No vaccine or drugs exist for a virus disease found in more than 100 countries and placing some 2,000 million people at risk. This is the reality of dengue, which occurs in tropical and subtropical regions and is a potential threat to residents and tourists alike.
Here at Monash University in Melbourne we are examining the growth of dengue virus using the most recent genetic engineering techniques. Such studies are fundamental to the development of new vaccines and antiviral agents.
There are four types of dengue virus, all transmitted by day-biting aedes mosquitoes (malaria, in contrast, is spread by anopheles mosquitoes that bite mostly at dusk and by night). The common and mild form of the disease is dengue fever characterised by fever, rash, aches and pains. However, a small proportion of patients may die after showing more severe symptoms of haemorrhage and shock, usually following a second infection.
Australia is presently free of the severe disease but dengue disease is a major concern in southeast Asia and the Pacific Islands, and further afield in Central and South America.
The development of dengue vaccines presents special problems. The four types of viruses are relatively difficult to grow under laboratory conditions. The disease is not mimicked accurately in any animal species - a complication for vaccine testing - and most importantly, there is evidence that the severe disease may occur in individuals with only partial immunity to the infecting virus type. A future vaccine must provide total protection against all four types, otherwise severe and fatal disease may occur in a vaccine recipient upon natural exposure to the virus.
The traditional approach to producing live virus vaccines is to grow or passage virus repeatedly in laboratory animals or cell culture. Mutations that attenuate or weaken a virus may accumulate, providing strains that induce immunity but no disease. In the past, some vaccines were produced by this method without any understanding of how the mutations worked. Examples are the current polio virus and yellow fever virus vaccines.
We now have techniques to manipulate directly the genes of viruses like these and dengue. At Monash, we are focusing on genes that specify the proteins of the dengue virus particle, or enzymes needed to synthesise the virus components. These studies have a twofold purpose. First, we are identifying mutations that weaken virus growth, for subsequent introduction into potential vaccines by genetic engineering - a more direct and rational method than the traditional approach. Second, our experiments provide information on potential targets for antiviral agents and assays for the testing of such agents.
Another of our interests is gastroenteritis caused by "Norwalk-like" viruses. This group of viruses were first described in 1972 after an outbreak of vomiting and diarrhoea in Norwalk, Ohio. They cause outbreaks of gastroenteritis frequently following the consumption of contaminated food or water.
The current interest is to identify the number of different types of these viruses circulating the world. Since the typing methods are relatively new, the total number of virus types is unknown. They may be a few as with polio viruses or many as for the common cold viruses.
We are collaborating with the Victorian Infectious Diseases Reference Laboratory to monitor outbreaks and determine virus types in southeast Australia. With up-to-date data, the spread of novel viruses via food or infected carriers will be recognised rapidly, so that the sources can be found and eliminated as quickly as possible.
Australian researchers are using the latest genetic engineering techniques to find a vaccine for the dengue virus.