The management of infectious diseases remains a critical challenge for public health professionals who face increasing demand to control the spread of existing and novel diseases. To provide appropriate healthcare assistance, it is imperative to diagnose the exact form of infection from an array of complicated symptoms expressed by the host. As the outcome of diagnosis is time-bound, the test accuracy—sensitivity and specificity—plays a key role in determining the disease type, which is vital for delivering enhanced patient care. Point-of-care testing (POCT) has the potential to rapidly identify infectious diseases and provide actionable information to improve disease management, especially in resource-limited settings.
Near-patient testing may yield more accurate results than when patient samples have to be transported to laboratories. Proper handling of patient samples is extremely crucial to achieving accurate POCT results. Mistakes carried out during sample handling prior to testing can lead to a 32-75% margin of error, which can cost anywhere from $200 to $2000 per incident.
Innovations and advancements in technology are anticipated to pave the way to highly accurate, simple, and portable devices which can be used in resource-constrained locations. Predominantly, there are two types of POCT—immunoassay-based tests and molecular tests.
The immunoassay tests essentially work by detecting analytes which are extracted from a host / patient. The two key analytes assessed are microbial antigens and host antibodies.
Molecular POCT are polymerase chain reaction (PCR)-based tests which have a higher sensitivity and specificity compared to immunoassay tests or rapid antigen detection tests (RADT). However, the segment holds only 20% of the infectious disease POCT market in the United States. The superior molecular test has clinically proven better sensitivity and specificity (>95% on an average). For example, for the detection of group A streptococcus (GAS), molecular GAS tests can detect pathogens from as little as 5 to 20 bacteria per milliliter of sample when compared to RADT which require 10,000 to 100,000 bacteria per milliliter of sample to generate positive results. The market for molecular POCT tests started expanding from 2012, with the launch of products such as Alere i (Alere-Abbott), BioFire FilmArray (BioFire-bioMérieux), GeneXpert Omni (Cepheid), and Cobas Liat System (Roche).
Some of the upcoming technological innovations are described below.
New multiplexing ecosystem with 100 plus tests for the detection of infectious diseases
Alveo Technology’s innovative rapid test combines nucleic acid detection in a highly efficient design package where the device is connected to the cloud to provide inputs on 100 infectious diseases. Sample preparation, nucleic acid amplification, and real-time detection are all performed in a single isothermal microfluidic channel. The technology helps in multiplexing 100 or more simultaneous tests from a single sample.
The technology is based on reverse-transcription loop-mediated isothermal amplification (RT-LAMP) coupled with quenching of unincorporated amplification signal reporters (QUASR) technique. The testing device is supplemented with a smartphone and the entire assembly can be powered by a 5 V USB source, making it cost-effective and enabling usage in resource-limited settings. The effectiveness of this technology is 5 times better than traditional POCT for diseases such as dengue, chikungunya, or Zika.
Biochip Array Technology (BAT)
Biochip Array Technology (BAT) is a novel assay technology which is used as a multiplex assay for screening infectious disease in a rapid, accurate, and easy to use format. BAT’s surface chemistry and analysis platform allow for a range of biological samples viz. whole blood, serum, saliva, urine, and tissue biopsy which can be used to identify diseases. BAT is exclusively marketed by Randox and the products in the infectious disease segment are STI Multiplex Array, Respiratory Multiplex Array, and Antimicrobial Array.
The platform uses nanotechnology to perform a comprehensive analysis of nucleic acid from a single drop of body fluid such as urine, blood, and saliva. At present, molecular rapid tests are time-consuming and involve expensive laboratory processes. Lab-in-a-drop provides results within 35 minutes and requires a lower level of technical expertise and training. The technology can be used to identify fungi, bacteria, and viruses in the infectious disease category.
Host biomarkers can be used to differentiate between infectious disease types viz. bacterial from viral infections. The application of biomarkers can be used as point of care in resource-limited settings and as biodefense countermeasures strategy. Some of the host biomarkers are C-reactive protein, interferon gamma-inducible protein 10, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), heparin binding protein, procalcitonin, etc. At present, none of the above proteins can be detected through FDA approved POCTs.
Paper-based Assays (PBA)
Paper-based diagnostic tools are emerging as a promising, cost-effective format for quick screening of diseases. PBA formats include lateral flow assays (LFAs), dipstick assays, microfluidic paper-based analytical devices (mPADs). The most common substrates are filter paper, chromatography paper, nitrocellulose membrane, and paper / polymer nanomaterial composites. Additional functionality and qualitative analysis can be achieved by combining PBAs with smartphone-based technologies.
Portable Molecular Diagnostics (MDx)
This is a miniaturised and portable platform that runs on battery. It performs complex molecular biology analysis similar to PCR. Its major application is in infectious diseases. It efficiently reduces incubation time in comparison with the conventional microbiology lab testing (Ex: Cobas LIAT). UK-based QuantumDx has developed a portable MDx test which focuses on infectious diseases like TB, HPV, and other STIs like chlamydia and gonorrhea.
When patients exposed to infectious diseases are left unattended or undiagnosed for more than 24 hours they can experience unnecessary suffering or even death, which underscore the critical need for innovative and efficient rapid diagnostic tests at the site of medical assistance. The emergence of new innovations in this market will aid in the identification of the direction that will move this market forward.