Each year, infectious diseases are responsible for millions of deaths, most of which occur in the rural areas of developing countries. Many of the infectious disease diagnostic tools used today require a great deal of time, a laboratory setting, and trained personnel. Due to this, the need for effective point-of-care (POC) diagnostic tools is greatly increasing with an emphasis on affordability, portability, sensitivity, specificity, timeliness, and ease of use. In this Review, we discuss the various diagnostic modalities that have been utilized toward this end and are being further developed to create POC diagnostic technologies, and we focus on potential effectiveness in resource-limited settings. The main modalities discussed herein are optical-, electrochemical-, magnetic-, and colorimetric-based modalities utilized in diagnostic technologies for infectious diseases. Each of these modalities feature pros and cons when considering application in POC settings but, overall, reveal a promising outlook for the future of this field of technological development.
Contact tracing was one of the core public health strategies implemented during the first months of the COVID-19 pandemic. In this essay, we describe the rapid establishment of a volunteer contact tracing program in New Haven, Connecticut. We describe successes of the program and challenges that were faced. Going forward, contact tracing efforts can best be supported by increased funding to state and local health departments for a stable workforce and use of evidence-based technological innovations. (Am J Public Health. Published online ahead of print November 19, 2020: e1–e4. https://doi.org/10.2105/AJPH.2020.305959 )
Background Contact tracing is an important tool for suppressing COVID-19 but has been difficult to adapt to the conditions of a public health emergency. This study explored the experiences and perspectives of volunteer contact tracers in order to identify facilitators, challenges, and novel solutions for implementing COVID-19 contact tracing. Methods As part of a study to evaluate an emergently established volunteer contact tracing program for COVID-19 in New Haven, Connecticut, April-June 2020, we conducted focus groups with 36 volunteer contact tracers, thematically analyzed the data, and synthesized the findings using the RE-AIM implementation framework. Results To successfully reach cases and contacts, participants recommended identifying clients’ outreach preferences, engaging clients authentically, and addressing sources of mistrust. Participants felt that the effectiveness of successful isolation and quarantine was contingent on minimizing delays in reaching clients and on systematically assessing and addressing their nutritional, financial, and housing needs. They felt that successful adoption of a volunteer-driven contact tracing model depended on the ability to recruit self-motivated contact tracers and provide rapid training and consistent, supportive supervision. Participants noted that implementation could be enhanced with better management tools, such as more engaging interview scripts, user-friendly data management software, and protocols for special situations and populations. They also emphasized the value of coordinating outreach efforts with other involved providers and agencies. Finally, they believed that long-term maintenance of a volunteer-driven program requires monetary or educational incentives to sustain participation. Conclusions This is one of the first studies to qualitatively examine implementation of a volunteer-run COVID-19 contact tracing program. Participants identified facilitators, barriers, and potential solutions for improving implementation of COVID-19 contact tracing in this context. These included standardized communication skills training, supportive supervision, and peer networking to improve implementation, as well as greater cooperation with outside agencies, flexible scheduling, and volunteer incentives to promote sustainability.
Enterohemorrhagic Escherichia coli O157:H7 presents a serious threat to human health and sanitation and is a leading cause in many food- and waterborne ailments. While conventional bacterial detection methods such as PCR, fluorescent immunoassays and ELISA exhibit high sensitivity and specificity, they are relatively laborious and require sophisticated instruments. In addition, these methods often demand extensive sample preparation and have lengthy readout times. We propose a simpler and more sensitive diagnostic technique featuring multiparametric magneto-fluorescent nanosensors (MFnS). Through a combination of magnetic relaxation and fluorescence measurements, our nanosensors are able to detect bacterial contamination with concentrations as little as 1 colony-forming unit (CFU). The magnetic relaxation property of our MFnS allow for sensitive screening at low target CFU, which is complemented by fluorescence measurements of higher CFU samples. Together, these qualities allow for the detection and quantification of broad-spectrum contaminations in samples ranging from aquatic reservoirs to commercially produced food.
Background: Contact tracing is a core element of the public health response to emerging infectious diseases including COVID-19. Better understanding the implementation context of contact tracing for pandemics, including individual- and systems-level predictors of success, is critical to preparing for future epidemics.Methods: We carried out a prospective implementation study of an emergency volunteer contact tracing program established in New Haven, Connecticut between April 4 and May 19, 2020. We assessed the yield and timeliness of case and contact outreach in reference to CDC benchmarks, and identified individual and programmatic predictors of successful implementation using multivariable regression models. We synthesized our findings using the RE-AIM implementation framework.Results: Case investigators interviewed only 826 (48%) of 1,705 cases and were unable to reach 545 (32%) because of incomplete information and 334 (20%) who missed or declined repeated outreach calls. Contact notifiers reached just 687 (28%) of 2,437 reported contacts, and were unable to reach 1,597 (66%) with incomplete information and 153 (6%) who missed or declined repeated outreach calls. The median time-to-case-interview was 5 days and time-to-contact-notification 8 days. However, among notified contacts with complete time data, 457 (71%) were reached within 6 days of exposure. The least likely groups to be interviewed were elderly (adjusted relative risk, aRR 0.74, 95% CI 0.61–0.89, p = 0.012, vs. young adult) and Black/African-American cases (aRR 0.88, 95% CI 0.80–0.97, pairwise p = 0.01, vs. Hispanic/Latinx). However, ties between cases and their contacts strongly influenced contact notification success (Intraclass Correlation Coefficient (ICC) 0.60). Surging caseloads and high volunteer turnover (case investigator n = 144, median time from sign-up to retirement from program was 4 weeks) required the program to supplement the volunteer workforce with paid public health nurses.Conclusions: An emergency volunteer-run contact tracing program fell short of CDC benchmarks for time and yield, largely due to difficulty collecting the information required for outreach to cases and contacts. To improve uptake, contact tracing programs must professionalize the workforce; better integrate testing and tracing services; capitalize on positive social influences between cases and contacts; and address racial and age-related disparities through enhanced community engagement.
K-RAS driven non-small-cell lung cancer (NSCLC) represents a major cause of death among smokers. Recently, nanotechnology has introduced novel avenues for the diagnosis and personalized treatment options for cancer. Herein, we report a novel, multifunctional nanoceria platform loaded with a unique combination of two therapeutic drugs, doxorubicin (Doxo) and Hsp90 inhibitor ganetespib (GT), for the diagnosis and effective treatment of NSCLC. We hypothesize that the use of ganetespib synergizes and accelerates the therapeutic efficacy of Doxo via ROS production, while minimizing the potential cardiotoxicity of doxorubicin drug. Polyacrylic acid (PAA)-coated cerium oxide nanoparticles (PNC) were fabricated for the targeted combination therapy of lung cancers. Using "click" chemistry, the surface carboxylic acid groups of nanoceria were decorated with folic acid to target folate-receptor-overexpressing NSCLC. As a result of combination therapy, results showed more than 80% of NSCLC death within 48 h of incubation. These synergistic therapeutic effects were assessed via enhanced ROS, cytotoxicity, apoptosis, and migration assays. Overall, these results indicated that the targeted codelivery of Doxo and GT using nanoceria may offer an alternative combination therapy option for the treatment of undruggable NSCLC.
Rapid detection and diagnosis of pathogenic strains of influenza is necessary for expedited treatment and quicker resolutions to the ever-rising flu pandemics. Considering this, we propose the development of novel magnetic relaxation nanosensors (MRnS) for the rapid detection of influenza through targeted binding with hemagglutinin. 2,6- and 2,3-sialic acid ligands and entry blocker peptides are conjugated to iron oxide nanoparticles to create functional MRnS. Positive detection of various hemagglutinin variants (H1 and H5) is possible with protein concentrations as little as 1.0 nM. Most importantly, detection using functional MRnS is achieved within minutes and differentiates between influenza subtypes. This specificity allows mixtures of MRnS to screen for multiple pathogens at once, discarding the need to conduct multiple individual tests. Current methods used to diagnose influenza, such as RT-PCR and viral culturing, while largely effective, are complex, time-consuming and costly. As well, they are not as sensitive or specific, and have been known to produce false-positive results. In contrast to these methods, targeted MRnS are robust, point-of-care diagnostic tools featuring simple, rapid and low-cost procedures. These qualities, as well as high sensitivity and specificity, and low turnaround times, make a strong case for the diagnostic application of MRnS in clinical settings.
The aim of this research is twofold: 1) to shed light on zika’s binding and entry mechanism while 2) demonstrating the effectiveness of our magnetic relaxation platform to achieve this goal. Magnetic relaxation-sensitive nanoparticles (MRNPs) are used in a novel fashion to analyze binding interactions between the zika envelope protein (ZENV) and proposed host cell receptors: AXL, HSP70, and TIM-1. Computational analysis is also utilized to examine these binding interactions for the first time. In addition, the role of crizotinib as a potential binding inhibitor is demonstrated and the possibility of ligand-independent phosphatidylserine-mediated binding is explored. Our findings suggest that while the extracellular domain of AXL has the highest affinity for ZENV; HSP70, TIM-1, and phosphatidylserine might also play active roles in zika tropism, which offers a potential explanation for the variety of zika-associated symptoms. This is, to our knowledge, the first time that MRNPs have been used to examine and quantify host-zika interactions. Our magnetic relaxation platform allows for timely and sensitive analysis of these intricate binding relationships, and it is easily customizable for further examination of additional host-pathogen interactions.
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