"Sentinel surveillance of imported dengue in returning travelers - trends and virus evolution"

Dengue is the most rapidly spreading mosquito-borne viral disease in the world.
In the last 50 years, the incidence of dengue has increased 30-fold with
increasing geographic expansion to new countries and, in the present decade,
from urban to rural settings. As a consequence of the expanding geographical
distribution of both the virus and the mosquito vector, increased frequency of
epidemics, and the emergence of dengue hemorrhagic fever in new areas, the WHO
has classified dengue as a major international public health concern. The
reasons for the resurgence are complex, and are likely a combination of
multiple factors, including population growth associated with rapid
uncontrolled urbanization, demographic changes, poor vector control, genetic
changes in circulating or introduced viruses, modulating climatic factors, and
foremost, increased movement of viruses in people among countries and regions
via international travel.
Dengue is caused by four antigenically related but genetically distinct viruses
(DENV-1, -2, -3 and -4) belonging to the genus Flavivirus, family Flaviviridae.
A considerable number of studies have revealed that each serotype of DENV is
composed of phylogenetically distinct clusters that have been classified into
"genotypes" or "subtypes," and each genotype is also composed of
phylogenetically distinct "groups" or "clades." The evolution of dengue virus
(DENV) is characterized by phylogenetic trees that have a strong temporal
structure punctuated by dramatic changes in clade frequency. Studies have
suggested that specific viral structures may contribute to increased
replication in human target cells and to increased transmission by the mosquito
vector. In addition, mutations to the non-structural genes could also play an
important role in mediating epidemic transmission and increase disease
severity. Phylogenetic and epidemiological analyses suggest that the genotypes
and subtypes with greater epidemic potential are now displacing those that have
lower epidemiological impact.
Dengue viruses are transmitted by mosquitoes of the genus Aedes, subgenus
Stegomyia. The principal vector, Aedes aegypti is now well established in much
of the tropical and subtropical world, particularly in urban areas. A second
species, Ae. albopictus, is generally considered a less effective vector
because, unlike Ae. aegypti, it feeds on many species of vertebrate other than
humans, and is less tied to the domestic environment. Nevertheless, the species
has been responsible for epidemic transmission in some regions, and in recent
years its importance has increased because it has been rapidly expanding its
range due to global commerce in used tires and other water-holding items. The
introduction and rapidly expanding range of Ae. albopictus in Europe is an
iconic example of the growing risk of the globalization of vectors and
vector-borne diseases.

• to describe the epidemiological trends of dengue infections imported to
Europe by returning travelers

• to describe the full clinical spectrum of dengue disease imported to Europe
by returning travelers

• to report the phylogeny, selection pressure, genotype replacement and
molecular clock analyses of dengue viruses imported to Europe by returning
travelers

• to compare the 2009 revised WHO dengue case classification to the classical
case definition in a non-endemic population (European travelers) in terms of
accuracy, sensitivity, simplicity, and acceptability

• to compare clinical manifestations of dengue in a non-endemic population
(European travelers) to a endemic population (Sri Lanka) in terms of
application of the 2009 revised WHO dengue case classification

• to compare viral genetic factors and clinical manifestations of dengue in a
non-endemic population (travelers) and an endemic population (Sri Lanka)

prospective observational multi-centre study

The only risks of participating in this study are those related to the blood
drawn, such as pain at the site of the vein puncture, local hematoma, and the
very low risk of infection linked to the vein puncture. There is no direct
benefit to the patient for participating in this study. The medical care will
be the same whether participating in this study or not.