`If I weren't a hypochondriac, my son wouldn't be alive today," believes Muriel O'Connor. Mother's instinct told her that her son's life was at risk hours before she could convince anyone else to believe her. On the morning of September 27th, 1996, Muriel's two-year-old son Conor Thornton seemed robustly healthy. Yet a lethal meningococcal septicaemia infection was already lurking in his respiratory system and preparing to rip through his small body. Muriel and her husband, Kevin Thornton, could not have known that by midnight, their son would be near death, his inflamed organs going into terminal failure one by one and his skin bruised black by thrombotic necrotic lesions - lethal blood clots beneath the skin.
Meningococcal infection is every parent's - and doctor's - worst nightmare because it strikes so swiftly and without warning. One in 10 people - including children - have the potentially lethal meningococcal bacteria in their respiratory tracts. No one knows why the bacteria chooses to run rampant in only a fraction of the people who play host to it. There may be a genetic influence towards susceptibility to the disease. Whatever the cause, the Republic has one of the highest rates in Europe of meningococcal infection.
Meningococcal bacteria can cause two illnesses: most commonly, it causes meningitis, an inflammation of the lining of the brain. Less commonly, it results in meningococcal septicaemia, a shock syndrome which shuts down the body's main organs within hours. Parents are more afraid of meningitis, but meningococcal septicaemia is actually far more dangerous.
More than 90 per cent of cases of meningitis are cured with antibiotics when treated early, which is the key and why parents must be vigilant. But with meningococcal septicaemia, even vigilance and early treatment may not be enough, as the death rate in this condition may be as high as 80 per cent.
Hundreds of Irish people are infected annually with meningococcal infection and up to 30 actually have the severe form - meningococcal septicaemia. Many of these die as the disease speeds through the body forcing the immune system to overreact, so that the organs become inflamed and go into failure. Of those who survive, there is usually significant long-term damage, such as amputations, skin grafting and kidney failure requiring lifelong dialysis.
This was what two-year-old Conor faced as he walked happily around town with his parents shopping. At lunch-time, he was irritable and had difficulty settling for his nap. This was the only sign that the meningococcal bacteria was taking hold. When Conor began to vomit, Muriel put it down to over-tiredness and maybe a tummy bug. By 4 p.m. however, Conor had a slight temperature and Muriel took him to the doctor, who reassured her that it was "not the Big M".
Back at home, Conor was cranky and lethargic. Muriel thought his heartbeat seemed too fast and she became even more alarmed when he began vomiting bile. By 6 p.m. Muriel's instincts were telling her that something was very wrong. She rang the doctor again, and again he reassured her that it was only a 'flu-type illness. Muriel felt that she was being told to relax and stop overreacting.
At 10 p.m. Muriel noticed an odd, dark red dot - like a tiny, burst blood vessel - on Conor's chest. Then she noticed a small bruised mark on Conor's leg which hadn't been there an hour before. She asked herself how he could have bruised himself lying on her lap on the sofa.
At 10.15 p.m. Muriel was too worried to sleep and again rang the doctor and described the strange red marks. The doctor arrived within minutes, took one look and dashed to the car with Conor and drove him to the hospital himself - there wasn't time for the ambulance. By the time they got to Harcourt Street, the red lesions were visibly multiplying on Conor's body like something out of a horror movie.
"In casualty they told me, `five minutes more and he would have been dead'," Muriel says. "This is the most malignant disease in paediatric medicine, more malignant than acute leukaemia. This thing goes through children within 12 to 24 hours," says Dr Owen Smith, haemotologist at the National Children's Hospital, Harcourt Street and St James's Hospital, Dublin. It was Dr Smith that staff at the National Children's Hospital rang when Conor Thornton was brought into casualty in extremis. They already knew there was probably only one chance for Conor: Protein C, a remarkable new treatment for meningococcal septicaemia which was revealed to the world yesterday in the Lancet medical journal.
Conor was stabilised at Harcourt Street, then transferred to the intensive care unit at Temple Street Hospital in Dublin. While medical staff at the hospital battled to keep him alive on total life support, the Eastern Health Board was already tracing his contacts. Conor had been in a supermarket creche and the board issued a warning through the media that all children who had been in the creche must receive prophylactic antibiotics. All around the country, parents searched their children's skin for signs of the tell-tale rash.
Comatose and connected by a dozen tubes to a dozen machines, Conor hovered in a "pre-morbid state", the medical term for the edge of the abyss. Kevin and Muriel remained at their son's bedside, willing him to live. They spoke bright words of encouragement, unsure whether he heard them not.
The machines keeping Conor alive included a ventilator, which breathed for him, intravenous antibiotics, which grappled with the bacteria, and a dialysis machine which filtered his blood of toxins as his kidneys were not working. Until 1996, this aggressive therapy would have been Conor's only chance. But this was September 1996, and since January of that year Dr Smith had been on call 24 hours a day, waiting to hear of cases just like Conor's. Dr Smith had been working on an experimental treatment based on the idea that meningococcal septicaemia wasn't only about a bacterium rampaging through the body - there had to be some other mechanism at work.
The bizarre red and black spotting was the key. This was originally thought to be due to internal bleeding, but in fact it was actually caused by thrombosis - blood clotting, in other words. Dr Smith realised that there had to be some other explanation as to why the blood began to clot uncontrollably beneath the skin - and maybe if you could treat this, you could save lives.
There is a condition where new-borns come in to the world with a low level of one particular factor in the blood, Protein C, a natural anticoagulant. These infants rapidly develop blood clots similar to those in meningococcal septicaemia and die without Protein C replacement. It has been known for five years, that in patients with meningococcal septicaemia, the lower the Protein C level, the worse the outcome.
When Protein C level drops, the patient starts to thrombose - in other words, they get widespread blood clots in the small vessels of the skin and all the other organs including the liver, kidneys, heart and lungs. It is this precipitous drop in Protein C levels which makes the bizarre skin "rash" spread before your eyes. But it is not this clotting which kills the patient. Rather, it is the adverse immune response that threatens life. The immune system goes into overdrive in an attempt to rescue the body but overdoes it. This adverse immune response inflames the organs, a process which Dr Smith believes is closely linked to the depletion of Protein C. Therefore, Dr Smith postulates that replacing the Protein C in these patients will have a beneficial effect both for the clotting, but also in returning the immune system to normal. Muriel and Kevin gave Dr Smith permission to use Protein C as their son lay paralysed, unconscious and barely recognisable as the little boy he was a few days before. Every bodily function was supported by a machine. His lungs had to be suctioned out and when doctors first removed the ventilator, Conor couldn't breathe and turned blue. After 10 days, he reached out for his mother's nose - a gesture he had made ever since he was an infant, and Muriel knew he would survive undamaged. After several weeks, he went home. "He seemed a happier boy. As if he knew that he was lucky to be alive," says his mother.
As reported in the Lancet yesterday, Conor is one of 12 children and adults aged from three months to 25 years who have been given Protein C. The 12 were from four paediatric hospitals and two adult hospitals in the Eastern Health Board region. All were on the brink of death. All were saved - a 100 per cent cure rate.
Another of the 12 people was 28-year-old Lorraine Duffy Kirwan, from Dublin, who was struck by meningococcal septicaemia in August 1996. On a Friday, she began feeling vaguely unwell and nauseous, but thought perhaps she had partied a little too hard. By Saturday, she felt worse and by Sunday she could hardly get out of bed. On Monday, she couldn't stand.
Lorraine began vomiting bile, and wondered if she should call a doctor, although she didn't have her own GP. At 2.30 p.m. she rang a friend's doctor and got a locum, who promised to visit. At 4.30 p.m. she was sweating and cold and her mother noticed the first bruises. At 5.30 p.m the locum arrived and gave her a shot of penicillin, then left. By 8.15 p.m. Lorraine's entire body was covered in red and black patches. "It was like her skin was being eaten away," says her mother.
Lorraine was rushed by ambulance to St James's and was so sick that she didn't feel the lumbar puncture used to diagnose meningitis, even though this is ordinarily an excruciating procedure. She drifted in an out of a coma on total life support.
As the meningococcal septicaemia picked off Lorraine's vital organs one by one, Lorraine's parents, Imelda and Tommy, were told by a doctor: "There's no hope for your daughter." Imelda didn't want to believe the doctor, but a nurse told her, "He's never wrong."
As they saw Lorraine turning black, putting her at risk of limb amputation, Imelda and Tommy wondered if perhaps their daughter wouldn't be better off dead. Lorraine, despite being unconscious, remembers being aware of her imminent death. In her unconscious state, she had visions of meeting St Peter, who was a burly, red-haired bouncer in a Leeson Street-style nightclub and wouldn't give her the time of day.
When Dr Smith offered to put Lorraine on the experimental Protein C, Imelda and Tommy immediately agreed. After 10 days, Lorraine moved one finger. Soon afterwards, she regained consciousness. A year later, Tommy can hardly look at his daughter without tears in his eyes. "I still can't believe she's alive. It's a miracle", he says.
Dr Smith warns that Protein C must not be given in isolation without an expert support team. The patient's coagulation system must be carefully monitored by doctors who are expert in treating the disease, such as those at the National Coagulation Unit at the National Children's Hospital and St James's Hospital. And it is crucial that the right patients receive this therapy. Not everyone with meningococcal septicaemia will drop their Protein C to such an extent that they need replacement of it.
The use of Protein C must be guarded for two reasons: it is expensive - about £20,000 per patient - and it is derived from blood donations, carrying a small theoretical risk of blood-borne infection. "Patients who are not in extremis should not get Protein C," cautions Dr Smith.
He stresses that Protein C on its own is not a miracle cure: it must be used as part of a cocktail approach including other anticoagulants such as antithrombin (another natural anticoagulant) and heparin together with ventilation, filtration and antibiotics.
Precisely how Protein C works still isn't fully understood. Dr Smith's research team is actively pursuing the role played by Protein C in turning off the adverse immune response, a catastrophic event that results in death.
Funding would bring greater hope for children and adults afflicted with meningococcal septicaemia - not just in Ireland, but around the world. So far, up to 20 lives have been saved. And in five weeks time, Lorraine Duffy, who married soon after her illness, will be giving birth to her first child a mere 12 months after she nearly died. Protein C and the extraordinary effort of a small group of Irish doctors may have made an impression on the international medical scene this week, but for families like the Duffys it just means they have their daughter back, and the prospect of a new grandchild to celebrate.
The warning signs
Children and adults with meningococcal infection (meningitis or meningococcal septacaemia) may show one or more of these warning signs, if they are lucky:
Red spots which do not turn white under pressure;
Sudden red or black bruising which does not fade under pressure;
Fever, possibly with cold hands and feet;
Vomiting;
High-pitched moaning, crying, whimpering;
Irritability;
Lethargy;
Stiff neck, or neck pulled back at an odd angle;
Blank, staring expression;
Severe dislike of bright light;
Headache;
Coma.