Epidemiology and vaccination strategies against type-2 vaccine -derived poliovirus

In 1988, the World Health Assembly passed a resolution to eradicate poliomyelitis, a disease which was endemic in 125 countries and paralyzed 350,000 children per year. Primarily through the large-scale use of oral poliovirus vaccine (OPV), two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been declared as globally eradicated and transmission of type 1 remains uninterrupted only in Afghanistan and Pakistan. Unknown at the time of declaring eradication, vaccine-derived poliovirus (VDPVs)— strains that have genetically mutated from the poliovirus contained in OPV, pose a major challenge to eradication. Outbreaks of circulating VDPV (cVDPVs), mostly caused by the type 2 strain of OPV, have become particularly difficult to interrupt in recent years after the elective, globally synchronized cessation of routine use of type 2-containing live poliovirus vaccine. In the context of on-going outbreaks and declining population immunity, optimal vaccination strategies to prevent and control cVDPV2s are uncertain. The aims of this thesis are to evaluate the epidemiology of type 2 cVDPVs and synthesize optimal vaccination strategies: firstly, through generating evidence on the immunogenicity of alternative routine immunization schedules to understand population immunity; secondly, to understand the origin and dynamics of type 2 VDPV outbreaks; and finally, by incorporating the findings of these analyses into a compartmental transmission model, to evaluate outbreak response vaccination strategies with the novel type 2 oral poliovirus vaccine (nOPV2). This thesis has been targeted to inform the evolving policy questions of the Global Polio Eradication Initiative through generation of original evidence.