Updated July 13, 2018
On June 27-29, 2018, Bethesda, Maryland, hosted the 3-day Biodefense World Summit 2018
during which experts from around the world gathered to discuss everything from food safety to point-of-care (POC) testing. We know that from the hospital to an emergency treatment center at the epicenter of an outbreak, POC testing is critical for rapid diagnoses and medical interventions. In fact, such efforts can be life-saving, which makes their presence in biodefense efforts that much more critical. Two such presentations from the summit discussed the potential for early diagnostic testing for certain infectious diseases, as well as the application of POC for more emergent, biological event situations.
The first presentation, "Far-forward early diagnosis of biothreat agents," by Charles Young, PhD, Principal Professional Staff and Chief Scientist of the Applied Biology Group at Johns Hopkins University’s Applied Physics Lab, raised a question many of us in the health care field have been asking; how can we improve the diagnosis of an infectious disease through earlier detection? Current diagnostics for biological weapons pose a problem as they only diagnose a disease after symptoms have begun or near the invasive stage. By the time that most tests pick up on a disease, such as Ebola, an individual is already experiencing symptoms and thus, contagious. To circumvent this, Dr. Young is working to reduce the delay from exposure to infection and subsequent diagnosis. If we can cut down the time to diagnosis, especially in the event of a biological weapons attack, we can not only treat patients more effectively but also reduce the spread of disease.
Furthermore, imagine if we could test for Ebola before the patient was symptomatic; proper isolation, treatment, and contact-tracing could occur days earlier than they are happening now, which could drastically reduce the risk of disease transmission. The delay in identification for patients was especially damning during the 2013-2016 Ebola outbreak in West Africa. Patients being ruled out for the disease were frequently placed in the same treatment units as those confirmed with the disease, which meant that they were exposed if there were not already infected. Rapid detection, especially before symptoms have begun and a patient is infectious, is a game-changer for outbreak response. Dr. Young highlighted the limited presence of diagnostics, especially in a military setting (or for rural outbreak response), where diagnostics tend to be available and utilized further down the road and in designated care centers, versus field first-aid and mobile units. This presents 2 areas for improvement—more readily available POC testing that can be used during initial patient interactions, and also the ability to make these interactions inclusive of pre-symptomatic diagnostic assays that would allow rapid public health and medical response.
Although we have been fortunate not to have a large-scale biological weapons attack on US soil, the concern for one that would involve a large group of people at an event, etc, underscores why far-forward testing would be wholly beneficial. Such diagnostics would help reduce patient morbidity and mortality, and also the burden of unnecessary treatment and infection control measures that fall upon the health care systems. Ultimately, far-forward testing would allow medical providers and public health officials to get a head start on response measures, which would be extremely helpful during a biological attack where fear and anxiety are prevalent. It would translate to more improved hospital response measures such as more efficient staffing, isolation practices, medical management, etc. Identifying patients who were exposed, and will become symptomatic, allows for a faster approach to treatment and isolation should symptoms occur. Infectious disease response (both in medical management and infection control), in many ways, could then move way from being reactive and become proactive. Far-forward diagnostics mean that only those patients who were truly infected would be evaluated for admission and monitoring, instead of casting a wide net all of those who were potentially exposed and then quarantining them. An example of this would be during the SARS outbreak in Toronto, Canada, when the city implemented large-scale quarantine efforts to manage those individuals who had been exposed to cases. Such practices have mixed efficacy and result in significant emotional stress and financial burden to those quarantined. If far-forward diagnostics were available at that time, it could have been avoided.
Unfortunately, a far-forward molecular diagnostic instrument has not been achieved, yet, and there are still many hurdles to overcome. Dr. Young pointed to several early exposure markers that are promising for immunoassay detection, such as the viral glycoprotein GP1 in Lassa Fever Virus and the dimeric glycoprotein (sGP) in Ebola virus, which indicates that there might be a window during the early stages of infection that the viral glycoproteins can be detected (before the whole virions are rampant in the bloodstream). This would give medical providers a chance for earlier isolation, treatment, etc. These exposure markers also mean that we have a window of opportunity during the early stage of infection and the exploitation of this window could truly make a difference in future outbreaks or in the event of a bioterrorism attack.
The potential for future tests to identify an exposure before a full-blown infection is exciting, but what about our current tests? Moreover, what about the use of POC testing during an outbreak or during a public-health crisis such as a biological attack? In their presentation entitled, Application of Point-of-Care Testing for Pathogen Detection and Patient Management, Kent Lewandrowski, MD, and Elizabeth Lee-Lewandrowski, PhD, MPH from the Harvard Medical School and Massachusetts General Hospital in Massachusetts addressed this very issue.
POC testing is important as it helps reduce turnaround time for results, administrative work, and the chances of a delay in the lab, or a mix-up. Unfortunately, such tests are also more expensive and carry with them more operator errors, and regulatory requirements to consider. Think about the gained time and faster medical management that is already available from a simple POC like that of a glucose meter with a single-use disposable test strip or a rapid pregnancy test, etc. In their presentation, Drs. Lewandrowski highlighted the expanding menu of POC testing—dipstick urinalysis, metabolic panels, HIV and hepatitis C testing, influenza A/B testing, complete blood counts, coagulation testing, etc. Such efforts are available for hospitals during a biothreat event, bio-surveillance efforts, disasters settings, biothreats in a remote environment, or in the event of bioterrorism. During emergent situations, health care systems are stressed with an over abundance of patients and desperate need to ensure proper medical management and patient safety, which means that time is of the essence. POC testing reduces the time for many critical results, which can be life or death on a normal day, so you can imagine the importance of their availability during a crisis. During an outbreak, it is critical to be able to rule out other diseases, especially if laboratory resources are limited. For example, POC tests like the rapid malaria test were hugely beneficial during the Ebola virus outbreak in West Africa to help rule-out malaria as a potential cause of the, at the time, unknown disease. Because of their added value, such POC tests should be utilized and expanded upon for future health crises and public health events.
The speakers also discussed the challenges labs face during such events or during outbreaks of highly-infectious diseases. From the costliness to limited space, personal protective equipment requirements, and user knowledge required, the availability of such tests (and the labs able to analyze them) can be limited. Highly infectious disease diagnostics are limited in that only certain labs have the capacity to confirm the disease. For example, during the 2013-2016 Ebola outbreak, laboratory confirmation became an increasingly complex part of hospital preparedness and response. Patient labs tests had to be sent to designated laboratories (usually state labs or even the CDC) for confirmation due to the biosafety level requirements for handling the Ebola virus.
Although there has been much focus on increasing the availability of diagnostics for high-consequence pathogens, there is also the inherent risk of biosafety failures and biosecurity incidents. Improving laboratory capacity presents a mixed bag of pros and cons, but that does not make it any less necessary.