Necrotising fasciitis. Words you really don't want to hear when you turn up at hospital with a small cut or abrasion that's causing a preposterous amount of pain.
Recognised since the 18th century as phagedena, and also described as a variety of gangrenes - hospital, gas, Meleney's, Fournier's - necrotising fasciitis usually features in today's media reports alongside "flesh-eating bacteria".
Bacteria are involved but they don't eat anything, preferring instead to release toxins which kill human cells.
That's the necrotising bit.
While flesh dies, it's well below the skin's layers - the fibrous stuff that surrounds organs, muscle and bone - the fascia.
When necrotising fasciitis gets hold, it spreads very quickly and can be fatal.
If the bacteria get into the blood it can lead to toxic shock syndrome, which can rapidly result in stupor, coma, multi-organ failure and death.
Fortunately, it's quite rare.
Unfortunately, in a relatively short space of time, there's been a fivefold increase in its incidence.
"We are now seeing around 80 necrotising fasciitis cases a year - a rate of two per 100,000 - compared with the early '90s when we had an average of 13 hospitalised cases a year," Assoc Prof Michael Baker, of the Department of Public Health at Otago University, says.
"An extremely rare disease is now a far less rare disease."
Prof Baker is co-author of a study, supported by the Ministry of Health, which took a wider look at the changing epidemiology of necrotising fasciitis and serious skin infections in New Zealand.
National hospitalisation and mortality records, plus 300 patient files from 1990 to 2006, showed there was, on average, a 21% chance of dying from the disease.
Prof Baker doesn't have an explanation, but says whenever there is a change in incidence a trinity of factors - host, organism and environment - comes into play.
"A possible change in the organism is probably one of the first hypotheses you're going to think about. These bugs that invade our bodies have the ability to surprise us. They can evolve very swiftly, and they can become more virulent."
Males are about 40% more likely to get the disease, Maori 85% and Pacific people about 135%.
Those aged under 10 are least likely to get the disease, and those aged 70 and above have 20 times more risk.
Prof Baker says ethnicity is often a marker for other things.
"We know there are big socio-economic and health inequalities in these groups, and this really does suggest basic health determinants are operating."
Further analysis is needed to look at things such as housing conditions, income, access to medical care and nutrition.
"We know a lot of these cases had other chronic illnesses such as diabetes, which may predispose people to the disease, but we haven't established those associations yet."
The research also compared the incidence of the far more common cellulitis - a skin inflammation caused by bacteria which, if it isn't treated, can develop into necrotising fasciitis.
In 2006 there were about 7000 discharges from our hospitals with cellulitis - about 100 times more than necrotising fasciitis.
Cellulitis is also hardly ever fatal, but it too is on the increase - its incidence almost doubled between 1990 and 2006.
"We need far more regular scrutiny because this increase has really gone under the radar for many years," Prof Baker says.
Middlemore Hospital has also done some research into necrotising fasciitis, looking retrospectively at 82 patients between 2000 and 2006.
Specialists Dr David Holland and Dr Mitzi Nisbet found mortality for the disease was around 30%.
"We found it was more common in Pacific Islanders," says Dr Holland - not unexpected because the hospital is in an area with a large Pacific Island population.
Chronic renal failure and gout were independent predictors of mortality.
"Patients with these conditions and sepsis especially need early assessment, aggressive triaging and rapid intervention," says Dr Holland.
Chief adviser of Pacific Health Dr Api Talemaitoga says the Ministry of Health commissioned the report to address concerns about an apparent increase in the disease.
The concerns stemmed from a cluster of cases in 2006, when four young Samoan men were admitted to hospital with severe infections - including necrotising fasciitis that nearly killed one of the victims - after receiving traditional Samoan tattoos.
There had also been similar cases in 2002.
Dr Baker's research showed the tattooing cases were not significant in the increase of the disease.
Specialists have since worked with a number of Samoan tattooists to improve sterilisation and hygiene standards, and the ministry is about to put new customary tattooing guidelines on its website.
The ministry says it's currently looking at what interventions could improve outcomes in the incidence of serious skin infections.
Battle to beat bacteria pressing as cases rise
Dr Thomas Proft isn't surprised by Prof Baker's research showing necrotising fasciitis is on the rise.
The trend, he says, has been signalled since the '80s.
Dr Proft should know. The senior lecturer in microbiology and infectious diseases at Auckland's School of Medical Sciences has been researching the prime culprit in the disease - Group A streptococcus - for 14 years.
So what's going on?"There are theories, but there is no proof," says Dr Proft.
"The general feeling is that the bacteria has developed more virulent strains."
But while the bacterium may be getting more virulent, it can still be knocked out by plain old penicillin.
Which makes it something of an enigma - especially when compared to superbugs like staphylococcus, which is mostly resistant to antibiotics.
Group A streptococcus is often found on the throat or skin, causing no problems at all, or it causes relatively mild illnesses such as "strep throat" or impetigo.
But left untreated, those infections can go on to more serious diseases.
Sometimes the bacteria seem to go berserk - especially when they get into the blood, muscle, or lungs where they don't belong.
That's where "invasive Group A streptococcus diseases" happen.
Two of the most severe are necrotising fasciitis and streptococcal toxic shock syndrome.
Dr Proft began his research identifying superantigens, the powerful toxins secreted by the bacteria and involved in toxic shock syndrome.
"What they do is send the immune system into a hyper-response - overstimulated, completely out of control and leading to systemic inflammation all over the body."
He likens the bacteria's interaction with the immune system to a war.
"Everybody has these weapons and tactics to fight each other. The immune system tries to surround the enemy. With an abscess, you try to keep the bacteria contained and then fight them and kill them off. But all the time the bacteria are trying to get out. They want to spread."
Dr Proft's bacteria-busting research is happening on two different fronts.
The first, funded by Health Research Council, goes after the bacteria's pili - long, extremely thin, hair-like tendrils, known to exist on many bacteria, but only discovered on streptococcus in 2005.
The pili have an adhesant at the end of them, which is how the bacteria attach to their host.
Dr Proft's team is using lactococcus lactis, a non-pathogenic bacterium used in the cheese industry, similar to streptococcus.
By introducing a bit of streptococcus gene sequence into lactis so it grows the streptococcus pilus, the researchers hope to use the reconstituted lactis as a vaccine.
Once vaccinated, when streptococcus bacteria enter the body, the immune system would have plenty of antibodies to overwhelm the streptococcus pili, making them unable to bind to host cells.
The research team has already grown the pili from one strain of streptococcus on lactis, but there is still a way to go as there are at least five different types of pili.
Dr Proft's other research, funded by a Marsden grant, shows just how fiendishly clever streptococcus can be.
When the body has an infection, the immune response sends millions of neutrophil cells to the site.
A defence mechanism of the neutrophils is to lay down strands of DNA to form net-like structures, called neutrophil extracellular traps, which catch and kill the bacteria.
But streptococcus has a clever trick to break out of the net - a coating on its surface which acts like scissors and cuts the net trap, setting the bacterium free to spread.
Dr Proft's team has identified the coating and has been able to reproduce it and its cutting action - the long-term aim being to design drugs that inhibit the coating's escape mechanism.
Samples of all serious streptococcus infections are sent to the ESR (Environmental Science and Research) laboratories in Wellington for analysis - to determine what strains of the bug are occurring and what kind of action might be taken to deal with specific bacteria.
ESR isn't seeing the same numbers of necrotising fasciitis seen in Prof Baker's research - noting just eight to ten cases a year since 2007.
But, as ESR microbiologist Dr Diana Martin points out, streptococcus isolates, mostly from blood cultures, are referred from a wide range of throat and skin infections - including scarlet fever, septicaemia, rheumatic fever, toxic shock syndrome, and sepsis.
So necrotising fasciitis may not always be clearly identified.
Plus there is no legal requirement for all isolates to be sent.
"We have no way of knowing we've got everything," says Dr Martin.
For Group A streptococci referred to ESR there is a worrying trend.
For the first nine months of this year ESR has already received 358 isolates - well up on the 342 in 2008 and 332 in 2007.
That means 2009 is on track for a record-breaking 400 isolates.
"There is no clear reason for this increase," says Dr Martin.
Radical measures needed to halt spread of dangerous infection
Frontline specialists dealing with necrotising fasciitis have a consistent message about the disease.
It's very difficult to diagnose - characterised by high levels of pain out of proportion to what appears on the skin.
When it strikes, it moves extremely quickly and the key to successful recovery depends on how quickly you get into surgery to have the dead tissue removed.
"Until you've seen how rapidly it spreads and have respect for the danger it possesses, you won't understand why radical surgery, something that no-one likes, is crucial," says Dr Tony Williams at Middlemore Hospital's intensive care unit.
"You can go from aches and pains and a very painful tissue infection with maybe a bit of bruising to low blood pressure, acute kidney failure and shock within 12 hours."
Dr Williams says debridement - removal of dead, damaged, or infected tissue - often takes several surgeries.
"We can have it below the knee and surgeons operating and saying they think they got it all and then we can have them operating way up on the thigh or even past the hip 24 hours later."
The worst case he has seen was a young person with no risk factors needing 15% of their total body skin removed.
Microbiologist and infectious diseases specialist Dr David Holland says surgery is vital to arrest the spread of the disease.
"Streptococcus has certain enzymes and toxins which allow it to lyse or dissolve the connective tissue, so it can actually streak along. We often see it in its less severe form, cellulitis, streaking along the leg, rapidly advancing along the tissue planes."
Dr Holland says often streptococcus is not the only germ involved, and that polymicrobial cases where several germs are causing the infection can make treatment even more difficult - especially if antibiotic-resistant staphylococcus bugs are present.
Clinical molecular medicine and pathology associate professor Mark Thomas, of the Auckland School of Medical Sciences, says surgery is important because when there is dead tissue there is a poor supply of antibiotics.
"The organisms that are multiplying in that dead tissue are not really being exposed to concentrations of antibiotic required to kill them."
Dr Williams points out that the bacteria's toxins often coagulate the blood vessels in that area of infection.
"Any antibiotics we normally give for an infection can't reach the site - the blood supply is blocked by blood vessels being clotted."
Dr Holland says the difficulty in diagnosing necrotising fasciitis is that at first people don't look that unwell.
"Some people stay at home and put up with it for a while - take painkillers and stick it out."
Which is, of course, the worst thing to do because the disease can progress so quickly.
Early recognition, says Dr Holland, is key.
And doctors seeing the more common cellulitis always need to be thinking whether a deeper infection could be at work.
But recognising the difference is not easy.
"You recognise that the pain locally is more severe," says Thomas.
Easier said than done.
"If you've got a tough 30-year-old guy, he might say the pain is not that bad, but you or I would say it's atrocious."