Diagnostics in a digital age- ASSURED approach- An opportunity to strengthen health systems

Diagnostics play a critical role in clinical decision making, disease control and prevention. Rapid point of care (POC) tests for infectious diseases can improve access to diagnosis and patient management, but the quality of these tests vary, as quality of testing is often not assured and there are few mechanisms to capture test results for surveillance when the testing is decentralised. A new generation of POC molecular tests that are highly sensitive and specific, robust and easy to use are now available for deployment in low resource settings.

Decentralisation of testing outside of the laboratory can put tremendous stress on the healthcare system and presents challenges for training and quality assurance. A feature of many of these POC molecular devices is that they are equipped with data transmission capacities. In a digital age, it is possible to link data from diagnostic laboratories and POC test readers and devices to provide data on testing coverage, disease trends and timely information for early warning of infectious disease outbreaks to inform design or optimisation of disease control and elimination programmes.

Data connectivity also allows control programmes to monitor the quality of tests and testing and optimise supply chain management. Thus, increasing the efficiency of healthcare systems and improving patient outcomes. Diagnostics and laboratory are important tools in prevention and treatment of diseases. In the past, ineffective laboratory services resulted in a mistrust of laboratory results, which in turn led to a decreasing demand for laboratory services. Recent outbreaks of influenza, Covid-19 and Ebola virus disease illustrate the importance of diagnostics in outbreak investigations. With rapid technological innovations in the last 10 years and investments in the development of improved diagnostics for infectious diseases of public health importance, it is time to re-examine the capabilities and explore the promises and role of diagnostics in a digital age.

The role of diagnostics
Accurate diagnostic tests play a key role in clinician trust and patient management. Diagnostic testing is traditionally considered as a tool to rule in or rule out a condition or infection when clinical presentation in a patient is nonspecific. Diagnostics are used to screen for infection so that treatment can be given to prevent the development of long-term complications.

Beyond patient management, diagnostics play a critical role in various aspects of public health through disease prevention and control. Diagnostics are critical in surveillance, to monitor trends in disease and antimicrobial resistance and assess the impact of interventions.

There is often little commercial interest in the development of diagnostics that are used mainly for surveillance because of the low return on investment.

Recent technological advances in diagnostics
Diagnostic testing is usually performed in laboratories. In countries where the laboratory infrastructure is limited, WHO advocates for the use of a syndromic approach for patient management whereby patients are treated for all the major causes of that syndrome. This often leads to overtreatment and increases risk for the development of antimicrobial resistance. In the last decade, rapid point-of-care (POC) diagnostic tests fulfilling the ASSURED criteria (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free and Deliverable) have become commercially available and are widely used for infectious diseases such as malaria, HIV and Hepatitis.

These tests have allowed control of programmes to increase access to testing, identify those who need to be put on treatment, optimize disease control and save lives. However, the quality of these tests varies, quality of testing is often not assured and there are few mechanisms to capture test results for surveillance when the testing is so decentralized.

Improving surveillance
The simplest POC diagnostic tests that are widely used today are rapid diagnostics tests (RDTs) in a lateral flow format. These are read with the naked eye, which is subjective and prone to human error and may be further exacerbated by poor lighting in health posts. In addition, RDTs lack on-board quality control and are often used in remote areas where health workers receive minimal training. As a result, accuracy of RDTs performed in the field can be quite variable. This may adversely affect patientcare and the accuracy of the data gathered for surveillance.

Several RDT readers are already in the market and others are in the pipeline. Given the widespread adoption of smartphones in resource-limited settings, RDT readers using this technology have the potential to combine high-resolution test images with the computing capability required to run image analysis software and transmit data. The readers range in price depending on the technical complexity of the instrument and their compatibility with the type of RDTs.

POC molecular assays
Molecular assays offer superior diagnostic performance compared to the limit of detection of immunoassays. In the last two decades, nucleic acid amplification tests (NAATs) have become the ‘gold’ or reference standard to which the performance of other diagnostic tests are compared. Until recently, they have remained largely laboratory based and are expensive and inaccessible. Several POC molecular assays, with or without amplification, are now on the horizon that may transform the delivery of health services.

Emerging diagnostic technologies to transform disease surveillance
A new generation of immunoassays, molecular and nanotechnology platforms has been developed in recent years that can improve patient management and disease surveillance. These platforms have superior performance and make use of optical readers, mobile phones and data transmission capabilities to improve reading of results and data transmission. Such technologies provide real-time results to inform patient management decisions.

Data, linked to precise geographical locations using GPS, can be transmitted to a central database to inform disease control programmes or to monitor progress towards elimination. Many of these assays can also yield quantitative results to give estimates of pathogen copy number or, in the case of HIV, to monitor treatment compliance or efficacy. These technology platforms can also be used to detect multiple targets from a single specimen.

For geographic areas with multiple diseases targeted for elimination, if surveillance is conducted in the same sentinel population, such as children under the age of 10 years, using the same specimen, such as a blood sample, exposure to multiple NTDs can be detected on a multiplex platform. This may be a more cost-effective means of conducting post-MDA surveillance than collecting specimens and testing for a single NTD at a time, although cost-effectiveness of using these platforms for multiple NTDs remains to be demonstrated. Increased sensitivity of detection using these advances has made it possible to have tests that detect antibodies from oral fluids. The use of these non-invasive specimens has made it possible to design HIV tests for self-testing or for home use internationally.

The promise of diagnostics in a digital age
In a digital age, data from social media and POC diagnostics in communities can be used to provide early warning for infectious disease outbreaks, and timely information to inform disease control and elimination programmes. For example, iSense project running in UK. The iSense project (http://www.i-sense.org.uk/research), an EPSRC IRC funded project in Early Warning Sensing systems in Infectious Diseases, aims to create low-cost latent sensing systems to analyze self-reported symptoms on the web, including social networks and micro-blogging sites (Twitter) and searches (Bing, Google). iSense will develop a new generation of early warning sensing systems to identify outbreaks of deadly infectious diseases, such as flu, methicillin-resistant staphylococcus aureus (MRSA) and HIV, by linking self-reported symptoms on the web to a new sensor-enabled disease surveillance infrastructure for an early warning sensing system for infectious diseases.

Improving supply chain management
Real-time data monitoring via electronic readers could help to improve coordination of supply chain management by multiple partners. Operational data on stocks, device usage and condition can be uploaded via Wi-Fi or cellular networks and transmitted to central databases. By linking the data to supply chain management software, stock-outs can potentially be avoided and health system efficiency improved.

Outlook
The new generation of diagnostics equipped with digital technologies are transforming the field of clinical decision-making and disease control and prevention. Rapid POC tests for infectious diseases can improve access to diagnosis and patient management, but the quality of these tests varies, quality of testing is often not assured and there are few mechanisms to capture test results for surveillance when the testing is so decentralized. Electronic readers have the potential to provide fast, accurate, standardized RDT interpretation and real-time data reporting with a huge range of positive functions, including improving quality assurance, supply chain management and providing accurate timely data for surveillance.

Although countries need to consider data governance and confidentiality issues, data connectivity allows control programmes to monitor the quality of tests and testing, and optimize supply chain management; thus, increasing the efficiency of healthcare systems and improving patient outcomes.