title: Periodic re-emergence of endemic strains with strong epidemic potential-a proposed explanation for the 2004 Indonesian dengue epidemic.
abstract: Indonesia experienced a severe dengue epidemic in the first quarter of 2004 with 58,301 cases and 658 deaths reported to the WHO. All four dengue virus (DENV) serotypes were detected, with DENV-3 the predominant strain. To ascertain the molecular epidemiology of the DENV associated with the epidemic, complete genomes of 15 isolates were sequenced from patient serum collected in Jakarta during the epidemic, and two historical DENV-3 isolates from previous epidemics in 1988 and 1998 were selectively sequenced for comparative studies. Phylogenetic trees for all four serotypes indicate the viruses are endemic strains that have been circulating in Indonesia for a few decades. Whole-genome phylogeny showed the 2004 DENV-3 isolates share high similarity with those isolated in 1998 during a major epidemic in Sumatra. Together these subtype I DENV-3 strains form a Sumatran-Javan clade with demonstrated epidemic potential. No newly-acquired amino acid mutations were found while comparing genomes from the two epidemics. This suggests re-emergence of little-changed endemic strains as causative agents of the epidemic in 2004. Notably, the molecular evidence rules out change in the viral genomes as the trigger of the epidemic.
authors.affiliation: Novartis Institute for Tropical Diseases Pte. Ltd., Singapore, Singapore.
authors.forename: Swee Hoe
authors.initials: SH
authors.lastname: Ong
authors.forename: Jin Teen
authors.initials: JT
authors.lastname: Yip
authors.forename: Yen Liang
authors.initials: YL
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Syahrial
authors.initials: S
authors.lastname: Harun
authors.forename: Erlin
authors.initials: E
authors.lastname: Lystiyaningsih
authors.forename: Bambang
authors.initials: B
authors.lastname: Heriyanto
authors.forename: Charmagne G
authors.initials: CG
authors.lastname: Beckett
authors.forename: Wayne P
authors.initials: WP
authors.lastname: Mitchell
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.forename: Agus
authors.initials: A
authors.lastname: Suwandono
authors.forename: Subhash G
authors.initials: SG
authors.lastname: Vasudevan
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Schreiber
mesh_terms: D003715:Dengue / Q000453:epidemiology*; D003716:Dengue Virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D004196:Disease Outbreaks; D019353:Endemic Diseases; D014644:Genetic Variation; D016679:Genome, Viral; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D008969:Molecular Sequence Data; D010507:Periodicity; D010802:Phylogeny; D017354:Point Mutation; D017422:Sequence Analysis, DNA