title: Failure to clear persistent vaccine-derived neurovirulent poliovirus infection in an immunodeficient man.
abstract: BACKGROUND
  Individuals who chronically excrete neurovirulent poliovirus of vaccine-origin are of considerable concern to the Global Polio Eradication programme. Chronic infection with such polioviruses is a recognised complication of hypogammaglobulinaemia.
  
  
  METHODS
  We did a series of in-vitro and in-vivo therapeutic studies, with a view to clearing persistent neurovirulent poliovirus infection in an individual with common variable immunodeficiency, using oral immunoglobulin, breast milk (as a source of secretory IgA), ribavirin, and the anti-picornaviral agent pleconaril. We undertook viral quantitation, antibody neutralisation and drug susceptibility assays, and viral gene sequencing.
  
  
  RESULTS
  Long-term asymptomatic excretion of vaccine-derived neurovirulent poliovirus 2 was identified in this hypogammaglobulinaemic man, and was estimated to have persisted for up to 22 years. Despite demonstrable in-vitro neutralising activity of immunoglobulin and breast milk, and in-vitro antiviral activity of ribavirin, no treatment was successful at clearing the virus, although in one trial breast milk significantly reduced excretion levels temporarily. During the course of study, the virus developed reduced susceptibility to pleconaril, precluding the in-vivo use of this drug. Sequence analysis revealed the emergence of a methionine to leucine mutation adjacent to the likely binding site of pleconaril in these isolates.
  
  
  CONCLUSIONS
  Chronic vaccine-associated poliovirus infection in hypogammaglobulinaemia is a difficult condition to treat. It represents a risk to the strategy to discontinue polio vaccination once global eradication has been achieved.
authors.affiliation: MRC Centre for Immune Regulation, Division of Immunity and Infection, University of Birmingham, Birmingham, UK. cmaclennan@mlw.medcol.mw
authors.forename: Calman
authors.initials: C
authors.lastname: MacLennan
authors.forename: Glynis
authors.initials: G
authors.lastname: Dunn
authors.forename: Aarnoud P
authors.initials: AP
authors.lastname: Huissoon
authors.forename: Dinakantha S
authors.initials: DS
authors.lastname: Kumararatne
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Paula
authors.initials: P
authors.lastname: O'Leary
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Thompson
authors.forename: Husam
authors.initials: H
authors.lastname: Osman
authors.forename: Philip
authors.initials: P
authors.lastname: Wood
authors.forename: Philip
authors.initials: P
authors.lastname: Minor
authors.forename: David J
authors.initials: DJ
authors.lastname: Wood
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
mesh_terms: D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D036022:Capsid Proteins / Q000235:genetics; D002353:Carrier State / Q000276:immunology / Q000628:therapy* / Q000821:virology; D017074:Common Variable Immunodeficiency / Q000276:immunology / Q000821:virology*; D005243:Feces / Q000821:virology; D000882:Haplorhini; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D008895:Milk, Human / Q000276:immunology; D009154:Mutation; D011051:Poliomyelitis / Q000209:etiology / Q000276:immunology / Q000628:therapy / Q000821:virology*; D017955:Poliovirus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects*; D017211:Treatment Failure; D014774:Virulence
chemical_list: D000998:Antiviral Agents; D036022:Capsid Proteins; D016756:Immunoglobulins, Intravenous; D011055:Poliovirus Vaccine, Oral; C062481:VP1 protein, polyomavirus