Severe H1N1 and Lung Damage: A Pefect (Cytokine) Storm ?

Necrotizing Bronchiolitis

Necrotizing Bronchiolitis

Medical evidence continues to accumulate on lung damage in severe cases of H1N1 influenza.

Researchers at Sao Paul University Medical School found three distinct patterns of lung damage revealed from autopsies conducted on 21 patients who died from H1N1. Their findings, published in the American Journal of Respiratory and Critical Care Medicine, indicated that acute lung injury and acute respiratory distress syndrome were prevailing patterns. In some cases, acute lung injury was associated with necrotizing bronchiolitis (premature death of lung cell tissue), in other cases, a hemorrhagic (excessive bleeding) pattern was found.

Some patients showed traces of a ‘cytokine storm’, where their immune systems had over-reacted, causing an inflammatory response that spilled over and damaged lung tissue, which led to fatal respiratory failure.”

Similar findings on an H1N1 connection to a “cytokine storm” (or hypercytokinemia) were published in the journal Critical Care. Canadian and Spanish researchers found high levels of a molecule called interleukin 17 in the blood of severe H1N1 patients. Interlukin 17 is important in the regulation of white blood cells which fight infection and disease. In certain instances, the molecule can go awry leading to inflammation and autoimmune diseases.

Earlier research employing computed tomography (CT) scans also highlighted the connection between lung damage and H1N1. Findings published in the American Journal of Roentgenology revealed the presence of ground glass opacities (associated with lung inflammation) and pulmonary emboli (sudden blockage in lung artery) in the lungs of severe H1N1 cases.

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AJRCCM: Lung Pathology in Fatal Novel Human Influenza A (H1N1) Infection
Critical Care: Th1 and Th17 Hypercytokinemia as Early Host Response Signature in Severe Pandemic Influenza
Medical News Today: H1N1 Swine Flu Deaths Reveal New Pattern Of The Disease, Brazilian Study
MedPage: Autopsies Reveal Three Patterns of H1N1 Death
Reuters: H1N1 flu causes unusual damage to lungs: studies
Science Daily: First Immunological Clue to Why Some H1N1 Patients Get Very Ill or Die
UPI: New Pattern in H1N1 Deaths
Wikipedia: Cytokine Storm

H1N1 Research: Scientists discover natural flu-fighting proteins

CHICAGO, Dec. 18, 2009 (Reuters) — U.S. researchers have discovered antiviral proteins in cells that naturally fight off influenza infections, a finding that may lead to better ways to make vaccines and protect people against the flu.

Comment: The scientists published their findings in the journal Cell in a paper titled The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus.

Using a new research technique called RNA interference (which involves systematically switching off individual genes and exposing cells to the H1N1 Influenza A flu virus), the researchers discovered a family of flu-fighting proteins called interferon-indicible transmembrane (IFITM) proteins that “restrict an early step in influenza A viral replication” and “confer basal (basic/fundamental) resistance to the influenza A virus.”

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Reuters: Scientists discover natural flu-fighting proteins
Cell: “The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus.” – PDF

World Notes: Avian Influenza – Situation in Cambodia

Update from the World Health Organization

18 December 2009 — The Ministry of Health of Cambodia has announced a new confirmed case of human infection with the H5N1 avian influenza virus.

  • The 57-year-old male, from Ponhea Kreak District, Kampong Cham Province, developed symptoms on 11 December. The case was admitted to Kampong Cham Provincial Hospital on 16 December, where he received treatment. He is in a stable condition.
  • Of the 9 cases confirmed to date in Cambodia, 7 have been fatal. This is the first diagnosed case in Cambodia during 2009.

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 WHO: Avian influenza – situation in Cambodia

Public Health Service Preparedness: “Ready or Not ?”

A report by the Trust for America’s Health and the Robert Wood Johnson Foundation revealed the H1N1 flu outbreak has exposed serious underlying gaps in states’ ability to respond to public health emergencies.  The report titled, Ready or Not? Protecting the Public’s Health from Diseases, Disasters, and Bioterrorism, concluded had the outbreak had been more severe, the “nation’s public health safety system could have been stretched beyond the breaking point.”

Despite recent improvements in pandemic preparedness, key concerns were:

Editor’s Comment:  The report makes a compelling case for more investment in public health infrastructure and a comprehensive array of reforms for emergency preparedness.  All of which should happen.  The report provides the contours of a 24/7 public health emergency response capability. What isnt clear is the eventual standard for the public health service system, i.e. gold, silver or bronze, in terms of capacity for prevention, planning, preparedness, detection, surveillance, mitigation, response and recovery. 

Some news accounts have described the public health service system as “fragile”; that characterization may be somewhat overdrawn. Given the circumstances, the public health system responded reasonably well to the second H1N1 wave. However, the report correctly observes that the system was not severely tested by a relatively moderate pandemic.


TFAH: Ready or Not ?,  Executive Summary
UPI Health News: H1N1 Exposed Fragile Public Health System

World Notes: Avian Influenza – Situation in Vietnam – Update 7

According to the World Health Organization, Vietnam’s Ministry of Health confirmed a new case of human infection with the H5N1 avian influenza virus. The case involved a man from Dien Bien Phu city who died on 28 November, 10 days after developing flu symptoms. The source of the exposure is under investigation. The man’s family reportedly kept chickens and wild geese.

Of 112 cases of H5N1 confirmed to date in Vietnam, 57 have been fatal.

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WHO: Avian Influenza – situation in Vietnam – update 7

Press Release: PBS Newshour website features H1N1 experts and resource guide for “Anatomy of a Pandemic”

Press Release: December 8, 2009                       Contact: Kate Kelly, WETA
Airing on PBS stations nationwide                         703.998.2072/
Monday, December 14, 2009, at 9 p.m. ET                                
(Check local listings.)~

— Interviews, Latest News, Local and National Resources Featured in Companion Website to PBS Flu Special that Airs Nationwide on December 14 —

WASHINGTON, D.C. — “PBS NewsHour,” the premiere news and public affairs website at, will launch today, Tuesday, December 8, the companion website to “Anatomy of a Pandemic,” a television special and on-going digital media initiative about a pandemic’s impact on modern society, in response to the 2009 H1N1 influenza virus pandemic.  The “Anatomy of a Pandemic” website ( will feature a forum after the program’s premiere to ask questions of influenza experts from the Centers for Disease Control (CDC) and the Center for Infectious Disease Research and Policy.  The site will also provide the latest public media news on H1N1, as well as national and local resources for viewers to learn more about H1N1, get information from their local health departments and find a vaccine site.  Segments of the documentary will be available online, along with web-exclusive extended interviews and lesson plans.  “Anatomy of a Pandemic” premieres Monday, December 14, 2009 at 9 p.m. ET on PBS stations nationwide.  (Check local listings.)

The public may send in questions to the website for an online forum that will take place on Tuesday, December 15 at 4 p.m. ET with Dr. Anne Schuchat, the Director of the CDC National Center for Immunization and Respiratory Diseases (NCIRD), and Dr. Michael Osterholm, world-renown influenza expert and Director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota.  The guests will respond to viewers’ questions and concerns about H1N1 and pandemics.  Betty Ann Bowser, health correspondent for “PBS NewsHour,” will moderate.  (Subject to change).  For more information, or to submit questions, visit

PBS: Anatomy of a Pandemic portal
PBS: Anatomy of a Pandemic webcast

World Notes: H1N1 influenza activity continues to decline in U.S. and Western Europe; virus remains active and intense in Eastern Europe and Central Asia zones

Recent CDC data reveal sharp declines in H1N1 activity in the U.S., however the virus remains geographically widespread. Deaths from influenza and pnuemonia, although still above epidemic levels, appear on a firm downward trend.

According to the World Health Organization (WHO), H1N1 patterns across the rest of the world are uneven. While H1N1 activity is subsiding across Western Europe, H1N1 virus transmission is increasing across parts of Central and Eastern Europe. Within the Russian Federation, influenza activity has been described in some areas as “active and intense.”

Influenza-related disease is increasing in Central Asia, and parts of South Asia (specifically northwest India, Nepal, and Sri Lanka). Respiratory diseases are also increasing in Southern China and Japan. In the tropics, overall influenza activity has been declining except for focal zones in Jamaica, Venezuela, and Ecuador.

WHO expects to hold consultations with its Strategic Advisory Group of Experts (SAGE) on adjustments to H1N1 pandemic alert levels in January. WHO assesses the overall global impact of the H1N1 pandemic has been moderate.

Pandemic (H1N1) 2009 – update 77
WHO use of advisory bodies in responding to the influenza pandemic
WHO Virtual Press Conference (03 Dec) – PDF

Situation Update: H1N1 activity declining in U.S.; Hospitalizations and deaths continue above epidemic thresholds

The good news.  In the week ending Nov. 21, CDC reports that 32 states were reporting widespread influenza activity, down from 48 states a month ago.  Influenza-like illnesses accounted for 4.3 % of outpatient visits, down from nearly twice that proportion in October, but still well above the seasonal norm of 2.3%.

CDC - Percentage of Influenza Mortality for 122 Cities - Week Ending Nov 21

The bad news.  H1N1 continues to exert a toll on young persons.  There were 35 pediatric deaths (persons aged 17 and younger) for the week ending 21 Nov. and 27 of these deaths were confirmed due to H1N1. This represents the largest one-week increase since the advent of H1N1 in April.

In the wider picture, mortality from pnuemonia and influenza, which was 8.2% of all deaths reported to CDC, has been above epidemic thresholds for eight consecutive weeks. The ongoing epidemic also appears a factor behind a “worrisome spike” seen in dangerous pneumonias in patients under age 65, in particular, among those at greater risk for pnuemonia due to chronic health conditions.

The forecast.  The consensus among public health experts is that another wave of H1N1 activity will occur.  However, opinions are mixed as to the timing of that wave. With the onset of winter, the best conditions for flu transmission, an increase in seasonal influenza is expected.  Hence, the dropoff in H1N1 presents a paradox.

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Baltimore Sun: Doctors wary of swine flu’s apparent dip
CP: Is there a 3rd wave of H1N1 in the cards for this winter? Who knows?
HealthDay: U.S. Swine Flu Cases Chart Sharp Decline
The Lancet: H1N1-Associated Invasive Pneumonia Increasing 
LA Times: Decline in H1N1 continues

H1N1 Influenza Internet Resource Guide

The H1N1 Influenza Internet Resource Guide is now maintained on Influenza Monitor.

This guide provides a Top 10 list of the best swine flu information resources on the Internet across an array network media to include: newswires, forums, social
network sites, blogosphere, mashups and wikis.

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H1N1 Influenza Internet Resource Guide: The Best Swine Flu Sites

World Notes: Public health implications of H1N1 virus mutation found in Norway

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The Norwegian Institute of Public Health reported finding a mutated H1N1 virus in three patients, including the first two H1N1 fatalities in Norway. The H1N1 virus mutation does not appear to be circulating and may have spontaneously arisen in the three patients.

“The mutation, known as D222G (also as D225G), reportedly allows the virus to bind to receptors on cells lining the lungs.” The same mutation has been found in Ukraine, which is experiencing an acute H1N1 outbreak and where significant “numbers of people have died with lung hemorrhages.” Only three of Norway’s 70 tested samples had the mutation.

World Health Organization (WHO) comment: “In addition to Norway, the mutation has been observed in Brazil, China, Japan, Mexico, Ukraine, and the US,” with the earliest detection occurring in April. Viruses showing the same mutation have been detected in fatal as well as some mild cases. The mutation “remains sensitive to antiviral drugs, oseltamivir (Tamiflu) and zanamivir (Relenza),” and “studies show that currently available pandemic vaccines confer protection.”

U.S. Center for Disease Control (CDC) comment: The mutation has been seen “sporadically” in the US, and had been associated with mild disease. The mutation carries no implications for treatment with vaccines or antivirals.

Life Extension - Health And Medical Findings

FHI: Mutation of pandemic influenza A(H1N1) in Norway
MedPage: CDC Watching H1N1 Mutation, but No Cause for Alarm
NY Times: Signs That Swine Flu Has Peaked
Recombinomics: WHO Confirms D225G in Lung Cases in Norway and Ukraine
WHO: Public health significance of virus mutation detected in Norway