title: Modeling the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus excretors and the potential benefits of antiviral drugs.
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.
authors.affiliation: Kid Risk, Inc., 10524 Moss Park Rd., Ste. 204-364, Orlando, FL, 32832, USA. rdt@kidrisk.org.
authors.forename: Radboud J
authors.initials: RJ
authors.lastname: Duintjer Tebbens
authors.affiliation: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. map1@cdc.gov.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Pallansch
authors.affiliation: Kid Risk, Inc., 10524 Moss Park Rd., Ste. 204-364, Orlando, FL, 32832, USA. kimt@kidrisk.org.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Thompson
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D008962:Models, Theoretical; D011051:Poliomyelitis / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D017955:Poliovirus / Q000276:immunology; D011055:Poliovirus Vaccine, Oral / Q000276:immunology; D015995:Prevalence; D012308:Risk Management; D016019:Survival Analysis
chemical_list: D000998:Antiviral Agents; D011055:Poliovirus Vaccine, Oral