Next in the war against dengue: Bacteria v virus

SINGAPORE - Singapore is mulling over using the Wolbachia bacteria to help wipe out dengue-spreading mosquitoes.

Despite intensive efforts ranging from destroying mosquitoes to eliminating breeding areas, the nation faces a serious dengue problem.

So far this year, more than 7,700 people have come down with the viral infection, with almost one in five needing to be hospitalised, while last year saw the highest number of dengue cases to date.

So, any additional arsenal in fighting the disease should be welcome.

Wolbachia is a bacterium found naturally in many insects - though not the Aedes mosquito, the main dengue carrier.

Professor Duane Gubler, an epidemiologist from Duke-NUS Graduate Medical School who is on the newly appointed Dengue Expert Advisory Panel, sees only benefits in such an experiment.

"All available data suggest the strain of Wolbachia to be introduced will not alter Aedes aegypti genetically, and in fact is not sustainable in the population without continued introduction," he said.

The panel will advise Singapore on the best method of introducing Wolbachia to mosquitoes here.

Wolbachia - introduced into laboratory mosquitoes for the first time about eight years ago - appeared to work miracles.

In females, it either shortens their lives so they die before they can start infecting people with dengue; or blocks the virus from multiplying in their bodies - and from transmitting the disease when they next bite a victim.

In males, it makes them sterile, but still strong and capable of beating their natural peers in mating with female mosquitoes, leaving them to lay eggs that never hatch.

Laboratory and controlled field experiments also appear promising.

But tinkering with the genetic make-up of mosquitoes - or anything for that matter - can have serious consequences, and evolution has a tendency to undermine Man's efforts at thwarting it.

Because the history of Wolbachia in Aedes mosquitoes is less than a decade old, there is no long-term data available.

So many questions remain and, if things go wrong, the dengue situation in Singapore could well end up becoming worse, because none of the Wolbachia interventions is totally foolproof, say experts.

Method 1: Wolbachia is put into male mosquitoes to make them sterile.

What happens if a tiny fraction of male mosquitoes with the bacteria remain potent? Nothing to worry about if they produce normal offspring. But if their progeny turn out to be even more virile, could it actually increase the mosquito population?

Method 2: The bacteria are introduced to female mosquitoes - as it is the females that spread the virus.

What if the virus evolves to overcome the bacteria's ability to stop it from multiplying and spreading? Will it become stronger and more virulent? Evolution could even produce a new strain of the virus to add to the four current ones.

Method 3: Wolbachia is used to shorten the lives of mosquitoes so they do not live long enough to spread the disease.

What if the mosquitoes evolve so that their full life-cycle is crammed into a shorter lifespan?

Even worse, the mosquitoes could evolve to transmit the dengue virus from mother to baby, rather than just getting it after biting an infected person. That would mean a new generation of mosquitoes born with the virus and able to spread it from the first bite.

These negative outcomes might be unlikely, but are not impossible.

Faced with extinction, a species' fight for survival can be fierce.

A paper, Wolbachia Versus Dengue, published at the end of last year in the journal Evolution, Medicine and Public Health noted: "In any regime that kills entire populations, there is intense selection for escape."

The authors, Dr James Bull, professor in molecular biology at the University of Texas, and geneticist Michael Turelli of the University of California, also cautioned: "Evolution may alter the disease control effectiveness of the released Wolbachia for decades to come."

Antibiotic resistance that has transformed easy-to-treat infections into death sentences is a lesson from history.

When antibiotics were introduced to medicine, they were hailed as the holy grail of medicine.

And they have saved hundreds of millions of lives.

Then Nature fought back.

Bacteria evolved into superbugs to beat the best medicine man could produce.

Now, antibiotic-resistance is considered a major health threat worldwide.

In the United States alone, its Centres for Disease Control and Prevention (CDC) says that every year, two million people get infected, and 23,000 die of an antibiotic-resistant bug; and that it adds US$20 billion (S$25 billion) in additional direct health-care costs and US$35 billion in lost productivity.

But keep in mind too, that dengue is a looming and immediate menace.

The World Health Organisation estimates that there are 50 million to 100 million dengue infections a year - up from just over a million cases worldwide in 1998.

The figure just keeps going up.

There is currently no vaccine against the disease, and insecticides have to be continually changed as mosquitoes gain immunity.

Last year, Vietnam released Wolbachia-infested mosquitoes - but did it on Tri Nguyen Island, home to 3,250 people and far enough from the mainland that should things go wrong, the mosquitoes would be contained on the island.

Australia has been field testing them in small batches, since 2011, in northern Queensland where incidence of dengue is high. Scientists there are now calling for larger-scale releases.

Prof Gubler said he supports any means that can contain the disease: sterile males, new insecticides, vaccines, drugs and therapeutic antibodies.

"All are experimental at this point and we do not know which ones will be the most effective. It is unlikely that any of them will be completely effective when used alone," he said.

The Wolbachia experiment may have many positives. But as professors Bull and Turelli point out, the actual risk is largely unknown.

salma@sph.com.sg

This article was first published on June 22, 2014.
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