What lurks within

A MYSTERIOUS flesh-eating disease that hit a township in the tropical north - and another in the cool south - has scientists puzzled. Do its origins lie in the forest?

flesh eating bugs

WHEN eight-year-old Georgie Crimmins came home from school with a blemish on her ankle, her mother barely gave it a second glance. Why would she? Insect bites go with the territory around the Daintree rainforest in far north Queensland and this one seemed to be no bother at all. It wasn't hurting.

It didn't even itch. Larisa Broadley told her little girl to leave the thing alone. Then something strange happened. The spot became a red lump that suddenly burst open. The wound was framed by a teardrop of angry, infected flesh that grew bigger and bigger over the coming days. Broadley, born and bred in the area, knew a Daintree ulcer when she saw one. "Here we go," she said to her husband, Wade.

A year on, mother and daughter are comparing surgical scars. Georgie's has healed to a glowing pink. She is back at school, healthy and happy after her brush with the flesh-eating bacterium that causes Daintree ulcer disease, a not-so-distant relation of tuberculosis and leprosy. Broadley, 30, also contracted it, though not from her daughter - one of the many mysteries of the disease is that it can't be spread from person to person. Their next-door neighbour in Snapper Island Drive got it too, along with another man a few doors along the street of tin-roofed bungalows that backs on to a canefield in Wonga Beach, 90km north of Cairns.

Two of Georgie's classmates at Wonga Beach State School also developed the disease, along with Jan Sargent, 73, who had a sensation of "ants working away" under the skin of her left arm. At South Arm Drive, Wonga Beach, Tania Toy noticed that her three-year-old son, Aiden, had a swollen left foot. At first the doctor thought it was broken, but the little boy would end up having 11 operations to fight the infection, plus a skin graft. Between February and December last year, 60 people came down with Daintree ulcer. Given that only 110 cases had been reported since records started in 1966, it was an extraordinary development. All except one lived within a 20-minute drive of Wonga Beach, the epicentre; 25 of the cases came out of the township itself, which has a population of just 800. No one had seen the like of it.

"We didn't really know what was going on," Broadley says, as her daughter fidgets beside her on their patio. "It was all a bit of an ordeal. Then I got mine, here," she says, pointing to the scar on her left thigh. "I just thought, 'You have got to be joking. Both of us? All those other people? This couldn't be happening.' "I think people assume in the tropics we just get bugs," Broadley adds. "But this was something else. No one knew what the cause was, where it was coming from or, really, who would be next."

The forbearance of the local parents, particularly, was remarkable. Imagine the outcry if children were coming down with voracious, necrotising ulcers in Sydney's Woollahra, or Wilston in inner Brisbane: you wouldn't be able move for TV news crews. Here in the Daintree, it went under the radar.

Christina Steffen was aghast. When it came to Daintree ulcer, she thought she had just about seen it all. The majority of those who contract the disease end up on her operating table at Cairns Base Hospital.

In a bad year, Steffen, a general and vascular surgeon, might have treated eight people. During last October and November, at the height of the Wonga Beach outbreak, she was seeing that number of patients in a week. By the time it burnt out she'd performed surgery on 45 people, including Georgie. "I was a bit concerned," she recalls. "It's a small community and some of them were quite serious infections."

Steffen was baffled by the flare-up, and she's not alone. The culprit, Mycobacterium ulcerans, is one of those germs that can be found just about anywhere in nature, clinging to anything from rotting vegetation to the stingers of biting insects. Yet for some reason, eruptions are intensely localised. The main troublespot in the world is equatorial west Africa, where the near-identical Buruli ulcer causes untold misery. Australia and Japan are the only developed countries in which it regularly occurs. The lush, tropical rainforests of the Daintree make sense as an incubator: the hothouse conditions are not all that removed from the jungles of Cote D'Ivoire, which reports about 2500 new cases annually.

Unfathomably, another form of the disease has been identified in the temperate climes of southern Victoria. This, too, is named after its place of origin in East Gippsland. Eighty cases of Bairnsdale ulcer were diagnosed last year, up from 32 in 2010. Whether this was linked to what happened in the Daintree is anyone's guess. "I wish I could tell you," Steffen says.

"But the fact is we know very little about the mode of transmission and why people get infected in one place but not another. It's all a bit of a mystery."

Unlike TB and leprosy, the infection cannot be spread directly between people: mosquitoes and other biting insects are likely responsible for transmitting it to humans. Antibiotics will kill the mycobacterium, known by the medical shorthand of M. ulcerans, but more often than not the damage has already been done. The bugs emit a toxin that reduces skin and fat cells to a custard-like sludge while simultaneously suppressing the body's immune response. Once an ulcer takes hold, surgery is generally required.

The necrotic flesh is not all that has to go: tissue around the lesion needs to be cut out as well. A severe ulcer can work its way down to the bone, especially on thinly covered elbows, ankles and knees. But in its worst form, the skin initially stays intact as the infection shifts into what Steffen calls "galloping" mode. An entire limb can become inflamed, and if the infection isn't controlled, amputation may be required. "It's similar to having a full-thickness burn in a way because all the skin is destroyed," Steffen says. "It has to be removed and grafted."

This was what confronted Tania Toy and her then three-year-old, Aiden, in August last year, after the child's foot blew up. To make matters worse, Toy was heavily pregnant. By the time she gave birth by caesarean section to baby Julian, Aiden was in agony. He was admitted to the local Mossman Hospital for an intravenous course of antibiotics but, looking back, Toy says the doctors "had no idea" what was wrong.

At Cairns Base Hospital the infection was diagnosed but the family had to endure another harrowing wait until he had completed a pre-surgical course of antibiotics. The foot had ulcerated and "we just had to watch it get worse and worse", Toy says. Aiden would undergo a succession of operations, each of them under general anaesthetic, to clean out the gaping wounds. He then had follow-up surgery to apply a skin graft. Eleven months on, Aiden continues to wear a compression bandage to the knee. "I can't tell you how awful it's been," his mother says quietly. "The best thing I can say is that he's come through it."

Jemma Bolton, then two, also suffered terribly. Her parents had packed up their home in Miallo, between Mossman and Wonga Beach, to hit the road for a camping holiday in the Northern Territory. They were two weeks into the trip when Dawn Bolton noticed what she thought was a mosquito bite on her daughter's leg. They saw a local GP, who prescribed antibiotics and told Bolton not to worry. When she mentioned the possibility of Daintree ulcer, the doctor looked her in the eye and said: "It's not an ulcer."

That was June last year. Jemma didn't get out of hospital until this February. The lump on her leg was the size of a golf ball before it was finally diagnosed. In desperation, Bolton emailed photos to her GP in Mossman, who had no doubt what it was. The initial surgery, performed in Darwin, was a disaster. Some of the infection was missed and Jemma ended up being flown to Cairns to be treated by Steffen. So much tissue had to be removed that the little girl's lower leg was "hollowed out" between the knee and the ankle, Bolton says. When the skin grafts didn't take, they ended up in Brisbane for yet more surgery on Jemma.

"You wouldn't read about it, not in this day and age, not in this country," says Bolton, 38. She believes her daughter's infection would have been picked up earlier were Daintree not the descriptor. It simply didn't occur to doctors in the Northern Territory to test for the disease before the lesion ulcerated. "They need to change the name," she says.

In Victoria, Bairnsdale ulcer cases have been notifiable since 2004, but elsewhere mandatory reporting is limited to medical laboratories when they turn up a positive test result. If there is a consolation, it's the rarity of severe infections in Australia.

Provided an ulcer is caught early, it's generally no great drama, Steffen says. "The message that went out, pretty successfully, is 'just don't ignore it'." But that's hardly the point. The elevation of Daintree ulcer from nuisance to genuine public health threat got her thinking about how much she didn't know about the disease. What actually transmitted it? Why didn't anyone south of Port Douglas seem to catch it? How could it be that Larisa Broadley and Georgie were infected, but not any of the males in the household? Curious as it sounds, some of the answers lie in chilly, distant Victoria.

Professor Paul Johnson was in the bottom of a drain with colleagues Janet Fyfe and Caroline Lavender when he realised they were approaching the problem from the wrong way. He had thought it was going to be their Eureka moment. Australia's ranking expert on M. ulcerans had been called to the holiday town of Point Lonsdale, south of Melbourne, by a retired microbiologist who was convinced that the mosquitoes responsible for her Bairnsdale ulcer were breeding in the culvert outside her home.

Johnson, the deputy director of Austin Hospital's infectious diseases department and boss of a World Health Organisation collaborating centre on the disease, had been tracking how it spread to people. The local mosquito was the prime suspect. Yet, as was the case with malaria, the insect would prove to be the vector, or intermediary host, not the "reservoir" of the disease. Johnson's team had in 1997 developed a breakthrough test for M. ulcerans, opening up new opportunities to pinpoint where it came from. DNA analysis had shown that the Bairnsdale strain was closely related to its northern twin. There was one puzzling difference, though: while Daintree ulcer was confined to a sliver of land between the Daintree River, Port Douglas and the coast, Bairnsdale ulcer had leapfrogged across Gippsland to the doorstep of Melbourne.

Johnson had also noted that the incidence of Bairnsdale ulcer in Victoria reflected that of another mosquito-borne disease, Ross River virus. So when he climbed into the drain with his colleagues, he had expected to find a pool of water teeming with mosquito larvae. Wrong. It was bone dry inside; there was no way the insects were multiplying there. Crestfallen, they took samples and headed back to the lab. The results came back with bells on them, denoting one of the highest readings of M. ulcerans they had seen. They twigged that the contaminated material might be coming from above. "Suddenly, the whole game changed," Johnson says. "Instead of looking down in the swamp, we were looking up in the trees."

And at Point Lonsdale, the trees happened to be full of ringtail possums. On testing, the animals' droppings were found to contain mycobacterium in concentrations far exceeding those detected in mosquitoes. "We were finding something like 10 to 100 bacterial cells per mosquito, but then with the possums it was in the hundreds of thousands, millions and in some cases tens of millions ... orders of magnitude stronger," Johnson says.

The team made another startling discovery: the possums didn't just carry the infection; they were also susceptible to it, with up to 25 per cent of them contracting the very ulcers people got. "The idea we have is that the possums are the reservoir. There is an epidemic in them and it is the humans who are the spillover ... the accidental hosts," Johnson argues.

The catch is that, to date, no one has found another animal host outside of the Point Lonsdale area. Johnson and his team published their findings on the possums in 2009, and since then all kinds of creatures have been trapped and tested in Africa and, less intensively, in north Queensland, without returning a single positive result. Just about everybody has a theory about the root cause of the disease. Some old-timers in the Daintree swear they have even seen ulcers on the skin of saltwater crocodiles.

Yet GP Robert Lanskey, who heads the Mossman practice that the Bolton family turned to, thinks the transmission chain in the Daintree might not involve an animal carrier at all. Could it be that the rainforest itself was the host? Over the years, he had noticed that ulcer cases spiked on the back of heavy rain events. Not immediately, but several months later, during the winter-spring dry season. The delayed effect got him thinking about leaf mould. During last year's outbreak he saw two patients who were convinced they had contracted their ulcers from bites - one from a March fly, the other from a leech. March flies breed in leaf mould and leeches live in the stuff, which is usually found in the depths of the forest, especially on the thickly covered ranges that mark the western boundary of the known catchment for Daintree ulcer, places where people rarely ventured. But a big wet might just wash the mould into the open, closer to settled areas. Once the M. ulcerans began to multiply, the insects and nasties would do the rest, Lanskey believes.

His theory was buttressed by another observation: locals complained bitterly about the plague of March flies that had erupted early last year after one of the biggest wets on record. The first patient presented in February 2011, and by June there were 11 in total. Then it really took off. Seven new cases of Daintree ulcer were reported in August, 13 in September and 14 in October. A further seven cases came in before the year was out, surpassing anything Lanskey, 68, had seen in his three decades of practice in the area.

Lanskey admits he has no evidence to back his suspicions about the leaf mould - "it's a gut feeling, really" - but given the absence of research data it's probably a good place to start. No one, with the possible exception of Steffen, is more qualified to talk about the management of last year's outbreak. Of the 60 ulcer cases last year, 43 were seen at his clinic and 11 by the veteran GP personally. Most patients were referred to Steffen for surgery in Cairns. Looking back, Lanskey says: "People were pretty calm about it, but to me it was of great concern. So many cases in such a short space of time was something we had not seen before, especially with the numbers we were getting from the Wonga area."

Among them was Luke Roberts, 11. He arrived home from school with what his mother, Lynn Cronin, took to be a gravel rash on his left knee. A few days later, in mid-July last year, she thought it had become infected and slapped a dressing on the wound. By next morning the ulcer was full-blown. "It seemed to grow before our eyes," she says. "You could actually see the skin splitting - it was terrible."

The treatment protocol calls for an extended course of rifampicin, a powerful antibiotic used against TB, and another anti-bacterial drug, clarithromycin, prior to surgery. For Luke, this meant a delay of six weeks. Cronin says the ulcer had eaten through to his kneecap by the time Steffen operated on the swollen mess. The wound was too large to be stitched closed, and he had follow-up surgery to graft it with skin taken from his thigh. He is still getting boils, and stays indoors more than he used to. "Since his knee happened he won't go outside very much," Cronin sighs. "I think he's worried about being bitten by something."

Emma Vizard, aged nine, fared better with the ulcer that developed behind her right knee. She was in Luke's class at Wonga Beach State School and knows all about what he went through. Like her friend Georgie - the little girl introduced at the beginning of this article - Emma got away without a skin graft, hastening her recovery. In all, eight children aged 10 or under were infected. But it didn't stop there for Emma's family. Her father Scott, an arborist, developed an ulcer on his leg, requiring surgery last month. "I suppose it's just part and parcel of living here," he says.

Jan Sargent agrees. She and her husband, Pirrie, 76, created their slice of tropical heaven in an old cane field at High Falls in the Whyanbeel Valley, 10 minutes from Wonga Beach. Insect bites are an occupational hazard of their work with ornamental plants. Sargent, 73, thinks a March fly got to her. She noticed the lump on her upper left arm in the autumn of 2010, before it ulcerated. Another of Steffen's patients, she was glad to be rid of it. "Some days I could feel it underneath my skin ... like there was a little section of ants working away there," she remembers. The surgeon says most people feel the same way. In some cases, antibiotics alone will kill the bugs and control an ulcer, but this takes time, and most people opt for surgery. "They want the closure and you can't really blame them for that," Steffen says.

She finds one aspect of the Daintree disease particularly baffling. Why is it so static? If mosquitoes and March flies are the instruments of transmission to humans, why aren't more people being infected over a vastly wider area?

Then there is Daintree ulcer's southern twin. It's difficult to imagine two more different environments. On the day we meet Steffen it's a steamy 28 degrees in Wonga Beach; at Point Lonsdale, south of Melbourne, the grey-green Moonah trees are shivering in the icy wind blasting out of Bass Strait. Possums are found in the rainforests of north Queensland, but in nowhere near the numbers that the Melbourne research team zeroed in on. After the Bairnsdale ulcer was identified 80 years ago near Lakes Entrance, 260km east of Melbourne, sizable outbreaks occurred at Western Port and on Phillip Island. The disease then jumped across Port Phillip Bay to the Bellarine Peninsula. "It's behaving like it does in Queensland in that it is very focal and can produce big outbreaks that change from year to year," Johnson says. "Yet, unlike Queensland, it is moving towns, over quite big distances. That's a difference we don't understand."

Steffen has a hunch that the intermediate "animal reservoir", if it exists in the Daintree, might be the local variety of bandicoot. The animal lives on the edge of the rainforest and tends to be territorial. That would explain the limited catchment of the disease. If the mammalian host didn't range far, it stood to reason that the insect vector would stay close, too. She would like to have bandicoots trapped in the wild and tested - though to date, M. ulcerans in infectious concentrations have not been detected in the local water supply or in anything living bar people, including the ubiquitous March fly.

Johnson has the germ of an idea, you might say, to account for what a tropical disease is doing in Victoria. "We're wondering whether our tropical disease can be explained this way: the swamp where it breeds is in fact the gastro-intestinal tract of the possums themselves," he says. "In Queensland and Africa, you might be looking at a more direct mode of transmission out of the rainforest. But here, it needs a little incubator to get cooking and we're starting to think that might just be inside the possum."

Steffen argues that the events of last year demand that the mystery of Daintree ulcer be unravelled, and it's hard to gainsay her. She wants some serious resources to be devoted to research, as was the case in Victoria until the state government pulled most of the funding for Johnson and his collaborators. Medical scientists appear from time to time in the north, but there has been nothing like an intensive and sustained effort to identify how the infection is transmitted, let alone where it comes from. In this respect, Daintree ulcer is the poor relation to the Bairnsdale disease.

Lanskey, the Mossman GP, has noticed that Aboriginal people rarely present with the ulcers. He suspects it might have something to do with the BCG vaccine for tuberculosis, which was phased out for the general population in the 1980s but continues as an indigenous health program. Johnson agrees that there could be merit to the idea that the BCG jab also confers a level of immunity to M. ulcerans infection.

Responding on behalf of state agency Queensland Health, public health physician Richard Gair says he is aware of the potential link but "there is no evidence available to confirm or refute it". Asked what lessons were gleaned from last year's outbreak, he acknowledges that it exposed "some gaps" in surveillance as not all cases were reported to the public health unit in Cairns, as was required. He accepts Steffen's complaint that rifampicin is difficult to access; the drug can only be prescribed by specialists, who generally don't live locally. A standby supply will be made available at Mossman Hospital, he says.

As for prevention, Gair supports the need for increased research but concedes: "The mode of transmission remains unclear [and] for this reason we are unable to give definitive preventative advice."

So far this year, 10 new cases have been reported in the so-called catchment area in north Queensland. Yet only one of them is from Wonga Beach. For now, the reason for last year's events must be filed among the many unknowns of Daintree ulcer disease. Steffen can only hope that the epidemiology will be better understood before another serious outbreak occurs. She has no doubt where the answers ultimately lie, should someone get the chance to properly look. "In there," she says, pointing to the lush and tangled foliage that clings to the Daintree's mountains like an emerald carpet. "The key is in the rainforest."