A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases

Date: Thu 18 Jun 2009
Source: Google news,The Canadian Press report [edited]

Risk factors for severe swine flu a wide umbrella under which many stand
Whether speaking of a 58-year-old man or a 38-year-old woman, or a little boy of 9, officials announcing swine flu deaths are almost always quick to note "underlying health conditions" may have contributed to the fatal outcome. Asthma, heart disease, diabetes, maybe even obesity are among the conditions used to help explain why swine flu infection is hospitalizing and killing younger people, people who would be expected to make a full recovery from seasonal flu.

It could create the impression that only the sickly are dying from the new H1N1 flu virus -- a claim no one is making. To the contrary, many, including the World Health Organization, say between one-third and one-half of swine flu deaths have occurred in people who were previously healthy. But how healthy is previously healthy? The answer depends on who you ask.

Dr Anand Kumar is a critical care specialist who has been treating swine flu cases in embattled intensive care units (ICU) in several Winnipeg hospitals. He says a small portion of the ICU patients look like flu's typical victims, people with health conditions know to be badly exacerbated by a bout of influenza. But more are younger and -- until they got sick -- healthier than flu patients hospitals typically see during a regular influenza season. "For the most part, these young, relatively healthy people aren't marathon runners or anything like that," he admits. "They're normal people.... If you asked them 'Are you healthy?' they'd say 'Yeah, pretty healthy."'

Dr Michael Gardam, head of infectious disease prevention and control for Ontario's public health agency, believes the constant refrain of "underlying conditions" bespeaks a sort of wishful thinking, an attempt to explain away the unusual age range of the people the new virus is sending to hospital or to the morgue. "That's the story that I think people haven't really registered," says Gardam. "We're clinging to these 'Oh, they had underlying illness, therefore it's OK."' "But ... I would argue that the 30-year-old with mild asthma -- how big of an underlying illness is that compared to again the 80-year-old person with bad lung disease from smoking, who's got heart disease? That's the usual group that unfortunately gets really sick with flu, not this healthy adult group." You'll find little argument that this virus, at this time, is causing more severe disease in people far younger than those normally hospitalized and killed by flu or its complications in a typical flu season.

"This is not a disease of older adults. There's no question," says Dr Allison McGeer, an influenza expert with Toronto's Mount Sinai Hospital. "For people under 50, this is a significantly more severe disease than seasonal flu. For people over 50, it's much better," she notes. But are the people under 50 who are being badly hit by the virus specimens of perfect health or are many of them already shaded by the broad umbrella known as "pre-existing health conditions?" How you view a condition like asthma -- seen in 41 per cent of the hospitalized cases in New York City -- may influence how you answer that question. "A lot of that is about labelling people," McGeer admits. "Half of me doesn't want you to think you're diseased if you have asthma, and the other half of me wants you to get your flu vaccine because you're at increased risk." "How do you walk that line?"

Year in and year out, public health authorities get plenty of evidence many people who have some health issues plunk themselves firmly on the "healthy" side of the divide. Scans of people with asthma, diabetes and other conditions, and women who are pregnant forego the flu shots public health officials urge them to get, suggests Dr Scott Harper, an influenza expert with New York City's Department of Health. New York City has had one of the biggest swine flu outbreaks to date. As of Tuesday [16 Jun 2008], more than 700 New Yorkers have been hospitalized with swine flu and 23 people in the city have died from infections. With those kinds of numbers, one might expect to see patterns emerge. But Harper says in fact the department believes that many of the health conditions known for years to increase the risk posed by flu are being seen in the people suffering serious disease with swine flu. "The majority of deaths that are being seen have well recognized underlying health risks," he insists. "Those that don't may have and we just haven't seen them yet. And then we may also find new risk factors, but they have not yet been adequately described analytically to be able to say it's a legitimate risk factor."

One such potential new risk factor is obesity. An early study from the US Centers for Disease Control suggested it may be contributing to poor outcomes in people who contract the new H1N1. The WHO is concerned about that possibility. "Obesity is now a huge global problem," says Dr Nikki Shindo, an expert with the WHO's global influenza program. "And if obesity is a risk factor, then I would be very much worried about some of the populations that are living with obese conditions." Four of the people who died in New York City were obese. Still, Harper says it's too soon to say whether that's a risk factor in and of itself, or if some of the things that go hand-in-hand with obesity -- like early heart disease, like diabetes
-- are the real risk factors. Teasing out that answer will be tough but necessary, he says, noting that knowing who is truly at the most risk from this virus will dictate who stands where in the queue for swine flu vaccine once it becomes available and who should get priority access to antiviral drugs.

[Byline: Helen Branswell]

Communicated by:
ProMED-mail Rapporteur Mary Marshall

[In the absence of clearly defined risk factors it remains reasonable to assume that older people have some degree of protection due to earlier exposure to an immunologically similar agent. In which case it would be appropriate to give younger age groups priority for vaccination with a swine-origin A (H1N1)-type vaccine when available, and to continue vaccination of older age groups with seasonal influenza vaccine if still available. - Mod.CP]

[The article above is a timely discussion on the issue of identifying risk factors associated with more severe disease in this current wave of influenza A (H1N1). One factor that should be highlighted when discussing any comparisons with prior pandemic influenza patterns is that it has been 41 years since the last influenza pandemic (the "Hong Kong flu" in 1968), and much has changed in the interval since the last pandemic in terms of basic health conditions. For example there has been an observed pandemic of obesity, so that if obesity has always been a risk factor for more severe disease with influenza infection, the number of individuals at risk may have crossed a threshold now allowing the "tip of the iceberg" to be large enough to be seen. Another change has been an increase in morbidity and mortality due to asthma in many countries. In the USA prevalence rates of asthma have increased since 1978 (in table 7 of the American Lung Association 2005 report on 'Trends in asthma morbidity and mortality,' the reported asthma prevalence rates per 1000 population in the 18-44 year old age group went from 29.0 in 1982 to 56.9 in
1996. For full report with all tables and analyses, see <{7A8D42C2-....

For the reverse side, in studies addressing risk factors for influenza among children, asthma has fairly consistently been identified as a key risk factor for disease and co-morbidity among hospitalized cases (see refs 1 and 2 below). Pregnancy has been observed to be a risk factor of serious disease in many viral infections, so it is not surprising that it is showing up as a risk factor for serious disease in this present pandemic. Excess deaths were observed among pregnant women in the 1918 pandemic and the 1957 pandemic (see refs 3 and 4.) Widelock, Csizmas, and Klein present an analysis of the excess mortality among pregnant women in New York during the 1957 pandemic period when compared with the same influenza periods in 1958, 1959, and 1960.

This moderator has been leaning towards the question of "how healthy are those who are reportedly healthy" or are there underlying conditions that had not previously been identified in the reportedly "otherwise healthy" individuals who have had severe disease associated with influenza A (H1N1) infection? Having worked in major inner city emergency rooms in a large urban center in the USA, it was not uncommon for individuals to present with later stage severe disease associated with chronic illnesses that had previously not been identified, yet had most likely been present for a significant amount of time prior to presentation to the health sector. Often it was co-morbidity with an acute disease that precipitated presentation to the emergency room where the "underlying disease" was then identified.

As for the observation that there is more disease and more serious disease attributable to influenza A (H1N1) infection among younger age groups, the explanation for this observation may either reflect a cross over immunity in older age groups from previously circulating H1N1 influenza viruses, or it may reflect the bias that the initial age group affected were younger ages, and these cohorts have greater co-mingling to facilitate transmission among them, or most likely, a combination of both. A study on serum cross reactive antibody response to the novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine revealed at baseline, cross-reactive antibody was detected in 6-9 percent of those aged 18-64 years and in 33 percent of those aged greater than 60 years (see ref 5 below), demonstrating that the younger age groups were more uniformly susceptible to infection with influenza A (H1N1). Given this observation it appears prudent to include younger age groups in vaccination activities, but with only one third of older age groups with cross reactive antibodies, they should also be included as targeted for vaccination activities. Hence, a significant challenge for vaccine production.

This is the 1st time that pandemic influenza activity has been subjected to such intense scrutiny under a myriad of different microscopes (both literally and figuratively) in a prospective manner and the medical community is there validating and disproving many previous "observations" and "theories." There is a lot to be learned, and as each answer becomes available, new questions arise.