The Infectious Dose of Variola (Smallpox) Virus

Abstract

Quantitative estimation of an individual's risk of infection due to airborne pathogens requires knowledge of the pathogen's infectious dose, in addition to estimates of the pathogen's airborne concentration and the person's exposure duration. Based on our review of the published literature on poxvirus infection, we conclude that the infectious dose of variola (smallpox) virus is likely one virus particle and that infection can be initiated in either the upper respiratory tract or pulmonary region. Studies of airborne transmission of poxvirus in monkeys and rabbits show that primary infection can occur in both regions of the respiratory tract. A quantitative study of poxvirus inhalation transmission in rabbits indicates that the deposition of one pock-forming unit (PFU) carried on respirable particles can cause infection. Findings in both in vitro and in vivo studies of the number of virus particles comprising a PFU are consistent with a "one-hit" phenomenon-namely, the cellular uptake of just one virus particle can lead to infection of a cell or an area of cell growth, creating a pock (an infected area of cells). Variability in virulence among different virus strains may involve differences inthe probability of infection per virus particle, where a highly virulent strain has a probability close to one of successful infection for each virus particle. In an analogous manner, variability in susceptibility to the same virus strain among different hosts may involve differences in the probability of infection per virus particle across different hosts. Applied Biosafety, 9(3) pp. 118-127

Experimental Study of Dispersion and Deposition of Expiratory Aerosols in Aircraft Cabins and Impact on Infectious Disease Transmission

“…Whether this will favor the transmission of disease or not may depend on the infectivity of the pathogen carried by the aerosols. For highly infective pathogens such as M. tuberculosis bacilli and variola (smallpox) virus (Wells 1955;Nicas et al 2004), i.e., there is high infection risk even with a very low dose of pathogens, an increase in the supply airflow rate may result in more passengers being infected. In contrast, a higher supply airflow rate may significantly reduce the exposure and, hence, the infection risk for pathogens with low infectivity.…”

The attenuated NYCBH vaccinia virus deleted for the immune evasion gene, E3L, completely protects mice against heterologous challenge with ectromelia virus

“…Similarly, in VACV-vaccinated macaques, recovery from heterologous challenge with monkeypox virus requires B cells or antibodies [25]. The difference in immunological requirements for protection from ECTV challenge in comparison to VACV is not completely understood, however ECTV is a natural mouse pathogen and requires low doses to initiate a robust infection, similar to the low dose that is estimated to cause variola infection in humans [26]. It is possible that a rapid B cell response is required following challenge of an immunized subject with a highly robust naturally-occurring pathogen whereas either a T or B cell response is protective against a laboratory-induced pathogen like VACV.…”

Some Bioterrorism Issues of Quantitative Biosafety

“…Though for most BW agents the infectious doses have not yet been precisely established (Johnson, 2003;Raber et al, 2001), there are reasons to believe that some agents, such as smallpox (Henderson et al, 1999;Nicas et al, 2004), tularemia (Dennis et al, 2001;Jones et al, 2005), and Qfever (Fournier et al, 1998;Johnson, 2003), have a very low ID50 index (in single units). For others, like Marburg virus (Chermashentsev et al, 1993) and plague (Iglesby et al, 2000), it seems to be higher-approximately 100 units and approximately 1,000 units for anthrax (Iglesby et al, 2002;Meselson, 1994).…”

“…Zero risk might be a necessity in this case because according to the model and other recent theoretical estimations (Nicas et al, 2004), even tiny airborne concentrations of the agent seem to have unacceptable risks of infection. For instance, concentrations as small as 11 virions/1000m 3 still pose an infection risk of the order of 1x10 -4 ( Table 1).…”

“…(3) Recently, a conceptual modeling approach was successfully used for the theoretical estimation of the risks of infection with smallpox virus and Francisella tularenis (Jones et al, 2005;Nicas et al, 2004). Though for most BW agents the infectious doses have not yet been precisely established (Johnson, 2003;Raber et al, 2001), there are reasons to believe that some agents, such as smallpox (Henderson et al, 1999;Nicas et al, 2004), tularemia (Dennis et al, 2001;Jones et al, 2005), and Qfever (Fournier et al, 1998;Johnson, 2003), have a very low ID50 index (in single units).…”