scholarly journals A 3D-printed magnetic digital microfluidic diagnostic platform for rapid colorimetric sensing of carbapenemase-producing Enterobacteriaceae

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Pojchanun Kanitthamniyom ◽  
Pei Yun Hon ◽  
Aiwu Zhou ◽  
Mohammad Yazid Abdad ◽  
Zhi Yun Leow ◽  
...  
Keyword(s):  
Point Of Care ◽  
Resistance Mechanism ◽  
Turnaround Time ◽  
World Health ◽  
Colorimetric Sensing ◽  
Resource Limited ◽  
Reaction Chambers ◽  
Technological Platform ◽  
Health Organization ◽  
Digital Microfluidic

AbstractCarbapenemase-producing Enterobacteriaceae (CPE) are a group of drug-resistant Gram-negative pathogens that are classified as a critical threat by the World Health Organization (WHO). Conventional methods of detecting antibiotic-resistant pathogens do not assess the resistance mechanism and are often time-consuming and laborious. We have developed a magnetic digital microfluidic (MDM) platform, known as MDM Carba, for the identification of CPE by measuring their ability to hydrolyze carbapenem antibiotics. MDM Carba offers the ability to rapidly test CPE and reduce the amount of reagents used compared with conventional phenotypic testing. On the MDM Carba platform, tests are performed in droplets that function as reaction chambers, and fluidic operations are accomplished by manipulating these droplets with magnetic force. The simple droplet-based magnetic fluidic operation allows easy system automation and simplified hands-on operation. Because of the unique “power-free” operation of MDM technology, the MDM Carba platform can also be operated manually, showing great potential for point-of-care testing in resource-limited settings. We tested 27 bacterial isolates on the MDM Carba platform, and the results showed sensitivity and specificity that were comparable to those of the widely used Carba NP test. MDM Carba may shorten the overall turnaround time for CPE identification, thereby enabling more timely clinical decisions for better clinical outcomes. MDM Carba is a technological platform that can be further developed to improve diagnostics for other types of antibiotic resistance with minor modifications.

scholarly journals Immobilization of Proteinase K for urine pretreatment to improve diagnostic accuracy of active tuberculosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257615
Author(s):  
Yosita Panraksa ◽  
Anita G. Amin ◽  
Barbara Graham ◽  
Charles S. Henry ◽  
Delphi Chatterjee
Keyword(s):  
Point Of Care ◽  
Sample Pretreatment ◽  
Urine Samples ◽  
Proteinase K ◽  
World Health ◽  
Clinical Samples ◽  
Hiv Status ◽  
Capture Elisa ◽  
Resource Limited ◽  
Health Organization

The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of tuberculosis (TB) at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample matrix. For obtaining optimal sensitivity, we and others have shown that some form of sample pretreatment is necessary to remove background from patient urine samples. A number of systems are paper-based often destined for resource limited settings. Our current work presents incorporation of one such sample pretreatment, proteinase K (ProK) immobilized on paper (IPK) and test its performance in comparison to standard proteinase K (SPK) treatment that involves addition and deactivation at high temperature prior to performing a capture ELISA. Herein, a simple and economical method was developed for using ProK immobilized strips to pretreat urine samples. Simplification and cost reduction of the proposed pretreatment strip were achieved by using Whatman no.1 paper and by minimizing the concentration of ProK (an expensive but necessary reagent) used to pretreat the clinical samples prior to ELISA. To test the applicability of IPK, capture ELISA was carried out on either LAM-spiked urine or the clinical samples after pretreatment with ProK at 400 μg/mL for 30 minutes at room temperature. The optimal conditions and stability of the IPK were tested and validation was performed on a set of 25 previously analyzed archived clinical urine samples with known TB and HIV status. The results of IPK and SPK treated samples were in agreement showing that the urine LAM test currently under development has the potential to reach adult and pediatric patients regardless of HIV status or site of infection, and to facilitate global TB control to improve assay performance and ultimately treatment outcomes.

scholarly journals Profiles of Volatile Biomarkers Detect Tuberculosis from Skin

2020 ◽  
Author(s):  
Hossam Haick ◽  
Rotem Vishinkin ◽  
Rami Busool ◽  
Elias Mansour ◽  
Falk Fish ◽  
...  
Keyword(s):  
Point Of Care ◽  
World Health ◽  
Disease Spread ◽  
Clinical Samples ◽  
Resource Limited ◽  
Tb Diagnostics ◽  
Health Organization ◽  
Low Sensitivity ◽  
Test Requirements

Abstract Tuberculosis (TB) is an infectious disease that threatens >10 million people annually. Despite advances in TB diagnostics, millions of patients continue to receive insufficient diagnosis, as TB symptoms are not specific. Many existing bio-diagnostic tests are slow, have low sensitivity and/or specificity, and can be too expensive or complex for resource-limited settings. Early diagnosis of TB contributes to morbidity mitigation and prevents the disease spread. Here, we report on a new physiological pathway for TB diagnostics via TB-specific profile of volatile organic compounds (VOCs) that are detected and quantified from air trapped above the skin (“skin headspace”). Beyond the exploration aspect that relies on clinical samples from 636 individuals in two clinical sites, we demonstrate the utility of these VOC profiles in a point-of-care diagnosis, by means of specifically-designed intelligent nanoarray, both in lab setting and online, in-situ wearable devices. The results show excellent discrimination between active pulmonary TB patients and controls with 89.4% accuracy. This fulfills the triage TB test requirements according to the World Health Organization (WHO).

scholarly journals Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing

2018 ◽  
Vol 57 (1) ◽  
Author(s):  
Radha Rajasingham ◽  
Rachel M. Wake ◽  
Tafese Beyene ◽  
Andrew Katende ◽  
Emilio Letang ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Laboratory Testing ◽  
Point Of Care ◽  
World Health ◽  
The Past ◽  
Resource Limited ◽  
India Ink ◽  
Highly Sensitive ◽  
The World ◽  
Health Organization

ABSTRACT Over the past ten years, standard diagnostics for cryptococcal meningitis in HIV-infected persons have evolved from culture to India ink to detection of cryptococcal antigen (CrAg), with the recent development and distribution of a point-of-care lateral flow assay. This assay is highly sensitive and specific in cerebrospinal fluid (CSF), but is also sensitive in the blood to detect CrAg prior to meningitis symptoms. CrAg screening of HIV-infected persons in the blood prior to development of fulminant meningitis and preemptive treatment for CrAg-positive persons are recommended by the World Health Organization and many national HIV guidelines. Thus, CrAg testing is occurring more widely, especially in resource-limited laboratory settings. CrAg titer predicts meningitis and death and could be used in the future to customize therapy according to burden of infection.

scholarly journals Multiplex paper-based designs for point-of-care (POC) diagnostics

2017 ◽  
Vol 5 (11) ◽  
pp. 5052 ◽  
Author(s):  
Misago Seth ◽  
Joram Buza
Keyword(s):  
Limit Of Detection ◽  
Point Of Care ◽  
Low Cost ◽  
World Health ◽  
Virus Surface ◽  
Resource Limited ◽  
Wax Printing ◽  
Reaction Zones ◽  
Health Organization ◽  
Single Strip

Background: Accurate and timely diagnosis is usually the first step towards appropriate disease management. In resource-limited settings, healthcare workers lack proper facilities to perform vital tests, and the diagnosis of disease is often determined by non-specific, physiological symptoms alone. Simple and rapid tests are needed as prerequisite tools for patient care and must conform to the criteria set out by the World Health Organization. To address the challenge of specific diagnosis for diseases that present with similar symptoms, multiplex diagnostic platforms must be designed.Methods: Simple designs for multiplexed paper-based diagnostic platforms were developed. Laser cutting and wax printing were used to create specific patterns on paper to guide the flow of sample and reagents towards reaction zones. Multi-arm and single strip multiplex platforms were designed and tested using Human Immunoglobulin G, Hepatitis B virus surface antigen (HBsAg), and Helicobacter pylori antigens.Results: All designs produced promising results with the lowest limit of detection for antigens being 30ng/ml for single strip designs.Conclusions: The use of glass fibre conjugate pad was found to be more sensitive compared wax-printed chromatography paper. Results from this study indicate great potential for further application in development of diagnostic low-cost paper-based diagnostic devices.

scholarly journals A Scoping Review Protocol for Supply Chain Management Systems for Point of Care Diagnostics Services: Optimising COVID-19 Testing Capacity in Resource-limited Settings

2021 ◽  
Author(s):  
Kuhlula Maluleke ◽  
Thobeka Dlangalala ◽  
Alfred Musekiwa ◽  
Kabelo Kgarosi ◽  
Sphamandla Nkambule ◽  
...  
Keyword(s):  
Supply Chain ◽  
Supply Chain Management ◽  
Scoping Review ◽  
Point Of Care ◽  
Scientific Journal ◽  
World Health ◽  
Future Research ◽  
Resource Limited Settings ◽  
Chain Management ◽  
Resource Limited

Abstract BackgroundRapid and specific diagnostic tests are essential for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) testing to allow prompt isolation and early treatment initiation if necessary. Currently, reverse transcription polymerase chain reaction (RT-PCR) tests are the gold standard for SARS-CoV-2 testing but are difficult to implement in resource-limited settings with poor access to laboratory infrastructure. Point of care (POC) testing may be more feasible in resource-limited settings because POC testing is cost-effective, easy to perform, results are rapid, and they can be performed at all levels of healthcare by health professionals with minimal training. To ensure equitable access, it is important that SARS-CoV-2 testing is optimised through well-established supply chain management (SCM). Here we outline a protocol for a scoping review aimed at mapping literature on SCM for POC testing in resource limited settings to guide both future research and the implementation of SARS-CoV-2 POC diagnostics. MethodologyThis scoping review will be guided by an adapted version of the Arksey and O’Malley methodological framework. We will search the Medline Ovid, Medline EBSCO, Scopus, PubMed, PsychInfo, Web of Science and EBSCOHost databases. We will search gray literature in the form of dissertations/theses, conference proceedings, websites of international organisations such as the World Health Organisation and government reports. We will include articles reporting evidence published since inception. Language restrictions will not be applied. We will use a search summary table to test the effectiveness of the search strategy. Two reviewers will screen eligible studies using a tool developed for this scoping review. The quality of the included studies will be appraised using the mixed method appraisal tool (MMAT) version 2018. Discussion The proposed scoping review will gather relevant studies on SCM systems for POC diagnostics services globally. We anticipate that this review’s findings will guide future research on SCM systems for POC diagnostics services in resource-limited settings. The results will be published in a scientific journal, presented at relevant conferences and form part of workshops with key stakeholders involved in SCM systems for POC diagnostics services.

scholarly journals Detecting tuberculosis: rapid tools but slow progress

2019 ◽  
Vol 9 (3) ◽  
pp. 80-83
Author(s):  
K. England ◽  
T. Masini ◽  
E. Fajardo
Keyword(s):  
Point Of Care ◽  
Scale Up ◽  
Critical Issue ◽  
World Health ◽  
High Turnover ◽  
Low Resource Settings ◽  
Laboratory Staff ◽  
Low Resource ◽  
Point Of Care Test ◽  
Health Organization

The World Health Organization (WHO) currently recommends Xpert® MTB/RIF as the initial test for all people with presumptive tuberculosis (TB). A number of challenges have been reported, however, in using this technology, particularly in low-resource settings. Here we examine these challenges, and provide our perspective of the barriers to Xpert scale-up as assessed through a survey in 16 TB burden countries in which the Médecins Sans Frontières is present. We observed that the key barriers to scale-up include a lack of policy adoption and implementation of WHO recommendations for the use of Xpert, resulting from high costs, poor sensitisation of clinical staff and a high turnover of trained laboratory staff; insufficient service and maintenance provision provided by the manufacturer; and inadequate resources for sustainability and expansion. Funding is a critical issue as countries begin to transition out of support from the Global Fund. While it is clear that there is still an urgent need for research into and development of a rapid, affordable point-of-care test for TB that is truly adapted for use in low-resource settings, countries in the meantime need to develop functional and sustainable Xpert networks in order to close the existing diagnostic gap.

scholarly journals Multidrug-resistant tuberculosis infection and disease in children: a review of new and repurposed drugs

2019 ◽  
Vol 6 ◽  
pp. 204993611986473 ◽  
Author(s):  
Julie Huynh ◽  
Ben J. Marais
Keyword(s):  
Clinical Care ◽  
Multidrug Resistant ◽  
World Health ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Resource Limited ◽  
Prevention And Treatment ◽  
Mdr Tb ◽  
Repurposed Drugs ◽  
Health Organization

The World Health Organization estimates that 10 million new cases of tuberculosis (TB) occurred worldwide in 2017, of which 600,000 were rifampicin or multidrug-resistant (RR/MDR) TB. Modelling estimates suggest that 32,000 new cases of MDR-TB occur in children annually, but only a fraction of these are correctly diagnosed and treated. Accurately diagnosing TB in children, who usually have paucibacillary disease, and implementing effective TB prevention and treatment programmes in resource-limited settings remain major challenges. In light of the underappreciated RR/MDR-TB burden in children, and the lack of paediatric data on newer drugs for TB prevention and treatment, we present an overview of new and repurposed TB drugs, describing the available evidence for safety and efficacy in children to assist clinical care and decision-making.

scholarly journals A Model of Tuberculosis Screening for Pregnant Women in Resource-Limited Settings Using Xpert MTB/RIF

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Eleanor R. Turnbull ◽  
Nzali G. Kancheya ◽  
Jennifer B. Harris ◽  
Stephanie M. Topp ◽  
German Henostroza ◽  
...  
Keyword(s):  
Pregnant Women ◽  
World Health ◽  
Diagnostic Tools ◽  
Tuberculosis Screening ◽  
Pilot Studies ◽  
Resource Limited ◽  
Highly Sensitive ◽  
Mother And Child ◽  
Health Organization ◽  
Diagnostic Technologies

Timely diagnosis and treatment of maternal tuberculosis (TB) is important to reduce morbidity and mortality for both the mother and child, particularly in women who are coinfected with HIV. The World Health Organization (WHO) recommends the integration of TB/HIV screening into antenatal services but available diagnostic tools are slow and insensitive, resulting in delays in treatment initiation. Recently the WHO endorsed Xpert MTB/RIF, a highly sensitive, real-time PCR assay forMycobacterium tuberculosisthat simultaneously detects rifampicin resistance directly from sputum and provides results within 100 minutes. We propose a model for same-day TB screening and diagnosis of all pregnant women at antenatal care using Xpert MTB/RIF. Pilot studies are urgently required to evaluate strategies for the integration of TB screening into antenatal clinics using new diagnostic technologies.

scholarly journals Factors Associated with Outcomes of Pre-ART HIV Care

2018 ◽  
Vol 17 ◽  
pp. 232595821875960
Author(s):  
Kristen A. Stafford ◽  
Lucy W. Nganga ◽  
Tuhuma Tulli ◽  
Karen G. Fleischman Foreit
Keyword(s):  
Disease Progression ◽  
Opportunistic Infections ◽  
World Health ◽  
Hiv Care ◽  
Cox Models ◽  
Factors Associated ◽  
Art Initiation ◽  
Resource Limited ◽  
Health Organization ◽  
Lost To Follow Up

The World Health Organization recommended removing all CD4 requirements for initiation of antiretroviral therapy (ART) in resource-limited settings. We examined the pre-ART period to identify and assess factors associated with outcomes of pre-ART care. Four modes of transition out of pre-ART care were considered. Beta estimates from the competing risks Cox models were used to investigate whether the effects of covariates differed by mode of transition. Median CD4 counts at entry showed no meaningful change over time. Advanced disease progression and presence of opportunistic infections were significant predictors of pre-ART mortality. Men were more likely to die before initiating ART, transfer to another facility, or be lost to follow-up than were women. Removing CD4 thresholds is not likely to substantially reduce program mortality prior to ART initiation unless and until patients enroll earlier in disease progression. Care programs should focus on diagnosis and treatment of opportunistic infections to reduce pre-ART mortality.

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