There are four serotypes of DENV (DENV1–DENV4), which differ at the amino-acid level by 30–35%. As a consequence of this heterogeneity, immunity to one serotype does not necessarily protect against infection with another serotype. Sequential infections are therefore common in DENV-endemic countries, where all four serotypes often circulate at the same time or replace each other in a cyclical manner. Epidemiological studies have further shown that adverse clinical outcomes are more frequent during secondary or recurrent infections.