The northern front in the war on dengue

QWeekendLOGOFar North Queensland’s wet season begins with a drumroll of heavy raindrops splattering on roofs and sidewalks and the inevitable arrival of hordes of newly hatched mosquitoes. Floating in and around houses and yards, these tiny blood-suckers are on a relentless search for unprotected human flesh.

Usually the mosquitoes leave nothing worse than an irritating harvest of itchy welts, but too often they inject their human hosts with a potentially fatal virus: dengue fever.

Cairns resident Ron Crew has endured three bouts of dengue, most recently in late January this year, when he was so ill he could hardly see, and so weak he couldn’t push the pill out of a blister pack.

Now 71, the semi-retired air-conditioning contractor and his wife, Mena, moved to this tropical city in 1978. Life is fine in Stratford, in the north of Cairns near the Barron river, he says, but dengue regularly rips through the city. Queensland Health recorded 136 confirmed cases of dengue in the most recent outbreak in and around Cairns and Innisfail. One of them was Crew.

“This time it was absolutely shocking,” he remembers with a wince in his voice. “I thought I was going to the other side. I’ve had polio; I’ve had rheumatic fever; I’ve had Ross River fever. Nothing was a patch on the pain I felt with the dengue.”

DENGUEsmall6Crew and his wife fell ill with the virus about the same time, along with dozens of other Cairns residents. Cared for by friends, neighbours and public nurses, the Crews recovered. Yet any of the four dengue viruses can kill, and a severe case of dengue fever, or dengue haemorragic fever, is far more likely with subsequent bouts.

With three dengue battles behind him, Crew knows he has to be extremely careful to dodge another run-in with the debilitating disease. He’s constantly aware of the almost invisible bugs constantly trying to hone in on his bare flesh whenever he’s not watching. So, naturally, he’s an enthusiastic supporter of the potentially revolutionary Australian research now underway on dengue and the Aedes aegypti mosquitoes – the species best known for carrying dengue.

In a world-first that has excited interest from Rio to Hanoi, Costa Rica to Yogyakarta, Australian scientists have discovered that certain strains of ‘Wolbachia’ bacteria have valuable disease-blocking properties. Already common in many species of insect, Wolbachia is now seen as the best hope for limiting the rapid spread of dengue around the world. The bacteria stop the female Aedes aegypti mosquito from passing on the dengue virus when she probes human flesh for a blood meal.

Only female mosquitoes feed on blood: they need the iron and protein to produce eggs, and Aedes aegypti females infected with particular strains of Wolbachia will still bite, and leave itchy welts on human skin. Crucially, though, the Wolbachia bacteria interfere with the dengue virus’s growth in the mosquito.

Adult mosquitoes infected with Wolbachia have been released in several small Cairns field trial sites for three years now. By the end of this year there will be as many as ten sites in the city with Wolbachia mosquito populations. The carefully-bred Wolbachia mosquitoes mate with wild local mosquitoes and the subsequent mosquito offspring inherit Wolbachia. The mosquito populations of the trial site are then regularly tested to assess whether Wolbachia is taking hold.

With time, the trials indicate that entire populations of Aedes aegypti mosquitoes in the local area will carry Wolbachia: effectively a wholesale and self-sustaining eradication of dengue. The Queensland trial results have been applauded around the world: the available evidence indicates not one resident of any of the small trial sites has contracted dengue from a trial site mosquito.

The Crews have had a mosquito trap in their house for two years, so the Eliminate Dengue scientists can catch and study specimens from the prevalent mosquito populations of the area, and this month (subs June) their home will also host regular Wolbachia mosquito releases. Crew loves the whole idea. He first heard about the research at a Rotary meeting, and he has spread the word.

Acquainted with residents of Yorkey’s Knob and Gordonvale, the first Cairns trial sites, he knows there was some deep-seated concern there, at least initially. “They were very apprehensive at first, ‘we don’t want bloody millions more mosquitos to bite us’,” he remembers. “But they changed their minds very quickly.”

Across town, Dr Scott Ritchie is at work at James Cook University’s Mosquito Research Facility, where the Aedes aegypti mosquitoes carrying Wolbachia are bred and housed. A vector-borne disease expert who oversees research work at the Facility, Ritchie has collaborated on the ‘Eliminate Dengue’ project since it was first established in 2005 and he’s a believer. He even has his own little colony of the Wolbachia super-bugs floating around his old Queenslander home in Cairns, and he sees a day in the future when big business will get interested.

“Right now, this project is a research project,” he explains. “But at some point it will evolve, especially if it’s shown to block dengue well, I think you will see – potentially – commercial interest. We have areas in Cairns where we’ve had it (Wolbachia mosquitos) established for three years running now. Once you get it in, it’s in; it’s all sorted out.”

If the Wolbachia plan is successful, and many eminent scientists believe it will be, a small group of Australians could find themselves making medical history, along with the likes of Jonas Salk and Albert Sabin and their defeat of polio.

The search for the best Wolbachia strain hasn’t always been easy. Field trials in Australia and Vietnam using one particular strain were disappointing. While an extremely effective dengue blocker, that strain eventually killed the mosquitoes, and the entire Wolbachia mosquito population died out.

Shrugging off the setback, the scientists kept working – the job was simply too important to abandon. The World Health Organisation estimates as many as 22,000 people are killed by dengue each year – mostly children.

At the other end of the battle to quench dengue’s appetite, scientists have been labouring to find an effective vaccine for decades. The giant pharmaceutical company Sanofi-Pasteur recently produced the best candidate to date and production is already underway. Ritchie sounds a note of warning though; this vaccine is only 56 per cent effective, providing no protection against one of the four dengue viruses, and it requires three injections over a long period of time, a regime which might be difficult to convince people to follow.

Meanwhile, on the mosquito control side, the British company Oxitec has produced a genetically-modified male Aedes aegypti mosquito with a “lethal dominant gene”: so when the GM mosquito mates with a wild mosquito, all the offspring die. So far, so good. Yet genetically-modified organisms have yet to win wide popular support, and in some countries the shrill cries of “frankenmosquito” might stop the Oxitec mosquito before it takes off.

Perhaps even more of a problem, this mosquito solution has a natural dead end. All the offspring die. Theoretically that could mean the entire Aedes aegypti population of a locality is eliminated, forever, but usually there are pockets of mosquitoes left over and ready to repopulate at speed. Still, field trials and commercial releases of these mosquitoes are underway in Brazil and Panama.

Aedes aegypti at one time was eliminated from all of South and Central America and then it got re-introduced, or there were very low cryptic populations that no-one picked up,” Ritchie says. “And now it’s back worse than it ever was, and they’ve got more dengue and disease than they had in the first place.”

So Wolbachia, which bubbles along on its own, reproduced in generation after generation of Aedes aegypti mosquitoes, looks ever more promising. The bacteria also block the dengue-like disease “chikungunya”, which can cause months of aches and pains. “Chik”, as it’s known to some scientists, is also carried by Aedes aegypti and the disease is making inroads in Papua New Guinea. No locally-acquired cases of the disease have been recorded in Queensland, but several tourists and travellers have contracted the disease abroad.

Wolbachia, those incredibly versatile bacteria, may well also block dengue in the Asian Tiger mosquito, Aedes albopictus. An extremely invasive insect that has spread through many nations, it has yet to make the jump into mainland Australia (although some scientists believe its arrival is a foregone conclusion), this Tiger mosquito can bite dozens of times a minute. It can happily live in much colder climates than the Aedes aegypti can manage (climates as temperate as Brisbane, Sydney and even Melbourne). “The threat is a real one and we continue to have a control program in the Torres Strait,” Ritchie says. “So far it’s been reasonably successful.”

The Eliminate Dengue program has research work underway on the Asian Tiger mosquito in southern China. Although this insect already carries two strains of naturally-occurring Wolbachia bacteria, research has suggested yet another strain may block dengue. Field trials are on the way.

So the Eliminate Dengue program gets bigger and bigger. Partly funded by the Bill and Melinda Gates Foundation, the multi-million dollar program now has Aedes aegypti field trials underway in Vietnam, Indonesia and Australia, and trials in Brazil and Colombia are in the pipeline.

Going from strength to strength, later this year the world’s first city-wide trial of Wolbachia mosquitos will begin in the sprawling coastal metropolis of Townsville, where 16 cases of dengue have been recorded so far this year, and a further 16 an hour or so inland, in Charters Towers.

The Townsville field trial won’t use adult mosquitos, but eggs: dry Aedes aegypti mosquito eggs can remain viable for six months and they are remarkably resilient. They can even be put in the post without coming to much harm.

The plan is to deploy thousands of small plastic buckets (with lids) across the city of almost 200,000 people sometime around October, just before the rainy season starts. With holes drilled in the sides just above the waterline, the buckets will become tiny Wolbachia breeding sites. Just add eggs.

Emily Wright, a 29-year-old technician, says she would be happy to host a breeding bucket in the dark backyard of her low-slung Townsville cottage. Originally from the US, she has lived in Townsville for seven years and she recently became an Australian citizen. She already has a mosquito trap out back, used by the Eliminate Dengue team to catch mosquitos and analyse the spread of various mosquito populations.

“I had vaguely heard about dengue, but I learned a lot more when I got here and people told me to watch out for the mosquitos with stripes on the legs,” Wright says. She knows how much time and effort has gone into beating back rampaging mosquito populations around the world, where various species of the insect carry everything from malaria to yellow fever.

“This is revolutionary,” she says. “This is a much better solution, to try and use the mosquitos themselves to try and solve the problem. In the meantime, I’ll just keep wearing my bug spray to feel a little bit safer that even if I do get bitten, hopefully I won’t get really ill.”

The Townsville trial will go a long way toward proving that Wolbachia can be a cost-effective and efficient way to limit the spread of dengue. Using eggs in buckets is a far cheaper way to introduce the Wolbachia mosquitos – hand-releasing adults was time-consuming and comparatively expensive.

Geoff Wilson, Eliminate Dengue’s field trial manager in Queensland, says using Wolbachia eggs in the Townsville city-wide trial is a crucial step in working out ways to cover big towns and cities: understanding how many releases are needed to establish widespread continuing populations, while keeping the cost down. “In the most recent deployments, we’ve visited one in four houses, and each house is visited fortnightly for six visits,” Wilson says. “Across a city of a million people, that’s a lot of resources.”

Eliminate Dengue leaders are considering a range of possibilities for the Townsville field trials, including providing schools with buckets and eggs and letting the children get on with it: both educational and useful.

For his part, Dr Steven Donohue, director of Townsville’s Public Health Unit, has high hopes of Wolbachia. “I’m really excited about it,” he says. “The chances are that if this thing works, it will make a big difference to the number of dengue outbreaks we get in Townsville. It could render us a non-dengue area.”

Queensland Health does its best to deal with dengue outbreaks, but Aedes aegypti mosquitos can hatch in a driblet of water, as much as the rainwater found in an upturned bottle-top or a puddle in a discarded tyre, and their eggs are extremely resilient. Townville’s older suburbs often feature picturesque old Queenslanders surrounded by luxuriant greenery. Sometimes there’s junk in the yard. All perfect conditions for mosquitoes.

Fogging doesn’t work, Donohue says. “Fogging is highly visible, but almost totally ineffective for dengue. It’s known throughout the world that it’s a useful trick if you want to show the population you’re doing something.” Fogging kills mosquitoes in flight, and just about every other kind of airborne insect, but dengue mosquitoes hide in sheltered places, under houses and sheds, and they’re hard to reach, rarely travelling further than a couple of hundred metres from where they were hatched.

Queensland Health, he adds, prefers to use a residual surface spray in dengue-infected households, and in the houses of their near neighbours, and a specialised ovitrap: a little bucket of water with an insecticide strip hanging in it, along with a growth regulator tablet to prevent any “wrigglers” from taking ever wing. If Wolbachia takes firm hold across Queensland, of course, the spray, the ovitraps and the tablets might never be needed again.

The Eliminate Dengue project has backing of many Townsville residents. Steve Beck and his wife Christine Kleese know the science and they’ve given it the thumbs up. They have a mosquito trap whirring away under their Townsville house near the Ross river: a little electric fan pulls the mosquitos in to their doom.

Professionals in their late 50s, the couple are happy to assist the project as much as they can. He works in a museum, she works with community welfare, and they have had two dengue scares so far: a “scare” is when someone living within a couple of hundred metres of their house comes down with the disease. Aedes aegypti mosquitos rarely travel more than a couple of hundred metres from where they were hatched, so a dengue eruption nearby can be frightening.

“We’ve had a number of dengue scares in our neighbourhood, and the last thing we want is for us or anyone around the place to contract dengue,” Beck says. “So, yes, by all means, we have no trouble with them releasing the altered mosquitoes to help get rid of it. If they can eliminate dengue, that’s a marvellous, marvellous step forward.”