Rethinking Smallpox

Abstract

The potential consequences of a competently executed smallpox attack have not been adequately considered by policy makers. The possibility of release of an aerosolized and/or bioengineered virus must be anticipated and planned for. The transmission and infectivity of variola virus are examined. Arguments for and against pre-event vaccination are offered. The likely morbidity and mortality that would ensue from implementation of a mass pre-event vaccination program, within reasonable boundaries, are known. The extent of contagion that could result from an aerosolized release of virus is unknown and may have been underestimated. Pre-event vaccination of first responders is urged, and voluntary vaccination programs should be offered to the public. Two defenses against a vaccine-resistant, engineered variola virus are proposed for consideration. Methisazone, an overlooked drug, is reported to be effective for prophylaxis only. The extent of reduction in the incidence of smallpox with use of this agent is uncertain. It is useless for treatment of clinical smallpox. N-100 respirators (face masks) worn by uninfected members of the public may prevent transmission of the virus.

Development of the Small-Molecule Antiviral ST-246 ® as a Smallpox Therapeutic

“…A very small dose is required for infectivity [6] and the ‘attack rate’ or the likelihood that a susceptible individual will contract disease if exposed to an infected individual ranges from 26% to as high as 90% [7]. Although the CDC estimates that an infected individual will spread the disease to three others, some in the scientific community consider this to be an overly optimistic prediction, and historical records suggest that one infected individual may spread the disease to ten or 20 others [6].…”

“…Fourth, the widespread dispersal of the virus may be enhanced by ‘weaponization’ [13] or aerosolization [7]. Fifth, decontamination may be difficult.…”

“…Sixth, there is no US FDA-approved effective therapy for smallpox (although ST-246 ® may eventually negate this statement). Postexposure vaccination may prevent or limit the disease if administered within 4 days of exposure [102] but is unlikely to be effective thereafter [7]. Cidofovir has been shown to be effective at controlling poxviral disease in animals but is toxic, causing kidney damage [7].…”

Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L

“…Historically, molecules incorporating the thiosemicarbazone functionality have been used as antiviral and antibacterial agents in the treatment of smallpox 41-43 and tuberculosis. 44 In addition to the inhibition of cathepsins, 45-51, 52 incorporation of the thiosemicarbazone moiety as an electrophilic warhead has proved useful in the identification of potent small-molecule inhibitors of cysteine proteases found in Trypanosoma cruzi and Trypanosoma brucei , 53-57 Plasmodium falciparum , 57-59 Leishmania Mexicana , 60 and Eimeria tenella .…”

Expert Opinion: What To Do When There IsCoccidioidesExposure in a Laboratory

“…For example, this would apply if laboratory air is recirculated to the building supply or if a laboratory room is at positive pressure to common hallways or other areas of the building. During smallpox outbreaks in a UK research center and in a German hospital, persons were infected on floors other than the floor where the laboratory exposure occurred, owing to building airflow patterns [19].…”