Tuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific ...research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses. This revised understanding leads us to propose two additional clinical states: incipient and subclinical TB. The recognition of incipient and subclinical TB, which helps divide latent and active TB along the clinical disease spectrum, provides opportunities for the development of diagnostic and therapeutic interventions to prevent progression to active TB disease and transmission of TB bacilli. In this report, we review the current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium.
Summary The aim of diagnostic point-of-care testing is to minimise the time to obtain a test result, thereby allowing clinicians and patients to make a quick clinical decision. Because point-of-care ...tests are used in resource-limited settings, the benefits need to outweigh the costs. To optimise point-of-care testing in resource-limited settings, diagnostic tests need rigorous assessments focused on relevant clinical outcomes and operational costs, which differ from assessments of conventional diagnostic tests. We reviewed published studies on point-of-care testing in resource-limited settings, and found no clearly defined metric for the clinical usefulness of point-of-care testing. Therefore, we propose a framework for the assessment of point-of-care tests, and suggest and define the term test efficacy to describe the ability of a diagnostic test to support a clinical decision within its operational context. We also propose revised criteria for an ideal diagnostic point-of-care test in resource-limited settings. Through systematic assessments, comparisons between centralised testing and novel point-of-care technologies can be more formalised, and health officials can better establish which point-of-care technologies represent valuable additions to their clinical programmes.
Rapid Diagnostic Testing for SARS-CoV-2 Drain, Paul K
New England journal of medicine/The New England journal of medicine,
01/2022, Letnik:
386, Številka:
3
Journal Article
Recenzirano
Odprti dostop
RDTs for SARS-CoV-2 — either molecular nucleic acid amplification tests or antigen-based immunoassays to detect proteins — are approved for persons with Covid-19 symptoms and asymptomatic persons ...with known exposure to SARS-CoV-2 or those in a high-transmission setting. Antigen-based tests have lower sensitivity than PCR tests, but they may correlate better with replication-competent virus.
Since the site of human subjects research has public health, regulatory, ethical, economic, and social implications, we sought to determine the global distribution and migration of clinical research ...using an open-access trial registry.
We obtained individual clinical trial data including location of trial sites, dates of operation, funding source (United States government, pharmaceutical industry, or organization), and clinical study phase (1, 1/2, 2, 2/3, or 3) from ClinicalTrials.gov. We used the World Bank's classification of each country's economic development status "High Income and a Member of the Organization for Economic Co-operation and Development (OECD)", "High Income and Non-Member of the OECD", "Upper-Middle Income", "Lower-Middle Income", or "Low Income" and United Nations Populations Division data for country-specific population estimates. We analyzed data from calendar year 2006 through 2012 by number of clinical trial sites, cumulative trial site-years, trial density (trial site-years/106 population), and annual growth rate (%) for each country, and by development category, funding source, and clinical study phase.
Over a 7-year period, 89,647 clinical trials operated 784,585 trial sites in 175 countries, contributing 2,443,850 trial site-years. Among those, 652,200 trial sites (83%) were in 25 high-income OECD countries, while 37,195 sites (5%) were in 91 lower-middle or low-income countries. Trial density (trial site-years/106 population) was 540 in the United States, 202 among other high-income OECD countries (excluding the United States), 81 among high-income non-OECD countries, 41 among upper-middle income countries, 5 among lower-middle income countries, and 2 among low-income countries. Annual compound growth rate was positive (ranging from 0.8% among low-income countries to 14.7% among lower-middle income countries) among all economic groups, except the United States (-0.5%). Overall, 29,191 trials (33%) were funded by industry, 4,059 (5%) were funded by the United States government, and 56,397 (63%) were funded by organizations. Countries with emerging economies (low- and middle-income) operated 19% of phase 3 trial sites, as compared to only 6% of phase 1 trial sites.
Human clinical research remains concentrated in high-income countries, but operational clinical trial sites, particularly for phase 3 trials, may be migrating to low- and middle-income countries with emerging economies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The number of people living with HIV (PLHIV) in need of treatment monitoring in low-and-middle-income countries has been rapidly expanding, placing an increasing burden on laboratories. Promising new ...point-of-care (POC) test have the potential to reduce laboratory workloads, but the implementation cost is uncertain. We sought to estimate the costs of decentralized POC testing compared to centralized laboratory testing for PLHIV initiating treatment in South Africa.
We conducted a microcosting analyses comparing clinic-based POC testing to centralized laboratory testing for HIV viral load, creatinine, and CD4 count monitoring. We completed time-and-motion studies to assess staff time for sample collection and processing. Instrument costs were estimated assuming five-year lifespans and we applied a 3% annual discount rate. Total costs and cost per patient were estimated over a five-year period: the first year of ART initiation and four years of routine HIV monitoring, following World Health Organization ART monitoring guidelines.
We estimated that per-patient costs of POC HIV viral load, CD4, and creatinine tests were USD $25, $11, and $9, respectively, assuming a clinic volume of 50 patients initiated per month. At centralized laboratories, per-patient costs of POC HIV viral load, CD4, and creatinine tests were USD $26, $6, $3. Total monitoring costs of all testing over a 5-year period was $45 higher for POC testing compared to centralized laboratory testing ($210 vs $166).
POC testing for HIV care and treatment can be feasibly implemented within clinics in South Africa, particularly those with larger patient volumes. POC HIV viral load costs are similar to lab-based testing while CD4 count and creatinine testing are more costly as POC tests. Our cost estimates are useful to policymakers in planning resource allocation and can inform cost-effectiveness analyses of POC testing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most antibiotics used to treat tuberculosis (TB) were developed over 50 years ago and have nonspecific mechanisms of action, leading to potential adverse drug reactions. Treatment guidelines ...recommend weight-based dosing for several first-line anti-TB drugs to achieve optimal drug concentrations. However, supratherapeutic concentrations can lead to toxicities, while subtherapeutic concentrations can result in treatment failure or drug resistance. The implementation of fixed-dose combination pills has simplified treatment regimens but limited personalized dose adjustments. Genomic testing for personalized TB drug dosing has not been widely endorsed due to the lack of a practical and cost-effective assay. Verma and colleagues developed a customized sequencing panel on a rapid nanopore assay to detect key mutations in genes that affect TB drug metabolism. The study demonstrated the accuracy of the assay and its potential for personalized treatment.
Lipoarabinomannan (LAM), a component of the Mycobacterium tuberculosis (MTB) cell wall, is detectable in the urine of MTB infected patients with active tuberculosis (TB). LAM-specific antibodies ...(Igs) have been developed by a variety of traditional and recombinant methods for potential use in a rapid diagnostic test (RDT). We evaluated the analytical performance of the TB LAM Igs to identify pairs that offer superior performance over existing urine LAM tests. We assessed 25 new and 4 existing Igs in a matrixed format using a multiplex electrochemiluminescence-based liquid immunoassay. A total of 841 paired Ig combinations were challenged with in vitro cultured LAM (cLAM) derived from MTB strains representing diverse phylogenetic lineages, alongside urinary LAM (uLAM) from the urine of adults with active pulmonary TB. Analytical sensitivity of down-selected Ig pairs was determined using MTB Aoyama-B cLAM, while diagnostic accuracy was determined using clinical samples. When testing cLAM, the reactivity of Ig pairs was similar across MTB lineages 1-4 but lineage 5:6 had significantly more reactivity among Ig pairs. Overall, 41 Ig pairs had a strong binding affinity to cLAM, as compared to the reference pair of S4-20/A194-01, and 28 Ig pairs therein exhibited a strong affinity for both cLAM and uLAM. Retrospective testing on clinical urine specimens demonstrated varying sensitivities (12-80%) and specificities (14-100%). The five top pairs had a similar analytical limit of detection to the reference pair but in four instances, the sensitivity and specificity with clinical uLAM samples was poor. Overall, epitopes presented by uLAM are different from cLAM, which may affect antibody performance when testing uLAM in patient samples. Several new Ig pairs had similar ranges of high sensitivity to cLAM but overall, there were no new candidate Ig pairs identified in this round of screening with increased performance with uLAM as compared to an existing optimal pair.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several supply chain components are important to sustain point-of-care (POC) testing services in rural settings. To evaluate the availability of POC diagnostic tests in rural Ghana's primary ...healthcare (PHC) clinics, we conducted an audit of the supply chain management for POC diagnostic services in rural Upper East Region's (UER) PHC clinics, Ghana to determine the reasons/causes of POC tests deficiencies.
We conducted a review of accessible POC diagnostics in 100 PHC clinics in UER, Ghana from February to March 2018. We used a monitoring audit tool adopted from the World Health Organization and Management Science for Health guidelines for supply chain management of diagnostics for compliance. We determined a clinic's compliance with the stipulated guidelines, and a composite compliant score was defined as a percentage rating of 90 to 100%. We used univariate logistic regression analysis in Stata 14 to determine the level of association between supply chain management and the audit variables.
Overall, the composite compliant score of supply chain management for existing POC tests was at 81% (95%CI: 79%-82%). The mean compliance with distribution guidelines was at 93.8% (95%CI: 91.9%-95.6%) the highest score, whilst inventory management scored the lowest, at 53.5% (95%CI: 49.5%-57.5%) compliance. Of the 13 districts in the region, the results showed complete stock-out of blood glucose test in all selected PHC clinics in seven (53.8%) districts, haemoglobin and hepatitis B virus test in three (23.1%), and urine protein test in two (15.4%) districts. Based on our univariate logistics regression models, stock-out of tests at the Regional Medical and District Health Directorates stores in the region, high clinic attendance, lack of documentation of expiry date/expired tests, poor documentation of inventory level, poor monitoring of monthly consumption level, and failure to document unexplained losses of the various POC tests were significant predictors of complete test stock-out in most of the clinics in the Upper East Region.
There is poor supply chain management of POC diagnostic tests in UER's PHC clinics. Improvement in inventory management and human resource capacity for POC testing is critical to ensure accessibility and sustainability of POC diagnostic services in resource-limited settings PHC clinics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Outbreaks in vaccine-preventable diseases among children have increased, primarily among under- or unvaccinated subgroups. The influence and interaction of a child's school community on parental ...health care decisions, such as vaccination, has not been explored. Our study examined childhood coronavirus disease 2019 (COVID-19) vaccine hesitancy within the context of school communities.
This study combines data from 4 independent research studies funded by the National Institutes of Health Rapid Acceleration of Diagnostics Underserved Populations Return to School Initiative. We examined focus group data to better understand the apprehension surrounding parental and child COVID-19 vaccination among underserved school populations.
Across all study sites, 7 main themes emerged with regard to COVID-19-related vaccination concerns for children: (1) potential side effects, (2) vaccine development, (3) misinformation (subthemes: content of vaccine and negative intent of the vaccine), (4) vaccine effectiveness, (5) timing of vaccine administration/availability for children, (6) fear of needles, and (7) mistrust.
School settings offered unique access to youth and family perspectives in underserved communities. Our studies highlighted several factors contributing to COVID-19 vaccine hesitancy in school communities, which align with existing literature on vaccine hesitancy. These concerns centered primarily on potential harm of vaccines, as well as misinformation, mistrust, and timing of vaccines. Related recommendations for increasing vaccination rates are provided. Developing specific strategies that address parent and child concerns will be critical to reducing health inequities related to COVID-19 vaccination.
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