Zika Countermeasure Options Explored

A recent review article published in PLoS Neglected Tropical Diseases on the status of the Zika virus outbreak may provide clinicians with the knowledge they need regarding medical countermeasure options. The review focuses on several key aspects of Zika virus biology.

In the review, author Robert W. Malone, MD, MS, Managing Director of Clinical Development and Government Affairs for Avancer Group, Inc. and adjunct associate professor of biotechnology at Kennesaw State University, describes the recent history and clinical consequences of Zika virus infection with an emphasis on microcephaly and Guillain—Barré syndrome (GBS), the lineage of the virus, the evolving epidemiology of Zika virus spread into the Americas, as well as the neuropathology, teratology, virology and immunology of the virus.

All of this information is presented in prior to a discussion of medical countermeasure development strategies. The review concludes with a discussion of the importance of outbreak modeling, tracking, and public health communications. Armed with such knowledge, clinicians may be better able to devise and implement methods and policies designed to delay the spread of the virus into uninfected regions with the ultimate aim of using this critical time to develop medical countermeasures. Malone notes that, "Expedited research will be required to address open questions and to better inform countermeasure development and clinical management."

According to Malone et al, the recent focus on the Zika virus reflects concerns based on reports describing high rates of primary microcephaly and GBS associated with Zika virus infection in both French Polynesia and Brazil. Furthermore, it has become clear that the virus circulating in these regions represents a rapidly developing public health threat with neuropathic and teratogenic manifestations. This situation seems particularly grim due to the absence of vaccines, therapies, or preventive drugs available for Zika virus infection and disease. Malone reinforces the troubling nature of the current public health threat by referring to the findings of the Pan American Health Organization, which predicts that, "Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes."

Beyond the information presented in the review, Malone et al describe what may be considered as the primary challenge involved in Zika virus infection and disease: a lack of sufficient knowledge of the disease or models for countermeasures. These challenges necessitate efforts to expand our understanding of the virus itself, while at the same time developing effective countermeasures. Malone and colleagues note that, "In many ways Zika presents a much more complex challenge than Ebola, and it may impact more lives."

Unfortunately, the Zika epidemic is moving very rapidly. Like the West Nile virus, the Zika virus is vector-borne, which would normally affect its range of transmission based on the ecosystem of the vector. In our ever-shrinking world, however, simply attempting to limit the movement or contact of infected people will be insufficient for containment. Furthermore, acute infection may not be apparent, removing quarantine as an effective strategy.

Malone et al point out that, "Research reagents, animal models, and fundamental science knowledge are much less well developed than they were for Ebola." This places Zika virus researchers at a distinct disadvantage. On a more optimistic note, Malone explains that decades of experience with other similar viruses, such as West Nile and dengue, may be helpful in devising vaccine development strategies.

The authors conclude with the speculation that, "Zika virus is likely a harbinger of future diseases driven by ecosystem change and global interconnectedness." Additionally, Malone and colleagues assert that the biggest challenge associated with the Zika virus may be, "... to recognize it for what it is: a new disease which does not fit the epidemiology or response paradigm of Ebola or dengue and which will demand effort, resources, unparalleled collaboration, and above all, open mindedness in formulating responses."

Key learning points from the review were provided, and are as follows:

• The pattern of Zika-associated disease observed in Brazil represents a significant public health risk.
• The relationship between infection with Zika virus and primary microcephaly meets most accepted criteria for causality.
• A causal linkage between Zika infection and GBS is plausible, but analysis is complicated by regional co-endemnicity of dengue and chikungunya.
• Possible pathophysiologic interactions between Zika virus infection, microcephaly, other birth defects and GBS are not understood.
• Expedited research will be required to address open questions and to better inform countermeasure development and clinical management.
• Blood banks must promptly implement infection control procedures to secure the supply of critical blood products.
• Methods and policies designed to delay the spread of the virus into uninfected regions will buy critical time to develop medical countermeasures.
• Development of a general use prophylactic vaccine for Zika virus will require considerable time and careful evaluation to mitigate typical vaccine-associated risks in previously healthy unexposed general populations.

William Perlman, PhD, CMPP is a former research scientist currently working as a medical/scientific content development specialist. He earned his BA in Psychology from Johns Hopkins University, his PhD in Neuroscience at UCLA, and completed three years of postdoctoral fellowship in the Neuropathology Section of the Clinical Brain Disorders Branch of the National Institute of Mental Health.