Contributed Commentary by David Wilson
September 16, 2021 | When a disease outbreak occurs, the first stage of the response is detection. During the initial stages of Zika and COVID-19 outbreaks, The World Health Organization (WHO) identified effective diagnostic testing as one of the key factors in monitoring and managing the spread of the disease.
For infectious diseases caused by viruses, diagnostics are particularly important to rule out other infections that present similar symptoms, and to evaluate the severity of the patient’s condition. This is also important when considering the correct treatment to administer – especially since some treatments for Zika virus for example, including aspirin and similar nonsteroid anti-inflammatory drugs, exacerbate negative outcomes for patients suffering from other closely related diseases, and can even trigger haemorrhage in patients suffering from Dengue Fever.
Which Test is Best?
Polymerase chain reaction (PCR) is currently considered the ‘gold standard’ of infectious disease diagnostics. However, despite being highly sensitive and reliable, it is limited by the need to be processed and analysed by trained staff in specialised laboratories, which increases the time required to diagnose and isolate infected individuals. Additionally, in times of crisis test reagents and laboratory capacity are in high demand, with limited supply. To alleviate this strain, the successful development and application of alternative testing techniques is vital.
Lateral flow assays (LFAs) are becoming increasingly popular as a rapid testing platform for qualitative, semi-quantitative or quantitative analysis of a variety of target analytes, such as pathogens or biomarkers. They are also widely used for point-of-care (POC) diagnostics due to their ability to combine rapid results with cost-effective testing devices, achievable by non-specialists.
The design of an LFA test strip is also very simple, involving the chromatographic separation of a test solution across a nitrocellulose membrane and the identification of a specific analyte by binding to antibodies or other affinity reagents on the test strip to give a signal.
The timeline of test development and evaluation is a major limiting factor in the ability of diagnostics companies to respond to outbreaks fast enough. As LFAs are typically antibody-based, one of the barriers to rapid creation of a test against a novel pathogen can be the well-documented limitations of these large, complex molecules. These include high development costs, time to manufacture, and poor specificity against certain targets, with some targets too difficult to generate antibodies for using traditional processes. The development of diagnostics, including LFAs, that use non-antibody protein scaffolds, such as Affimer proteins, therefore offers an attractive, rapid and robust alternative to both PCR and antibody-based methods, expanding the options available to develop diagnostic tests.
Rapid Diagnostics For Disease Management
As a vital aspect of effective disease management, it is increasingly important that the limitations preventing fast development of rapid diagnostics, including POC diagnostics, are addressed. Enabling the timely identification and quarantine of cases, such as COVID-19, these testing advancements can limit further spread to protect more vulnerable communities that may be less equipped to tackle and recover from the outbreak.
Speed is also crucial when responding to emerging variants of an infectious virus. Since the start of the current COVID-19 pandemic, we have already seen several SARS-CoV-2 variants circulating in the worldwide population. Particular concerns arose over Alpha (B.1.1.7), originally sequenced in the UK, Beta (B.1.351), originally sequenced in South Africa, and more recently, Delta (B.1.617.2) originating in India. These viral variants have been shown to be more transmissible and more infectious, which is why sensitive diagnostics able to detect infectious levels of viral load are needed.
These variants have so far remained detectable by some but not all current diagnostic technologies, but with the threat of further changes to the identifier proteins looming, the ability to quickly develop and produce updated tests remains an important weapon in our arsenal.
Preparing For Future Outbreaks
The current pandemic has shone a light on diagnostic technology on a global scale and given us the opportunity to consider and prepare for future outbreaks based on lessons learnt from dealing with COVID-19. The social, economic, and political strain caused by such outbreaks is enormous; emphasising the need to examine our approach for identifying and developing diagnostics, therapeutics, and vaccines quickly and efficiently.
By adopting the most advanced technology to expand the range of tests available, and consequently varying the constituent reagents required, we gain a more complete defence against the uncontrolled spread of infectious diseases.
David Wilson is Commercial Director of Avacta’s Diagnostics division. David has over 25 years’ international experience in business development, marketing and sales management in the in vitro diagnostic medical devices industry. He is a Board member for two early-stage diagnostic businesses developing novel point-of-care diagnostic testing platforms and has served on the Executive Committee of the British In Vitro Diagnostics Association. He can be reached at david.wilson@avacta.com.