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