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Pieter Libin, Lize Cuypers, Peter Simmonds, Ann Nowe, Jorge Muñoz-Jordán, Luiz Alcantara, Anne-Mieke Vandamme, Gilberto Santiago, Kristof Theys
 

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Abstract 

Dengue virus (DENV) is estimated to cause 390 million infections per year worldwide. A quarter of these infections manifest clinically and are associated with a morbidity and mortality that put a significant burden on the affected regions. Reports of increased frequency, intensity, and extended geographical range of outbreaks highlight the virus{\textquoteright}s ongoing global spread. Persistent transmission in endemic areas and the emergence in territories formerly devoid of transmission have shaped DENV{\textquoteright}s current genetic diversity and divergence. This genetic layout is hierarchically organized in serotypes, genotypes, and sub-genotypic clades. While serotypes are well defined, the genotype nomenclature and classification system lack consistency, which complicates a broader analysis of their clinical and epidemiological characteristics. We identify five key challenges: (1) Currently, there is no formal definition of a DENV genotype; (2) Two different nomenclature systems are used in parallel, which causes significant confusion; (3) A standardized classification procedure is lacking so far; (4) No formal definition of sub-genotypic clades is in place; (5) There is no consensus on how to report antigenic diversity. Therefore, we believe that the time is right to re-evaluate DENV genetic diversity in an essential effort to provide harmonization across DENV studies.

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