http://www.sciencedaily.com/releases/2006/03/060308213147.htm

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.

http://scienceblogs.com/aetiology/2006/08/dengue.php

The name “dengue” means “breakbone fever” due to the extreme bone pain it causes. The virus is a member of the flavivirus family, which includes the virus that causes yellow fever. Both viruses are arboviruses–viruses that are transmitted by arthropods. In the case of dengue and YF, the arthropod in question is the mosquito; specifically, the Aedes aegypti, an urban mosquito that lives in close contact with humans.

Dengue infections cause an enormous amount of morbidity and mortality in areas where the virus is endemic. It’s estimated to infect 50-100 million people each year. Though many cases are mild, in its most severe form, infection with dengue virus can result in a fatal hemorrhagic fever. Dengue fever is considered a re-emerging disease, as the vector mosquito has spread into new areas and infections have increased in number. Additionally, infections in travelers have increased dramatically over the last 5 years.

Dengue viruses are grouped into four different serotypes. Though related, each viral serotype is different enough that infection with one type doesn’t lead to lasting cross-protection against the other serotypes; therefore, an individual can theoretically be infected with dengue at least 4 times during their life. Additionally, during the past several decades, the distribution of these viruses has spread, so that viruses of multiple serotypes may be present in the same area. During the same time period, the overall number of annual dengue cases has increased, and the number of dengue hemorrhagic fever (DHF) cases has jumped 6-fold.

This latter statistic has been the impetus for much research into the effect a prior dengue infection has on later infections with viruses of different serotypes. Though I mentioned that infection with one serotype doesn’t protect an individual from infection with a virus of a different serotype, there does appear to be a short-lived cross-reactive antibody response in the months following viral infection. Conversely, this isn’t necessarily a good thing, as previous studies have shown that this actually seems to increase the risk of developing DHF when individuals are infected with a dengue virus of a different serotype during this time period. (This is referred to as “antibody-dependent enhancement,” or ADE, meaning that the presence of antibodies at a concentration that’s not high enough to neutralize the virus, and therefore instead actually have the effect of enhancing viral replication).

While the increased geographic overlap of viral serotypes coupled with ADE is an attractive explanation for the increase in DHF, the story is more complicated. Not all serotypes of dengue virus are equivalent in virulence, so an increase in prevalence of a more virulent serotype may also lead to an increase in DHF, regardless of any effect of ADE. Indeed, one challenge in the study of dengue has been to figure out the role that ADE and/or hypervirulent strains of dengue play in transmission of the virus. Do they allow the virus to replicate to higher levels, increasing transmission? Or does their effect on host mortality shorten the host’s infectious period, leading to a decrease in circulating virus? A new paper in PNAS takes a modeling approach in order to address this question.

The model they used was another variation on the SEIR model I described here. However, because dengue is a vector-borne virus, they have to model not only infection in the human host, but also infection in the mosquito vector, adding an additional layer of complexity to the analysis.

To carry out the analysis, they model a number of parameters and assumptions, and compare the results from their models to data they have from years of surveillance in Thailand. They found that the best fit to the data occurred when short-lived cross-immunity alone was examined. They note, however, that “additional moderate amounts of ADE and increased virulence are also compatible but not necessary.” This has important implications for vaccine policy; a vaccine targeted to a single serotype could actually have the effect of increasing serious dengue infections.

A limitation of the study, however, is that all strains within a serotype are considered to be equivalent; that is, it’s assumed that all serotype 1s are of equal virulence, even though in reality, it’s likely that there are differences in virulence within a serotype, as well as between serotypes. Modeling this requires an even more complicated algorithm, however, and they currently lack significant data about the molecular epidemiology of dengue beyond serotype–certainly an area ripe for future investigation.

http://medicine.com.my/wp/?p=1217

Of Vaccines and Dengue
by Palmdoc @ 6:03 am. Filed under - General, - Palmdoc
The local council has been fogging our neighbourhood again. Apparently someone in the adjacent road came down with dengue. As I entered the house, I was assailed by the choking smell of insecticide. How unhealthy this all is. Worse still, how futile all this fogging is as it does nothing to the eggs of the Aedes mosquito which are quite hardy and will merely hatch after the next spell of rain.
What I think the world desperately needs is an effective Dengue vaccine. I am not a virologist and have not been keeping up with the latest in this field so I Googled a bit and came out with some interesting links.

Firstly, the CDC is pessimistic in it’s assessment that “an effective dengue vaccine for public use will not be available for 5 to 10 years.” (article reviewed in 2005). However, The Walter Reed Army Institute of Research is recruiting patients for a Phase I Clinical Trial of a Dengue-1 DNA Vaccine. Work on the vaccine has been gonig on for years, as in this 2003 paper on the Progress of the Development of a live-attenuated viral vaccine by the US Army.
The Cubans are also in the race and apparently Phase I trials are being planned next year for a Recombinant vaccine against Dengue virus . Big Pharma is also in the picture as I came across this 2005 report that GSK is involved in a Vaccine For Dengue Fever On Trial In Asia-Pacific.
All this is hopeful news. A lot of effort, time and money needs to go into research before an effective and safe vaccine can be deployed to the population. Will this happen before the end of this decade?

Related MMR posts on Dengue

Related recent News items:
Dramatic rise in dengue cases

i just wanna ask if you know the top 10 latest causes of mortality in pangasinan??your immediate response is appreciated…thanks!!!