Video Digest: H1N1 Vaccine Demand Slowing in the USA – Vignettes from Coast to Coast (Jan/Feb)

 

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Of Mice and Men: H1N1 Immunity in the USA; Effects of H1N1 Vaccines Past and Present

A recent study published in PLoS Pathogens found that vaccines developed from “classical H1N1 viruses (Sw/30 or NJ/76), 1918 virus-like particles, and a human H1N1 virus isolated in 1943 (Wei/43) protected against death from 2009 pandemic H1N1…” when tested in vivo in mice.

Another study finding was that the “H1N1 virus underwent little antigenic drift in pigs, as shown by the ability of the NJ/76 strain to induce protective immunity in mice against the 2009 H1N1 virus.” The fact that H1N1 influenza virus proteins are antigenically frozen in pigs, make them natural resorvoirs for future pandemics.

This research suggests that the much-maligned 1976 swine flu vaccination effort, which had an uptake of around 40 million Americans, may have conferred some protective effect on the population, in particular for persons aged 35 and up. This is one of the conclusions drawn from a review by Professor Ranaciello in Virology.

Quantifying the extent of this protective effect (in terms of pre-existing immunity) gets a little complicated. An exchange with Professor York, who pens Mystery Rays from Outer Space, (MRFOS) suggests some protective effect from the 1976 vaccines exists, but that it should not be overstated.

A study published last year in the New England Journal of Medicine (NEJM)assessed levels of pre-existing immunity to 2009 H1N1 to be 4% in children, 6% in young adults and 34% in older adults (those born before 1950). Assuming the 1976 vaccine was proportionally distributed by age, rough calculations suggest 7% (13 million persons) of the present day young adult cohort (aged 19-64) could have pre-existing immunity from the 1976 vaccine, close to the 6% estimate in NEJM.

However, the hard part is reconciling similar patterns of immunity to H1N1 observed elsewhere in the world among populations who had no access to the 1976 vaccine.

MRFOS estimates that current immunity to H1N1 in the US is in the range of 49-52%. These projections take into account estimated H1N1 vaccine uptake (80 million) and H1N1 infection rates (55 million) and adjusts for potential overlap between both. This level of immunity augurs well against a winter wave of H1N1.

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CDC: Emerging Infectious Disease Volume 15, Number 11–November 2009, Letter, Preexisting Immunity to Pandemic (H1N1) 2009
MRFOS: How many Americans are immune to H1N1?
NEJM: Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus
PLoS Pathogens: Protection of Mice against Lethal Challenge with 2009 H1N1 Influenza A Virus by 1918-Like and Classical Swine H1N1 Based Vaccines
Virology: Protection against 2009 influenza H1N1 by immunization with 1918-like and classical swine viruses

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A Tale of Two Essays on Vaccine-Preventable Diseases; Risk Perception, Misinformation and other Barriers to H1N1 Vaccination Among Adults and Children

Vaccine-preventable disease outbreaks are on the rise, and are taking an increasing toll in lives and money. Moreover, the recent experience with the 2009 novel H1N1 flu outbreak served as a stark reminder that “there is no strong mechanism in place for vaccinating adults in the United States.” This is the latest brief from Trust for America’s Health, “Adult Immunization: Shots to Save Lives.”

“Millions of American adults go without routine and recommended vaccinations each year, which leads to an estimated 40,000 to 50,000 preventable deaths, thousands of preventable illnesses, and $10 billion in preventable health care costs each year” according to the report.

Structural barriers include fragmented insurance coverage for preventative care and vaccinations. The costs of some vaccines can be a disincentive, particularly in the case of HPV. Access to adult vaccines is limited by the lack of institutional or other established mechanisms to schedule and track adult vaccinations. The uninsured lack access altogether. A limited market along with long lead times and expense for R&D and regulatory approval discourages investment in adult vaccines.

Misunderstanding and misinformation, especially as impacts public perceptions of H1N1 vaccine safety, is a pervasive problem. And it is not just confined to patients, but also extends to some clinicians and heathcare workers who dissuade patients from getting vaccines. A recent national poll conducted from University of Michigan, found that parents were more concerned about the safety of H1N1 vaccines (66%) than were worried about their children getting infected with H1N1 (55%).

Diminishing flu activity and a relatively quiet flu season are also adding to (mis)perceptions that the danger of H1N1 has receded.

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TFAH: Issue Brief, Adult Immunization: Shots to Save Lives (PDF)
UMICH C.S. Mott Childrens Hospital: National Poll on Children’s Health; Is the Vaccine Worse than the Disease? Parent Concerns Hinder National H1N1 Immunization Efforts.

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H1N1 Virus Mutation and Oseltamivir (Tamiflu) Resistance; Duke University Medical Center Patient Cluster Raises Questions

In its Weekly Epidemiological Report (WER), the World Health Organization (WHO) confirmed a worldwide count of 225 cases of H1N1 that were resistant to oseltamivir (Tamiflu). The “225 cases came from 20 countries and included 65 cases in the Americas, 77 in Europe, 1 in Africa, and 82 in the Western Pacific region. All cases had the H275Y mutation that confers resistance to oseltamivir
… but not to the other antiviral medication in general use, zanamivir (Relenza).

In 142 cases for which data was available, the plurality (56 cases or 40%) involved severely immunocompromised patients, 38% were linked to flu treatment, 11% were associated with chemoprophylaxis (preventative) treatment.

WHO further looked at two clusters of oseltamivir-resistant H1N1 treated at Duke University Medical Center (four cases), and University Hospital in Cardiff, Wales (eight cases). The report underscored “that severely immunocompromised patients are at a higher risk of developing oseltamivirresistant virus during treatment.”

WHO also examined a cluster of previously unreported oseltamivir-resistant H1N1 cases in Vietnam among seven healthy adults who were traveling together by train.

Editor’s Comment: Three of the four cases were fatal at Duke University Med Center and WHO concluded… “the role of H1N1 infection in contributing to the deaths is uncertain.” The Recombinomics blog finds this curious, since the patients were isolated “in the same ward, infected with the same virus, at the same time.”

Somewhat more disquieting was the revelation… “In 3 of the 4 cases, the H275Y mutation was identified before oseltamivir was administered.” This raises the question of why these patients were treated with oseltamivir? Press releases from the medical center have not shed any light on the matter, but would only confirm the underlying conditions in the patients, and that an assessment was in progress.

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CIDRAP: Global Tamiflu-resistant H1N1 cases reach 225
Duke UMC: CDC Confirms Four New Cases of Oseltamivir (Tamiflu)-Resistant H1N1
Duke UMC: Tests Show No Further Cases of Oseltamivir-Resistant H1N1 at Duke University Hospital
Recombinomics: Recombinomics Commentary 15:58 February 09, 2010
WHO: Weekly epidemiological record No. 6, 2010, 85, 37–48, Update on oseltamivirresistant pandemic A (H1N1) 2009 influenza virus: January 2010 (PDF)

Diminshed H1N1 Activity in the USA: Forgotten but not Gone

According to the latest influenza surveillance from CDC, no states have reported widespread flu activity for four consecutive weeks. However, pneumonia and influenza (P&I) mortality as a percentage of recorded deaths was 8.1% and is hovering above epidemic threshold (7.8%). One expert, speaking on background said the H1N1 epidemic has “one foot in the grave.”

Supplies of H1N1 vaccine are ample with 155 million doses shipped around the country up to date. However, H1N1 vaccine uptake has been estimated at over 70 million doses, approximately 23.4% of all Americans. By contrast, 114 million doses of seasonal flu vaccines were produced; CDC says nearly all were used.

Public attitudes suggest no sense of urgency to get the vaccine. According to the latest surveys from the Harvard School of Public Health, “almost half of Americans believe the H1N1 flu outbreak is over (44%).” Few (18%) think it is “very likely” there will be another widespread outbreak of H1N1 in the U.S. in the next 12 months. Some 61% of adults have not received the H1N1 vaccine and do not intend to get it. This is up from 55% at the close of 2009.

More than half of parents either got the vaccine for their children (40%) or intend to get it before the end of February 2010 (13%).” This more or less tracks with CDC figures, which estimates H1N1 vaccine uptake for children under 18 years at 37%. CDC has also warned that only 37% of children under age 10 have received the recommended two shots.

Editor’s Comment: These attitudes suggest public health communicators and planners have an uphill climb at best to increase H1N1 vaccine demand. Question: Should flu experts, either within or outside the government, speak on background? Though H1N1 is localized, it unfortunately continues to send some to their graves.

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AP: Is the US swine flu epidemic over?
CIDRAP: US H1N1 vaccine uptake estimated at 75 million
Harvard SPH: Press Releases, 2010 Releases, Nearly Half of Americans Believe H1N1 Outbreak is Over, Poll Finds
MedPage: H1N1 Vaccination Still a Good Idea, CDC Says
MSNBC: 60 million in U.S. vaccinated against swine flu
Reuters: Swine flu still out there, officials caution

Video Digest: H1N1 in the USA – Almost Quiet Winter Flu Season – Spike in pH1N1 Hospitalizations in Memphis

Op-Ed: Fake H1N1 Pandemic Claims Assailed – Anti-Vaccine Communications Challenges Remain

Credibility and transparency are essential to building trust in public health communications. During unfolding public health crises, the problem of what and when to warn is an enduring policy dilemma that goes to the heart of public trust.

Last week the World Health Organization (WHO) persuasively refuted spurious claims from the Council of Europe that H1N1 was a “fake pandemic” engineered for pharmaceutical companies profit by calmly presenting the timeline of pandemic events. H1N1 turned out to be a pandemic of moderate pathogenicity. However, at the outset clinical indicators revealed a spreading global hazard in the form of a rare but progressively fatal viral pneumonia that was straining intensive care units.

A more complex communications challenge comes from the influential grassroots antivaccine movement, which claims a link between vaccines and asthma, allergies or autism. Concerned parents in small but growing numbers are opting not to vaccinate their children. These decisions weaken “herd immunity” and have led to the reemergence of vaccine-preventable diseases, e.g. measles outbreak in NYC. In some parts of the US, vaccination rates reportedly have dropped so low that occurrences of some children’s diseases are approaching pre-vaccine levels.

Two-way dialogue is needed on issues of vaccine safety and vaccine additives. A one-sided public communications campaign probably will not make full headway. Public distrust of pharmaceutical companies will not make the task any easier.

An example anti-vaccine movement video, these kinds of presentations are crowding out other H1N1 multimedia in Internet queries.

Don't get the flu.  Don't spread the flu.  Get Vaccinated. www.cdc.gov/flu

ABC News: H1N1 Experts Assail ‘Fake’ Pandemic Claim
Discover: Vaccine Phobia Becomes a Public Health Threat
Harris: Large Numbers of People Do Not Trust the Institutions They Identify as Most Responsible for Drug Safety
Harvard: Nieman Foundation Guide to Covering Pandemic Flu – Outbreak Communication: How the Sources See the Story
NEJM: Vaccine Refusal, Mandatory Immunization, and the Risks of Vaccine-Preventable Diseases
UPI: WHO: H1N1 is a not a ‘fake’ pandemic
USA Today: Missed vaccines weaken ‘herd immunity’ in children
WHO: Statement by Dr Keiji Fukuda on behalf of WHO at the Council of Europe hearing on pandemic (H1N1) 2009
WHO: Statement of the World Health Organization on allegations of conflict of interest and ‘fake’ pandemic
WIRED: An Epidemic of Fear: How Panicked Parents Skipping Shots Endangers Us All

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World Notes: Avian Influenza (H5N1) in Egypt – Situation Critical

Cases of highly pathogenic avian influenza (H5N1) are surging in Egypt. Last year Egypt recorded 39 human cases of H5N1, a vast jump over eight cases in 2008. Four new cases were reported this month, bringing the country’s case count to 94. Of these, 27 have been fatal. These numbers position Egypt just behind Indonesia and Vietnam as third highest in the world for reported human cases and fatalities.

A statistical analysis recently published in Eurosurveillance described the situation
in Egypt as “critical.” The study looked at 85 cases reported to the World Health Organization over a timeframe spanning March 2006 to August 2009.

KEY findings and concerns were:

According to CIDRAP the rise in H5N1 human cases in Egypt mirrors a spike of poultry infections in the country.  However, agricultural practices and public perceptions of risk are contributing to the problem. The government does not compensate for destroyed poultry and farmers perceive little risk from handling it.

Last April, Egyptian authorities ordered the mass culling of 400K pigs in an effort
to control swine flu, which is at elevated levels in the country. With H5N1 and H1N1 in co-circulation, this raises the potential for coinfections and virus reassortment.

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CIDRAP: Egypt reports four new H5N1 infections
Eurosurveillance: Volume 15, Issue 4, 28 January 2010, Surveillance and outbreak reports, Avian influenza A(H5N1) in humans: lessons from Egypt
ProMed: PRO/AH/EDR> Avian influenza, human (07): Egypt, case analysis
AVIAN INFLUENZA, HUMAN (07): EGYPT, CASE ANALYSIS

Reuters: Egypt starts pig slaughter, some farmers resist
WHO: Avian influenza – situation in Egypt – update 27

Op-Ed: Internet Mashups and H1N1 Experience – Google Analytics Potential to Augment Traditional Influenza Surveillance

In the comparatively short lifespans of Influenza Monitor and counterpart blog Market@Flu-Monitor, one of the more striking outcomes as revealed through Google Analytics has been relatively high visitation rankings from countries as diverse as Ukraine, Egypt and India. All of these countries have experienced public health pressures coping with either H1N1 or H5N1.

Google researchers have long-noted a close connection between flu-trends and search activity on flu topics. In the experiences of these blogs, similar correlations by city and province have appeared with respect to visitation patterns to both blogs as revealed through Google Analytics data across flu-affected countries. Google Analytics is described as an “enterprise-class web analytics solution” that provides insights into “website traffic and marketing effectiveness.”

Some caution has to be exercised in interpreting flu activity and trends in Google Analytics. Geographic patterns of visits at a minimum show where populations, internet infrastructures, and lines of communications are clustered. Both blogs are running modest global ad campaigns that do not specifically target any country nor region; ad dissemination is entirely driven by provider seach/content algorithms.

However, the striking visitation patterns observed from flu-impacted countries do not appear random and could be indicative of intrinsic demand for H1N1 information in flu-infected countries, and by proxy of the spread of H1N1 within such countries.

Because of privacy concerns in connection with this kind of data, expressed among several countries, we choose not to disclose our Google Analytics visitation maps.

Nonetheless, the limited experiences here suggests the geospatial capabilities resident in Google Analytics to an extent reflects demand for H1N1 information. This carries great potential to augment traditional influenza surveillance systems. Any major public health information reservoir on pandemic influenza ought to leverage its visitation statistics for geospatial use in response planning.

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Google.org: Google Flu Trends – How does this work ?
The Official Google Blog: Google Flu Trends Expands to 16 additional countries

Medical Research: German Scientists Identify Human Host Factors Crucial for H1N1/H5N1 Influenza Virus Replication

Despite substantial development efforts that go into antiviral drugs and vaccines for influenza, viruses are able to develop resistance due to their high mutation rates.

In a recent issue of Nature, a team of German moleclar biologists make the case that by targeting host rather than viral factors, it may be possible to develop flu treatments against a wide array of influenza viruses, while minimizing the likelihood of drug resistant mutations.

Employing a technique called RNA Interference (RNAi) screening, the scientists were able to identify 287 human genes affecting flu virus replication.  This included several genes previously implicated in flu replication such as NXF1 and XPO1.

RNA interference is a process in which translation of some of a cell’s messenger RNA (mRNA) sequences is prevented or interrupted. RNA interference is believed to protect the cell against viruses and other threats.” “Two types of small RNA molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference. These small RNAs can bind to specific other RNAs and either increase or decrease their activity.”

When siRNAs were targeted at the 287 genes in flu-infected lung tissue cells, the scientists found 119 of the genes inhibited non-pandemic H1N1, and 121 of the genes inhibited pandemic H1N1 (a five times or greater decrease). There was a 60% overlap between both gene groups. Another subset of both groups inhibited replication of the highly lethal H5N1 virus “by at least two orders of magnitude.”

Editor’s Note: These findings, along with earlier research by American researchers who employed similar molecular techniques, are providing a greater insights into the body’s natural defenses against the flu.

See also: H1N1 Research: Scientists discover natural flu-fighting proteins.

Life Extension - Health And Medical Findings

Answers.com: RNA Interference
GWDN: German Team Finds Host Factors Needed For Flu Virus Replication
Nature: Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication

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