TROPICAL MEDICINE Surprising New Dengue Virus Throws a Spanner in Disease Control Efforts Dennis Normile BANGKOK—Dispatches from the frontlines of the war on dengue are growing more and more dispiriting. In September 2012, pharmaceuticals giant Sanofi Pasteur revealed that a vaccine against the centuries-old tropical malady had stumbled in clinical trials. Meanwhile, dengues toll is heavier than thought. According to an April report based on modeling, the annual global incidence, close to 390 million, is about three times higher than the number of cases estimated by the World Health Organization (WHO) for 2009. At a meeting here earlier this week, scientists described the latest blow on the battlefield: a fifth dengue virus. The first new serotype discovered in a half century could complicate control efforts, especially the quest for a vaccine that protects against all types simultaneously. No other vector-borne disease strikes fear into the hearts of public health workers like dengue, says Lulu Bravo, a pediatrician at the University of the Philippines, Manila. There is no vaccine or drug against dengue, which is spread by Aedes aegypti mosquitoes and called breakbone fever for the excruciating joint pain in severe cases. Although dengue deaths have dropped thanks to improved patient care, the disease remains the leading cause of hospitalization of children in Thailand, says pediatrician Usa Thisyakorn here at Chulalongkorn University. Urbanization is fueling dengues rapid advances. Water collecting in gutters, abandoned tires, and septic tanks, for example, provides convenient breeding grounds for Aedes mosquitoes. As investigators reported at the meeting, even as the mosquitos range expands, possibly thanks to climate change, efforts to control it by eliminating standing water and spraying arent keeping pace. Malaysia is a case in point. The nation used to suffer major dengue outbreaks once or twice a decade. Since 1991, we have had yearly outbreaks, says Mohd Zaki, a vector-borne disease specialist with Malaysias Ministry of Health. Dengue is spreading from urban to rural areas and to countries, such as Nepal, where it has not been seen before, adds Samlee Plianbangchang, WHOs Southeast Asia regional director. A 2010 outbreak in Nepal even hit Kathmandu, which sits at an elevation of 1400 meters and was presumed to be inhospitably cool for Aedes. It seems there is some correlation between climate change and dengue moving to higher altitudes, says Basu Dev Pandey, an official with Nepals health department. Most dengue infections are mild. But in about 10% of cases, the disease progresses to dengue hemorrhagic fever, in which leaky blood vessels can, in rare instances, lead to death. Infection confers lifetime immunity to a particular serotype, but subsequent infection with a different dengue virus increases the likelihood of severe disease. For that reason, vaccine developers have been striving to concoct a vaccine that protects against the four known serotypes simultaneously. But with limited insight into the complex interactions between the human immune system and the dengue virus, progress has been slow, says infectious disease specialist Scott Halstead, a senior adviser to the Dengue Vaccine Initiative in Seoul. We have to cope with the fact that we dont understand the science, he says. The fifth serotype, which almost escaped detection, clouds the picture even more. In 2007, when a dengue outbreak struck Malaysias Sarawak state, on Borneo, blood and serum samples from a severe case labeled dengue 4 were collected through a surveillance network set up by Jane Cardosa, a virologist now retired from Universiti Malaysia Sarawak. Later, a researcher found that the samples did not respond to dengue 4 diagnostic tests. Nikos Vasilakis, a virologist at the University of Texas Medical Branch in Galveston, sequenced its entire genome and found that the virus occupies a new branch on the dengue family tree. Vasilakis and his collaborators then determined that antibodies elicited in monkeys and humans by the Malaysian virus differ significantly from those elicited by the other four strains. When injected into monkeys previously stricken with types 1, 2, and 3, the new strain replicated like mad. In monkeys that had recovered from type 4, it replicated poorly, indicating that the monkey immune system saw similarities in the two. Theyve done a very good job in characterizing the virus, and its convincing that it is distinct from the other four, says Thomas Scott, a dengue ecologist at the University of California, Davis. The public health implications are unclear. Vasilakis says there doesnt seem to be a sustained transmission cycle of serotype 5 in humans, though his team suspects that the virus circulates among nonhuman primates, possibly macaques, on Borneo. For vaccine developers, factoring in a new strain could be a major headache. Scott says the dengue community is realizing that current control approaches are too simplistic. And vaccines in the pipeline dont appear to provide complete immunity. Just one tool isnt going to do it, Scott says. Dengue will be with us for many years, Plianbangchang laments. And as bad as it is, he says, it could get worse.
Posted on: Fri, 25 Oct 2013 12:53:28 +0000
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