title: Chloroquine and its derivatives exacerbate B19V-associated anemia by promoting viral replication.
abstract: BACKGROUND
  An unexpectedly high seroprevalence and pathogenic potential of human parvovirus B19 (B19V) have been observed in certain malaria-endemic countries in parallel with local use of chloroquine (CQ) as first-line treatment for malaria. The aims of this study were to assess the effect of CQ and other common antimalarial drugs on B19V infection in vitro and the possible epidemiological consequences for children from Papua New Guinea (PNG).
  
  
  RESULTS
  Viral RNA, DNA and proteins were analyzed in different cell types following infection with B19V in the presence of a range of antimalarial drugs. Relationships between B19V infection status, prior 4-aminoquinoline use and anemia were assessed in 200 PNG children <10 years of age participating in a case-control study of severe infections. In CQ-treated cells, the synthesis of viral RNA, DNA and proteins was significantly higher and occurred earlier than in control cells. CQ facilitates B19V infection by minimizing intracellular degradation of incoming particles. Only amodiaquine amongst other antimalarial drugs had a similar effect. B19V IgM seropositivity was more frequent in 111 children with severe anemia (hemoglobin <50 g/L) than in 89 healthy controls (15.3% vs 3.4%; P = 0.008). In children who were either B19V IgM or PCR positive, 4-aminoquinoline use was associated with a significantly lower admission hemoglobin concentration.
  
  
  CONCLUSIONS
  Our data strongly suggest that 4-aminoquinoline drugs and their metabolites exacerbate B19V-associated anemia by promoting B19V replication. Consideration should be given for choosing a non-4-aminoquinoline drug to partner artemisinin compounds in combination antimalarial therapy.
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bönsch
authors.forename: Christoph
authors.initials: C
authors.lastname: Kempf
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: Laurens
authors.initials: L
authors.lastname: Manning
authors.forename: Moses
authors.initials: M
authors.lastname: Laman
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
authors.forename: Carlos
authors.initials: C
authors.lastname: Ros
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000009:adverse effects*; D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000009:adverse effects* / Q000494:pharmacology*; D004279:DNA, Viral / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D010219:Papua New Guinea; D010322:Parvoviridae Infections / Q000821:virology; D016732:Parvovirus B19, Human / Q000187:drug effects* / Q000254:growth & development*; D012367:RNA, Viral / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D004279:DNA, Viral; D036341:Intercellular Signaling Peptides and Proteins; D012367:RNA, Viral; D002738:Chloroquine