Study: Kids, Underlying Conditions, And The 2009 Pandemic Flu

Credit CDC FluView

 

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The chart above illustrates the sharp rise in pediatric deaths from flu-related complications during the 2009-2010 H1N1 pandemic seasons in the United States.  As grim as this charts is, it probably doesn’t fully represent the burden the 2009 pandemic placed on the pediatric community.

 

In another chart, again from the CDC, we get an estimate of deaths related to the 2009 pandemic, broken down by age groups through April of 2010.

 

 

While just over 300 pediatric deaths were recorded during this time period, the CDC estimates that 4 times (n=1280) that many children likely died from flu-related illness in the United States.

 

Globally, the number was undoubtedly many times higher than that (see Lancet: Estimating Global 2009 Pandemic Mortality).

 

 

All of which serves as prelude to a new study that appears today in the journal  Pediatrics, that looks at 336 documented pH1N1-associated deaths, and finds a high number of kids with underlying neurologic conditions.

 

Two-thirds of all deaths in children under the age of 17 occurred in kids with at least 1 underlying medical condition (n=227), and just under half of all cases (n=146) involved neurological disorders, such as cerebral palsy, epilepsy, or intellectual disability.

 

 

Neurologic Disorders Among Pediatric Deaths Associated With the 2009 Pandemic Influenza

Lenee Blanton, MPH^a,Georgina Peacock, MD, MPH, FAAP^b, Chad Cox, MD, MPH^a, Michael Jhung, MD, MPH^a, Lyn Finelli, DrPH^a, and Cynthia Moore, MD, PhD^b

ABSTRACT (Excerpts)

RESULTS: Of 336 pH1N1-associated pediatric deaths with information on underlying conditions, 227 (68%) children had at least 1 underlying condition that conferred an increased risk of complications of influenza. Neurologic disorders were most frequently reported (146 of 227 [64%]), and, of those disorders, neurodevelopmental disorders such as cerebral palsy and intellectual disability were most common.

CONCLUSIONS: Neurologic disorders were reported in nearly two-thirds of pH1N1-associated pediatric deaths with an underlying medical condition. Because of the potential for severe outcomes, children with underlying neurologic disorders should receive influenza vaccine and be treated early and aggressively if they develop influenza-like illness.

 

According to a statement released last night by the CDC:

 

Of the children with neurologic disorders for whom information on vaccination status was available, only 21 (23 percent) had received the seasonal influenza vaccine and 2 (3 percent) were fully vaccinated for 2009 H1N1.

 

 

With September just around the corner, the annual push for flu vaccinations is upon us, and today’s study will hopefully help inspire parents to get all kids – regardless of underlying conditions - vaccinated against influenza.

 

While the effectiveness of flu vaccines vary from year-to-year, and indeed, from one person to the next, they remain the single most important preventative step you can take to avoid getting the flu each year.

 

Despite the hyperbolic anti-vaccine rhetoric often found on the Internet, the truth is, serious adverse reactions to the vaccine are exceedingly rare (see the CDC’s  Influenza Vaccine Safety).

 

With two new strains of seasonal flu expected to be in circulation this winter (Yamagata B, and the Victoria H3N2) – ones that will be covered by this year’s vaccine – getting the flu shot this year is doubly important.

 

CDC recommends that just about everyone aged 6 months and older get an annual influenza vaccination, and stresses their importance for those who are at greater risk of serious complications.

 

For more on vaccine safety and effectiveness, the CDC maintains extensive web pages, and resources, on seasonal flu vaccines, including:

 

What You Should Know for the 2012-2013 Influenza Season

 

Preventing Seasonal Flu With Vaccination

 

Children, the Flu, and the Flu Vaccine

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Revisiting The Influenza-Parkinson’s Link

 

Influenza Virons – Credit CDC PHIL

 

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We’ve a new study, conducted by the University of British Columbia, that finds a linkage between a past history of severe bouts of influenza and the likelihood of developing Parkinson’s disease later in life.

 

In fact, according to their research, a severe bout of influenza doubles a person’s chances of developing the neurological condition.

 

If all of this sounds vaguely familiar, it may be because we explored the idea of a Parkinson’s-Influenza link back in 2009 (see More On The Influenza-Parkinson’s Link).

 

Interestingly, the UBC researchers found that those who caught red measles as a child were 35% less likely to develop the disabling disease.   

 

The article appears in the journal Movement Disorders, and the abstract may be read at:

 

Association of Parkinson's disease with infections and occupational exposure to possible vectors

M. Anne Harris PhD, Joseph K. Tsui MB, Stephen A. Marion MD, Hui Shen PhD, Kay Teschke PhD

 

While the study is behind a pay wall, we’ve a short press release from the University of British Columbia  with some of the details.  After which I will return with more.

 

Severe flu increases risk of Parkinson's: UBC research

Severe influenza doubles the odds that a person will develop Parkinson's disease later in life, according to University of British Columbia researchers.

 

However, the opposite is true for people who contracted a typical case of red measles as children – they are 35 per cent less likely to develop Parkinson's, a nervous system disorder marked by slowness of movement, shaking, stiffness, and in the later stages, loss of balance.

 

The findings by researchers at UBC's School of Population and Public Health and the Pacific Parkinson's Research Centre, published online this month in the journal Movement Disorders, are based on interviews with 403 Parkinson's patients and 405 healthy people in British Columbia, Canada.

(Continue . . .)

 

 

Were this all the evidence – medical and occupational histories of a fewer than 1,000 people – then this might not be a terribly convincing study. But we’ve plenty of other research that suggest that some strains of influenza may be neurotropic - capable of infecting and damaging brain cells.

 

In 2009 a study appearing in PNAS found that the H5N1 virus was highly neurotropic in lab mice, and in the words of the authors `could initiate CNS disorders of protein aggregation including Parkinson's and Alzheimer's diseases’.

Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration

Haeman Jang, David Boltz, Katharine Sturm-Ramirez, Kennie R. Shepherd, Yun Jiao, Robert Webster and Richard J. Smeyne

 

Providing more analysis of this study, we’ve an article published on the  St. Jude Children’s Research Hospital website, again from 2009.

 

Avian influenza strain primes brain for Parkinson’s disease

At least one strain of the H5N1 avian influenza virus leaves survivors at significantly increased risk for Parkinson’s disease and possibly other neurological problems later in life, according to new research from St. Jude Children’s Research Hospital.

<SNIP>

This avian flu strain does not directly cause Parkinson’s disease, but it does make you more susceptible,” said Richard Smeyne, Ph.D., associate member in St. Jude Developmental Neurobiology. Smeyne is the paper’s senior author.

 

“Around age 40, people start to get a decline in brain cells. Most people die before they lose enough neurons to get Parkinson’s. But we believe this H5N1 infection changes the curve. It makes the brain more sensitive to another hit, possibly involving other environmental toxins,” Smeyne explained.

 

Smeyne noted the work involved a single strain of the H5N1 flu virus, the A/Vietnam/1203/04 strain. The threat posed by other viruses, including the current H1N1 pandemic flu virus, is still being studied.

(Continue . . . )

 

In 2011 a study by Boise State biology professor Troy Rohn  appeared in PLOS ONE , which unexpectedly found immunohistochemical evidence of prior influenza A infection in the post-mortem brain tissues of 12 Parkinson’s patients they tested.

 

Immunolocalization of Influenza A Virus and Markers of Inflammation in the Human Parkinson's Disease Brain

Troy T. Rohn^*, Lindsey W. Catlin

 

 

We’ve seen other (albeit largely anecdotal) evidence to support an  influenza-neurological disorder link, and not just with Parkinson’s Disease.

 

During the 1918 pandemic, and the decade that followed, more than a million people around the world were afflicted by a mysterious neurological disorder called Encephalitis Lethargica (EL), which some researchers believe may have been precipitated by the influenza virus.  

 

Other forms of neurological symptoms were also reported in the years (and decades) following the 1918 pandemic, leading some researchers to question whether or not it might be a part of some long-term sequelae of the virus.

 

Other scientists have linked EL with a post-streptococcal immune response, or believe it was an autoimmune response, and dismiss the link with the 1918 pandemic.  

 

The cause remains a mystery.

 

Last year a study appeared in the Annals of Neurology, that suggests a link between contracting an upper respiratory infection and developing narcolepsy (cite Narcolepsy Onset is Seasonal and Increased Following the H1N1 Pandemic in China).

 

What these researchers found was, that in China, among a largely unvaccinated population, the incidence of Narcolepsy increased dramatically in the spring after the winter flu season.

 

This increase was most pronounced following the emergence of the H1N1 swine flu virus in 2009.

 

Those results are reminiscent of another study we saw in 2010 (see Lancet: The Influenza - Guillain Barré Syndrome Connection) that suggested the risks of developing GBS – another type of autoimmune disease - were far greater following a bout of the flu, than from receiving the flu vaccine.

 

While conclusive proof of a link between severe influenza A infection and the later development of neurological disorders has not yet been produced, the anecdotal evidence continues to mount.

 

All of which should provide additional motivation to get that seasonal flu shot every year, since the evidence suggests that it may be protecting you against something far worse than simply spending a miserable week in bed.

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BMJ: Another Pandemrix Study To Ponder

 

 

Photo Credit CDC 

 

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Whenever there is a hint or a suggestion that a vaccine might have caused some sort of serious side effect, it invariably becomes big news. 

 

Even when the reports are preliminary, and the evidence less than rock solid, these stories often end up on the front pages of newspapers and quickly become fodder for the anti-vaccination brigade.

 

When more reassuring vaccine studies come out, they rarely get that kind of media play, since it isn’t the sort of thing that sells newspapers. 

 

Case in point:

 

A little over a year ago GSK’s Pandemrix vaccine was associated with a perceived increase in narcolepsy among children and adolescents in Finland. For early coverage of this story, you may wish to revisit Finland Suspends Use of Pandemrix Vaccine and EMA To Review Pandemrix Vaccine, both of which I wrote in August of 2010.

 

Despite some conflicting and incomplete data the European Medicines Agency issued a statement last July recommending:

 

In persons under 20 years of age Pandemrix to be used only in the absence of seasonal trivalent influenza vaccines, following link to very rare cases of narcolepsy in young people.

 

Finland also convened a Narcolepsy Task Force (see Finland: Task Force Report On Pandemrix-Narcolepsy Link) that confirmed an association – as yet unexplained  – between receipt of the vaccine and an increase in narcolepsy in children between the ages of 4 and 19.

 

Complicating matters, more than a dozen countries reported an increase in narcolepsy during the 2009 pandemic, even those where the adjuvanted vaccine was not used.

 

You can find details on one such study in Stanford Study Finds Influenza – Narcolepsy Connection  that linked narcolepsy not to the vaccine . . . but to infection by influenza virus itself.

 

Confused yet?

 

Alas, science isn’t always neat and tidy.  Good studies take time, and we don’t always get consistent results.

 

Today, we’ve another study that appears in the BMJ that is a bit more reassuring on the safety of the Pandemrix vaccine, but fails to answer the question of narcolepsy. 

 

It is called:

 

Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden

OPEN ACCESS

Carola Bardage, epidemiologist, Ingemar Persson, professor of pharmacoepidemiology and senior expert, Åke Örtqvist, county medical officer and associate professor, Ulf Bergman, professor of pharmaco-epidemiology and clinical pharmacologist, Jonas F Ludvigsson, paediatrician and epidemiologist, Fredrik Granath, senior biostatistician

 

This was a population based cohort study conducted in Stockholm, Sweden during the 2009 pandemic where 1,024,019  people were vaccinated with the Pandemrix vaccine and 921,005 remained unvaccinated.

 

Using the detailed healthcare registers for Stockholm County Council, researchers tracked all admissions to hospitals and visits to specialists for autoimmune or neurological diagnoses.

 

The conditions flagged in this study included:

 

• Guillain-Barré syndrome
• Bell’s palsy
• multiple sclerosis
• polyneuropathy
• anaesthesia or hypoaesthesia
• paraesthesia
• narcolepsy
• rheumatoid arthritis
• inflammatory bowel disease (ulcerative colitis, Crohn’s disease)
• type 1 diabetes

 

This study further divided this cohort into those who received the vaccine within the first 45 days of its availability, and those who received it later. Those in high risk groups, with comorbid conditions, were more likely to be vaccinated during the first 6 weeks of the vaccination campaign. 

 

The results (which are far more detailed in the open access report) indicated:

 

Conclusions

Results for the safety of Pandemrix over 8-10 months of follow-up were reassuring —notably, no change in the risk for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, or rheumatoid arthritis.

 

Relative risks were significantly increased for Bell’s palsy, paraesthesia, and inflammatory bowel disease after vaccination, predominantly in the early phase of the vaccination campaign.

 

Small numbers of children and adolescents with narcolepsy precluded any meaningful conclusions.

 

The report summary states:

 

What is already known on this topic

• Studies are lacking on adverse events (except for narcolepsy) with any of the three vaccines used in the European Union against H1N1 during the pandemic period

• Available data are limited to case series or highly selected populations with short follow-up or no control group

What this study adds

• Excess risks for Bell’s palsy, paraesthesia, and inflammatory bowel disease after H1N1 vaccination with adjuvanted Pandemrix in Sweden were small but significant among more than one million vaccinated, but only in high risk groups targeted for early vaccination and who were likely to have earlier comorbidity

• The risk of Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis remained unchanged

• Small numbers of children and adolescents with narcolepsy precluded any meaningful conclusions

 

While the low number of children and adolescents with narcolepsy may have precluded making any firm conclusions, their scarcity is nonetheless a bit reassuring.

 

The authors suggest that the small, but statistically significant increase in Bell’s palsy, paraesthesia, and inflammatory bowel disease among the early recipients of the vaccine may be partly, or perhaps entirely, explained by the higher number of high risk patients in that cohort.

 

We are still left with the mystery of what caused the increase in narcolepsy reported in Finland, of course. And there will no doubt be additional studies that will look at the safety of the Pandemrix vaccine in other regions.

 

But for now, as the authors state,  the news is `reassuring’.

 

For previous reports on the safety of (adjuvanted and unadjuvanted) flu vaccines, you may wish to revisit.

 

IOM Report On Vaccine Safety Concerns

 

BMJ: No Substantial Link Between Flu Vaccines And Guillain-Barre Syndrome

 

Lancet: Immunogenicity and safety Of Adjuvanted Flu Vaccines

 

NEJM: Study On China’s H1N1 Vaccine Safety

 

Harvard Study Reaffirms Safety Of Flu Vaccine

 

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Study: Pediatric Neurological Complications With H1N1

 

 

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Despite being relatively mild for the vast majority of those it infected, the novel H1N1 virus – at least in a small percentage of victims – showed unusual, and sometimes severe, symptoms.

 

The most obvious difference between the pandemic virus and seasonal influenzas of the past has been the age shift in infections, hospitalizations, and deaths.

 

Unlike seasonal influenza, novel H1N1 has taken its biggest toll on those under the age of 65.

 

While the total number of flu-related fatalities appears to be less than normally seen with seasonal flu, In terms of years of life lost, novel H1N1 was anything but benign (see Study: Years Of Life Lost Due To 2009 Pandemic).

 

 

But the difference between pandemic H1N1 and seasonal flu go beyond this profound age shift. The symptomology of this virus differed for many people as well.

 

A brief review, before we get to today’s study.

 

Researchers in Hong Kong discovered that the H1N1 virus – unlike seasonal flu – easily infects and replicates in the conjunctival tissues of the eye  (see I Only Have Eyes For Flu).

 

Another difference observed with novel H1N1 has been its unusually high rate of gastro-intestinal symptoms. Diarrhea and vomiting have both been commonly reported with H1N1 pandemic influenza as evidenced by this report from Maggie Fox of Reuters.

 

US flu study confirms H1N1 more serious in youth

Thu Oct 8, 2009 10:41pm BST

* 45 percent of those hospitalized were under 18

* Diarrhea, vomiting in 42 percent of children with H1N1

* Quick drug treatment may save lives

 

 

And in December of last year, we saw a report from the NIH on autopsies performed on H1N1 victims in New York that showed unusual levels of lung damage.

 

 Virus Damages Entire Airway

Monday, Dec. 7, 2009

In fatal cases of 2009 H1N1 influenza, the virus can damage cells throughout the respiratory airway, much like the viruses that caused the 1918 and 1957 influenza pandemics, report researchers from the National Institutes of Health (NIH) and the New York City Office of Chief Medical Examiner.

 

 

Beyond the gastro-intestinal and pulmonary symptoms, we’ve also seen a number of neurological complications, particularly (but not exclusively) in children.

 

The first hint of this came last summer when the CDC’s MMWR (July 23rd issue) reported on 4 pediatric patients with the novel H1N1 virus who presented with neurological symptoms including unexplained seizures and altered mental status.

 

Neurologic Complications Associated with Novel Influenza A (H1N1) Virus Infection in Children --- Dallas, Texas, May 2009

. . .  On May 28, 2009, the Dallas County Department of Health and Human Services (DCHHS) notified CDC of four children with neurologic complications associated with novel influenza A (H1N1) virus infection admitted to hospitals in Dallas County, Texas, during May 18--28.

 

In November, in a blog entitled Japan: Influenza Related Encephalopathy we looked at a report in the Yomiuri Shimbun on 132 flu patients with neurological complications during the opening four months of the pandemic.

 

 

All of which serves as prelude to today’s study by researchers at the University of Utah which is to be published later today in the Annals of Neurology  (link not available yet).  

 

Heightened Neurologic Complications in Children with Pandemic H1N1 Influenza

Jeffrey J. Ekstrand, Amy Herbener, Julia Rawlings, Beth Turney, Krow Ampofo, E. Kent Korgenski, Joshua L. Bonkowsky. Annals of Neurology; Published Online: September 20, 2010 (DOI:10.1002/ana.22184)

 

Since the link has not appeared, what we do have is the press release on this study:

 

 

Higher incidence of seizures seen in children with H1N1 virus compared to seasonal flu

Vaccination important to combat flu-related neurological complications

 

 

This was a retrospective study, where researchers identified 303 children hospitalized with the pandemic H1N1 virus, 18 of which developed neurological symptoms.  

 

They compared these cases to records of 234 children admitted to the hospital in previous years due to seasonal influenza.

 

The most common neurological complications exhibited with novel H1N1 were seizures (12 patients or 67%), with seven exhibiting status epilepticus, a potentially life-threatening condition involving continuous or recurrent seizures that can last for a half hour or longer.

 

The mean age of children admitted with neurological symptoms from H1N1 was more than twice the age (6.5 years) than usually seen with seasonal flu (2.4 years).

 

And abnormal EEG (electroencephalogram) readings were more common in pandemic H1N1 cases than in seasonal influenza.

 

The researchers are unsure why these neurological manifestations appear more common in novel H1N1 influenza, but suggest that it may be part of an autoimmune response.

 

You can find more details of this study in an review published today by Medpage Today:

 

Seizures in Kids Linked to H1N1 Flu

By Nancy Walsh, Staff Writer, MedPage Today

 

 

While it is easy to dismiss the 2009 pandemic virus as overblown based simply on the total number of fatalities, when one looks a little deeper one discovers that the virus played by its own set of rules.

For the demographic group usually hit hardest by the flu – those in their 70s and 80s and most likely to die from the infection - novel H1N1 was almost like a year without influenza.  

But for many children, and younger adults, H1N1 proved to be a serious challenge.

 

This year, we’ve a double threat looming with this fall’s flu season.   The (former) pandemic H1N1 virus is likely to return, along with (potentially) the new Perth H3N2 strain.

 

And H3N2, if it returns, is unlikely to spare the elderly as did the pandemic virus.

 

The good news is both of these are covered (along with an influenza B strain) in this year’s trivalent flu vaccine. 

Three good reasons to get your flu shot early this year.

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