Dengue diagnosis, treatment and vaccine design: are efforts hampered by multiple serotypes and cross-reactivity with Zika?

Dengue is acknowledged to be the world’s foremost arboviral infection of humans. This Aedes mosquito-borne pathogen is recognized as the aetiological agent of a preeminent re-emerging tropical disease and serious public health threat. Four discrete but genetically similar serotypes of dengue virus, DENV 1-4, trigger a range of clinical symptoms from mild fever to severe haemorrhagic complications. The existence of a phylogenetically more distant fifth serotype was recently suggested. Verification of identity is now needed before it can be officially ratified as DENV-5. Still, the prospect of another serotype calls into question the intrinsic efficacy of anti-dengue vaccines and therapies founded on DENV 1-4 that are now being developed. Accordingly, the presence of DENV-5 and other closely related sylvatic arboviruses, such as Zika, may hamper attempts to identify and treat dengue fever and related pyrexias of unknown origin. The ramifications of this should be considered when updating protocols for diagnosis, therapy, control and prevention.