Contributed Commentary by Konstanze Stiba
October 23, 2018 | Among the pathogens included on the World Health Organization (WHO) priority list is the ominously named “Disease X.” The WHO priority list highlights infectious diseases for which we lack medical countermeasures and need to focus R&D efforts to enhance preparedness. Serving as a placeholder for a yet-to-be-identified potential disaster, Disease X—added to WHO’s list in February 2018—represents emerging pathogens that present a significant health risk and potential for an international epidemic. Emerging pathogens can be microbes newly introduced to humans from other species, or existing, but rare, human pathogens that suddenly have an increased prevalence or pathogenicity.
Whether the villain is new or a reemergence of an old enemy, the challenge of diagnosing, treating, and preventing such pathogens is formidable. Infectious diseases are evolving and spreading more rapidly than ever due to societal, technological, and environmental factors, while acquired resistance of pathogens to antimicrobials is enabling known diseases to reemerge. Conditions that favor the spread of infectious diseases include rapid population growth, more densely populated areas, humans coming into closer contact with wild animals, and migration and movement across international borders. It is reported that in the last three and a half decades, at least 30 new infectious agents affecting humans have emerged. A map of global emerging and re-emerging diseases published by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institutes of Health (NIH) bears a troubling resemblance to a dartboard (Figure 1).
A critical element of preparedness and response to an unexpected infectious disease is availability of a diagnostic. Just as creation of new vaccines must advance at a breakneck speed when an outbreak occurs, so too does the ability to properly diagnose patients with diseases such as MERS, SARS, Zika and the next Disease X. While prompt diagnosis of infectious diseases plays a crucial role in treatment and prevention strategies, the pathway to the development of a diagnostic with the necessary sensitivity and specificity can be challenging. The process can take a few months or a few years, as it requires insight into how the disease unfolds once a patient is infected and is highly dependent on the level of cooperation across geographies by governmental organizations, research institutes, and manufacturers.
A significant bottleneck, and often the rate-limiting step in development, is the ability of diagnostics manufacturers to gain access to samples of the infectious agent. Establishing a network with reference institutes and experts in emerging diseases around the world is one strategy that can help facilitate the transfer of samples. For example, at EUROIMMUN, we maintain a close working relationship with two main competence centers in Germany which focus on identification, surveillance, and prevention of diseases, especially infectious diseases.
Another essential factor in the development of a successful diagnostic is understanding the course of the disease and the course of the immune response. For viral diseases, it is often valuable to develop both a molecular-based diagnostic, such as PCR, for detection of the virus in the blood during the viremic phase and a serology-based test to detect antibody response later in the course of the infection when there is no detectable virus (Figure 2). Typical serology tests include immunofluorescence, ELISA and immunoblot. This dual approach is essential as the response of patients to infection can vary. A patient may have symptoms during the viremic phase but within a few days, the molecular test may already be negative. Availability of a serology test can confirm whether the patient does in fact have an acute infection. Development of a molecular diagnostic creates an even greater need for timely access to patient samples which must be available from the early viremic phase.
For differentiation of viral fever diseases with similar symptoms or regional distribution, sensitive and specific assays are highly required. Laboratory physicians, unsure what disease is causing symptoms, can also investigate multiple different viruses in parallel using multiplexing assays like EUROIMMUN’s immunofluorescence mosaics or molecular-based EUROArrays.
Access to samples and insight into the course of the disease, along with a constant state of readiness, are important prerequisites for timely development of an effective diagnostic. From the black death in Madagascar to Marburg virus in Uganda, Legionnaire’s at Disney and in New Hampshire, to the emergence of Zika, the last few years have seen no letup in our exposure. An effective response to emerging and re-emerging pathogens – including Disease X – depends on a deep understanding of infectious diseases, backed by a global network of experts and governmental organizations committed to prompt and full cooperation.
Dr. Stiba is a product manager in infectious diseases at EUROIMMUN AG, a PerkinElmer company. She earned her PhD at University of Greifswald, Germany, in the field of molecular biology, biochemistry and biotechnology. She spent several years in research at University of Lund, Sweden and Potsdam, Germany before moving into industry. She can be reached at k.stiba@euroimmun.de.