RxPG News : Dengue

Tiny fly can keep dengue-causing mosquito in check

Tue, 09 Jun 2009 13:35:24 PST

( from http://www.rxpgnews.com ) The larvae of a tiny fly or midge can help decimate a number of invasive Asian tiger mosquitoes, that infect 50 to 100 million people with dengue fever every year in the tropics.

Once found only in tropical and sub-tropical regions of Southeast Asia, the Asian tiger

mosquito has now spread to Africa, the Americas, Australia, the Caribbean, Europe and the Middle East.

Midge larvae do not harm native mosquitoes, helping them survive, even though the invasive mosquitoes are better at gobbling up resources.

The researchers found inherent size differences between the mosquito species. The

tree hole - mosquito is larger than the Asian tiger mosquito, which makes it less vulnerable to predation from the small but voracious predatory midge.

Previous studies have found that the native mosquito larvae also adopt less 'risky'

behaviours than the invasive mosquito larvae, making them less susceptible to being eaten.

'Size is having a major effect in terms of how the prey are getting consumed,' said Barry Alto, medical entomologist with the State Natural History Survey at the University of Illinois -.

'This is another mechanism that allows the native mosquito to hang on and co-exist with the invasive mosquitoes in certain areas where predators are present,' Alto said.

The Asian tiger mosquito was first detected in the US in 1985 in a shipment of used tyres to a Texas port. Like the native mosquito, it lays its eggs in watery containers, including tyres.

Even if the water evaporates, a splash of rain and a supply of nutrients such as the microbes that feed on dead leaves are all that the larvae need to hatch and grow.

Like the yellow fever mosquito -, another invasive mosquito that

is now well established in the Americas, the Asian tiger mosquito can carry several viral diseases that afflict humans.

The interaction between predators and native and invasive mosquitoes is one of several

factors that may contribute to disease transmission, Alto said, according to a U of I release.

These findings were published in the British Ecological Society's Journal of Animal Ecology.

New Test to Establish In-Vivo Safety of Dengue Vaccine

Mon, 16 Feb 2009 16:35:46 PST

( from http://www.rxpgnews.com ) Washington, Feb 16 - Researchers have developed a test to determine whether vaccines against a virus that infects 100 million people annually, now ready for clinical trials, should really protect patients from infection, or would make it more dangerous for them.

'Our study shows that the new test is likely superior to the standard test in its ability to tell whether a patient's response to a vaccine is safe,' said Xia Jin, associate professor of medicine at the University of Rochester Medical Centre - and co-author of the study.

Cases of tropical, mosquito-borne dengue fever have been expanding globally for more than 50 years, with nearly a third of the human population in 100 countries now at risk of infection with the four types of dengue virus.

Infection with the dengue flavivirus, which is related to West Nile Virus and Yellow Fever, annually results in an estimated half a million hospitalisations and 22,000 deaths, mostly among infants, according to WHO.

After decades of absence in the US, the disease is causing illness again along the Texas-Mexico border, experts say and add that widespread dengue infection in the continental US is a real possibility.

A typical dengue infection confines a patient to bed for more than a week with fever and severe limb pains, but most recover. In less than five percent of cases, however, dengue hemorrhagic fever - and dengue shock syndrome -, often deadly complications, develop just as the fever breaks.

Mostly affecting babies between five and eight months, DHF causes victims to vomit and pass blood in their feces and urine. If diagnosed quickly, patients respond to intensive hospital treatment and fluids, but mortality can reach 15 percent when undiagnosed.

DSS comes when the infection has caused so much fluid to leak out of capillaries that there is not enough blood to supply organs. As of 2008, there were no antiviral drugs designed to treat dengue and no drug candidates in late-stage development, said an URMC release.

These findings were published in Clinical and Vaccine Immunology.

Explaining peaks and troughs of dengue epidemics

Mon, 31 Jul 2006 11:30:37 PST

( from http://www.rxpgnews.com ) Scientists have long known that epidemics of dengue fever wax and wane over a period of several years, but they've never been quite sure why. With the incidence and range of the potentially deadly mosquito-borne illness increasing, understanding the factors that influence these epidemics has never been more important.

A new study by researchers at the University of Georgia suggests that a brief period of cross-immunity conferred by any one of the four viral strains, or serotypes, that cause dengue explains the timing of epidemics.

"We found that since about the mid 1980s, there's been a sequential replacement of the dominant serotype," said lead author Helen Wearing, a post-doctoral researcher at the UGA Institute of Ecology. "So, for example, one year serotype three is 60 percent of the cases and the next year serotype two is dominant and so on. Epidemics of individual serotypes recur every eight to 10 years, but, at the same time, if you look at all the data together, you see about an average three-year cycle with some seasonal component to it."

In addition to helping resolve a long-standing debate in public health, the study, published this week in the early online edition of the journal Proceedings of the National Academy of Sciences, gives researchers a framework that can be used to create models that predict dengue outbreaks in both space and time.

"It's a framework that highlights the key elements you need to take into account while developing a forecasting model," Wearing said. "Because if you were to build a forecasting model without understanding the trends in cross-immunity, you would not necessarily predict what we observe."

The researchers examined 30 years of data from the government of Thailand and from a Thai clinic that keeps what is widely regarded as the most comprehensive set of data on dengue. Southeast Asia has been a dengue hot spot since the 1950s, but the researchers note that their model applies to other regions where all four dengue strains circulate.

The researchers compared the data with results from mathematical models that explore both independently and collectively the role factors such as temporary cross-immunity and variation in serotype virulence play in epidemics. They found that cross-immunity alone is enough to create the patterns that are observed in nature.

The study is a major departure from other theories about what drives dengue epidemics. The conventional wisdom is that an amplification of the severity of disease caused by repeat infections with different strains, a phenomenon known as antibody-dependent enhancement, drives the boom and bust cycles of dengue epidemics.

"Temporary cross-immunity has been ignored by the epidemiological community," said study co-author Pejman Rohani, associate professor of ecology and UGA Biomedical and Health Sciences Institute researcher.

"It's discussed in the scientific literature," Wearing added, "but no one ever considers it an important factor in generating the epidemiological cycles."

Cross-immunity, which lasts from two to nine months, results when overall antibody levels created by the body in response to infection by one serotype are high enough to protect against infection by related serotypes. After this period, however, antibody levels drop to levels that are no longer neutralizing but instead are exploited by the dengue virus to enhance replication and cause more severe illness.

"You can't deny the empirical fact that people who get severe dengue may well have had cases before," Rohani said. "But our work suggests it's not the mechanism that's underlying the big-picture pattern that we see."

Several factors are contributing to an increase in dengue epidemics. Global warming is allowing the species primarily responsible for spreading dengue (Aedes aegypti, also known as the yellow fever mosquito) to expand its range. Population growth in developing nations is pushing more people into substandard housing in mosquito-infested areas. And the ease of travel brings the virus to areas that were previously dengue-free when a mosquito bites an infected traveler and then spreads it to others. According to the Centers for Disease Control and Prevention, Aedes aegypti and the related Aedes albopictus (the Asian tiger mosquito) have the potential to spread dengue in sporadic outbreaks in the Southern and Southeastern United States.

Rohani said the same modeling techniques he and Wearing used to study dengue can help shed light on the transmission of other multi-strain diseases such as cholera, malaria and influenza. He calls a better understanding of such diseases, "one of the most important issues in public health and epidemiology in general."

"Until now, it's been very much a single-host, single-pathogen type of framework," Rohani said. "Now with avian influenza being very much on everyone's mind, we're beginning to realize that the genetic diversity of infectious agents is really important."

Genetically engineered mosquitoes show resistance to dengue fever virus

Wed, 08 Mar 2006 21:35:37 PST

( from http://www.rxpgnews.com ) Researchers have successfully created a genetically engineered mosquito that shows a high level of resistance against the most prevalent type of dengue fever virus, providing a powerful weapon against a disease that infects 50 million people each year.

Anthony James, a UC Irvine vector biologist, is one of a team of researchers who injected DNA into mosquito embryos, creating the first stable transgenic mosquito resistant to Type 2 dengue fever virus, the most prevalent strain of the disease. The mosquitoes that survived the procedure also remained fertile and were able to reproduce, a key factor for any future strategies that may involve replacing mosquito populations with their genetically modified counterparts.

These results are very exciting because they provide us a genetic tool we can use to control mosquito-borne diseases such as dengue fever, James said. We have been working for some time on the individual components of creating a genetically modified mosquito that would fend off dengue infection, but this is the first time we have brought all the pieces together to create a stable model that can also reproduce.

In the study, the researchers exploited a vulnerability of the dengue virus to make the mosquitoes resistant to infection. This vulnerability occurs when the virus replicates and its single strand of RNA a chemical cousin of DNA briefly becomes doublestranded. At this point, the virus is vulnerable because of a naturally occurring protein called dicer-2. This protein initially has no effect on a single strand of RNA, but acts like scissors on the double strand, chopping it up and rendering its genetic material useless. Once this process is started, the single-stranded RNA also becomes vulnerable to dicer-2 and is cut up, thereby preventing further virus replication.

On its own, this process of self-destruction happens only after the virus has already replicated and been transmitted; however, the researchers found a way to control and speed up the process. They accomplished this by cloning a section of the virus RNA and injected two inverse copies of it into mosquito embryos. The copies formed a double-stranded RNA, which, as expected, bound with dicer-2 and was chopped up. The virus never had the opportunity to replicate. As a result, they could inoculate mosquitoes with a form of the virus that would essentially be benign.

Joining James on the study, funded by a 2001 grant from the National Institutes of Health, were researchers from Colorado State University and from Virginia Polytechnic Institute and State University.

James and his colleagues performed tests on a family of mosquitoes descended from one of the original embryos that survived the procedure. They found that the vast majority of that family was highly resistant to dengue infection. They also were able to detect the engineered RNA in the mosquitoes, a sign that the genetic alteration had been successful and passed down through reproduction. Furthermore, when that genetic modification was reversed, the mosquitoes were as susceptible to the virus as they had been before the procedure.

Dengue fever is endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, Southeast Asia and the Western Pacific. The virus is transmitted to people by mosquitoes of the species Aedes aegypti. The World Health Organization estimates 50 million cases of dengue infection each year. Approximately 20,000 people die annually from the disease.

James, a professor of microbiology and molecular genetics, and of molecular biology and biochemistry, has made a number of significant advances on genetic approaches to interrupt malaria parasite and dengue virus transmission by mosquitoes. He has received a number of international awards for his research.

In 2005, he received a $19.7 million grant from the Foundation for the National Institutes of Health to lead an international effort to develop new methods to control the transmission of dengue fever. The project is among 43 groundbreaking research projects to improve health in developing countries, supported by $436 million for the Grand Challenges in Global Health Initiative, launched by the Bill and Melinda Gates Foundation.

According to James, the next step of this research will be to use the FNIH grant to explore population replacement strategies using the genetically modified mosquitoes. He stressed that no genetically altered mosquitoes will be released at any time during these studies.

The Complicated Art of Tracking Dengue

Tue, 26 Apr 2005 22:25:38 PST

( from http://www.rxpgnews.com ) Compared with malaria, dengue fever has a rather lower profile in the public mind, although to those who have had it, it leaves a great impression. The name dengue fever is derived from the Swahiliwords Ki denga pepo (it is a sudden overtaking by an evil spirit), which gives an idea of the rapid onset of the disease. The dengue virus is carried by the mosquito Aedes aegypti, and the disease often occurs as epidemics. Although the classic illness is a fairly benign acute febrile syndrome, it may be very painfulhence the English nickname, breakbone fever.

The virus can also cause a much more serious illness known as dengue hemorrhagic fever, which can progress to dengue shock syndrome. There are four main serotypes of the dengue RNA virus; dengue hemorrhagic fever is more likely to occur during dengue infection in people with preexisting active or passive (e.g., maternally acquired) immunity who are exposed to a different dengue virus serotype. In contrast to classic dengue, the hemorrhagic fever and shock syndromes are mostly diseases of children and, if untreated, have a mortality of around 50%.

Around two-fifths of the world's population are now at risk of the disease (one estimate is that 80 million people are infected each year). The number at risk will increase as population growth, urbanization, international travel, and climate change influence transmission of the disease. Understanding how all these factors interact is important in planning for disease outbreaks. However, the incidence of dengue is not easily predictable, varying with season, and also between years. For example, although dengue is most prevalent in the wet season, dengue epidemics have also been associated with drought in some countries. El Niño is the best known climatic event affecting climate between years, and some research already suggests that there is a relationship between the timing of dengue epidemics and El Niño in the Pacific Islands and in other countries.

Previous research has uncovered traveling waves of dengue in Thailand, but the cause of these has been obscure. In a paper in this month's PLoS Medicine Bernard Cazelles and colleagues looked at the details of the relationship between dengue incidence and El Niño in Thailand. Their results, based on complex mathematical analysis, do not provide easy answers for those who might want to plan for dengue outbreaks, though they do go some way to helping to understand the complex interplay between the various factors. In essence, the researchers found that there was a significant association between El Niño oscillations, climate variables, and dengue hemorrhagic fever incidence with a 2- to 3-year repeat, for both Bangkok and the rest of Thailand. However this association was significant only for the years 19861992, and outside these years factors other than climate were probably responsible for triggering the disease outbreaks.