At the 64th gathering of the World Health Assembly in May 2011, a majority of delegates reaffirmed the view that the remaining stocks of variola virus, the causative agent of smallpox, should be destroyed. But consideration of precisely when that action should be taken was postponed for several years pending completion of crucial research addressing the development and assessment of tools for the treatment and control of the disease should it ever reoccur. This agenda of research includes the development and testing of vaccines and therapeutics, at the heart of which involves understanding the mechanisms that govern variola’s virulence and its capability to evade host defenses. But how can these questions be addressed when naturally occurring disease has been eliminated and no satisfactory animal model exists?
In the absence of smallpox, human infections with monkeypox virus constitute the most significant communicable Orthopoxvirus-associated illnesses extant in the world today. Monkeypox is not a direct research-proxy or substitute for smallpox (monkeypox is a zoonosis that can affect a broad range of animal taxa, whereas smallpox was an exclusive disease of humans) but vaccines and therapies developed for smallpox may be useful for the prevention and treatment of monkeypox, and many of the cornerstones of pathogenesis and immunomodulation for both variola and monkeypox probably emanate from conserved homologous processes. Both variola and monkeypox viruses are considered threat agents that could be used unlawfully for acts of bioterrorism. With monkeypox, there is the added question of its persistence in nature, and its potential for expansion in a world that is now more than 30 years without smallpox. A significant expansion of monkeypox in the world today could pose many of the same challenges as a resurgence of smallpox.
Outbreaks of human monkeypox after cessation of smallpox vaccination. Trends Microbiol. 10 Jan 2012
The recent observation of a surge in human monkeypox in the Democratic Republic of the Congo (DRC) prompts the question of whether cessation of smallpox vaccination is driving the phenomenon, and if so, why is re-emergence not universal throughout the historic geographic range of the virus? Research addressing the virus’s mechanisms for immune evasion and induction, as well as that directed at elucidating the genes involved in pathogenesis in different viral lineages (West African vs Congo Basin), provide insights to help explain why emergence appears to be geographically limited. Novel vaccines offer one solution to curtail the spread of this disease.