As toll mounts, researchers peer into the H1N1 death spiral
So far, 309 people have died across Canada since the pandemic began in the spring, and roughly one-third had no underlying health conditions
Lisa Priest and Caroline Alphonso
From Saturday's Globe and Mail
November 28th 2009
The lungs were heavy, difficult to deflate, and beefy looking. To the pathologist who held them, they belied their own anatomy, resembling a liver.
They belonged to an Ontarian who, until contracting H1N1, had been healthy and in early middle age. Within days, the person was dead, being dissected at Toronto's University Health Network. Pathologists concurred on the likely mechanism of death – an immune system reaction, most common among the young and people in their prime, called a cytokine storm. “Once the inflammatory cascade gets established, it's like a runaway freight train – it's just going to keep going,” said pathologist David Hwang, who consulted on the samples. “In some of these patients, even if you clear the virus, the cytokine storm has already taken hold and it takes on a life of its own.”
It's a fatal irony: A robust immune system can be hazardous to your health. In some cases, it's the reaction to the flu – more so than the virus itself – that sets off the death spiral.
So far, 309 people have died across Canada since the pandemic began in the spring, and roughly one-third had no underlying health conditions. That challenges the collective memory of a population that had never seen an influenza strike down people in their salad days. And it is reminiscent of 1918, when upward of 50 million worldwide died from the Spanish flu, many believed caught in cytokine storms.
This year, even as polls show public concern over H1N1 is levelling off, there has been a sharp spike in H1N1 fatalities nationwide, with 208 new deaths reported since Nov. 3. And interviews with intensive-care specialists and microbiologists reveal many Canadian casualties experienced one or more of the following: viral pneumonia, a devastating secondary bacterial infection, or a cytokine storm. These conditions can strike together, to deadly effect.
When a person becomes infected by H1N1 or other viruses, the immune system releases cytokines – small proteins that help recruit cells to destroy the virus. Side effects include fever, chills and muscle aches that for the vast majority of people are transient. But in some, the immune response goes berserk – a cytokine storm that can rage even after the virus has cleared.
That inflammatory response causes fluid buildup in the lungs. The simple act of breathing – getting oxygen in and carbon dioxide out – becomes too daunting even for a high-tech ventilator. Damage caused by viral injury makes lungs vulnerable to a bacterial infection.
While the H1N1 virus still kills the elderly and those with underlying health conditions, it can attack the young and healthy with shocking velocity.
“This is not the same influenza [as seasonal flu]. It's literally a different disease,” said Winnipeg-based intensive care and infectious diseases specialist Anand Kumar. “… Any rules that anybody had about what influenza does or doesn't do, they're gone.”
Dr. Kumar has treated 30 patients with H1N1, reviewed a further 30 and studied eight autopsies since the pandemic began this past spring. Virtually all of his patients – and those cases he reviewed – developed viral pneumonia, sometimes with a secondary lung infection. Among those who died, nearly all succumbed to respiratory failure.
With these patients, the body tries to expel the virus through an inflammatory response, which causes the buildup of fluid. Blood vessels leak, creating a frothy pink pool of liquid in the lungs.
It can be an unmerciful end. Some of Dr. Kumar's patients have spent weeks or occasionally months in medically induced comas. Attempts to revive some were unsuccessful. Unable to breathe, they had to be put back on a ventilator. Several died.
Some go so quickly they never reach a ventilator. Among them was a teenaged Toronto hockey player who gasped his last breath at home, in front of his father.
“In 24 hours, it took him over,” said Paul Frustaglio, of his 13-year-old son, Evan, who died of H1N1 a day after being seen by a physician at a walk-in clinic.
“… He just laid down in a fetal position and within two minutes of me talking to him, he's gone. That's what it was.”
A storm with no warning
There is no lab test for a cytokine storm. Typically, if death from H1N1 is sudden and acute – defined as being within a matter of just a few days – a cytokine storm is suspected.
That is especially true if routine cultures, such as Streptococcus pneumoniae or Staphylococcus aureus , are negative, said Andrew Simor, head of microbiology and infectious diseases at Sunnybrook Health Sciences Centre in Toronto.
“But if the tempo of the disease was they had a flu-like illness for four or five days and then they developed pneumonia,” Dr. Simor said, “then you start to think about a secondary bacterial infection.”
Even with today's sophisticated laboratory tests, it is still difficult to identify bacteria. That's because patients are often on antibiotics that, while potentially lifesaving, can hinder the ability to grow bacteria from lung tissue, says Jonathan Gubbay, medical microbiologist at the Ontario Agency for Health Protection and Promotion.
“We're doing enhanced testing, including molecular testing,” Dr. Gubbay said. “But that doesn't rely on being able to grow the bacteria so we're hoping that will increase our yield.”
The experience in Canada is similar to that in the United States, where officials said this week that they observed a worrying pattern of serious bacterial infections, such as Streptococcus pneumoniae , mostly among younger adults not normally vulnerable to them.
That was also the case with the early middle-aged Ontarian, one of the few who underwent an autopsy after dying of H1N1 during the pandemic's first wave.
While the upper respiratory tract – the gateway for H1N1 – looked fine, destruction lay in tiny lung air sacs where gas exchanges occur, said veteran pathologist Jagdish Butany, who performed the autopsy. The person died quickly, within a few days after being infected with H1N1. Rapid inflammation caused excessive damage to the lungs, which caused fluid buildup – suggesting a cytokine storm got the fatal reaction rolling.
“Young up to middle-aged people are much more likely to not just get it,” Dr. Butany said, “but to really suffer and be admitted and perhaps succumb to it.”
The Qur'an itself repeatedly recommends Muslims to become better educated in order better to understand God's creation: Aga Khan IV(2007)
The Quran tells us that signs of Allah's Sovereignty are found in the contemplation of His Creation: Aga Khan IV(2007)
This notion of the capacity of the human intellect to understand and to admire the creation of Allah will bring you happiness in your everyday lives: Aga Khan IV(2007)
Islam, eminently logical, placing the greatest emphasis on knowledge, purports to understand God's creation: Aga Khan IV(2006)
The Holy Qu'ran's encouragement to study nature and the physical world around us gave the original impetus to scientific enquiry among Muslims: Aga Khan IV(1985)
The first and only thing created by God was the Intellect(Aql): Prophet Muhammad(circa 632CE)