 27-year-old woman presented with confusion, agitation and fever. Having initially been treated as an infective encephalitis case her initial and subsequent lumbar punctures revealed cerebrospinal fluid with a worsening pleocytosis and elevated protein. It was initially felt she had been suffering from tuberculous meningitis and started on treatment it later became apparent that she had a severe vitamin B deficiency related to recreational nitrous oxide use. She also was noted to have a peripheral neuropathy. After replacing her vitamin B and later stopping her tuberculous medication once cultures were negative her cognition and peripheral neuropathy continued to improve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2019-229380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001726PMC
December 2019

A cost comparison of amikacin therapy with bedaquiline, for drug-resistant tuberculosis in the UK.

J Infect 2020 01 21;80(1):38-41. Epub 2019 Sep 21.

Division of Medicine, Imperial College London, United Kingdom; Tuberculosis Service, St Mary's Hospital, Imperial College Healthcare NHS Trust, United Kingdom.

Objectives: Prioritisation of oral bedaquiline over the injectable agents in the treatment of multidrug-resistant Tuberculosis (MDR-TB) in the World Health Organisations (WHO) 2019 guidelines prompted this UK analysis of cost implications. The objective was to estimate the costs of amikacin versus bedaquiline in MDR TB treatment regimens using a historical cohort where the injectable agents were the standard of care.

Methods: This was a retrospective study using a known cohort of UK patients treated with an injectable agent, with data available on resource use, costs for the use of amikacin were compared with those for bedaquiline, based on recommended monitoring for bedaquiline.

Results: The estimated cost of treatment per patient had mean (sd) of £27,236 (4952) for the observed injectable group, £30,264 (3392) and 36,309 (3901) for the 6 and 8 month amikacin groups, and £31,760 (2092) for the bedaquiline group. The cost in the bedaquiline group was £30,772 (1855) with a 10% reduction and £27,079 (1234) with a 33% reduction in-patient stay.

Conclusions: In most scenarios, bedaquiline is close to cost neutral compared with injectable therapy, especially if, as expected, some reduction in duration of admission is possible as a result of bedaquiline's more rapid culture conversion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2019.09.006DOI Listing
January 2020

Contact tracing strategies in household and congregate environments to identify cases of tuberculosis in low- and moderate-incidence populations.

Cochrane Database Syst Rev 2019 08 28;8:CD013077. Epub 2019 Aug 28.

University Hospitals Birmingham Foundation Trust, Hawthorne House, Heartlands Hospital, Bordesley Green East, Birmingham, UK, B9 5SS.

Background: Tuberculosis is an infectious bacterial disease that is spread via respiratory droplets from infected individuals to susceptible contacts. To eliminate this disease from low- and medium-incidence settings, people who are most likely to be infected (contacts) must be identified. Recently, study authors have examined alternate approaches to contact tracing methods that demonstrate improved detection and prioritization of contacts. The comparative benefit of these methods has not been established.

Objectives: To assess the effectiveness of novel methods of contact tracing versus current standard of care to identify latent and active cases in low- to moderate-incidence settings.

Search Methods: We searched CENTRAL, MEDLINE, Embase, LILACS, Web of Science, and CINAHL up to 15 July 2019. We also searched for clinical trials and examined reference lists and conference proceedings.

Selection Criteria: Randomized controlled trials (RCTs) and cluster-RCTs of contact tracing strategies that included alternate approaches (other than standard practice).

Data Collection And Analysis: Two review authors independently assessed identified articles for eligibility and quality using prespecified criteria.

Main Results: No trials met the inclusion criteria of this review. Several study authors described an alternate method for examining contacts and performing social network analysis but did not compare this with the current contact tracing approach.

Authors' Conclusions: This Cochrane Review highlights the lack of research in support of the current contact tracing method and the need for RCTs to compare new methods such as social network analysis to improve contact tracing processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD013077.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713498PMC
August 2019

Health-related quality of life and prevalence of six chronic diseases in homeless and housed people: a cross-sectional study in London and Birmingham, England.

BMJ Open 2019 04 24;9(4):e025192. Epub 2019 Apr 24.

Collaborative Centre for Inclusion Health, University College London, London, UK.

Objectives: To compare health-related quality of life and prevalence of chronic diseases in housed and homeless populations.

Design: Cross-sectional survey with an age-matched and sex-matched housed comparison group.

Setting: Hostels, day centres and soup runs in London and Birmingham, England.

Participants: Homeless participants were either sleeping rough or living in hostels and had a history of sleeping rough. The comparison group was drawn from the Health Survey for England. The study included 1336 homeless and 13 360 housed participants.

Outcome Measures: Chronic diseases were self-reported asthma, chronic obstructive pulmonary disease (COPD), epilepsy, heart problems, stroke and diabetes. Health-related quality of life was measured using EQ-5D-3L.

Results: Housed participants in more deprived neighbourhoods were more likely to report disease. Homeless participants were substantially more likely than housed participants in the most deprived quintile to report all diseases except diabetes (which had similar prevalence in homeless participants and the most deprived housed group). For example, the prevalence of chronic obstructive pulmonary disease was 1.1% (95% CI 0.7% to 1.6%) in the least deprived housed quintile; 2.0% (95% CI 1.5% to 2.6%) in the most deprived housed quintile; and 14.0% (95% CI 12.2% to 16.0%) in the homeless group. Social gradients were also seen for problems in each EQ-5D-3L domain in the housed population, but homeless participants had similar likelihood of reporting problems as the most deprived housed group. The exception was problems related to anxiety, which were substantially more common in homeless people than any of the housed groups.

Conclusions: While differences in health between housed socioeconomic groups can be described as a 'slope', differences in health between housed and homeless people are better understood as a 'cliff'.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-025192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501971PMC
April 2019

Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection.

Sci Rep 2018 09 27;8(1):14480. Epub 2018 Sep 27.

The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

A major contribution to the burden of Tuberculosis (TB) comes from latent Mycobacterium tuberculosis infections (LTBI) becoming clinically active. TB and LTBI probably exist as a spectrum and currently there are no correlates available to identify individuals with LTBI most at risk of developing active disease. We set out to identify immune parameters associated with ex vivo mycobacterial growth control among individuals with active TB disease or LTBI to define the spectrum of TB infection. We used a whole blood mycobacterial growth inhibition assay to generate a functional profile of growth control among individuals with TB, LTBI or uninfected controls. We subsequently used a multi-platform approach to identify an immune signature associated with this profile. We show, for the first time, that patients with active disease had the greatest control of mycobacterial growth, whilst there was a continuum of responses among latently infected patients, likely related to the degree of immune activation in response to bacillary load. Control correlated with multiple factors including inflammatory monocytes, activated and atypical memory B cells, IgG1 responses to TB-specific antigens and serum cytokines/chemokines. Our findings offer a method to stratify subclinical TB infections and the future potential to identify individuals most at risk of progressing to active disease and benefit from chemoprophylaxis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-32755-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160428PMC
September 2018

Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis.

Lancet Respir Med 2018 04;6(4):265-275

Academic Tuberculosis Program, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Background: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ.

Methods: Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1-3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology.

Findings: Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8-9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1-7·3), but no significant effect on mortality (aOR 0·7, 0·4-1·1) or acquired rifampicin resistance (aOR 0·1, 0·0-1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2-0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates.

Interpretation: In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis.

Funding: World Health Organization and Canadian Institutes of Health Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(18)30078-XDOI Listing
April 2018

Clinical Management of Multidrug-Resistant Tuberculosis in 16 European Countries.

Am J Respir Crit Care Med 2018 08;198(3):379-386

1 Research Center Borstel, Clinical Infectious Diseases, German Center for Infection Research, Borstel, Germany.

Rationale: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in Europe. Reported treatment success rates are around 50% or less, and cure rates are even lower.

Objectives: To document the management and treatment outcome in patients with MDR-TB in Europe.

Methods: We performed a prospective cohort study, analyzing management and treatment outcomes stratified by incidence of patients with MDR-TB in Europe. Treatment outcomes were compared by World Health Organization and alternative simplified definitions by the Tuberculosis Network European Trialsgroup (TBNET).

Measurements And Main Results: A total of 380 patients with MDR-TB were recruited and followed up between 2010 and 2014 in 16 European countries. Patients in high-incidence countries compared with low-incidence countries were treated more frequently with standardized regimen (83.2% vs. 9.9%), had delayed treatment initiation (median, 111 vs. 28 d), developed more additional drug resistance (23% vs. 5.8%), and had increased mortality (9.4% vs. 1.9%). Only 20.1% of patients using pyrazinamide had proven susceptibility to the drug. Applying World Health Organization outcome definitions, frequency of cure (38.7% vs. 9.7%) was higher in high-incidence countries. Simplified outcome definitions that include 1 year of follow-up after the end of treatment showed similar frequency of relapse-free cure in low- (58.3%), intermediate- (55.8%), and high-incidence (57.1%) countries, but highest frequency of failure in high-incidence countries (24.1% vs. 14.6%).

Conclusions: Conventional standard MDR-TB treatment regimens resulted in a higher frequency of failure compared with individualized treatments. Overall, cure from MDR-TB is substantially more frequent than previously anticipated, and poorly reflected by World Health Organization outcome definitions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201710-2141OCDOI Listing
August 2018

Acquired Resistance to Antituberculosis Drugs in England, Wales, and Northern Ireland, 2000-2015.

Emerg Infect Dis 2018 03;24(3):524-533

Among tuberculosis (TB) patients, acquired resistance to anti-TB drugs represents a failure in the treatment pathway. To improve diagnosis and care for patients with drug-resistant TB, we examined the epidemiology and risk factors associated with acquired drug resistance during 2000-2015 among TB patients in England, Wales, and Northern Ireland. We found acquired resistance in 0.2% (158/67,710) of patients with culture-confirmed TB. Using multivariate logistic regression, we identified the following factors associated with acquired drug resistance: having pulmonary disease; initial resistance to isoniazid, rifampin, or both; a previous TB episode; and being born in China or South Africa. Treatment outcomes were worse for patients with than without acquired resistance. Although acquired resistance is rare in the study area, certain patient groups are at higher risk. Identifying these patients and ensuring that adequate resources are available for treatment may prevent acquisition of resistance, thereby limiting transmission of drug-resistant strains of mycobacteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2403.171362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823342PMC
March 2018

: an uncommon non-tuberculous infection in a UK patient.

BMJ Case Rep 2018 Feb 2;2018. Epub 2018 Feb 2.

Occupational Health Services, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

We present the case of a 69-year-old man with significant respiratory comorbidities who presented with slow growing pulmonary nodules which cavitated. Subsequent sputum sampling grew , a non-tuberculous mycobacterium species and an uncommon cause of infection in the UK. We describe the diagnostic process and subsequent treatment regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2017-221764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812415PMC
February 2018

A retrospective cohort study of patients treated with anti-tuberculous therapy for presumed ocular tuberculosis.

J Ophthalmic Inflamm Infect 2017 Dec 4;7(1):23. Epub 2017 Dec 4.

Birmingham and Midland Eye Centre, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, B18 7QH, UK.

Background: Uveitis involving the posterior segment is a significant and potentially blinding condition. The diagnosis and treatment of patients with uveitis associated with tuberculosis remains controversial, and commonly, patients are systemically well. Use of the interferon-gamma release assays has added to the controversy, as the significance of a positive test may be uncertain. We aim to report the outcomes of anti-tuberculous treatment in a cohort of patients treated in Birmingham, for presumed "ocular tuberculosis", based on clinical findings, systemic assessment and specific testing for tuberculosis.

Results: We found that in our cohort of 41 patients treated between 2010 and 2014, the majority achieved disease-free remission, even in cases where anti-tuberculous treatment was delayed.

Conclusions: Despite controversy, this study strongly supports the use of anti-tuberculous therapy in such patients and highlights the need for formal prospective trials and treatment protocols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12348-017-0141-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714940PMC
December 2017

Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis.

Antimicrob Agents Chemother 2017 09 24;61(9). Epub 2017 Aug 24.

Institute for Infection and Immunity, St. George's University of London, London, United Kingdom.

The prolonged use of injectable agents in a regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health Organization, despite its association with ototoxicity and nephrotoxicity. We undertook this study to look at the relative adverse effects of capreomycin and amikacin. We reviewed the case notes of 100 consecutive patients treated at four MDR-TB treatment centers in the United Kingdom. The median total duration of treatment with an injectable agent was 178 days (interquartile range [IQR], 109 to 192 days; = 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; = 12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324 to 735 days; = 8) for those with extensively drug-resistant tuberculosis (XDR-TB). Injectable use was longer for those started with capreomycin (183 days; IQR, 123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days) ( = 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated with an injectable for over 6 months and 12 of 85 (14%) were treated with an injectable for over 8 months. Forty percent of all patients discontinued the injectable due to hearing loss. Fifty-five percent of patients experienced ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.2 to 22.6; = 0.03) more likely to occur in those started on amikacin than in those treated with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of 37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number of patients experiencing a rise in the creatinine level of >1.5 times the baseline level. Hearing loss is frequent in this cohort, though its incidence is significantly lower in those starting capreomycin, which should be given greater consideration as a first-line agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02586-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571306PMC
September 2017

Drug resistant TB: UK multicentre study (DRUMS): Treatment, management and outcomes in London and West Midlands 2008-2014.

J Infect 2017 03 18;74(3):260-271. Epub 2016 Dec 18.

Institute for Infection and Immunity, St. George's University of London, London SW17 0RE, United Kingdom.

Objectives: Detailed information regarding treatment practices and outcomes of MDR-TB treatment in the UK is required as a baseline for care improvements.

Methods: 100 consecutive cases between 2008 and 2014 were reviewed retrospectively at 4 MDR-TB treatment centres in England to obtain information on drug treatment choices, hospital admission duration and outcomes for MDR-TB.

Results: Initial hospital admission was long, median 62.5 (IQR 20-106, n = 92) days, and 13% (12/92) of patients lost their home during this period. Prolonged admission was associated with pulmonary cases, cavities on chest radiograph, a public health policy of waiting for sputum culture conversion (CC) and loss of the patient's home. Sputum CC occurred at a median of 33.5 (IQR 16-55, n = 46) days. Treatment success was high (74%, 74/100) and mortality low (1%, 1/100). A significant proportion of the cohort had "neutral" results due to deportation and transfer overseas (12%, (12/100)). 14% (14/100) had negative outcomes for which poor adherence was the main reason (62%, 9/14).

Conclusions: Successful outcome is common in recognised centres and limited by adherence rather than microbiological failure. Duration of hospital admission is influenced by lack of suitable housing and some variation in public health practice. Wider access to long-term assisted living facilities could improve completion rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2016.12.005DOI Listing
March 2017

Using bedaquiline and delamanid in combination and safely.

Authors:
Martin Dedicoat

Int J Tuberc Lung Dis 2016 10;20(10):1282

Department of Infection, Heart of England Foundation Trust, Birmingham, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5588/ijtld.16.0522DOI Listing
October 2016

Can routine genetic testing help to end TB transmission?

Thorax 2016 08;71(8):681-2

Division of Infectious Diseases, Imperial College, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2016-208554DOI Listing
August 2016

Vitamin D deficiency and TB disease phenotype.

Thorax 2015 Dec 23;70(12):1171-80. Epub 2015 Sep 23.

Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK Tuberculosis Service, Department of Chest and Allergy Clinic, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.

Background: Extrapulmonary TB is increasingly common, yet the determinants of the wide clinical spectrum of TB are poorly understood.

Methods: We examined surveillance data (Birmingham, UK: 1980-2009 and USA Centers for Disease Control: 1993-2008) to identify demographic factors associated with extrapulmonary TB. We then directly tested association of these factors and serum 25-hydroxycholecalciferol (25(OH)D) concentration with extrapulmonary TB by multivariable analysis in a separate UK cohort.

Results: Data were available for 10,152 and 277,013 TB cases for Birmingham and US, respectively. Local-born individuals of white ethnicity had a lower proportion of extrapulmonary disease when compared with local-born non-whites (p<0.0001); both groups had a lower proportion of extrapulmonary disease when compared with foreign-born non-whites (p<0.0001). In a separate UK cohort (n=462), individuals with extrapulmonary TB had lower mean serum 25(OH)D concentration than those with pulmonary TB (11.4 vs 15.2 nmol/L, respectively, p=0.0001). On multivariable analysis, vitamin D deficiency was strongly associated with extrapulmonary TB independently of ethnicity, gender and other factors. Doubling in serum 25(OH)D concentration conferred substantially reduced risk of extrapulmonary disease (OR 0.55, 95% CI 0.41 to 0.73).

Conclusions: We identify vitamin D deficiency as a probable risk factor for extrapulmonary dissemination in TB, which may account for the associations of dark-skinned ethnicity and female gender with extrapulmonary disease. Our findings implicate vitamin D status in Mycobacterium tuberculosis containment in vivo and, given the high prevalence of deficiency, may inform development of novel TB prevention strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2014-206617DOI Listing
December 2015

Tuberculosis preventive chemotherapy: the times they are a-changin'.

Int J Tuberc Lung Dis 2015 Sep;19(9):1002

Division of Clinical Infectious Diseases, Research Center Borstel, Germany; German Center for Infection Research, Clinical Tuberculosis Center, Borstel, Germany; International Health / Infectious Diseases, University of Lübeck, Lübeck, Germany; Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Internal Medicine, University of Namibia School of Medicine, Windhoek, Namibia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5588/ijtld.15.0599DOI Listing
September 2015

Tuberculosis microepidemics among dispersed migrants, Birmingham, UK, 2004-2013.

Emerg Infect Dis 2015 Mar;21(3):524-7

To determine if local transmission was responsible for rising tuberculosis incidence in a recently dispersed migrant community in Birmingham, UK, during 2004-2013, we conducted enhanced epidemiologic investigation of molecular clusters. This technique identified exact locations of social mixing and chains of apparent recent transmission, which can be helpful for directing resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2103.140209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344256PMC
March 2015

Multidrug-resistant tuberculosis in Europe, 2010-2011.

Emerg Infect Dis 2015 Mar;21(3):409-16

Drug-resistant Mycobacterium tuberculosis is challenging elimination of tuberculosis (TB). We evaluated risk factors for TB and levels of second-line drug resistance in M. tuberculosis in patients in Europe with multidrug-resistant (MDR) TB. A total of 380 patients with MDR TB and 376 patients with non-MDR TB were enrolled at 23 centers in 16 countries in Europe during 2010-2011. A total of 52.4% of MDR TB patients had never been treated for TB, which suggests primary transmission of MDR M. tuberculosis. At initiation of treatment for MDR TB, 59.7% of M. tuberculosis strains tested were resistant to pyrazinamide, 51.1% were resistant to ≥1 second-line drug, 26.6% were resistant to second-line injectable drugs, 17.6% were resistant to fluoroquinolones, and 6.8% were extensively drug resistant. Previous treatment for TB was the strongest risk factor for MDR TB. High levels of primary transmission and advanced resistance to second-line drugs characterize MDR TB cases in Europe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2103.141343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344280PMC
March 2015

Low dose versus high dose stavudine for treating people with HIV infection.

Cochrane Database Syst Rev 2015 Jan 28;1:CD007497. Epub 2015 Jan 28.

Nelson R Mandela School of Medicine, Durban, KwaZulu-Natal, South Africa.

Background: Stavudine remains a component of combination antiretroviral therapy (ART) in resource-constrained countries due to its relatively low cost despite the WHO recommendation for its phasing out as a strategy to reduce stavudine associated toxicities. Where stavudine is still in use, it is recommended at a dose lower than the standard dose in order to reduce stavudine related toxicity.

Objectives: To compare the safety and virologic efficacy of low dose versus high dose stavudine for treating HIV-1 infection.

Search Methods: The comprehensive search strategy developed by the Cochrane HIV/AIDS Review Group was used to identify randomised controlled trials that compared the use of low dose versus high dose stavudine. The last search was conducted in February 2014 and the searches covered the period 1996 to 2014.

Selection Criteria: Randomised controlled trials comparing the use of low dose and high dose stavudine as part of ART combination therapy for treating adults.

Data Collection And Analysis: Two reviewers independently selected eligible trials, assessed methodological quality of the included studies and completed data extraction and analysis.

Main Results: The search identified 3952 abstracts which were scanned for relevance. Three trials met the inclusion criteria (Milinkovic 2007; McComsey 2008; Sanchez-Conde 2005). All three trials were conducted in developed countries, participants were ART experienced and all had sustained virologic suppression at baseline. A total of 157 participants were recruited to the trials. Sample sizes ranged from 24 to 92 and more than 79% of participants were male.The studies were at a high risk of selection, performance/detection and selective outcome reporting biases. Some baseline characteristics differed among the groups, including triglyceride levels in two studies and body mass index in one study. In light of variation in the design and follow-up of the study results, no meta-analysis was performed and the results of single studies are presented. There was no significant difference in virologic suppression in the included studies (Milinkovic 2007; McComsey 2008; Sanchez-Conde 2005); Risk Ratio (RR) 1.09 (95% CI: 0.93 to 1.28), 0.94 (95% CI:0.59 to 1.50) and 1.03 (95% CI: 0.90 to 1.18) respectively. Symptomatic hyperlactatemia was seen in the high dose arm of the Milinkovic 2007 study; RR 0.21 (95% CI: 0.01 to 4.66), in no participants in the McComsey 2008 trial and not reported on in the Sanchez-Conde 2005 trial. McComsey 2008 and Milinkovic 2007 demonstrated a reduction in bone mineral density (BMD), reduction in limb fat and an increase in triglycerides in the high dose arms. The studies did not indicate that any participants discontinued treatment due to adverse events.

Authors' Conclusions: This systematic review identified only three small trials that evaluated virologic efficacy and safety of high dose versus low dose stavudine. All three trials were conducted in developed countries and none reported from developing countries yet stavudine remains a component of ART combination therapy in many developing countries. It was not possible to perform a meta-analysis on these trails. Individual results from the trials were imprecise and have not identified a clear advantage in virologic efficacy or safety between low and high dose stavudine. Furthermore, enrolled participants were treatment experienced with sustained virologic suppression and so existing data cannot be generalized to settings where stavudine is currently used in ART naive patients with high viral loads. Stavudine dose reduction trials in ART naive patients, in developing countries where stavudine is still being used are warranted as the phasing out of stavudine that is recommended by WHO may not be immediately universally feasible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD007497.pub2DOI Listing
January 2015

Percutaneous breast implant herniation: a rare complication of miliary TB.

BMJ Case Rep 2015 Jan 7;2015. Epub 2015 Jan 7.

Department of Infectious Diseases and Tropical Medicine, Birmingham Heartlands Hospital, Heart of England NHS Hospital Trust, Birmingham, UK.

We describe the case of a 46-year-old female patient treated for disseminated tuberculosis (TB) infection involving the lungs, urinary tract and skin. Following initiation of antituberculous therapy, the patient's right breast implant eroded through the overlying skin and was seen to be herniating through the resulting defect. The breast implant was removed under local anaesthetic and histological analysis of the resected tissue demonstrated granuloma formation consistent with periprosthetic TB. Wound healing following implant removal was poor and future breast augmentation surgery was only considered following completion of 12 months anti-TB treatment. This case constitutes the first report in the literature of percutaneous breast implant herniation resulting from periprosthetic infection with TB. A high index of suspicion is required to ensure early detection and timely management of TB and, in cases where periprosthetic pus aspirate is sterile, mycobacterial infection must be actively excluded.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2014-207546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289805PMC
January 2015

Tuberculosis: a perennial pain in the posterior?

Int J Colorectal Dis 2015 Jun 6;30(6):849-50. Epub 2014 Nov 6.

Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB, UK,

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00384-014-2049-xDOI Listing
June 2015

Novel drugs and drug combinations for treating tuberculosis.

BMJ 2014 Oct 16;349:g5948. Epub 2014 Oct 16.

Department of Infection and Tropical Medicine, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.g5948DOI Listing
October 2014
-->