Abstract
The incidence and global spread of dengue are reaching alarming levels. Thailand represents a critical disease epicenter and demands an understanding of the environmental and evolutionary pressures that sustain DENV transmission. Unlike most affected countries experiencing recurrent outbreaks of the same serotype or replacement of one serotype for another, Thailand is an ecological niche for all four serotypes. Favorable climate and mosquito vector availability maintain a landscape defined by stable, endemic circulation of genotypes, with minimal genetic variation attributed to sporadic, external introductions. This equilibrium is achieved through inter-serotype competition, characterized by reproductive fitness levels that maintain infections (Re>1) and elevated evolutionary rates ( ~ 10(-4)), which steadily increase the genetic diversity of each serotype. This conclusion is reinforced by the identification of numerous positively selected mutations, skewed in the direction of non-structural proteins conferring replication and transmission advantages versus those present in structural proteins evading neutralizing antibodies. Precipitous drops in DENV cases following outbreaks of Chikungunya suggest that interactions with other arboviruses also impact DENV dynamics through vector competition, replication inhibition or partial cross-protection. Thailand is a major exporter of DENV cases and novel emergent lineages gaining fitness here are likely to spread internationally. Surveillance is therefore paramount to monitor diversification trends and take measures to avoid the establishment of similar sustained, local transmission in other countries.