title: Neurovirulent vaccine-derived polioviruses in sewage from highly immune populations.
abstract: BACKGROUND
  Vaccine-derived polioviruses (VDPVs) have caused poliomyelitis outbreaks in communities with sub-optimal vaccination. Israeli environmental surveillance of sewage from populations with high (>95%) documented vaccine coverage of confirmed efficacy identified two separate evolutionary clusters of VDPVs: Group 1 (1998-2005, one system, population 1.6x10(6)) and Group 2 (2006, 2 systems, populations 0.7x10(6) and 5x10(4)).
  
  
  RESULTS
  Molecular analyses support evolution of nine Group 1 VDPVs along five different lineages, starting from a common ancestral type 2 vaccine-derived Sabin-2/Sabin-1 recombinant strain, and independent evolution of three Group 2 VDPVs along one lineage starting from a different recombinant strain. The primary evidence for two independent origins was based on comparison of unique recombination fingerprints, the number and distribution of identical substitutions, and evolutionary rates. Geometric mean titers of neutralizing antibodies against Group 1 VDPVs were significantly lower than against vaccine strains in all age-group cohorts tested. All individuals had neutralizing titers >1:8 against these VDPVs except 7% of the 20-50 year cohort. Group 1 VDPVs were highly neurovirulent in a transgenic mouse model. Intermediate levels of protective immunity against Group 2 VDPVs correlated with fewer (5.0+1.0) amino acid substitutions in neutralizing antigenic sites than in Group 1 VDPV's (12.1+/-1.5).
  
  
  CONCLUSIONS
  VDPVs that revert from live oral attenuated vaccines and reacquire characteristics of wild-type polioviruses not only threaten populations with poor immune coverage, but are also a potential source for re-introduction of poliomyelitis into highly immune populations through older individuals with waning immunity. The presence of two independently evolved groups of VDPVs in Israel and the growing number of reports of environmental VDPV elsewhere make it imperative to determine the global frequency of environmental VDPV. Our study underscores the importance of the environmental surveillance and the need to reconsider the global strategies for polio eradication and the proposed cessation of vaccination.
authors.affiliation: Central Virology Laboratory, Public Health Services, Ministry of Health, Chaim Sheba Medical Center, Tel Hashomer, Israel. cvlsheba@netvision.net.il
authors.forename: Lester M
authors.initials: LM
authors.lastname: Shulman
authors.forename: Yossi
authors.initials: Y
authors.lastname: Manor
authors.forename: Danit
authors.initials: D
authors.lastname: Sofer
authors.forename: Rachel
authors.initials: R
authors.lastname: Handsher
authors.forename: Tiberio
authors.initials: T
authors.lastname: Swartz
authors.forename: Francis
authors.initials: F
authors.lastname: Delpeyroux
authors.forename: Ella
authors.initials: E
authors.lastname: Mendelson
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D005075:Biological Evolution; D002648:Child; D015331:Cohort Studies; D004196:Disease Outbreaks; D016679:Genome, Viral; D006801:Humans; D007223:Infant; D007557:Israel / Q000453:epidemiology; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D010802:Phylogeny; D011051:Poliomyelitis / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D017955:Poliovirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity*; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology; D012722:Sewage / Q000821:virology*; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014774:Virulence / Q000235:genetics; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D011055:Poliovirus Vaccine, Oral; D012722:Sewage; D014764:Viral Proteins