June 13, 2011 — More than a
thousand years ago, somewhere in Southeast Asia, a fateful meeting
occurred between a mosquito-borne virus that infected mainly monkeys and
a large, susceptible group of humans.
The result: the world's first outbreak of dengue fever.
Today, dengue virus -- which can produce high fever, excruciating
joint pain and even death -- has spread throughout tropical Asia, Africa
and South America, and in 2008 it re-appeared in the Florida Keys. It
could be even more widespread along the U.S. Gulf Coast but there is no
surveillance in place to detect it.
Annually dengue strikes about 100 million people and causes an
estimated 50,000 deaths, thriving in the urban environments infested by
Aedes aegypti, the mosquito species primarily responsible for human
dengue transmission.
Meanwhile, the virus' forest-dwelling counterpart -- known as
"sylvatic dengue" -- continues to flourish in Southeast Asia and West
Africa, cycling between non-human primates and the mosquitoes that feed
on them. Since the 1970s, sylvatic dengue has received very little
scientific attention -- a situation that badly needs to be remedied,
according to the authors of "Fever from the forest: Prospects for the
continued emergence of sylvatic dengue virus and its impact on public
health," an article published online June 13 in Nature Reviews Microbiology.
"This virus continues to circulate in the forests, and now economic
and ecological pressures are driving more and more people into the
forests in Africa and Southeast Asia," said University of Texas Medical
Branch at Galveston assistant professor Nikos Vasilakis, lead author of
the paper. "In the last 10 years we've seen a number of outbreaks of
disease with real public health impact caused by what we call zoonotic
viruses, viruses that start out in wild animals but can also be
transmitted to humans -- look at SARS, Nipah and Hendra, for example.
Sylvatic dengue could be capable of a similar emergence -- or rather,
re-emergence, since we know previous dengue spillovers into urban and
near-urban settings have occurred."
Dengue virus may also be capable of movement from the widespread
urban cycles into primates and forest mosquitoes of Latin America, which
would establish a new reservoir for human infections in the New World.
In the paper, Vasilakis and his collaborators identify two factors
that make a dengue re-emergence a "clear and present danger": rapid
human population growth near and in tropical forests, and the fact that
little or no genetic change would be needed for sylvatic dengue to adapt
to human hosts and urban mosquitoes.
"Experiments show that there is little or no adaptive barrier to the
emergence of sylvatic dengue into human populations," Vasilakis said.
"In other words, the virus can emerge from its current environment at
any time, without further adaptation."
The article also presents additional reasons for boosting research
into sylvatic dengue, among them the possibility that its behavior in
nonhuman primate animal models might offer critical new perspectives on
the pathology of human dengue. (Most monkeys tested so far show no
clinical signs of the disease, limiting their usefulness as experimental
models.) Another significant issue is the possibility that vaccines
against human dengue, which could be licensed in as little as five
years, might push the virus to the brink of eradication in the urban,
human transmission cycle, leaving an ecological opening that could be
filled by sylvatic dengue.
"We see a precedent for this with yellow fever, where we have a very
good vaccine -- urban yellow fever has been nearly eliminated in some
regions -- but we don't have good vector control programs, and
especially in South America we now have outbreaks fueled by sylvatic
yellow fever," Vasilakis said. "If we eradicate human dengue and then
stop vaccinating, as we often do after the disease disappears, we could
see a re-emergence of dengue from a sylvatic source."
With the exception of a research program in Malaysia that ended in
1975, fieldwork on sylvatic dengue has been minimal, according to
Vasilakis. In the article, he and his fellow authors call for new
surveillance programs to monitor mosquitoes, non-human primates and
humans in areas where sylvatic dengue is endemic, as well as the
development of new diagnostic tools that will enable researchers to more
easily accomplish those studies. (One such surveillance effort is now
underway in Senegal, funded by the National Institutes of Health and led
by UTMB professor Scott Weaver, the paper's senior author.)
"Of all the viruses with the potential to shift from animals into
humans, the most likely to do so are those that, like sylvatic dengue,
are carried by the non-human primates and/or bats," Vasilakis said. "For
our own good, we need to know as much as we can about this virus."
Other authors of the paper include Jane Cardosa of the Universiti
Sarawak Malaysia, Kathryn Hanley of New Mexico State University and
Edward Holmes of Pennsylvania State University. The National Institutes
of Health supported this work.
http://www.sciencedaily.com/releases/2011/06/110613142235.htm