• US Govt researchers compared the pathogenenicity of pandemic H1N1 in mice with several other viruses to include a reconstructed 1918 virus, a 1976 H1N1 virus, a highly pathogenic H5N1 (avian flu) virus, and a triple reassortment human virus that has been circulating in pigs for at least a decade prior to pH1N1. They found that all “2009 H1N1 viruses replicated efficiently in the lungs of mice and possessed a high degree of infectivity, but did not cause lethal disease or exhibit extrapulmonary virus spread.” 2009 H1N1 “viruses isolated from fatal cases did not demonstrate enhanced virulence in this model compared with isolates from mild human cases.”
• A similar experiment by Dutch researchers compared that pathogenicty of pH1N1 in ferrets with seasonal H1N1 and highly pathogenic H5N1. The results “showed that the new (i.e. pandemic) H1N1 virus causes pneumonia in ferrets intermediate in severity between that caused by seasonal H1N1 virus and by HPAI H5N1 virus. The new (pandemic) H1N1 virus replicated well throughout the lower respiratory tract and more extensively than did both seasonal H1N1 virus (which replicated mainly in the bronchi) and HPAI H5N1 virus (which replicated mainly in the alveoli).”
• Both studies are consistent with earlier research from a team led by Dr Yoshihiro Kawaoka at the University of Wisonsin, Madison, which compared the effects of H1N1 and seasonal in mice, ferrets and monkeys. Their results indicated that the “H1N1 virus (replicated) much more efficiently in the respiratory system than seasonal flu and (caused) severe lesions in the lungs similar to those caused by other more virulent types of pandemic flu.”
• Recent research also led by Dr. Kawaoka engineered 254 combinations of reassorted viruses between a low-pathogenic avian H5N1 and a human seasonal H3N2 strains and subsequently tested a subset of these in mice. Some 96 viruses in this mix were found to be highly replicable. The team tested 75 H5N1 and H3N2 hybrids in mice. Of this group “forty-five viruses were less pathogenic than the avian H5N1 parent, 8 were as pathogenic, and 22 were more pathogenic.” The findings suggested that “human PB2 (gene) is required for the emergence of substantially virulent hybrids.”

No mice, ferrets or monkeys were harmed in the making of this post.

CIDRAP: Study yields highly pathogenic avian, human flu virus mix
J Inf Disease: Severity of Pneumonia Due to New H1N1 Influenza Virus in Ferrets Is Intermediate between That Due to Seasonal H1N1 Virus and Highly Pathogenic Avian Influenza H5N1 Virus
J Virol: Pathogenesis of Pandemic Influenza A (H1N1) and Triple-Reassortant Swine Influenza A (H1) Viruses in Mice.
PNAS: Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence
UW Madison: A new, highly detailed study of the H1N1 flu virus shows that the pathogen is more virulent than previously thought

The committee ruled out a “post-pandemic” phase because, in its view, H1N1 is not yet behaving like normal seasonal infuenza, and that future waves of H1N1 were possible. WHO’s decision will be made public at 1000 GMT on 24 Feb.

Meanwhile, H1N1 has peaked and is waning across the globe. Pockets of “active, but declining H1N1 transmission persist in southern/eastern Europe as well South/East Asia.” Influenza B virus is circulating at elevated levels in China, displacing H1N1. H3N2 is co-circulating at low levels in Asia and China. H1N1 is the predominant strain in the Americas; flu activity in the USA is below baseline.

Last week WHO also recommended that A(H1N1) 2009 replace seasonal (A)H1N1 in the 2010-2011 trivalent seasonal influenza vaccine. As summarized by CIDRAP, the specific WHO recommendations were:

• H1N1 component: a strain similar to A/California/7/2009, replacing A/Brisbane/59/2007
• H3N2 component: a strain similar A/Perth/16/2009, replacing A/Brisbane/10/2007*
• B component: a strain similar to B/Brisbane/60/2008-like virus

* A/Wisconsin/15/2009 is a A/Perth/16/2009 (H3N2)-like virus and is a 2010 southern hemisphere vaccine virus.

Oseltamivir (Tamiflu) resistance in pandemic A(H1N1) 2009 viruses has been limited. However, WHO also noted “the majority of seasonal A(H1N1) viruses were oseltamivir resistant.” This resistance developed during the 2008-2009 flu season.

COMMENT: Flu watchers understandably keep an anxious eye on hot-zone countries like Indonesia, Vietnam and Egypt where H5N1 (avian flu) and H1N1 are in co-circulation, carrying potential for a pathogenic virus reassortment. The WHO report serves as a reminder that a reassortment between 2009 H1N1 and antiviral-resistant seasonal H1N1 viruses would also be an unwelcome development.

CIDRAP: CDC flu barometers show level activity
CIDRAP: WHO picks pandemic strain for next seasonal flu vaccine
Reuters: WHO may declare post-peak pandemic phase next week
Reuters: WHO to decide new flu vaccine formula
WHO: Pandemic (H1N1) 2009 – update 88
WHO: Recommended viruses for influenza vaccines for use in the 2010-2011 northern hemisphere influenza season (PDF)

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:

• All infected individuals with the exception of 3 (whose exposure status was uncertain) had been exposed to infected poultry or poultry products or to slaughtered or defeathered infected birds.
• In 2009, 17 of the 34 recorded cases involved children (between 12 and 30 months-old) and 79 percent of all infected individuals were under 10 years old. Most infected children tended to be male. Children exprienced lower death rates from H5N1 due to early diagnosis and hospital intervention.
• Among the 20-39-year age cohort, women had a greater tendency to be infected, and more women died post infection. Relatively more women than men are involved in poultry-related activities e.g. slaughtering/defeathering of chicken, food preparation, etc.

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.

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

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.

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

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.

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

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

WHO: Avian Influenza – situation in Vietnam – update 7