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Review
. 2013 Apr;33(4):544-605.
doi: 10.1111/j.1539-6924.2012.01864.x. Epub 2012 Jul 15.

Expert review on poliovirus immunity and transmission

Radboud J Duintjer Tebbens  1 , Mark A Pallansch, Konstantin M Chumakov, Neal A Halsey, Tapani Hovi, Philip D Minor, John F Modlin, Peter A Patriarca, Roland W Sutter, Peter F Wright, Steven G F Wassilak, Stephen L Cochi, Jong-Hoon Kim, Kimberly M Thompson
Affiliations
Review

Expert review on poliovirus immunity and transmission

Radboud J Duintjer Tebbens et al. Risk Anal. 2013 Apr.

Abstract

Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.

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Figures

Figure 1:
Figure 1:. Immunity states used by Duintjer Tebbens et al. (2005)(3) to represent immunity to poliovirus transmission from an “average” poliovirus serotype.*
Acronyms: IPV = inactivated poliovirus vaccine; LPV = live poliovirus Notes: * Arrows conditioned on “take” (i.e., successful IPV vaccinations or actual LPV infections). ** We scale the level of immunity to poliovirus transmission from low (fully susceptible) to high (fully immune to poliovirus transmission), with the level of immunity to poliovirus transmission calculated for this figure as the product of relative susceptibility, relative infectiousness, and relative duration of infectiousness compared to fully susceptibles.(8) The heights of boxes reflect the assumed uncertainty about the average level of immunity to poliovirus transmission and the centers correspond approximately to the assumed base case levels of immunity to poliovirus transmission.
Figure 2:
Figure 2:
Full set of immunity states in a world with only live polioviruses (LPVs) for one serotype with the LPV arrows conditioned on “take” (i.e., actual infections, including successful OPV vaccinations).
Figure 3:
Figure 3:
Full set of immunity states in a world with only inactivated poliovirus vaccine (IPV) for one serotype with IPV arrows conditioned on “take” (i.e., successful vaccinations).
Figure 4:
Figure 4:
Diagram of immunity states with waning, showing variability within groups as a function of time since last exposure (but ignoring variability due to other factors) and with inactivated poliovirus vaccine (IPV) and live poliovirus (LPV) arrows conditioned on “take” (i.e., successful IPV vaccinations or actual LPV infections).
Figure 5:
Figure 5:. Summary of data from monovalent oral poliovirus vaccine (mOPV) challenge studies that report rates of fecal excretion for at least two points in time after challenge, by assigned recent immunity state.(, , , , –, , , , –85)
Acronyms: CID50/g = cell- or tissue-culture infectious doses; FS = fully susceptible; IPV3 = ≥ 3 successful IPV doses; LPV1 = 1 LPV infection; LPV2 = ≥ 2 LPV infections; IPV+LPV = ≥ 1 successful IPV doses and ≥ 1 LPV infections; MI = maternally immune Notes: Legend indicates assigned immunity state, first author (year) with any applicable footnotes, challenge vaccine, maximum number of subjects tested for excretion at any given specimen collection time, poliovirus transmissibility setting, limitations applying to study results (see Table 1 for limitation symbols) * Study reports proportion of subjects excreting at 102 CID50/g or more ^ Combined results for different titers of challenge dose ** Proportion of subjects with positive sample at given day or later *** Results from mOPV1, mOPV2, and mOPV3 arms combined
Figure 6:
Figure 6:. Reported concentrations of virus excreted over time from 7 included OPV challenge studies(41, 52, 69, 78, 84, 88) demonstrating large variability in measurement methods and resulting measurement errors.
Acronyms: CID50/g = cell- or tissue-culture infectious doses per gram of stool; FS = fully susceptible; IPV3 = ≥ 3 successful IPV doses; IPV+LPV = ≥ 1 successful IPV doses and ≥ 1 LPV infections; mOPV(1,2,3) = monovalent oral poliovirus vaccine (type 1, 2, 3, respectively); Notes: Legend indicates assigned immunity state, first author (year) with any applicable footnotes, challenge vaccine, cumulative number of excretors, poliovirus transmissibility setting, limitations applying to study results (see Table 1 for limitation symbols) * Cumulative number of excretors unknown, n reflects peak proportion excreting; Excretors include children with pre-challenge antibody titers 1:4 and under as well as 2 type 2 excretors and 1 type 3 excretor with pre-challenge antibody titers of 1:16 ** Data differ from Figure 1 in Piirainen et al. (1999)(, p. 1088) because we included only positive specimens in calculation of geometric mean titers
Figure 7:
Figure 7:. Summary of data from 6 OPV challenge studies that report proportions excreting for different challenge doses.(25, 26, 46, 47, 55, 74)
Acronyms: CID50 = cell- or tissue-culture infectious dose; FS = fully susceptible; IPV3 = ≥ 3 successful IPV doses; LPV2 = ≥ 2 LPV infections; IPV+LPV = ≥ 1 successful IPV doses and ≥ 1 LPV infections; MI = maternally immune; mOPV1 = type 1 monovalent oral poliovirus vaccine; Notes: Legend indicates assigned immunity state, first author (year), challenge vaccine, approximate number of challenged subjects per dose, poliovirus transmissibility setting, limitations applying to study results (see Table 1 for limitation symbols)
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References

    1. World Health Assembly. Global eradication of poliomyelitis by the year 2000 (resolution 41.28) Geneva: World Health Organization; 1988. http://www.who.int/csr/ihr/polioresolution4128en.pdf
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