Disease exacerbation caused by sequential dengue infections: myth or reality?

Dengue can be caused by any one of four viruses that are antigenically related but not cross-protective. It has been proposed that the disease may be more severe if an infection with one dengue serotype follows infection with another serotype. Both experimental and epidemiologic data have been cited to substantiate this concept, but the present reviewer does not find the data convincing. The issue is of practical importance because of its relevance to the use of dengue vaccines now under development. It is impossible to prove that clinical manifestations of dengue are not exacerbated by sequential infections. Negative findings can always be countered by arguments that exacerbation occurs only with certain serotypes, only with certain strains of those serotypes, or only when infections occur at critical intervals. Interested persons can examine the relevant data and decide whether the concept of disease exacerbation following sequential dengue infections is myth or reality.