Fighting dengue's secret weapon

Researchers Ooi Eng Eong (left) and Kenneth Goh from the Duke-NUS Graduate Medical School.
PHOTO: Fighting dengue's secret weapon

Q: How would you rate Singapore's mozzie-control efforts?

Ooi Eng Eong (OEE): We have had very good vector control compared with the rest of the region. The most effective way is to physically remove or reduce the availability of larval habitats, which are water containers.

This is what has been practised here and, to a large extent, has worked.

The clearest evidence is that our epidemics happen in sixto seven-year cycles compared with three- to four-year cycles in most dengue-endemic countries. The increased length of each cycle is because there is a lower force of infection due to vector control.

But no matter how good we are at tackling the mosquito problem, we will continue to have cyclical epidemics, unless we find a way to eradicate the Aedes mosquito completely.

That's the nature of such viruses. We need a vaccine.

Q: When can we expect a vaccine?

OEE: I'm optimistic the day will come but not in the next three to five years. Vaccines on trial have so far had limited efficacy, and the most successful one to date has worked in only about one-third of patients - definitely not enough to prevent dengue.

Q: Why do we have to wait?

OEE: There are four different dengue viruses so, to immunise against dengue, four different vaccines need to be developed and delivered in one formulation, which then needs to protect adequately against all four viruses.

If not, antibodies against one dengue virus can potentially enhance infection with another strain to cause more severe disease.

Q: Companies create new flu vaccines all the time based on the dominant strain of the period. Why has it been such a struggle with dengue?

OEE: The dengue virus has a secret weapon. It needs to get into the white blood cells to multiply, and uses a specific "key" to do so.

But when the body creates antibodies to fight dengue, the virus is able to use these antibodies as an alternative but effective "key" - a back door entry.

The white blood cells don't recognise these intruders and kill them. Because of this, any vaccine must be able to protect against all four dengue serotypes, so there's no second opportunity for infection.

But the problem is that our body doesn't react to any of these four strains in the same way. There are also no good animal models to test potential vaccines.

Q: What research are you doing?

OEE: We're working with a leading vaccine company to measure exactly which serotype a patient has immunity against after vaccination. This hasn't been done before and could guide the way forward.

Another important part of our research is looking at the way the dengue virus mutates, and which mutations are instrumental in causing epidemics like the one we have now. How many mutations occur and when it happens - we still don't have any data on that.

We're now sequencing the virus from blood samples and the mosquitoes themselves to see where these mutations occur.

Q: What gives you an edge?

OEE: Clinician-scientists like those we aim to train in our pioneering Duke-NUS MD/PhD programme have a unique place in the overall research ecology.

We know how cases are managed, what happens to patients. This knowledge drives our research and helps us move from basic science to clinical medicine much faster.

In medicine, one of the difficulties has always been that doctors and scientists speak two different languages. By being "bilingual", we can bring these two worlds together.

Q: Why study dengue?

Kenneth Goh (KG): I was always interested in studying pathogens, probably because of watching the film Outbreak. Dengue happened to be available in Singapore, and the tools we're using to study dengue can also be applied to other diseases, so the training's portable.

Before I started this work, I thought of dengue as a boring mosquito virus. But now I know that it does so many things that other viruses do not.

Not a lot of viruses have figured out how to manipulate their way into the immune system and cause even more damage the second time round.

Q: Is there a difference in how dengue strikes here?

OEE: In most other countries, children get dengue because they are at home when the mosquito is active.

Here, they are 100 times less likely to get dengue at home.

What we are seeing is that about nine in 10 cases are adults. We are still trying to figure out where these mosquitoes are biting because, most of the time, it's not at home.

Q: Then where are the likely places where people are getting bitten?

OEE: We don't know. From a research standpoint, there are things we should be looking at.

With mobile phones all armed with GPS, with Facebook and Twitter, we can actually use today's technology to pinpoint where someone got dengue, and how it is transmitted from one person to another.

For instance, if we find through genomic sequencing that two people have genetically identical strains of dengue, then we should look at where their paths crossed to track where the mosquitoes are likely to be.

Right now, we're relying on doctors to report cases.

Q: You work with mosquitoes in your lab. How do you protect yourself?

OEE: Our chance of getting dengue is no different from anybody else's. Our mosquitoes are in cages and we are very careful. I don't use insect repellent but if you need to, the data suggests using one containing Deet. There's no evidence that those with no Deet work.

Q: Can you tell us more about the Aedes mosquito and who they like to bite?

KG: Most of the time, they're vegetarian and we feed them plant sap. Only the female feeds on blood when she needs to lay eggs.

Their black eggs look like rice grains.

The female mosquito likes the smell of human sweat and is also attracted to carbon dioxide. Other factors like body temperature and blood type are not proven to be enticing.

People react to bites differently.

It may not be that you haven't been bitten, just that you don't know you've been bitten.

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