Infectious diseases claim millions of lives each year. Robust and accurate diagnostics are essential tools for identifying those who are at risk and in need of treatment in low-resource settings. Inorganic complexes and metal-based nanomaterials continue to drive the development of diagnostic platforms and strategies that enable infectious disease detection in low-resource settings. In this review, we highlight works from the past 20 years in which inorganic chemistry and nanotechnology were implemented in each of the core components that make up a diagnostic test. First, we present how inorganic biomarkers and their properties are leveraged for infectious disease detection. In the following section, we detail metal-based technologies that have been employed for sample preparation and biomarker isolation from sample matrices. We then describe how inorganic- and nanomaterial-based probes have been utilized in point-of-care diagnostics for signal generation. The following section discusses instrumentation for signal readout in resource-limited settings. Next, we highlight the detection of nucleic acids at the point of care as an emerging application of inorganic chemistry. Lastly, we consider the challenges that remain for translation of the aforementioned diagnostic platforms to low-resource settings.

Background The 16S rRNA gene is used extensively in bacterial phylogenetics, in species delineation, and now widely in microbiome studies. However, the gene suffers from intragenomic heterogeneity, and reports of recombination and an unreliable phylogenetic signal are accumulating. Here, we compare core gene phylogenies to phylogenies constructed using core gene concatenations to estimate the strength of signal for the 16S rRNA gene, its hypervariable regions, and all core genes at the intra- and inter-genus levels. Specifically, we perform four intra-genus analyses (Clostridium, n = 65; Legionella, n = 47; Staphylococcus, n = 36; and Campylobacter, n = 17) and one inter-genus analysis [41 core genera of the human gut microbiome (31 families, 17 orders, and 12 classes), n = 82]. Results At both taxonomic levels, the 16S rRNA gene was recombinant and subject to horizontal gene transfer. At the intra-genus level, the gene showed one of the lowest levels of concordance with the core genome phylogeny (50.7% average). Concordance for hypervariable regions was lower still, with entropy masking providing little to no benefit. A major factor influencing concordance was SNP count, which showed a positive logarithmic association. Using this relationship, we determined that 690 ± 110 SNPs were required for 80% concordance (average 16S rRNA gene SNP count was 254). We also found a wide range in 16S-23S-5S rRNA operon copy number among genomes (1–27). At the inter-genus level, concordance for the whole 16S rRNA gene was markedly higher (73.8% — 10th out of 49 loci); however, the most concordant hypervariable regions (V4, V3-V4, and V1-V2) ranked in the third quartile (62.5 to 60.0%). Conclusions Ramifications of a poor phylogenetic performance for the 16S rRNA gene are far reaching. For example, in addition to incorrect species/strain delineation and phylogenetic inference, it has the potential to confound community diversity metrics if phylogenetic information is incorporated — for example, with popular approaches such as Faith’s phylogenetic diversity and UniFrac. Our results highlight the problematic nature of these approaches and their use (along with entropy masking) is discouraged. Lastly, the wide range in 16S rRNA gene copy number among genomes also has a strong potential to confound diversity metrics.

Background The COVID-19 pandemic has drastically changed life in the United States, as the country has recorded over 23 million cases and 383,000 deaths to date. In the leadup to widespread vaccine deployment, testing and surveillance are critical for detecting and stopping possible routes of transmission. Contact tracing has become an important surveillance measure to control COVID-19 in the United States, and mobile health interventions have found increased prominence in this space. Objective The aim of this study was to investigate the use and usability of MyCOVIDKey, a mobile-based web app to assist COVID-19 contact tracing efforts, during the 6-week pilot period. Methods A 6-week study was conducted on the Vanderbilt University campus in Nashville, Tennessee. The study participants, consisting primarily of graduate students, postdoctoral researchers, and faculty in the Chemistry Department at Vanderbilt University, were asked to use the MyCOVIDKey web app during the course of the study period. Paradata were collected as users engaged with the MyCOVIDKey web app. At the end of the study, all participants were asked to report on their user experience in a survey, and the results were analyzed in the context of the user paradata. Results During the pilot period, 45 users enrolled in MyCOVIDKey. An analysis of their enrollment suggests that initial recruiting efforts were effective; however, participant recruitment and engagement efforts at the midpoint of the study were less effective. App use paralleled the number of users, indicating that incentives were useful for recruiting new users to sign up but did not result in users attempting to artificially inflate their use as a result of prize offers. Times to completion of key tasks were low, indicating that the main features of the app could be used quickly. Of the 45 users, 30 provided feedback through a postpilot survey, with 26 (58%) completing it in its entirety. The MyCOVIDKey app as a whole was rated 70.0 on the System Usability Scale, indicating that it performed above the accepted threshold for usability. When the key-in and self-assessment features were examined on their own, it was found that they individually crossed the same thresholds for acceptable usability but that the key-in feature had a higher margin for improvement. Conclusions The MyCOVIDKey app was found overall to be a useful tool for COVID-19 contact tracing in a university setting. Most users suggested simple-to-implement improvements, such as replacing the web app framework with a native app format or changing the placement of the scanner within the app workflow. After these updates, this tool could be readily deployed and easily adapted to other settings across the country. The need for digital contact tracing tools is becoming increasingly apparent, particularly as COVID-19 case numbers continue to increase while more businesses begin to reopen.

Background Mobile health (mHealth) interventions have the potential to transform the global health care landscape. The processing power of mobile devices continues to increase, and growth of mobile phone use has been observed worldwide. Uncertainty remains among key stakeholders and decision makers as to whether global health interventions can successfully tap into this trend. However, when correctly implemented, mHealth can reduce geographic, financial, and social barriers to quality health care. Objective The aim of this study was to design and test Beacon, a mobile phone–based tool for evaluating mHealth readiness in global health interventions. Here, we present the results of an application validation study designed to understand the mobile network landscape in and around Macha, Zambia, in 2019. Methods Beacon was developed as an automated mobile phone app that continually collects spatiotemporal data and measures indicators of network performance. Beacon was used in and around Macha, Zambia, in 2019. Results were collected, even in the absence of network connectivity, and asynchronously uploaded to a database for further analysis. Results Beacon was used to evaluate three mobile phone networks around Macha. Carriers A and B completed 6820/7034 (97.0%) and 6701/7034 (95.3%) downloads and 1349/1608 (83.9%) and 1431/1608 (89.0%) uploads, respectively, while Carrier C completed only 62/1373 (4.5%) file downloads and 0/1373 (0.0%) file uploads. File downloads generally occurred within 4 to 12 seconds, and their maximum download speeds occurred between 2 AM and 5 AM. A decrease in network performance, demonstrated by increases in upload and download durations, was observed beginning at 5 PM and continued throughout the evening. Conclusions Beacon was able to compare the performance of different cellular networks, show times of day when cellular networks experience heavy loads and slow down, and identify geographic “dead zones” with limited or no cellular service. Beacon is a ready-to-use tool that could be used by organizations that are considering implementing mHealth interventions in low- and middle-income countries but are questioning the feasibility of the interventions, including infrastructure and cost. It could also be used by organizations that are looking to optimize the delivery of an existing mHealth intervention with improved logistics management.

Highlights Malaria diagnostics exist at a unique nexus where robustness and usability intersect with a significant need for increased sensitivity. Immobilized metal affinity-functionalized cellulose membranes are a promising tool for increasing the sensitivity of point-of-care malaria diagnostics. For the primary malaria biomarker, histidine-rich protein 2, IMAC membranes were found to increase sensitivity by 15.8-fold compared to traditional methods. IMAC membranes could also be used for capture and recovery of non-histidine rich biomarkers such as Plasmodium lactate dehydrogenase.