Scientists find new explanation for flu virus “antigenic drift” mutations; findings highlight the benefits of flu vaccination

H1N1 has been termed a “disease of the young” but all the reasons for this are not clear. In the 30 October issue of Science, researchers from the National Institute of Allergies and Infectious Diseases of the National Institute of Health suggest an answer may be found through closer examination of antigenic drift.

Antigenic drift is the means by which viruses evade infection-fighting antibodies through mutation, specifically by changing the shape of their major surface proteins, which are a form of antigens, or antibody generators. Antigenic drift can lead to a loss of immunity and is the reason flu vaccines are updated annually.

Influenza type A viruses are divided into types based on differences in two viral surface proteins hemagglutinin (H) and neuraminidase (N). There are 16 known H subtypes and nine known N subtypes. Hence, the nomenclature “H1N1” for the swine flu currently in circulation.

Using a strain of flu strain from 1934, NIAID scientitsts sequenced the gene from the influenza virus protein, hemagglutinin (H), after it mutated from nine successive rounds of exposure to unvaccinated and vaccinated mice, which developed antibodies to the strains.

Over time, the evolved virus became more “sticky” or tightly bound to infected cells it used enter the blood, lungs, nose or throat of a new host. When the mutated virus was introduced into unvaccinated, “immunologically naive” mice it reverted into a less-sticky form, a critical stage in enabling infection to spread to other cells.

The findings underscore the importance of vaccines, especially for young persons, who have been less exposed to multiple virus strains. Vaccination is also key to slowing the rate of antigenic drift in influenza viruses.

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MedicineNet: Flu, Influenza, H1N1
NIH: NIAID Scientists Propose New Explanation for Flu Virus Antigenic Drift
Science Magazine: Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift, 30 October 2009, Vol 326, no 5953

Researchers find Tamiflu-resistant H1N1 virus mutation

In a widely reported story this week, research presented by North Carolina
Division of Public Health at the annual conference of the Infectious Diseases
Society of America
, documented evidence of the passing of Tamiflu-resistant
H1N1 virus between two people

The North Carolina Division of Public Health had earlier reported warnings to
clinicians on this H1N1 mutation in a health alert issued dated 21 August.

Thus far, strains of H1N1 have responded to two antiviral medications oseltamivir (Tamiflu) and zanamivir (Relenza), both are widely used for treatment of H1N1.

In June and July of 2009, 65 campers and staff at a summer camp in North
Carolina were treated with Tamiflu after becoming ill with H1N1, while another
600 campers and staff took the antiviral to prevent the illness. Two females, who shared a cabin, developed mild symptoms after starting on Tamiflu, and were later found to have a H1N1 virus with two mutations that were resistant to the antiviral. Both fully recovered.

HealthDay news reports the principal recommendation from the study is that H1N1 vaccine, not antivirals should be used for prevention. CDC recommends priority use of antiviral medications for people hospitalized with influenza and those at increased risk of influenza-related complications.

Last week, in response to CDC requests, FDA authorized emergency use of the
investigational antiviral drug peramivir
for patients hospitalized with confirmed or suspected cases of H1N1. Peramivir is administered intraveneously and would provided to patients who are not reponsive to other therapies or in circumstances where IV treatments are more appropriate.

CDC: Updated Interim Recommendations for the Use of Antiviral Medications
in the Treatment and Prevention of Influenza for the 2009-2010 Season

FDA: FDA Authorizes Emergency Use of Intravenous Antiviral Peramivir for 2009 H1N1 Influenza for Certain Patients, Settings
HealthDay: Tamiflu-Resistant Swine Flu Passed Person-to-Person in U.S.
Infectious Diseases Society of America: 47th Annual Conference
NC Dept of Public Health: Oseltamivir-Resistant Novel H1N1 virus: Alert to North Carolina Clinicians, 8/21/09 – N.C. DPH

Virulent form of H1N1 isolated from swine herds

A recent abstract appearing in PubMed highights a recent study on a virulent form of H1N1 virus (KS07) isolated from swine herds in the midwest. The virus is similar to an H1N1 virus that infected humans and pigs in Ohio in 2007. Pigs are known reservoirs of H1N1 viruses, and the study advocates for continued surveillance of influenza in swine. The study will be published in the journal Virus Genes.

Identification and characterization of a highly virulent triple reassortant H1N1 swine influenza virus in the United States. Virus Genes:2009 October 28.

Ma W, Vincent AL, Lager KM, Janke BH, Henry SC, Rowland RR, Hesse RA, Richt JA.
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA, 50010, USA.

A highly virulent H1N1 influenza A virus, A/Swine/Kansas/77778/2007 (KS07), which caused approximately 10% mortality in finishing pigs, was isolated from herds in the Midwestern United States. Molecular and phylogenic analysis revealed this swine isolate was a triple reassortant virus, similar to an H1N1 virus that infected humans and pigs at an Ohio county fair in August 2007. A pig challenge model was developed to evaluate the pathogenicity and transmission capacity of the KS07 virus. The results confirmed that the KS07 virus is highly virulent in pigs and easily transmitted to sentinel animals. The KS07 virus failed to cross-react with a panel of H1-specific swine sera. Interestingly, the KS07 virus shed for a prolonged period up to 7 days in infected pigs, indicating that this virus can spread efficiently between animals. The highly virulent H1N1 swine influenza virus is further evidence of reassortment among avian, human and swine influenza viruses and justifies the need for continued surveillance of influenza viruses in swine.

PMID: 19862613 [PubMed – as supplied by publisher]

PubMed is a free resource that is developed and maintained by the National Center for Biotechnology Information (NCBI), at the U.S. National Library of Medicine (NLM), located at the National Institutes of Health (NIH).

Life Extension - Health And Medical Findings

PubMed: Identification and characterization of a highly virulent triple reassortant H1N1 swine influenza virus in the United States.
Virology Journal: Interspecies and intraspecies transmission of triple reassortant H3N2 influenza A viruses

Potential “H1N1 effect” in cyberspace ?

dreamstime_7968971-cyberspace abstract
A recent Government Accountability Office (GAO) report raises concerns that increased Internet use during a “severe” pandemic from students affected by school closures, telecommuters working from home and others could create serious network congestion in metropolitan and residential neighborhoods. The chief concern is apparently with data aggregation systems that are situated upstream from home users. These aggregation systems, which route network traffic to regional Internet service providers who in turn relay it to the Internet backbone, could experience severe congestion, especially in the event of increased bandwith intensive activities, such as streaming video, online gaming, and peer-to-peer (file sharing) . The resultant network congestion could interrupt the delivery of public informaton and possibly interfere with the efficient functioning of financial markets. Government and private-sector options to address a network congestion problems carry a host of legal complexities. However, any solution would require government, private-sector and public cooperation.

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Computer World: Can the Internet handle traffic in an H1N1 pandemic?
GAO: INFLUENZA PANDEMIC Key Securities Market Participants Are Making Progress, but Agencies Could Do More to Address Potential Internet Congestion and Encourage Readiness

H1N1 vaccine delays and shortages in the news

News accounts continue to circulate of long lines of anxious Americans waiting for H1N1 vaccinations. A Business Roundtable survey last month also cited the availability of the H1N1 vaccine as the top business concern.

H1N1 influenza vaccines are being manufactured by five multi-national companies: Paris-based Sanofi Aventis SA (NYSE:SNY); London-based concerns Glaxo Smith Kline Plc (NYSE:GSK) and AstraZeneca Plc (NYSE:AZN); Melbourne, Australia-based CSL Ltd (CSL.AX); and Basel, Switzerland-based Novartis AG (NYSE:NVS).

The U.S. government contracted for 250 million doses and had shipped 11 million doses as of 23 Oct, far below earlier government projections of 120 million doses for the month.

H1N1 vaccines are manufactured using the same processes as seasonal flu, by harvesting virus strains grown within fertilized eggs. Novartis Vaccines and Sanofi Pastuer reported the initial H1N1 seed strains were not growing well and this had resulted in lower vaccine yields. Better seed strains were not delivered until August.

MedImmune, the vaccine unit for AstraZeneca which manufactures the live-virus nasal spray vaccine, did not experience yield problems but had encountered logistical difficulties in packaging the vaccine. Glaxo Smith Kline had not yet received FDA approval.

AP: New powers given as swine flu declared national emergency
CNBC: H1N1 Vaccine Is Top Flu Concern For U.S. Businesses
Flu.Gov: 2009 H1N1 Influenza Vaccine Supply Status
NY Times: A Nation Battling Flu, and Short Vaccine Supplies
USA Today: Flu vaccine rush puts focus on calls for faster delivery

Video Digest: 60 Minutes report on H1N1, Youth still primary target, President declares national H1N1 emergency, Mom charged with stealing H1N1 vaccine

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H1N1 swine flu “A disease of the young”

Percentage of Hospitilizations by Age Group

Percentage of Hospitilizations by Age Group

According to CDC statistics released this week, forty-six states are reporting widespread influenza activity. Developing data trends also underscore how H1N1 impacts the yoing.

Over the period Sep 1 to Oct 10, reports from 27 states revealed that 52 percent of persons hospitalized with H1N1 flu were under the age of 25. Only 7 percent of hospitalizations were among people aged 65 and older. According to CDC, during seasonal flu, around 60 percent of hospitalizations occur in people 65 and over.

Reporting from 28 states over the same period, indicated nearly 24 percent of deaths due to H1N1 occurred in young people under the age of 25. Just 12 percent of deaths were among people over age 65. In a normal year, 90 percent of those who die from influenza are over 65.

Dr Anne Schuchat, who is the director of CDC’s National Center for Immunization and Respiratory Diseases, cautions the reporting is preliminary and may understate the extent of H1N1. However, the emerging picture is that H1N1 is, as she termed, “a disease of the young.”

Percentage of Deaths by Age Group

Percentage of Deaths by Age Group

Vitamin World

CDC: Q&A 2009 H1N1 Flu (“Swine Flu”) and You, 20 Oct 2009
Reuters: Swine flu sends mostly under-25s to hospital: CDC
LA Times: CDC: H1N1 is Disease of the Young

President declares H1N1 flu a national emergency

The president declared H1N1 a national flu emergency. This action will allow the Secretary of Health and Human Services to expedite waivers to hospitals and medical facilities, in turn providing them greater flexibility to implement emergency operations plans if confonted with surges in H1N1 patient loads.

Washington Post: President Obama declares H1N1 flu a national emergency

Intensive care units under strain in New Mexico

22 Oct 209, Albuqerque, New Mexico. KRQE newscast reported that Intensive Care Unit admissions to area hospitals are 40 percent higher than normal for this time of year. The report “H1N1 Challenges Ahead” issued earlier in the month, forecasted that New Mexico would be among 12 states, whose hospitals would be strained to maximum capacity in the event of an H1N1 patient surge.

KRQE: H1N1 strains intensive-care units

The H1N1 patient surge: Readiness of U.S. health system in focus

dreamstime_10977637-Hospital Bed Gray

According to CDC statistics for the week ending October 10, forty-one states are now reporting widespread influenza activity, and influenza-related deaths are above epidemic thresholds. This raises the question. Is the U.S. public health infrastructure prepared for a surge of critically-ill H1N1 patients ? The answer depends on whom is asked.

A poll conducted by the American College of Emergency Physicians found that nearly 90 percent of more than 1,000 emergency physicians expressed concerns about their emergency department’s ability to care for additional patients.

The non-profit, Trust for America’s Health, in a report titled “H1N1 Challenges Ahead” estimated that 15 states could run out of hospital beds assuming that 35% of Americans are sick with H1N1. An additional 12 states would reach 75-99% of their hospital bed capacity. The study employed the CDC’s FluSurge model based on the 1968 Hong Kong flu scenario, which is regarded as a mild outbreak.

The report cited that budget cuts and layoffs “are hampering preparedness efforts.” “Local health departments eliminated 8,000 staff positions in the first half of 2009” on top 7,000 public health jobs lost in 2008. Other challenges arise from the fact that “47 million Americans are without health coverage” and that nearly half of private sector workers lack paid sick leave. The report recommended that vaccination campaigns prepare for a potential “third wave” of H1N1 outbreaks.

On the plus side, the report notes that Congress “appropriated $1.9 billion in emergency supplemental funding, and $5.8 billion in contingency funding” to shore up the nation’s public health infrastructure. The Obama administration has drawn $1.4 billion in funds to assist states with H1N1 response and vaccination efforts.

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MedPage: H1N1 Flu May Cause Hospital Bed Shortage
Reuters: H1N1 vaccinations pose U.S. public health challenge
Trust for America’s Health, “H1N1 Challenges Ahead.”
ACEP: H1N1 Cases On The Rise Nationwide – Emergency Physicians Advise Public When To Seek Emergency Care