326 research outputs found
Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis.
BackgroundTuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV.MethodsA large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay's suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested.ResultsOur LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10-25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05-50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range.ConclusionsAn LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV
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Mentoring the Mentors: Implementation and Evaluation of Four Fogarty-Sponsored Mentoring Training Workshops in Low-and Middle-Income Countries.
A growing body of evidence highlights the importance of competent mentoring in academic research. We describe the development, implementation, and evaluation of four regional 2-day intensive workshops to train mid- and senior-level investigators conducting public health, clinical, and basic science research across multiple academic institutions in low- and middle-income countries (LMICs) on tools and techniques of effective mentoring. Sponsored by the Fogarty International Center, workshops included didactic presentations, interactive discussions, and small-group problem-based learning and were conducted in Lima, Peru; Mombasa, Kenya; Bangalore, India; and Johannesburg, South Africa, from 2013 to 2016. Mid- or senior-level faculty from multiple academic institutions within each region applied and were selected. Thirty faculty from 12 South America-based institutions, 29 faculty from eight East Africa-based institutions, 37 faculty from 14 South Asia-based institutions, and 36 faculty from 13 Africa-based institutions participated, with diverse representation across disciplines, gender, and academic rank. Discussions and evaluations revealed important comparisons and contrasts in the practice of mentoring, and specific barriers and facilitators to mentoring within each cultural and regional context. Specific regional issues related to hierarchy, the post-colonial legacy, and diversity arose as challenges to mentoring in different parts of the world. Common barriers included a lack of a culture of mentoring, time constraints, lack of formal training, and a lack of recognition for mentoring. These workshops provided valuable training, were among the first of their kind, were well-attended, rated highly, and provided concepts and a structure for the development and strengthening of formal mentoring programs across LMIC institutions
Environmental Monitoring of Water Quality as a Planning and Management Tool: A Case Study of the Rodrigo de Freitas Lagoon, Rio de Janeiro, Brazil
The Rodrigo de Freitas Lagoon is an urban water body, representing one of the most popular spots for the local community. It underwent serious environmental degradation, at first through its water mirror reduction and more recently through sewer inflows. Concurrently, the difficulty in renewing the water combined with adverse climatic conditions has repeatedly led to an alarming fish mortality rate. The monitoring of its water quality has been carried out as a management and planning tool that lead to the improvement of the environmental conditions. This study seeks to assess monitoring results by correlating the factors that might be the cause of a failure to comply with environmental regulations. Although it is evident that particular places in the Lagoon might be more often affected by illegal sewer discharges, no evidence could be found of any variations between the six sampling points. However, the rise in the levels of Escherichia coli, nitrogen and phosphorus, and the general temperature conditions, pH, and salinity of the water shows that the most significant alterations occurred in spring 2018.The complexity of the period of phytoplankton growth followed by the fish mortality from anoxia underlines the need for monitoring as a tool for a better understanding of the alterations, providing guidance with regard to the planning and management of the ecosystem
Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.
In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure
Isoniazid concentrations in hair and plasma area-under-the-curve exposure among children with tuberculosis.
We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment
Association of anti-tuberculosis drug concentrations in hair and treatment outcomes in MDR- and XDR-TB.
Therapeutic drug monitoring for drug-resistant tuberculosis (TB) is likely to improve treatment outcomes. While assessments of plasma drug levels can explain pharmacokinetic variability among trial participants, these measures require phlebotomy and a cold chain, and are generally not repeated frequently enough to characterise drug exposure over time. Using a novel multi-analyte assay, we found evidence that higher anti-TB drug concentrations in hair, a non-biohazardous and noninvasively collected biomatrix, predict extensively-drug resistant-TB clinical outcomes in a high-burden setting
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