Researchers here have a new target in the war on dengue and other mosquito-borne killers - the insect's saliva.
A $10 million research programme is being set up to understand how its spit helps in disease transmission.
The scientists believe they can cripple dengue, chikungunya and Zika viruses by making the body resistant to mosquito saliva, so that it will no longer be able to spread the diseases efficiently.
Fronted by the National University of Singapore (NUS) and Duke- NUS Medical School, the research programme will also look at factors affecting virus transmission as well as what makes certain mosquitoes better vectors, among other areas.
To do so, the scientists will collect the saliva of the Aedes aegypti and Aedes albopictus mosquitoes - major dengue culprits - after they are secreted in sugary solutions at a laboratory.
The long-term aim, said the programme's lead principal investigator Manjunatha Kini, is to come up with a vaccine that can target saliva proteins.
"Conventionally, the target is pathogens but these pathogens mutate and develop resistance... Once they develop resistance, you need to search for a new generation of drugs, like in the case of malaria," said Professor Kini, who is from the NUS Department of Biological Sciences.
"Our approach is to target vector saliva, particularly transmission-enhancing proteins. If you block (these proteins), you can block transmission."
He added: "I've been studying tick saliva for a decade, so I thought why not mosquitoes? At the end of the day, dengue and chikungunya are our (Singapore's) problems."
Multiple but complemen- tary methods must be urgently explored or developed to control dengue, including the use of Wolbachia, vaccines and antiviral drugs.
PROFESSOR OOI ENG EONG, deputy director of the Emerging Infectious Diseases Programme at the Duke-NUS Medical School.
Unlike current vaccine efforts, which have to work against the four different strains of dengue, the new vaccine would be a universal one, Prof Kini pointed out. The dengue vaccine by French pharamceutical company Sanofi Pasteur offers varying degrees of protection against each of the four types of dengue virus.
Previous research has shown that virus proteins in the spit of ticks and sand flies can increase the efficiency of virus transmission by thousands of times, compared with viruses which are not mixed with their saliva.
Although mosquito saliva is excreted in very small amounts of five to 10 nanolitres (one nanolitre is a billionth of a litre), it is believed to be potent.
Professor Ooi Eng Eong, deputy director of the Emerging Infectious Diseases Programme at the Duke-NUS Medical School, said there is already some evidence to show that mosquito saliva contents may play a role in enhancing the efficiency of virus infection, though exactly which component of the saliva that does this is unknown.
"It is thought that some of these proteins may modulate our early immune responses to the virus, enabling it to infect and then spread more efficiently," said Prof Ooi, one of the programme's principal investigators.
Commenting on the research, Professor Tikki Pang, visiting professor at the Lee Kuan Yew School of Public Policy at the National University of Singapore, said the team's research approach is interesting and could potentially result in a vaccine that would stop the virus from multiplying inside the human body.
"However, with all these new approaches, the big question is always whether it will actually work in practice," he cautioned.
New ways of tackling dengue are sorely needed.
Despite all efforts, the authorities have warned that the number of dengue cases this year may exceed 30,000 - higher than the record in 2013, when 22,170 cases were reported - unless immediate measures are taken to suppress the Aedes mosquito population.
This is due to various factors, including warmer temperatures and a switch in the predominant dengue virus serotype.
Figures from the National Environment Agency show that a total of 6,338 dengue cases were reported between January and March this year, almost three times as many as the 2,251 cases reported in the same period last year.
Earlier this week, the Government announced that it would commence a field study involving the release of male Wolbachia-carrying Aedes aegypti mosquitoes.
When such mosquitoes mate with wild female Aedes aegypti, they produce eggs which do not hatch.
"I think a lesson that should be learnt from the decades of effort to control dengue is that conventional methods of vector control can suppress the Aedes population, although the population suppression cannot be sustained... A recurrent theme in biology is that living things and micro-organisms such as viruses have the capacity to adapt to control measures," said Prof Ooi.
"Multiple but complementary methods must be urgently explored or developed to control dengue, including the use of Wolbachia, vaccines and antiviral drugs."
The latest programme also involves researchers from the Singapore-MIT Alliance for Research and Technology, the Agency for Science, Technology and Research (A*Star) and Oxford University, among others.
So far, scientists have managed to identify 154 saliva proteins in preliminary studies, though Prof Kini estimates that there are hundreds more.
The key lies in identifying those that play more critical roles in enhancing virus transmission.