BMC Infectious Diseases
http://www.biomedcentral.com/bmcinfectdis/content
(Accessed 19 September 2015)

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Research article
Modeling the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus excretors and the potential benefits of antiviral drugs
Radboud Duintjer Tebbens, Mark Pallansch, Kimberly Thompson BMC Infectious Diseases 2015, 15:379 (17 September 2015)
Abstract
Background
A small number of individuals with B-cell-related primary immunodeficiency diseases (PIDs) may exhibit long-term (prolonged or chronic) excretion of immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) following infection with oral poliovirus vaccine (OPV). These individuals pose a risk of live poliovirus reintroduction into the population after global wild poliovirus eradication and subsequent OPV cessation. Treatment with polio antiviral drugs may potentially stop excretion in some of these individuals and thus may reduce the future population risk.
Methods
We developed a discrete event simulation model to characterize the global prevalence of long-term iVDPV excretors based on the best available evidence. We explored the impact of different assumptions about the effectiveness of polio antiviral drugs and the fraction of long-term excretors identified and treated.
Results
Due to the rarity of long-term iVDPV excretion and limited data on the survival of PID patients in developing countries, uncertainty remains about the current and future prevalence of long-term iVDPV excretors. While the model suggests only approximately 30 current excretors globally and a rapid decrease after OPV cessation, most of these excrete asymptomatically and remain undetected. The possibility that one or more PID patients may continue to excrete iVDPVs for several years after OPV cessation represents a risk for reintroduction of live polioviruses after OPV cessation, particularly for middle-income countries. With the effectiveness of a single polio antiviral drug possibly as low as 40 % and no system in place to identify and treat asymptomatic excretors, the impact of passive use of a single polio antiviral drug to treat identified excretors appears limited. Higher drug effectiveness and active efforts to identify long-term excretors will dramatically increase the benefits of polio antiviral drugs.
Conclusions
Efforts to develop a second polio antiviral compound to increase polio antiviral effectiveness and/or to maximize the identification and treatment of affected individuals represent important risk management opportunities for the polio endgame. Better data on the survival of PID patients in developing countries and more longitudinal data on their exposure to and recovery from OPV infections would improve our understanding of the risks associated with iVDPV excretors and the benefits of further investments in polio antiviral drugs.

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Research article
The differential impact of oral poliovirus vaccine formulation choices on serotype-specific population immunity to poliovirus transmission
Kimberly Thompson, Radboud Duintjer Tebbens BMC Infectious Diseases 2015, 15:376 (17 September 2015)
Abstract
Background
Prior analyses demonstrated the need for some countries and the Global Polio Eradication Initiative (GPEI) to conduct additional supplemental immunization activities (SIAs) with trivalent oral poliovirus vaccine (tOPV) prior to globally-coordinated cessation of all serotype 2-containing OPV (OPV2 cessation) to prevent the creation of serotype 2 circulating vaccine-derived poliovirus (cVDPV2) outbreaks after OPV2 cessation. The GPEI continues to focus on achieving and ensuring interruption of wild poliovirus serotype 1 (WPV1) and making vaccine choices that prioritize bivalent OPV (bOPV) for SIAs, nominally to increase population immunity to serotype 1, despite an aggressive timeline for OPV2 cessation.
Methods
We use an existing dynamic poliovirus transmission model of northwest Nigeria and an integrated global model for long-term poliovirus risk management to explore the impact of tOPV vs. bOPV vaccine choices on population immunity and cVDPV2 risks.
Results
Using tOPV instead of bOPV for SIAs leads to a minimal decrease in population immunity to transmission of serotypes 1 and 3 polioviruses, but a significantly higher population immunity to transmission of serotype 2 polioviruses. Failure to use tOPV in enough SIAs results in cVDPV2 emergence after OPV2 cessation in both the northwest Nigeria model and the global model. Despite perceptions to the contrary, prioritizing the use of bOPV over tOPV prior to OPV2 cessation does not significantly improve serotype 1 population immunity to transmission.
Conclusions
Immunization leaders need to focus on all three poliovirus serotypes to appropriately manage the risks of OPV cessation in the polio endgame. Focusing on population immunity to transmission to interrupt WPV1 transmission and manage pre-OPV cessation risks of cVDPVs, all countries performing poliovirus SIAs should use tOPV up until the time of OPV2 cessation, after which time they should continue to use the OPV vaccine formulation with all remaining serotypes until coordinated global cessation of those serotypes.

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Research article
Health and economic consequences of different options for timing the coordinated global cessation of the three oral poliovirus vaccine serotypes
Kimberly Thompson, Radboud Duintjer Tebbens BMC Infectious Diseases 2015, 15:374 (17 September 2015)
Abstract
Background
World leaders remain committed to globally-coordinated oral poliovirus vaccine (OPV) cessation following successful eradication of wild polioviruses, but the best timing and strategy for implementation depend on existing and emerging conditions.
Methods
Using an existing integrated global poliovirus risk management model, we explore alternatives to the current timing plan of coordinated cessation of each OPV serotype (i.e., OPV1, OPV2, and OPV3 cessation for serotypes 1, 2, and 3, respectively). We assume the current timing plan involves OPV2 cessation in 2016 followed by OPV1 and OPV3 cessation in 2019 and we compare this to alternative timing options, including cessation of all three serotypes in 2018 or 2019, and cessation of both OPV2 and OPV3 in 2017 followed by OPV1 in 2019.
Results
If Supplemtal Immunization Activity frequency remains sufficiently high through cessation of the last OPV serotype, then all OPV cessation timing options prevent circulating vaccine-derived poliovirus (cVDPV) outbreaks after OPV cessation of any serotype. The various OPV cessation timing options result in relatively modest differences in expected vaccine-associated paralytic poliomyelitis cases and expected total of approximately 10–13 billion polio vaccine doses used. However, the expected amounts of vaccine of different OPV formulations needed changes dramatically with each OPV cessation timing option. Overall health economic impacts remain limited for timing options that only change the OPV formulation but preserve the currently planned year for cessation of the last OPV serotype and the global introduction of inactivated poliovirus vaccine (IPV) introduction. Earlier cessation of the last OPV serotype or later global IPV introduction yield approximately $1 billion in incremental net benefits due to saved vaccination costs, although the logistics of implementation of OPV cessation remain uncertain and challenging.
Conclusions
All countries should maintain the highest possible levels of population immunity to transmission for each poliovirus serotype prior to the coordinated cessation of the OPV serotype to manage cVDPV risks. If OPV2 cessation gets delayed, then global health leaders should consider other OPV cessation timing options.

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Research article
Vaccination of boys or catch-up of girls above 11 years of age with the HPV-16/18 AS04-adjuvanted vaccine: where is the greatest benefit for cervical cancer prevention in Italy?
Paolo Bonanni, Giovanni Gabutti, Nadia Demarteau, Sara Boccalini, Giuseppe La Torre BMC Infectious Diseases 2015, 15:377 (17 September 2015)