We determined the complete genomic sequences of nine type 1 immunodeficient vaccine-derived poliovirus (iVDPV) isolates obtained over a 337-day period from a poliomyelitis patient from Taiwan with common variable immunodeficiency. The iVDPV isolates differed from the Sabin type 1 oral poliovirus vaccine (OPV) strain at 1.84% to 3.15% of total open reading frame positions and had diverged into at least five distinct lineages. Phylogenetic analysis suggested that the chronic infection was initiated by the fifth and last OPV dose, given 567 days before onset of paralysis, and that divergence of major lineages began very early in the chronic infection. Key determinants of attenuation in Sabin 1 had reverted in the iVDPV isolates, and representative isolates of each lineage showed increased neurovirulence for PVR-Tg21 transgenic mice. None of the isolates had retained the temperature-sensitive phenotype of Sabin 1. All isolates were antigenic variants of Sabin 1, having multiple amino acid substitutions within or near neutralizing antigenic sites 1, 2, and 3a. Antigenic divergence of the iVDPV variants from Sabin 1 followed two major independent evolutionary pathways. The emergence of distinct coreplicating lineages suggests that iVDPVs can replicate for many months at separate sites in the gastrointestinal tract. Some isolates had mosaic genome structures indicative of recombination across and within lineages. iVDPV excretion apparently ceased after 30 to 35 months of chronic infection. The appearance of a chronic VDPV excretor in a tropical, developing country has important implications for the strategy to stop OPV immunization after eradication of wild polioviruses.The central strategy of the World Health Organization Global Polio Eradication Initiative is widespread use of oral poliovirus vaccine (OPV) at high rates of coverage. This strategy has reduced the global incidence of polio by over 99% since the start of the Initiative in 1988 and restricted wild poliovirus circulation to countries in western and central Africa and southern Asia (87). However, use of OPV is associated with some rare adverse events, including the appearance of cases of vaccine-associated paralytic poliomyelitis among OPV recipients and contacts (76), and the occurrence of polio outbreaks associated with circulating vaccine-derived poliovirus (cVDPV) (36). While cVDPV outbreaks can be prevented by maintenance of high rates of OPV coverage, the occurrence of vaccine-associated paralytic poliomyelitis is associated with the inherent genetic instability of the live, attenuated OPV strains (56).In immunocompetent individuals, the risk of vaccine-associated paralytic poliomyelitis is very low, estimated in the United States at 1 case per 2.4 million OPV doses distributed (75,76).

In 1998, an outbreak of enterovirus 71-associated hand, foot, and mouth disease occurred in Taiwan. Pathologic studies of two fatal cases with similar clinical features revealed two different causative agents, emphasizing the need for postmortem examinations and modern pathologic techniques in an outbreak investigation.

No abstract