Smallpox, although eradicated, has joined the growing list of potential biosecurity threats, according to experts, who say preparedness for the possible return of the virus should be prioritized around the world.
Smallpox, a contagious, disfiguring and often deadly disease, was eradicated globally in 1980 by the World Health Organization (WHO) — the result of an unprecedented global immunization campaign, according to the Mayo Clinic.
However, samples of the smallpox virus have been kept for research purposes, according to the clinic, which has led to concerns that smallpox could someday be used as a biological warfare agent.
Although most bioterrorism preparedness experts agree it’s likely that smallpox could return and cause a devastating regional or even global outbreak, the risk remains very low, says Michael T. Osterholm, distinguished teaching professor and director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
“Nonetheless, because of the potential consequences of such an outbreak, I believe that society has no choice but to have at least a moderate level of preparedness, in both the availability of effective vaccines and in strategies for responding to outbreaks quickly and effectively,” Osterholm writes in the editorial, “An Unfortunate Need to Revisit Smallpox Preparedness” in the first edition of Global Biosecurity, a peer-reviewed open access electronic journal published by the University of New South Wales (UNSW).
Osterholm, who also serves through May 2019 as a Science Envoy for Health Security on behalf of the U.S. State Department, said experts think that the smallpox virus is located in only two repository, high-security biosafety level 4 laboratories — in the United States and Russia.
“The likelihood that the virus remains in yet unidentified laboratories throughout the world is, at best, a theoretical possibility,” Osterholm writes in his Feb. 14 editorial. “For this reason, despite a call by some to maintain preparedness for the possible return of smallpox, such preparedness remains a low priority for almost all countries in the world.”
For that reason alone, he said, some of the work published in the new Global Biosecurity that resulted from an August 2018 simulated smallpox outbreak carried out by UNSW and the Fiji Ministry of Health and Medical Services deserves the world’s attention.
The hypothetical scenario, for example, was designed to test preparedness and response globally to a smallpox attack in the Asian Pacific region. The exercise brought together key international representatives from departments of health, foreign affairs, defense, law enforcement, non-government agencies, vaccine manufacturers and other global stakeholders.
“The results of the exercise are sobering,” said Osterholm. “The authors have provided us with substantial food for thought with regard to the speed at which a comprehensive outbreak response could be launched in one or more locations around the world and how the very limited supplies of our current smallpox vaccines will be most effectively deployed.”
Generally, the simulation uncovered that for a disease as infectious as smallpox, the most important determinants impacting the spread of the epidemic are finding and isolating people with smallpox, tracking their contacts and vaccinating them, and the speed of response, according to UNSW, where the simulation was held Aug. 16-17, 2018. It was funded by the National Health and Medical Research Council (NHMRC) Centre for Research Excellence, Integrated Systems for Epidemic Response (ISER), Emergent Biosolutions Inc., and Bavarian Nordic, with support from Global Security PLuS.
The resulting article published in Global Biosecurity, “Exercise Mataika: White Paper on response to a smallpox bioterrorism release in the Pacific,” is authored by numerous experts, including UNSW’s Raina MacIntyre, head of the university’s biosecurity program and a global biosecurity professor at its Kirby Institute; Kevin Yeo, director of clinical and medical affairs at Emergent BioSolutions; and Dr. J. Michael Lane, emeritus professor of preventive medicine at Emory University in Atlanta and a former special consultant to the WHO Smallpox Eradication Programme in Geneva, Switzerland, among several others.
MacIntyre said they used mathematical modelling of smallpox transmission to simulate the spread of the virus.
“If rates of isolation of people with smallpox and vaccination fall below 50 percent, smallpox may become endemic again, as our model shows it still going 10 years later,” she said. “We have been able to outline very clear disease control targets in terms of vaccination and also isolation of sick people. Both require physical and human resource, which are not a given in low-income countries.”
Following the exercise, experts reported that global efforts are essential and should be directed toward the areas worst-affected by such an outbreak.
However, “this is a challenge when nations are reluctant to provide resources outside their own borders,” said Associate Professor David Heslop from the UNSW School of Public Health and Community Medicine, another of the white paper’s authors.
Emergent’s Yeo also noted “that safeguarding the population against public health threats, whether by accidental, intentional, or naturally occurring causes, requires coordinated strategies at the national level.”
Yeo said that collaboration across stakeholders and input from myriad experts “are key to prepare for, prevent, and protect against these threats. It is vitally important for all countries to have a preparedness plan for such untoward events.”
In examining local, regional and global preparedness to a possible smallpox attack, authors of the white paper also provided the first-ever framework to develop national and international policy and legislation.
Additionally, Osterholm’s editorial cites another related and relevant article in Global Biosecurity: “The current and future landscape of smallpox vaccines,” by Dr. Lane, an article he called a comprehensive review of the current and future landscape of smallpox vaccines that serves as a primer on smallpox vaccine capability and developing safer and possibly more effective vaccines.
“As Lane points out, however, given the general sense by most countries that smallpox will not again be a serious public health challenge, it’s unlikely that we will see much investment in developing and stockpiling these fourth-generation vaccines any time soon,” Osterholm writes.
Lane concludes in his article that the first generation of smallpox vaccines are no longer acceptable due to serious side effects, among other reasons. Certain second-generation vaccines, he writes, have shown non-inferiority to the first-generation vaccine and have been added to the National Strategic Stockpile. Third-generation vaccines show some promise as practical vaccines, he said, while the effectiveness of many fourth-generation vaccine candidates, produced by modern immunologic and virologic techniques, may be too cost prohibitive and difficult to prove, which could inhibit their full development as smallpox vaccines.
“There is a need for better smallpox vaccines,” writes Lane.