Mobile health, or 'mHealth', is the application of mobile devices, their components and related technologies to healthcare. It is already improving patients' access to treatment and advice. Now, in ...combination with internet-connected diagnostic devices, it offers novel ways to diagnose, track and control infectious diseases and to improve the efficiency of the health system. Here we examine the promise of these technologies and discuss the challenges in realizing their potential to increase patients' access to testing, aid in their treatment and improve the capability of public health authorities to monitor outbreaks, implement response strategies and assess the impact of interventions across the world.
Ebola virus disease causes widespread and highly fatal epidemics in human populations. Today, there is still great need for point-of-care tests for diagnosis, patient management and surveillance, ...both during and post outbreaks. We present a point-of-care test comprising an immunochromatographic strip and a smartphone reader, which detects and semiquantifies Ebola-specific antibodies in human survivors. We developed a Sudan virus glycoprotein monoplex platform and validated it using sera from 90 human survivors and 31 local noninfected controls. The performance of the glycoprotein monoplex was 100% sensitivity and 98% specificity compared to standard whole antigen enzyme-linked immunosorbent assay (ELISA), and it was validated with freshly collected patient samples in Uganda. Moreover, we constructed a multiplex test for simultaneous detection of antibodies against three recombinant Sudan virus proteins. A pilot study comprising 15 survivors and 5 noninfected controls demonstrated sensitivity and specificity of 100% compared to standard ELISA. Finally, we developed a second multiplex subtype assay for the identification of exposure to three related EVD species: Sudan virus, Bundibugyo virus and Ebola virus (formerly Zaire) using recombinant viral glycoprotein. This multiplex test could distinguish between the host’s immunity to specific viral species and identify cross-reactive immunity. These developed serological platforms consisted of capture ligands with high specificity and sensitivity, in-house developed strips and a compatible smartphone application. These platforms enabled rapid and portable testing, data storage and sharing as well as geographical tagging of the tested individuals in Uganda. This platform holds great potential as a field tool for diagnosis, vaccine development, and therapeutic evaluation.
The COVID-19 pandemic is challenging diagnostic testing capacity worldwide. The mass testing needed to limit the spread of the virus requires new molecular diagnostic tests to dramatically widen ...access at the point-of-care in resource-limited settings. Isothermal molecular assays have emerged as a promising technology, given the faster turn-around time and minimal equipment compared to gold standard laboratory PCR methods. However, unlike PCR, they do not typically target multiple SARS-CoV-2 genes, risking sensitivity and specificity. Moreover, they often require multiple steps thus adding complexity and delays. Here we develop a multiplexed, 1–2 step, fast (20–30 min) SARS-CoV-2 molecular test using reverse transcription recombinase polymerase amplification to simultaneously detect two conserved targets - the E and RdRP genes. The agile multi-gene platform offers two complementary detection methods: real-time fluorescence or dipstick. The analytical sensitivity of the fluorescence test was 9.5 (95% CI: 7.0–18) RNA copies per reaction for the E gene and 17 (95% CI: 11–93) RNA copies per reaction for the RdRP gene. The analytical sensitivity for the dipstick method was 130 (95% CI: 82–500) RNA copies per reaction. High specificity was found against common seasonal coronaviruses, SARS-CoV and MERS-CoV model samples. The dipstick readout demonstrated potential for point-of-care testing in decentralised settings, with minimal or equipment-free incubation methods and a user-friendly prototype smartphone application. This rapid, simple, ultrasensitive and multiplexed molecular test offers valuable advantages over gold standard tests and in future could be configurated to detect emerging variants of concern.
•Rapid nucleic acid testing of SARS-CoV-2 simultaneously targeting multiple genes.•Isothermal amplification by RT-RPA using two complementary readouts.•Simple and equipment-free incubation methods for point-of-care application.•Towards a smartphone-connected dipstick test for decentralised testing.
Digital technologies are being harnessed to support the public-health response to COVID-19 worldwide, including population surveillance, case identification, contact tracing and evaluation of ...interventions on the basis of mobility data and communication with the public. These rapid responses leverage billions of mobile phones, large online datasets, connected devices, relatively low-cost computing resources and advances in machine learning and natural language processing. This Review aims to capture the breadth of digital innovations for the public-health response to COVID-19 worldwide and their limitations, and barriers to their implementation, including legal, ethical and privacy barriers, as well as organizational and workforce barriers. The future of public health is likely to become increasingly digital, and we review the need for the alignment of international strategies for the regulation, evaluation and use of digital technologies to strengthen pandemic management, and future preparedness for COVID-19 and other infectious diseases.
Schistosomiasis is a major neglected tropical disease targeted for elimination as a public health issue by 2030, however there is an urgent need for more sensitive and specific diagnostic tests ...suitable to resource-limited settings. Here we developed CATSH, a CRISPR-assisted diagnostic test for Schistosoma haematobium, utilising recombinase polymerase amplification, Cas12a-targeted cleavage and portable real-time fluorescence detection. CATSH showed high analytical sensitivity, consistent detection of a single parasitic egg and specificity for urogenital Schistosoma species. Thanks to a novel CRISPR-compatible sample preparation developed using simulated urine samples containing parasitic eggs, CATSH had a sample-to-result within 2 h. The components of CATSH can be lyophilised, reducing cold chain dependence and widening access to lower and middle-income countries. This work presents a new application of CRISPR diagnostics for highly sensitive and specific detection of parasitic pathogens in remote areas and could have a significant impact on the elimination of neglected tropical diseases.
Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to ...describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant.
In this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths.
Of 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio PR 0·97 95% CI 0·72–1·31), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 0·76–1·38). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 SD 4·7 vs 32·0 4·8; p=0·0085) and genomic read depth (1280 1004 vs 831 682; p=0·0011).
Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort.
University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council.
The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications
. However, fluorescent nanodiamonds also have attractive ...properties for in vitro biosensing, including brightness
, low cost
and selective manipulation of their emission
. Nanoparticle-based biosensors are essential for the early detection of disease, but they often lack the required sensitivity. Here we investigate fluorescent nanodiamonds as an ultrasensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity
and frequency-domain analysis
to separate the signal from background autofluorescence
, which typically limits sensitivity. Focusing on the widely used, low-cost lateral flow format as an exemplar, we achieve a detection limit of 8.2 × 10
molar for a biotin-avidin model, 10
times more sensitive than that obtained using gold nanoparticles. Single-copy detection of HIV-1 RNA can be achieved with the addition of a 10-minute isothermal amplification step, and is further demonstrated using a clinical plasma sample with an extraction step. This ultrasensitive quantum diagnostics platform is applicable to numerous diagnostic test formats and diseases, and has the potential to transform early diagnosis of disease for the benefit of patients and populations.
Paper-based lateral flow immunoassays (LFIAs) are one of the most widely used point-of-care (PoC) devices; however, their application in early disease diagnostics is often limited due to insufficient ...sensitivity for the requisite sample sizes and the short time frames of PoC testing. To address this, we developed a serum-stable, nanoparticle catalyst-labeled LFIA with a sensitivity surpassing that of both current commercial and published sensitivities for paper-based detection of p24, one of the earliest and most conserved biomarkers of HIV. We report the synthesis and characterization of porous platinum core–shell nanocatalysts (PtNCs), which show high catalytic activity when exposed to complex human blood serum samples. We explored the application of antibody-functionalized PtNCs with strategically and orthogonally modified nanobodies with high affinity and specificity toward p24 and established the key larger nanoparticle size regimes needed for efficient amplification and performance in LFIA. Harnessing the catalytic amplification of PtNCs enabled naked-eye detection of p24 spiked into sera in the low femtomolar range (ca. 0.8 pg·mL–1) and the detection of acute-phase HIV in clinical human plasma samples in under 20 min. This provides a versatile absorbance-based and rapid LFIA with sensitivity capable of significantly reducing the HIV acute phase detection window. This diagnostic may be readily adapted for detection of other biomolecules as an ultrasensitive screening tool for infectious and noncommunicable diseases and can be capitalized upon in PoC settings for early disease detection.
Although deep learning algorithms show increasing promise for disease diagnosis, their use with rapid diagnostic tests performed in the field has not been extensively tested. Here we use deep ...learning to classify images of rapid human immunodeficiency virus (HIV) tests acquired in rural South Africa. Using newly developed image capture protocols with the Samsung SM-P585 tablet, 60 fieldworkers routinely collected images of HIV lateral flow tests. From a library of 11,374 images, deep learning algorithms were trained to classify tests as positive or negative. A pilot field study of the algorithms deployed as a mobile application demonstrated high levels of sensitivity (97.8%) and specificity (100%) compared with traditional visual interpretation by humans-experienced nurses and newly trained community health worker staff-and reduced the number of false positives and false negatives. Our findings lay the foundations for a new paradigm of deep learning-enabled diagnostics in low- and middle-income countries, termed REASSURED diagnostics
, an acronym for real-time connectivity, ease of specimen collection, affordable, sensitive, specific, user-friendly, rapid, equipment-free and deliverable. Such diagnostics have the potential to provide a platform for workforce training, quality assurance, decision support and mobile connectivity to inform disease control strategies, strengthen healthcare system efficiency and improve patient outcomes and outbreak management in emerging infections.
Previous research has demonstrated that various properties of infectious diseases can be inferred from online search behaviour. In this work we use time series of online search query frequencies to ...gain insights about the prevalence of COVID-19 in multiple countries. We first develop unsupervised modelling techniques based on associated symptom categories identified by the United Kingdom's National Health Service and Public Health England. We then attempt to minimise an expected bias in these signals caused by public interest-as opposed to infections-using the proportion of news media coverage devoted to COVID-19 as a proxy indicator. Our analysis indicates that models based on online searches precede the reported confirmed cases and deaths by 16.7 (10.2-23.2) and 22.1 (17.4-26.9) days, respectively. We also investigate transfer learning techniques for mapping supervised models from countries where the spread of the disease has progressed extensively to countries that are in earlier phases of their respective epidemic curves. Furthermore, we compare time series of online search activity against confirmed COVID-19 cases or deaths jointly across multiple countries, uncovering interesting querying patterns, including the finding that rarer symptoms are better predictors than common ones. Finally, we show that web searches improve the short-term forecasting accuracy of autoregressive models for COVID-19 deaths. Our work provides evidence that online search data can be used to develop complementary public health surveillance methods to help inform the COVID-19 response in conjunction with more established approaches.
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