H1N1 Flu Skepticism Demands Deft Response

European scientists and health authorities are facing angry questions about why H1N1 flu has not caused death and destruction on the scale first feared, and they need to respond deftly to ensure public support.

Accusations are flying in British and French media that the pandemic has been "hyped" by medical researchers to further their own cause, boost research grants and line the pockets of drug companies.

Britain's Independent newspaper this week asked "Pandemic? What Pandemic?"

In their response, scientists are walking a fine line.

They say that although the virus is mild, it can still kill, and that the relatively low fatalities in Europe are in part the result of official response to their advice.

On suggestions of "hyping" the threat to boost research funding, they point out that while we know enough to start to protect the vulnerable, we need to know a lot more to conquer the virus, and funding for new research and drugs is vital to be equipped for future pandemics.

H1N1 is hitting a younger population -- adults in their 20s and 30s and children -- and the global death count so far is more than 6,000, according to the World Health Organization.

While seasonal flu attacks about 20% of the population in an average year, experts estimate that even in Britain -- the worst-hit country in Europe so far -- fewer than 10% of people have had H1N1 flu.

Fred Hayden, influenza research coordinator at the Wellcome Trust and a former World Health Organization expert, said early planning is paying off, but added, "I wouldn't characterize this as a 'mild' pandemic at all. We are seeing some very unfortunate loss of life. I think it a bit early to make that judgment."

Yet the word "mild" is used so often to describe H1N1's impact that it is prompting skeptical publics to ask what all the fuss is about. Why they should care? And why take a vaccine?

France's Le Parisien newspaper ran the headline: "Swine flu: why the French distrust the vaccine" and noted a gap between the predicted impact of H1N1 and the less dramatic reality.

"Although some 30-odd people have died....the disease is not really frightening," it said. "Dangerous liaisons between certain experts, the labs and the government, the obscurity of the contracts between the state and the pharma firms have added to the doubt."

In Britain, health authorities' original worst-case scenario -- which said as many as 65,000 could die from H1N1 -- has twice been revised down and the prediction is now for around 1,000 deaths, way below the average annual toll of 4,000 to 8,000 deaths from seasonal winter flu.

A group of eminent scientists who called a media briefing in London this week to announce 7.5 million pounds ($12.4 million) of new funding for British research into H1N1 found their plans hijacked by reporters asking why the pandemic was so weak.

Scientists say the truth is they can't win.

The World Health Organization has been urging countries to prepare for a flu pandemic since 1997, when H5N1 avian flu infected 18 people in Hong Kong and was stopped only after a mass slaughter of birds. The re-emergence of H5N1 in China and South Korea in 2003 fueled the urgency to get ready.

Now that it has arrived, the apparently low impact of the H1N1 pandemic so far may show that the planning is paying off, the Wellcome Trust's Hayden said.

British officials repeatedly said the nation was well-prepared for a flu pandemic. It had high stocks of antivirals and orders for enough vaccines to cover its population in place very early.

Hayden said comparisons with earlier flu pandemics like the one in 1918, which killed an estimated 230,000 people in Britain and up to 50 million worldwide, were skewed by the fact that there were so few effective treatments at that time.

"We didn't have antivirals then, and we didn't have antibiotics for the high frequency of bacterial complications," he said. "We have these kinds of interventions now and they are making a difference."

At the funding briefing, Peter Openshaw, director of the center for respiratory infection at Imperial College London, dismissed suggestions that scientists were enjoying the fruits of a pandemic in the form of big grants to keep them in work.

"This is not something that we are licking our lips and welcoming," he said. "But there is certainly an enormous outbreak of scientific information that has greatly enriched our understanding of flu."  (From From Reuters Health Information, November 13, 2009)

Do Yearly Influenza Vaccinations for Children Affect Immunity Against Pandemic Strains?

Whether yearly vaccinations for children against seasonal influenza might stop immunity developing against pandemic strains is debated in a personal view and reflection and reaction published online October 30 and will appear in the December print edition of The Lancet Infectious Diseases.

"Yearly vaccination is necessary because of the substantial antigenic drift of influenza viruses that necessitates the update of vaccines every year...driven by selective pressure mediated by antibodies induced by natural infection or vaccination," write Rogier Bodewes, DVM; Joost H.C.M. Kreijtz, PhD; and Guus F. Rimmelzwaan, PhD, from Erasmus Medical Center in Rotterdam, The Netherlands.

"The vaccination of healthy children aged 6–59 months against seasonal influenza has been recommended in several countries, including the USA and some European countries," the authors continue, "because the disease is an important cause of illness and admission to hospital in this age group. Although annual vaccination against seasonal influenza is beneficial for all patients at high risk, including children, vaccination of the 6–59 month age group every year against seasonal influenza might have a downside that has not been given much thought."

Previous studies, mostly in mice and other animals, have shown that infection with influenza A viruses can induce heterosubtypic immunity, which is protective immunity to influenza A viruses of other unrelated subtypes. Although heterosubtypic immunity does not offer full protection, it can limit virus replication and reduce influenza symptoms and mortality in the host.

The authors note that the ramifications of heterosubtypic immunity should be considered in humans when a new subtype of influenza A virus is introduced into the population. Pertinent examples include the novel influenza A H1N1 virus causing the present influenza pandemic and the highly pathogenic avian influenza H5N1 viruses responsible for increasing numbers of human infections, which are often fatal.

The authors suggest that an untoward effect of preventing infection with seasonal influenza viruses by vaccination might be to prevent the induction of heterosubtypic immunity to pandemic strains. Infants and other immunologically naive individuals would be at greatest risk were this to occur.

To test their theory, the authors suggest that hospitalizations and mortality rates among infants who have received yearly influenza vaccination since birth should be closely monitored and compared with those in age-matched children who were not vaccinated. The present H1N1 pandemic offers a unique opportunity to investigate heterosubtypic immunity and to determine potential harms of annual influenza vaccination.

In the meantime, the authors support the current vaccination program against H1N1 influenza and acknowledge that it will decrease morbidity and deaths in all age groups.

"Use of these pandemic influenza vaccines will override the theoretical issues associated with yearly vaccination against seasonal influenza," the study authors conclude. "The development and use of vaccines that can induce broad protective immunity might be a solution for these potential problems and we think this is a priority."

In an accompanying reflection and reaction, Terho Heikkinen, MD, and Ville Peltola, MD, from Turku University Hospital in Finland, argue that prevention of seasonal influenza in children by vaccination far outweighs the theoretical risk of preventing the induction of heterosubtypic immunity to pandemic strains. However, they agree with Dr. Bodewes and colleagues that more effective influenza vaccines that could induce broader immune responses are needed.

"The results of experimental animal studies can never be extrapolated directly to human beings, let alone form the basis of any vaccination policy," Dr. Heikkinen and Dr. Peltola write. "There is ample evidence for the great burden of influenza in young children, and this burden appears during every influenza season. By contrast, there is no clinical evidence that vaccinating children against influenza would prevent the induction of heterosubtypic immunity and thereby be disadvantageous to children in the long run."

Dr. Heikkinen and Dr. Peltola therefore advocate continuing the ongoing influenza vaccination program.

"While waiting for improved influenza vaccines, the simple question is should we let young children suffer from a severe and potentially lethal but easily preventable illness, just because there is a theoretical possibility that withholding vaccination might result in a slightly less severe illness sometime in the future?" they conclude. "We believe that the answer to this question is a simple one."

 (Laurie Barclay, MD, In Medscape Pediatrics, Original citation: Lancet Infect Dis. Published online October 30, 2009.)