Influenza and Pandemic Influenza: Are New Vaccines and Therapeuticals coming as current defense waning?

[tropical]

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

Re: Reuters AlertNet - Experts fight H5N1 bird flu using smallpox vaccine

from FDA site

FDA Approves Second-Generation Smallpox Vaccine

.... "This vaccine is manufactured using modern cell culture technology allowing rapid and large scale production of a vaccine with consistent product quality." ....... ACAM2000 is made using a pox virus called vaccinia, which is related to but different from the virus that causes smallpox. The vaccine contains live vaccinia virus and works by causing a mild infection that stimulates an immune response that effectively protects against smallpox without actually causing the disease. The vaccine is derived from the only other smallpox vaccine licensed by FDA, Dryvax, approved in 1931........
http://www.fda.gov/bbs/topics/NEWS/2007/NEW01693.html

"derived from ... 1931........"

Yes, an quite extended period of "derivations" until now ..., indeed.


But the above is about the new sp vaccine, not about the new (to be) "transfection" tec. on other kinds of vaccines, subjected to:

""Transfection can result in unexpected morphologies and abnormalities in target cells",
and many, many, many more experiments prior any aproval.

As cited in #1:
"In an article published in the current Journal of Immunology, the experts from Hong Kong and the U.S. National Institutes of Health described how they inserted five key components of the H5N1 virus into the smallpox vaccine."

There was an experiment in Aussi(?) where because of changing some gen. part. for other purposes (deminishing the rat proliferation, if I'm not wrong), it was pop out an deadly variant of mouse/rat spox.

After all this experimenting, it can be visible what the medical professionals thinks about vaccination in general, looking their apply at the field to the seasonal flu vaccinations ... :

"No thanks", "Mercury into", ... "inducing autism", ..., "I'm enaugh strong to beat any flu virus", ...

Also to look maybe into one of new adjuvated flu vacc. label text:
"... in 1:10.000 cases could appear ...", "tests can display ... "simil" HIV like ..."

Or maybe to compare a decade ago how was the response on preventive spox. vacc. of the firstliners/health sector when it was supposed the need of an vacc. campaign among them ...

What would be the response to these "bright new" multi-viral-gen.particle vaccines? The same.

Only if such bf deadly pandemic already starts, the population will maybe take it.

 

[Giuseppe]

Drug-resistant influenza A virus potentially serious to high-risk patients

Drug-resistant influenza A virus potentially serious to high-risk patients

Drug-resistant influenza A virus potentially serious to high-risk patients

Drug-resistant influenza A virus potentially serious to high-risk patients

A mutation of the influenza A(H1N1) virus that is resistant to the drug oseltamivir may pose a serious health threat to hospitalized patients who have a weakened immune system, according to a study to be published in the March 11 issue of JAMA, and being released early online because of its public health importance.


A global emergence and rapid spread of oseltamivir-resistant influenza A(H1N1) viruses carrying a neuraminidase (NA; an enzyme) gene H274Y mutation has been observed since January 2008. Viruses carrying this mutation have been presumed to be of lower risk and less likely to be transmitted.

"However, current widespread circulation of oseltamivir-resistant influenza A(H1N1) viruses associated with typical influenza illnesses and viral pneumonia suggest that these viruses retain significant transmissibility and pathogenicity [ability to cause disease]," the authors write.

Jairo Gooskens, M.D., of Leiden University Medical Center, Leiden, the Netherlands, and colleagues analyzed the transmission of the oseltamivir-resistant influenza A(H1N1) virus with NA gene H274Y mutation to two hematopoietic (the formation of blood or blood cells) stem cell transplant recipients and an elderly patient in a Dutch university hospital in February 2008.

The investigation included a review of the medical records and various influenza and genetic tests.

The analysis confirmed that four patients in the hospital had the virus mutation, and that the virus was most likely transmitted while these patients were in the hospital. Influenza virus pneumonia (3 patients) and attributable death (2 patients) during active infection was observed in patients with lymphocytopenia (having an abnormally low level of white blood cells, important to the immune system) at onset.

Five health care workers developed influenza-like illness during admission of the presumed index patient.

However, samples for influenza testing were not obtained from any of these health care workers, so their role in possibly contributing to this transmission could not be confirmed.

"Early identification and prolonged isolation precautions appear prudent in the care for infected immunocompromised patients to prevent [hospital] influenza virus outbreaks. This study confirmed that circulating H274Y-mutated A(H1N1) viruses can retain significant pathogenicity and lethality, as shown in these elderly or immunocompromised patients with lymphocytopenia, underlining the urgency for the introduction of new effective antiviral agents and therapeutic strategies," the authors write.

They add that because the study consisted of a small number of patients, the findings require careful interpretation and do not allow conclusions on the frequency of this complication in hospital settings.

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(JAMA. 2009;301[10]:1042-1046). Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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<cite cite="http://www.eurekalert.org/pub_releases/2009-03/jaaj-dri022609.php">Drug-resistant influenza A virus potentially serious to high-risk patients</cite>

 

[Giuseppe]

Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Influenza A viruses (H1N1 subtype) that are resistant to the drug oseltamivir circulated widely in the U.S. during the 2007-2008 influenza season, with an even higher prevalence of drug resistance during the current 2008-2009 influenza season, according to a study to be published in the March 11 issue of JAMA, and being released early online because of its public health importance.


During the 2007-2008 influenza season, increased levels of resistance to the influenza drug oseltamivir (marketed as Tamiflu) were detected for the first time in the United States and worldwide. In addition, early 2008-2009 influenza season surveillance data suggest that oseltamivir resistance among influenza A(H1N1) viruses will most likely be higher, according to background information in the article. It was unknown whether some resistant viruses would cause clinical illness similar to other influenza viruses.

Nila J. Dharan, M.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues examined the trends and characteristics of patients infected with oseltamivir-resistant and -susceptible influenza A(H1N1) virus.

These viruses, identified and submitted to the CDC by U.S. public health laboratories between September 2007 and May 2008 and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance.

During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19 percent of circulating influenza viruses in the United States. Resistance to oseltamivir was identified among 142 of 1,155 U.S. influenza A(H1N1) viruses (12 percent) tested during the 2007-2008 influenza season.

Data were available for 99 persons infected with oseltamivir-resistant influenza and 182 persons infected with oseltamivir-susceptible influenza from this period. Among resistant cases, median (midpoint) age was 19 years, 5 patients (5 percent) were hospitalized, and 4 patients (4 percent) died.

No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms.

The researchers did not find an association between use of oseltamivir and cases of illness due to infection with oseltamivir-resistant A(H1N1) viruses in the United States.

Preliminary data from the early 2008-2009 influenza season indicates that oseltamivir resistance among A(H1N1) viruses continues at high levels. As of February 19, 2009, resistance to oseltamivir had been identified among 264 of 268 (98.5 percent) U.S. influenza A(H1N1) viruses tested.


"The emergence of oseltamivir resistance has highlighted the need for the development of new antiviral drugs and rapid diagnostic tests that determine viral subtype or resistance, as well as improved representativeness and timeliness of national influenza surveillance for antiviral resistance," the authors write.

They add that on December 19th, 2008, the CDC released interim recommendations for the use of influenza antiviral medications based on the early surveillance data from the 2008-2009 influenza season.

"The guidelines recommend that clinicians consider the results of patient testing and local influenza surveillance data on circulating types and subtypes of influenza viruses in deciding whether oseltamivir alone could be used. These guidelines provide options, including preferential use of [the anti-viral drug] zanamivir or a combination of oseltamivir and [the anti-viral drug] rimantadine, which might be more appropriate in treating patients who might have influenza caused by an oseltamivir-resistant virus."

"Additional options for the treatment and prophylaxis of influenza virus infection are critically needed."

(JAMA. 2009;301[10]:1034-1041).
Available pre-embargo to the media at www.jamamedia.org)

Editor's Note:
Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial:
The Evolution of Influenza Resistance and Treatment

In an accompanying editorial, David M. Weinstock, M.D., of the Dana-Farber Cancer Institute, Boston, and Gianna Zuccotti, M.D., of Brigham and Women's Hospital, Boston, and Contributing Editor, JAMA, Chicago, comment on the findings regarding influenza.

"The understanding of influenza biology and epidemiology has advanced markedly; however, the global dissemination of oseltamivir-resistant influenza came as a great surprise. Undoubtedly, new surprises await in the perpetual struggle with influenza as one thing is certain?the organism will continue to evolve. Anticipating the rapid and endless changes in influenza biology and dynamics will require faster diagnostics to molecularly characterize specimens, extensive surveillance among humans and animals, and more rapid and [flexible] systems for translating basic and epidemiological discoveries into clinically applicable interventions. For now, the best tools to mitigate influenza infection are tried-and-true?vaccination, social distancing, hand washing, and common sense."

(JAMA. 2009;301[10]:1066-1069).

Available pre-embargo to the media at www.jamamedia.org)

Editor's Note:
Please see the article for additional information, including financial disclosures, funding and support, etc.

###​

<cite cite="http://www.eurekalert.org/pub_releases/2009-03/jaaj-sdi022609.php">Study documents increasing prevalence of influenza A resistance to drug oseltamivir</cite>

 

[Giuseppe]

JAMA. Oseltamivir Resistance.

JAMA. Oseltamivir Resistance.

[In this post: Three papers about antivirals resistance and vaccination strategies.

All papers are freely available at the linked site. EDITED.]

1.1) Abstract. Morbidity and Mortality Associated With Nosocomial Transmission of Oseltamivir-Resistant Influenza A(H1N1) Virus

1.2) Abstract. Live Attenuated or Inactivated Influenza Vaccines and Medical Encounters for Respiratory Illnesses Among US Military Personnel

1.3) Abstract. Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States

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Abstract. Morbidity and Mortality Associated With Nosocomial Transmission of Oseltamivir-Resistant Influenza A(H1N1) Virus.

Morbidity and Mortality Associated With Nosocomial Transmission of Oseltamivir-Resistant Influenza A(H1N1) Virus

[Free Full PDF Document at LINK. EDITED.]

Jairo Gooskens, MD - Marcel Jonges, MSc - Eric C. J. Claas, PhD - Adam Meijer, PhD - Peterhans J. van den Broek, MD, PhD - Aloys C. M. Kroes, MD, PhD

Context
The sudden emergence and rapid spread of oseltamivir-resistant influenza A(H1N1) viruses with neuraminidase (NA) gene H274Y amino acid substitution is the hallmark of global seasonal influenza since January 2008. Viruses carrying this mutation are widely presumed to exhibit attenuated pathogenicity, compromised transmission, and reduced lethality.

Objective
To investigate nosocomial viral transmission in a cluster of patients with influenza A(H1N1) virus infection.

Design, Setting, and Patients
Descriptive outbreak investigation of 2 hematopoietic stem cell transplant recipients and an elderly patient who developed hospital-acquired influenza A virus infection following exposure to an index patient with community-acquired H274Y-mutated influenza A(H1N1) virus infection in a medical ward at a Dutch university hospital in February 2008. The investigation included a review of the medical records, influenza virus polymerase chain reaction and culture, phenotypic oseltamivir and zanamivir susceptibility determination, and hemagglutinin chain 1 (HA1) gene and NA gene sequence analysis.

Main Outcome Measure
Phylogenetic relationship of patient cluster influenza A(H1N1) viruses and other 2007-2008 seasonal influenza A(H1N1) viruses.

Results
Viral HA1 and NA gene sequence analysis from the 4 patients revealed indistinguishable nucleotide sequences and phylogenetic clustering of H274Ymutated, oseltamivir-resistant influenza A(H1N1) virus, confirming nosocomial transmission. Influenza virus pneumonia (3 patients) and attributable mortality (2 patients) during active infection was observed in patients with lymphocytopenia at onset.

Conclusion
Seasonal oseltamivir-resistant influenza A(H1N1) viruses with NA gene H274Y mutation are transmitted and retain significant pathogenicity and lethality in high-risk patients.

JAMA. 2009;301(10)doi:10.1001/jama.2009.297) www.jama.com
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Abstract. Live Attenuated or Inactivated Influenza Vaccines and Medical Encounters for Respiratory Illnesses Among US Military Personnel

Live Attenuated or Inactivated Influenza Vaccines and Medical Encounters for Respiratory Illnesses Among US Military Personnel

[Free Full PDF Document at LINK. EDITED.]

Zhong Wang, PhD, MPH - Steven Tobler, MD, MPH - Jean Roayaei, PhD - Angelia Eick, PhD, ScM

Context
Since 2004, increasing numbers of military personnel have been immunized with the intranasal live attenuated influenza vaccine (LAIV) while most others received the trivalent inactivated vaccine (TIV). However, data about live virus vaccine effectiveness among healthy adults are limited.

Objective
To monitor the effectiveness of vaccines to better inform military vaccination policy.

Design, Setting, and Participants
Surveillance of population-based, propensity-matched, and/or vaccine-naive cohorts of more than a million active-duty, nonrecruit military service members aged 17 to 49 years stationed in the United States during the 2004-2005, 2005-2006, or 2006-2007 influenza season.

Main Outcome Measures
Incidence of health care encounters resulting in a primary diagnostic code consistent with pneumonia or influenza. Incident hospitalizations was a secondary outcome.

Results
In all 3 seasons, immunization with TIV was associated with lower incidence rates of health care encounters for pneumonia and influenza when compared with no immunization: 8.6 vs 19.4 for 2004-2005, 7.8 vs 10.9 for 2005-2006, and 8.0 vs. 11.7 per 1000 person-years for 2006-2007 (all P<.001). Similar estimates were obtained from propensity-matched and/or vaccine-naive cohorts. Consistently lower vaccine effect following LAIV immunization was only seen during the 2006-2007 influenza season in the total (10.7; 95% confidence interval [CI], 2.72 to 18.1; P=.03) and propensity-matched cohorts (11.8; 95% CI, 0.85 to 21.5; P=.04), and was less than effect from TIV (TIV vs LAIV, 19.8; 95% CI, 13.6 to 25.5; P<.001). Among vaccine-naive service members, however, estimates for LAIV effect were more robust for both the 2005-2006 and 2006-2007 seasons (P=.01) and were comparable with TIV (eg, LAIV, 30.2; 95% CI, 11.2 to 45.2; vs TIV, 35.3; 95% CI, 25.9 to 43.6; in 2005-2006).

Conclusions
Vaccination with TIV was associated with fewer medical encounters related to pneumonia and influenza compared with LAIV or no immunization. In this annually immunized population, this effect was less apparent in those vaccinated with LAIV.

JAMA. 2009;301(9):945-953 www.jama.com
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Abstract. Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States

Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States

[Free Full PDF Document at LINK. EDITED.]

Nila J. Dharan, MD - Larisa V. Gubareva, PhD - John J. Meyer, MPH - Margaret Okomo-Adhiambo, PhD - Reginald C. McClinton, MPH - Steven A. Marshall, MS - Kirsten St. George, MAppSc, PhD -
Scott Epperson, MPH - Lynnette Brammer, MPH - Alexander I. Klimov, PhD - Joseph S. Bresee, MD - Alicia M. Fry, MD, MPH - for the Oseltamivir-Resistance Working Group

Context
During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season.

Objectives
To describe patients infected with oseltamivir-resistant influenza A(H1N1) virus and to determine whether there were any differences between these patients and patients infected with oseltamivir-susceptible A(H1N1) virus in demographic or epidemiological characteristics, clinical symptoms, severity of illness, or clinical outcomes.

Design, Setting, and Patients
Influenza A(H1N1) viruses that were identified and submitted to the Centers for Disease Control and Prevention by US public health laboratories between September 30, 2007, and May 17, 2008, and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance. Oseltamivir resistance was determined by neuraminidase inhibition assay and pyrosequencing
analysis. Information was collected using a standardized case form from patients with oseltamivir-resistant A(H1N1) infections and a comparison group of patients with oseltamivir-susceptible A(H1N1) infections during 2007-2008.

Main Outcome Measures
Demographic and epidemiological information as well as clinical information, including symptoms, severity of illness, and clinical outcomes.

Results
During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19% of circulating influenza viruses in the United States. Among 1155 influenza A(H1N1) viruses tested from 45 states, 142 (12.3%) from 24 states were resistant to oseltamivir. Data were available for 99 oseltamivir-resistant cases and 182 oseltamivir-susceptible cases from this period. Among resistant cases, median age was 19 years (range, 1 month to 62 years), 5 patients (5%) were hospitalized, and 4 patients (4%) died. None reported oseltamivir exposure before influenza diagnostic sample collection. No significant differences were found between cases of oseltamivir-resistant and oseltamivirsusceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. Preliminary data from the 2008-2009 influenza season identified resistance to oseltamivir among 264 of 268 influenza A(H1N1) viruses (98.5%) tested.

Conclusions
Oseltamivir-resistant A(H1N1) viruses circulated widely in the United States during the 2007-2008 influenza season, appeared to be unrelated to oseltamivir use, and appeared to cause illness similar to oseltamivir-susceptible A(H1N1) viruses. Circulation of oseltamivir-resistant A(H1N1) viruses will continue, with a higher prevalence of resistance, during the 2008-2009 season.

JAMA. 2009;301(10)doi:10.1001/jama.2009.294)
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[Giuseppe]

Re: JAMA. Oseltamivir Resistance.

Re: JAMA. Oseltamivir Resistance.

Resistance to flu drug widespread in U.S.: study

Resistance to flu drug widespread in U.S.: study

By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) ?

Virtually all cases of the most common strain of flu circulating in the United States now resist the main drug used to treat it, the U.S. Centers for Disease Control and Prevention reported on Monday.


CDC researchers said 98 percent of all flu samples from the H1N1 strain were resistant to Roche AG's Tamiflu, a pill that can both treat flu and prevent infection. Four patients infected with the resistant strain have died, including two children.

This year, H1N1 is the most common strain of flu in the United States, although the flu season is a mild one so far, and still below the levels considered an epidemic.

Few doctors even test patients for flu, and Tamiflu is not widely prescribed. But the news is sobering because the pill, known generically as oseltamivir, is one of the few weapons against influenza, which kills an estimated 36,000 people in the United States in an average year.

It is also considered a key weapon against a potential pandemic of a new type of influenza, and this study suggests the virus can rapidly evade its effects.

This season, nine children have died from influenza, most apparently healthy before they died of flu, the CDC reports.

Last flu season, only 19 percent of H1N1 viruses tested were Tamiflu-resistant, Dr. Nila Dharan and colleagues at the CDC reported.

"As of February 19, 2009, resistance to oseltamivir had been identified among 264 of 268 (98.5 percent) U.S. influenza A(H1N1) viruses tested," the researchers wrote in the Journal of the American Medical Association.

YOUNG PATIENTS
They interviewed 99 patients and found 30 percent of them had been vaccinated against flu but became infected anyway. The vaccine is known not to fully protect against infection.

"Two patients died on the way to the hospital or in the emergency department. One patient was 4 years old and previously healthy, and one patient was 4 years old with neurological problems," Dharan's team wrote.

"Two deaths were among hospitalized patients, one patient was a 1-year-old with multiple medical problems and one patient, hospitalized for a stem cell transplant, was 22 years old and diagnosed with influenza infection on the fifth day of hospitalization," they added.

Dr. David Weinstock of the Dana-Farber Cancer Institute and Dr. Gianna Zuccotti of Brigham and Women's Hospital, both in Boston, said the quick spread of Tamiflu-resistant flu had surprised doctors.

"Undoubtedly, new surprises await in the perpetual struggle with influenza as one thing is certain -- the organism will continue to evolve," they wrote.

"For now, the best tools to mitigate influenza infection are tried-and-true -- vaccination, social distancing, hand washing, and common sense."

GlaxoSmithKline, which makes the rival flu drug Relenza, said there was no indication influenza viruses were resistant to its drug. Relenza, known generically as zanamivir, is squirted into the nose and is used even less commonly than Tamiflu.

Flu already resists two older drugs, rimantadine and amantadine. There is no indication the two other types of season flu now circulating, H3N2 and influenza B, resist the effects of Tamiflu.

(Reporting by Maggie Fox, editing by Will Dunham)
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<cite cite="http://news.yahoo.com/s/nm/20090302/ts_nm/us_flu_tamiflu">Resistance to flu drug widespread in U.S.: study</cite>

 

[AlaskaDenise]

Re: Drug-resistant influenza A virus potentially serious to high-risk patients

Re: Drug-resistant influenza A virus potentially serious to high-risk patients

four patients in the hospital had the virus mutation, and that the virus was most likely transmitted while these patients were in the hospital. Influenza virus pneumonia (3 patients) and attributable death (2 patients) during active infection was observed in patients with lymphocytopenia (having an abnormally low level of white blood cells, important to the immune system) at onset.

Five health care workers developed influenza-like illness during admission of the presumed index patient.

However, samples for influenza testing were not obtained from any of these health care workers, so their role in possibly contributing to this transmission could not be confirmed.

Are they saying the HCW were ill on-the-job while admitting an immuno-compromised patient? WHY are they exposing patients?

.

 

[Giuseppe]

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

CIDRAP >> H1N1 viruses gain Tamiflu resistance without losing fitness

H1N1 viruses gain Tamiflu resistance without losing fitness

Robert Roos * News Editor
Mar 2, 2009 (CIDRAP News) ?

Studies published today confirm that influenza A/H1N1 viruses have become widely resistant to oseltamivir (Tamiflu), the leading flu drug, without losing their ability to make people sick?thereby underlining the need for new antiviral drugs.


The findings also underscore the possibility that H5N1 avian influenza could gain resistance to oseltamivir, calling into question the value of stockpiling the drug in preparation for a potential flu pandemic, according to two experts who comment on the latest findings in an accompanying editorial. The research reports and editorial were released online today by the Journal of the American Medical Association.

To the surprise of many, H1N1 resistance to oseltamivir rose sharply last year, reaching 12.3% in the United States and 16% worldwide. So far this season, it is far higher: more than 98% (321 of 325) of H1N1 isolates tested by the Centers for Disease Control and Prevention (CDC) were resistant to the drug.

None of the H1N1 isolates have shown resistance to zanamivir (Relenza), the other flu drug in the neuraminidase inhibitor class. H1N1 is one of three flu subtypes that circulate each season, along with A/H3N2 and influenza B.

Because of the spread of resistance, the CDC in December changed its recommendations on antiviral treatment for flu. For patients suspected of having influenza A, the CDC recommended using zanamivir or a combination of oseltamivir and rimantadine (an older flu drug in a different class) instead of oseltamivir alone.In one of the new studies, a team from the CDC and several state health departments compared people infected with oseltamivir-resistant and oseltamivir-susceptible strains of H1N1 last season and found no differences in patient characteristics, symptoms, or severity of illness. They report that four patients infected with resistant strains died.

A second study describes an outbreak of resistant H1N1 infections in four patients in a Dutch hospital in February 2008. Three immunocompromised patients became ill after exposure to a patient who was sick with a resistant H1N1 strain, and genetic analysis showed that the viruses all matched, making it clear that the infection spread from person to person in the hospital.

Taken together, the two studies "dispel the notion that oseltamivir resistance compromises virulence," states the accompanying editorial by David M. Weinstock, MD, and Gianna Zuccotti, MD, of Harvard Medical School in Boston.

Resistance in 2007-08 US season

The CDC-state study reports that oseltamivir resistance was found in 142 of 1,155 (12.3%) H1N1 viruses tested last season. Resistant viruses were reported in 24 states. Of the 142 patients who had resistant viruses, 99 supplied information.

None of the 99 reported taking oseltamivir before being tested for flu, nor did they have close contact with others who had taken it. Four of the patients died, two of them in hospitals and the other two on the way to a hospital or in the emergency department.

After seven cases from one state were excluded, the authors compared 92 patients who had resistant H1N1 infections with 182 who had susceptible strains. They found no differences by age, sex, race, underlying medical conditions, or clinical symptoms.

The analysis did indicate that patients with susceptible viruses were more likely to be hospitalized, but this difference disappeared when the two patients with resistant viruses who died before they could be admitted to hospitals were classified as hospital admissions.

Before last season, oseltamivir resistance had been seen only in patients who were treated with the drug, the authors note, adding that it is unclear why oseltamivir-resistant H1N1 viruses emerged during the season and continue to circulate.

"Additional options for the treatment and prophylaxis are critically needed," the report concludes.

Hospital outbreak

In the other report, the Dutch researchers write that three hospital patients apparently acquired oseltamivir-resistant H1N1 infections from another patient who was found to have the virus while being treated for systemic lupus erythematosus.

The three were in the same ward as the presumed index patient at the same time, though they never shared a room. Two patients, a hematopoietic stem-cell transplant recipient and an 89-year-old man, died of the illness.

Genetic sequencing revealed that isolates from the four patients matched closely. All four had not only the H274Y mutation associated with resistance, but also a rare mutation known as T284A.

Five healthcare workers got sick with flu-like symptoms while the index patient was hospitalized, but none of them were tested for flu, the report says.

"This study confirmed that circulating H274Y-mutated A(H1N1) viruses can retain significant pathogenicity and lethality, as shown in these elderly or immunocompromised patients with lymphocytopenia, underlining the need for the introduction of new effective antiviral agents and therapeutic strategies," the authors conclude.

Findings shouldn't be surprising

"The widespread belief that oseltamivir would retain activity against epidemic influenza strains has crumbled, but this should come as no surprise," write Weinstock and Zuccotti, in the editorial accompanying the two reports. They say that surveillance over the past several years indicated that resistance was rising on a path that closely paralleled the rise of adamantane (amantadine and rimantadine) resistance 3 years earlier.

Further, recent laboratory studies have shown that the H274Y mutation that confers resistance in H1N1 viruses does not necessarily interfere with the virus's ability to replicate in animal models, the editorial says.

One corollary of the new studies, according Weinstock and Zuccotti, is that "oseltamivir resistance is likely to develop during the treatment of other N1-containing strains, including avian influenza A(H5N1). Thus, stockpiles to mitigate an influenza pandemic should not be limited oseltamivir."

Oseltamivir is the leading antiviral drug in national stockpiles for pandemic preparedness. The US stockpile is about 80% oseltamivir and 20% zanamivir, federal officials have said.

Vaccination remains key tool

Other experts said the findings show that vaccination remains the key tool for battling influenza. They share the concern about the risk of resistance in H5N1 viruses.

"These developments further support the use of influenza vaccine as the cornerstone for influenza prevention and control," said Kathleen M. Neuzil, MD, MPH, a member of the Pandemic Influenza Task Force of the Infectious Diseases Society of America and director of the Influenza Vaccine Project at PATH in Seattle.

Concerning the risk of resistance in H5N1, she said, "These recent findings represent a paradigm shift. We need to be prepared for the possibility that H5N1, or other influenza strains, could become resistant to oseltamivir and still be pathogenic and transmissible. This advocates for research and development into new antiviral and effective pandemic vaccines."

Dr. Keiji Fukuda, director of the World Health Organization's Global Influenza Programme, called H5N1 resistance "a theoretical possibility."

"So far, oseltamivir resistance has been rarely reported in H5N1 human isolates (three in Vietnam with H275Y mutation, two in Egypt with N294S mutation which confers mild reduction of oseltamivir susceptibility)," he commented by e-mail. "This is another situation where monitoring is essential." (The resistance mutation is sometimes called H275Y, depending on the naming system.)

Fukuda observed that all the resistant H1N1 viruses tested so far have been sensitive to zanamivir and the adamantanes. "Of course, empiric therapy is difficult when you do not know the specific influenza virus type and subtype?as one typically does not in clinical practice?because in some countries most of the circulating H3N2 viruses are resistant to adamantanes," he added. "But when national surveillance is good, empirically selected therapy is rational and possible."

Both experts allowed for a possibility that H1N1 will eventually become susceptible to oseltamivir.

"As these [resistant Brisbane-like] strains continue to evolve and be replaced by other strains, it's possible that the resistance will go down. This needs to be monitored," said Fukuda.

Neuzil commented, "No one knows, but it [resistance] could certainly disappear as rapidly as it developed, as without widespread use of oseltamivir, it appears unlikely that antiviral pressure will favor resistant viruses."
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<cite cite="http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/mar0209osel.html">CIDRAP >> H1N1 viruses gain Tamiflu resistance without losing fitness</cite>

 

[Giuseppe]

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

WalesOnline - Drug call to halt ?super-flu? spread

Drug call to halt ?super-flu? spread

Mar 3 2009
by Gregory Tindle, Western Mail

A NEW drug-resistant ?super-flu? may pose a serious threat to high-risk patients, scientists warned yesterday.


The H1N1 ?A? virus is a strain that causes common seasonal flu outbreaks. But it carries an altered gene that makes it resistant to the popular anti-viral drug oseltamivir, better known as Tamiflu.

The emergence of the Tamiflu-resistant strain in the Netherlands and US over the past year prompted calls yesterday for a new flu drug to counter any spread of the virus.

Flu experts in Wales said, although they were already aware of the potential problems, a handful of similar cases in the UK last year had not yet led to an increase in overall flu levels.

But the Dutch and US scientists say the new H1N1 strain could seriously threaten hospital patients with weakened immune systems and say the spread of the resistant strain had been observed since January last year.

The researchers examined data on 99 people infected with Tamiflu-resistant flu during the 2007-2008 influenza season. Five patients were hospitalised and four died.

Three of those affected developed pneumonia and two died, all of whom had weakened immune systems. Five health care workers also developed an influenza-like illness, but it was not possible to confirm whether they had picked up the virus.

The US team found that 12% of influenza H1N1 viruses tested during the 2007-2008 flu season were resistant to Tamiflu.

But preliminary findings from the 2008-2009 season suggested much higher levels of Tamiflu resistance. Last month resistant strains had been identified among 264 out of 268 ? or 98.5% ? of influenza A (H1N1) viruses tested in the US.

Writing in the Journal of the American Medical Association (Jama), the researchers wrote: ?The study confirmed that circulating H274Y-mutated A (H1N1) viruses can retain significant pathogenicity and lethality, as shown in these elderly or immunocompromised patients, underlining the urgency for the introduction of new and effective antiviral agents and therapeutic strategies.?

They added: ?The emergency of oseltamivir resistance has highlighted the need for the development of new antiviral drugs and rapid diagnostic tests that determine viral subtype or resistance, as well as improved representativeness and timeliness of national influenza surveillance for antiviral resistance.?

Flu levels in Wales remained low this winter, reaching a high of 25 consultations per 100,000 visits to GP surgeries. A normal level of flu activity would be 100 consultations per 100,000 surgery visits.

Dr Roland Salmon, director of the National Public Health Service for Wales? Communicable Disease Surveillance Centre, yesterday played down any fears about the new strain.

He said: ?This is a piece of scientific research and I need to read the actual detail but I do not think it will alter our approach in dealing with flu and the best way of doing that is by a flu vaccine.

?We were aware of the circulation in the UK of a handful of similar H1N1 cases in the UK last year with a mutation of the virus and this will happen from time to time ? we?re all here this winter to tell the tale.

?In Wales we have mechanisms in place to ensure any such changes in the virus are isolated and these are also done in England. All it takes is a single mutation in a gene and that can make it resistant to the current vaccine such as Tamiflu.

?The scientists make the point that new anti-flu agents are needed but, until that happens, the current flu vaccine is the best option and, with the increasing uptake in recent years, has been very successful in cutting the high levels of flu that were around just 10 years ago.?
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<cite cite="http://www.walesonline.co.uk/news/wales-news/2009/03/03/drug-call-to-halt-super-flu-spread-91466-23047760/">WalesOnline - News - Wales News - Drug call to halt ?super-flu? spread</cite>

 

[Giuseppe]

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Study: Drug-Resistant Flu on the Rise

By Alice Park Monday, Mar. 02, 2009

When it comes to this year's flu season, health experts are saying so far, so good. The vaccine appears to be effective against the most widely circulating strains of influenza, and there is plenty of the drug to go around.

The only dark cloud has been a disturbing rise in drug-resistant flu, but new data published Monday in the Journal of the American Medical Assocation suggest that despite the resistant strain, things aren't as bad as they could be.

Researchers at the Centers for Disease Control and Prevention (CDC) first reported last December that 2% of influenza strains circulating in the 2007-08 season were resistant to the most popular antiflu remedy, oseltamivir, or Tamiflu.

They warned that the prevalence of these strains would likely continue to increase, and indeed, early data from the current season suggest they have. Influenza is composed of three subtypes of virus, and last year, 12% of one of those subtypes, known as H1, was resistant to oseltamivir. This year, almost all of the H1 contingent, 98%, are resistant.

But in the new J.A.M.A. study, the CDC scientists report that infection with drug-resistant flu does not cause more severe illness or lead to more hospitalizations than infection with non-resistant strains.

The study also finds that the resistant strain did not arise from overuse of Tamiflu; in fact, during the last flu season, the resistant strain was found widely in countries with low Tamiflu use like Norway, but less commonly in places like Japan where Tamiflu use is high.

If overuse had played a role in the emergence of resistant strain, health officials may have recommended that clinicians restrict prescriptions of the drug. Instead, it appears that the drug-resistant strains mutated on their own.

"Flu viruses mutate all the time," says Dr. Alicia Fry, a medical epidemiologist at the CDC and a co-author of the study. "We suspect this is just one of those spontaneous mutations that occurred, and is not related to overuse of the drug."

The resistant strain is also treatable with antiviral medications other than Tamiflu; zanamivir, or Relenza, still combats all three subtypes of influenza. And for those for whom zanamivir is inappropriate — the drug comes as an inhaled powder and is not recommended for children under seven — the combination of Tamiflu and an older antiviral, Flumadine (rimantadine), can also be effective in fighting the disease.

(In 2006, the CDC recommended against prescribing Flumadine because another of influenza's three subtypes was resistant to the drug. But in combination with Tamiflu, the medication can be effective.)

That's good news, but it also means that doctors treating flu patients need to be even more aware of how they treat the flu. "Treating flu is complicated, and we are worried that there will be some confusion among clinicians about what antiviral drugs to use," says Fry.

Most do not have the time or ability to test each patient's virus to determine whether it is a resistant strain, so CDC recommends that physicians stay updated on the predominant strains circulating in their communities.

If the Tamiflu-resistant variety is common, then they should prescribe either Relenza or the combination of Tamiflu and Flumadine instead.
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http://www.time.com/time/health/article/0,8599,1882306,00.html?xid=rss-topstories
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[Giuseppe]

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Experts stand by bird flu drug - The Standard

Experts stand by bird flu drug

Patsy Moyand
Reuters
Wednesday, March 04, 2009

Medical experts yesterday insisted flu drug Tamiflu remained effective in treating common flu and combating avian flu even though the H1N1 virus resistance to the drug had reached 98 percent in the United States.


The Department of Health said H1N1 resistance to Tamiflu had jumped from 68.4 percent in October to 93.8 percent in November and 97.8 percent in December, though it was still effective in treating H3N2 and is still highly recommended by the World Health Organization to combat the H5N1 avian flu.

Fears were raised after the US Centers for Disease Control and Prevention reported on Monday that 98 percent of all flu samples from the H1N1 strain were resistant to the drug produced by Roche.

Four patients infected with the resistant strain have died, two of them children.

Last flu season, only 19 percent of H1N1 viruses tested were Tamiflu-resistant, the CDC said.

The US researchers interviewed 99 patients and found 30 percent of them had been vaccinated against flu but became infected anyway.

Two patients died on the way to hospital or in the emergency department.

One patient was four years old and previously healthy, and the other was also four years old but with neurological problems.

Chinese University respiratory medicine head David Hui Shu- cheong said a study in northern Europe had shown flu patients who were resistant to Tamiflu were not worse off than those without resistance in terms of their length of hospital stay, clinical features and complication rate.

However, Hui admitted people who suffered from severe underlying diseases such as leukemia and blood disorders would be at high risk if exposed to the drug- resistant virus.

"Even so, Tamiflu is still very effective against H3N2. We have been hit by H1N1 in the recent flu seasons, but the strain will go away," he said.

Hui said other drugs like Amantadine and Relenza were also effective in combating flu while a new flu drug is under clinical trial.

In March last year, The Standard reported warnings by medical experts about doctors being compelled to prescribe Tamiflu by anxious patients, saying it could leave families vulnerable to the deadly H5N1 bird flu virus. A year ago, medical academics had also raised concerns about unscrupulous pharmacies selling the anti-flu drug without doctors' prescriptions.
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<cite cite="http://www.thestandard.com.hk/news_detail.asp?pp_cat=13&art_id=79060&sid=22960455&con_type=1">The Standard - Hong Kong's First FREE English Newspaper</cite>

 

[Giuseppe]

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

New medicines to be acquired for bird flu - Helsingin Sanomat - International Edition

New medicines to be acquired for bird flu

Finland is to buy new medicines to fight a possible outbreak of avian influenza, or bird flu. Up to now, preparations for a bird flu pandemic have consisted of stockpiling the anti-viral medicine Tamiflu.


However, the effectiveness of Tamiflu against one of the most common flu viruses has decreased considerably in the past couple of years.

Most of the versions of the H1N1 virus that have been found in recent years in Europe and the United States have been resistant to the commonly used Tamiflu.

This year?s Finnish influenza virus is a different one - H3N2, against which Tamiflu still works well, says Thedi Ziegler, head of the influenza laboratory of the National Institute for Health and Welfare (THL) The H1N1 virus, which has milder symptoms, appears in Finland at regular intervals.

Ziegler says that Tamiflu has rarely been used against it.

The increased resistance of H1N1 against Tamiflu has raised concerns that the feared bird flu could also evolve to become immune to medicines.

This is why Finland is acquiring other flu medicines in addition to Tamiflu, says Tapani Melkas of the Ministry of Social Affairs and Health.

Melkas notes that the issue is not an urgent one, as there has not been much bird flu around the world in recent times.
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<cite cite="http://www.hs.fi/english/article/New+medicines+to+be+acquired+for+bird+flu/1135244005486">Helsingin Sanomat - International Edition - Home</cite>

 

[Giuseppe]

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

ECDC Health Content. A Series of publications on oseltamivir resistance in seasonal influenza ? A(H1N1-H247Y)

A Series of publications on oseltamivir resistance in seasonal influenza ? A(H1N1-H247Y)

This week has seen a particular flock of article eto the influenza antiviral resistance topic which was first observed in Europe in January 2008 (1,2) but have since been recognised as a global phenomenon.


The first from Meijer et al is the definitive description of the emergence and rise of the proportions of A(H1N1) viruses in certain European countries that demonstrated these viruses were fully fit in terms of being able to transmit efficiently from human to human.

- Meijer A, Lackenby A, Hungnes O, Lina B, Van der Werf S, Schweiger B et al. Emergence and spread of Oseltamivir-resistant influenza A(H1N1) viruses in Europe during the 2007/2008 influenza season. Emerg Infec Dis. http://www.cdc.gov/eid/content/15/4/pdfs/08-1280.pdf

- Anne Moscona, Global Transmission of Oseltamivir-Resistant Influenza - The New England Journal of Medicine. Volume 360:953-956 - http://content.nejm.org/cgi/content/full/360/10/953?query=TOC

- Nila J. Dharan; Larisa V. Gubareva; John J. Meyer; Margaret Okomo-Adhiambo; Reginald C. McClinton; Steven A. Marshall; Kirsten St. George; Scott Epperson; Lynnette Brammer; Alexander I. Klimov; Joseph S. Bresee; Alicia M. Fry; for the Oseltamivir-Resistance Working Group - Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States - published 2 March 2009, 10.1001/jama.2009.294. http://jama.ama-assn.org/cgi/reprint/2009.294v1?papetoc

- Jairo Gooskens; Marcel Jonges; Eric C. J. Claas; Adam Meijer; Peterhans J. van den Broek; Aloys C. M. Kroes - Morbidity and Mortality Associated With Nosocomial Transmission of Oseltamivir-Resistant Influenza A(H1N1) Virus - published 2 March 2009, 10.1001/jama.2009.297 - http://jama.ama-assn.org/cgi/reprint/2009.297v1?papetoc

- David M. Weinstock; Gianna Zuccotti - The Evolution of Influenza Resistance and Treatment - published 2 March 2009, 10.1001/jama.2009.324 - http://jama.ama-assn.org/cgi/reprint/2009.324v1?papetoc

ECDC Comment (5/3/09):
Though these publication related to events of last season the reaction of the media this week to articles appearing in American peer-review journals JAMA & the New England Journal of Medicine was like this was the first news.
That must say something about ?impact factor?.
Certainly now it can be said that fully transmissible oseltamivir-resistant seasonal influenza A(H1N1-H247Y) have truly been discovered.(1,2)

1. Lackenby A, Hungnes O, Dudman SG, Meijer A, Paget WJ, Hay AJ, Zambon MC. Emergence of resistance to oseltamivir among influenza A(H1N1) viruses in Europe. Euro Surveill. 2008;13(5)ii=8026.
2. Nicoll A, Ciancio B, Kramarz P, on behalf of the Influenza Project Team . Observed oseltamivir resistance in seasonal influenza viruses in Europe - interpretation and potential implications. Euro Surveill. 2008;13(5)ii=8025.
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<cite cite="http://ecdc.europa.eu/en/health_content/sciadv/090305_sciadv_2.aspx">ECDC Health Content</cite>

 

[Giuseppe]

Re: Influenza and Pandemic Influenza: Are New Vaccines and Therapeuticals coming?

Re: Influenza and Pandemic Influenza: Are New Vaccines and Therapeuticals coming?

Merged threads: vaccinia-virus modified to enclose influenza viruses subunits, new vaccines approach to increase production capacity, improved vaccines and therapeuticals...

 

[Giuseppe]

Re: Influenza and Pandemic Influenza: Are New Vaccines and Therapeuticals coming as current defense waning?

Creating New, Innovative Vaccines - Forbes.com

Creating New, Innovative Vaccines

Josh Wolfe, Editor Forbes/Wolfe Emerging Tech Report, 03.09.09, 06:30 AM EDT

Technology is leading the way to developing innovative vaccines that could create enormous value in the future.


Staph Leavenworth Bakali has been involved in some of the biggest vaccine exits of all time. Through various senior operating and leadership positions over a 20-year career in vaccines, Leavenworth Bakali has played a critical role in some of the most successful and leading vaccine companies. Bakali was formerly the chief operating officer of both ID Biomedical, a Vancouver, Canada-based developer of influenza vaccines that was acquired by GlaxoSmithKline for $1.4 billion; and PowderJect Pharmaceuticals, an Oxford, U.K.-based vaccine developer acquired by GlaxoSmithKline for $930 million. Bakali was also previously the director of worldwide sales and marketing at Chiron Vaccines and the director of SmithKline Beecham's Vaccine Business Unit in France. He is currently a non-executive director at Vienna, Austria-based Intercell AG. Bakali holds a master's in management from London Business School.Josh Wolfe: Walk me through your background and how you came to develop an interest in vaccines.

Leavenworth Bakali:
In 1988, I joined Smith, Kline & French (now part of GlaxoSmithKline (nyse: GSK - news - people )) as part of the marketing department for the Middle East and Africa group, and soon progressed to become the youngest general manager within the company's international division. During time spent on the Ivory Coast, I gained firsthand experience with health care in the developing world. Quickly, I came to understand the rampant damages caused by infectious diseases in these countries, where people struggle to deal with life and death on a daily basis. Surviving victims of polio, left with the scars of missing limbs, frequent on street corners everywhere. Widespread malaria results in more than 2 million deaths a year--that's a person dying every 15 seconds! Yet, in the so-called "first world," these preventable diseases had been almost totally controlled through good sanitation and vaccination. I strongly felt that the developing world should be in the same position.

What was happening with vaccines at the time?
Vaccines were then seen as high volume, low value and low price commodities. Smith, Kline & French was developing a vaccine portfolio for the developing world, as well as antibiotics, anti-malarial and anti-worm products. I got involved in vaccination and anti-worming campaigns in partnership with the Ministry of Health and the Ministry of Education. I saw the success of those programs, and that's when I developed my passion for universal health care and my understanding that vaccination and prevention is a really critical intervention.

How did you transition to working more within the developed world?
After returning from Africa, SmithKline Beecham sponsored me to do a master's degree at London Business School. I was eventually asked to build the vaccine business for the company in France and subsequently made the shift to focusing more on the developed world. At that time, the vaccine business was becoming more strategically important to pharmaceutical firms due to the launch of several successful adult vaccines and combination vaccines for children. I later left SmithKline to become the worldwide head of sales and marketing for the vaccine division of U.S.-based Chiron. We supplied vaccines to both the developed and developing worlds. We worked closely with UNICEF, and during my time at the company, we developed and launched a Meningitis C vaccine that had a tremendous impact in the U.K. We also created a joint venture to specifically develop a combination vaccine for children in the 75 poorest countries in the world. The product was in partnership with GAVI (Global Alliance for Vaccine Initiatives) and funded by the Gates Foundation.

What experience do you have working in the U.S. market?
From Chiron, I joined publicly traded PowderJect Pharmaceuticals as COO. We were one of the very few suppliers of flu vaccine in the United States. We grew capacity to be able to supply Europe and meet the needs of the U.S. and also supplied the U.K. government with a smallpox vaccine as part of its bio-defense strategy. PowderJect was later sold to my previous company, Chiron, for nearly $1 billion. I subsequently became chief operating officer of ID Biomedical, a Vancouver-based company. I was part of the senior team that transitioned the company to become a major player in the North American vaccine market. We accomplished two significant things while I was there. First, we worked very closely with the Canadian government on the very first pandemic flu contract that, in the event of an influenza pandemic outbreak, would have meant that ID Biomedical supplied enough vaccines to protect the whole of the Canadian population. Secondly, when there was a flu vaccine shortage in the U.S. in 2004, we rapidly executed a $100 million expansion of our production facilities and worked closely with the FDA to gain fast-track status to get our product approved in the U.S., helping the country to have additional manufacturing capacity to help alleviate potential future product shortages. After just two years at the company, ID Biomedical was acquired by GlaxoSmithKline for $1.4 billion.

You have a tremendous track record in the vaccine industry. What is your secret to success?
I think successful company building requires four things: real assets you can build upon to control your own destiny, a focused strategy to create value, excellence in executing the strategy and luck. I have also been fortunate to work with a number of great people and teams at all levels.

How has the vaccine industry changed in the last several years?
This industry that used to be regarded as high volume, low value, low price has been transformed into an extremely high-value, first-world-focused industry. That's come about through the realization that vaccination is an extremely cost-effective health care intervention and through the development of new products for diseases that are a heavy health burden, such as influenza and early childhood diseases. Some of these new vaccines have become $1 billion-plus blockbusters for large pharmaceutical companies. In the last few years, the vaccine industry has seen a wave of consolidation driven by Big Pharma, and in my view, this is likely to continue. In addition we have also seen the emergence of strong regional players in the emerging markets such as India and China, as well as greater collaboration between the public and private sectors.

What opportunities and innovations do you see in the industry today?
The recent wave of changes has created a tremendous opportunity for innovative technologies in the space, as companies that can help discover and deliver new vaccines could create enormous value. I think it's a good market to be in right now, from both a shareholder's and health care provider's point of view. Some of the big advances in vaccine research are new ways to discover novel vaccines, manufacturing technologies and delivery systems. In the past, vaccines were always administered through a needle. Now, people are working on needle-free delivery, including skin patches, oral vaccines, intranasal sprays and even vaccination via food.

You recently signed on as the CEO of a start-up company called Genocea Biosciences. [Full disclosure: my venture firm Lux Capital is an investor.] What technology is the company pursuing?
In order to make effective vaccines, you need to know which proteins (called "antigens") of a given pathogen your body will target in order to give you the immune protection you desire. This is one of the most crucial elements of vaccine development. In the past, the process of discovering these antigens took quite a long time and was largely based on years of analysis and trial and error. The Genocea technology is one-of-a-kind breakthrough in discovering and understanding how we can develop vaccines for some of the world's most challenging diseases. The scientific founder, Darren Higgins, spent 10 years developing a platform technology that allows us to rapidly identify proven protective antigens in humans. This technology could turn research on its head--it's potentially game-changing. The process of identifying protective antigens normally takes up to a decade if not more, and this technology can cut that time down to months.

Beyond technology, what attracted you to the start-up?
Two things: the potential and the people. I really enjoy building companies, and particularly companies that can have a broad impact on health care. Genocea has real potential to be the next-generation vaccine company. In addition, the company has assembled some of the world's leading vaccine experts who have been responsible for developing and launching some of the most successful vaccines of all time. It's an honor to be able to work side-by-side with them in building this company.

What assets do you bring to the company?
Twenty years of experience in the industry has given me an intimate understanding of the vaccine market and the present challenges in the developed and the developing worlds. In addition, my experience living and working in practically every continent has given me a truly global perspective on business and health care. Through my passion for this space and my experience in building companies, I hope to enable Genocea to revolutionize vaccine discovery, developing effective vaccines and creating new jobs and tremendous value for our shareholders in the process.

Josh Wolfe is editor of the Forbes Wolfe Emerging Tech Report.
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<cite cite="http://www.forbes.com/2009/03/06/bakali-glaxosmithkline-powderject-leadership-clayton-christensen-innovation.html">Creating New, Innovative Vaccines - Forbes.com</cite>

 

[Sally Furniss]

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Re: Study documents increasing prevalence of influenza A resistance to drug oseltamivir

Finland is to buy new medicines to fight a possible outbreak of avian influenza, or bird flu.

Up to now, preparations for a bird flu pandemic have consisted of stockpiling the anti-viral medicine Tamiflu.

Is there any indication as to what new medicines Finland is buying?

 

[Giuseppe]

Re: Influenza and Pandemic Influenza: Are New Vaccines and Therapeuticals coming as current defense waning?

New therapy protects lungs from runaway inflammation

New therapy protects lungs from runaway inflammation

A novel anti-inflammatory therapy designed by Vanderbilt University Medical Center investigators prevents acute lung injury in mice exposed to an inflammation-causing toxin, the researchers report in the journal Molecular Therapy.


The new therapy may offer a way to protect the lungs from the "runaway inflammation" that can accompany bacterial or viral pneumonia, said Jacek Hawiger, M.D., Ph.D., the leader of the research team that has pioneered the new approach.

"Lung inflammation is an extremely perplexing problem," noted Hawiger, chair of the Department of Microbiology & Immunology.

The immune system sometimes overreacts to lung infection and produces excessive concentrations of inflammatory signals (cytokines and chemokines), which can damage the fine architecture of the lungs and lead to life-threatening acute respiratory distress syndrome (ARDS). Such damage is most likely when pneumonia has both viral and bacterial causes ? for example from combined influenza and Staphylococcus aureus infections.

"We believe that in addition to controlling the infection with antibacterial and antiviral agents, we need therapies that reduce this inflammation-induced collateral damage to the lung tissue," Hawiger said. "This would allow both faster clearance of the infecting organisms and faster healing of the lung."

Several years ago, Hawiger and colleagues began searching for new targets for anti-inflammatory therapy. They reasoned that a protein called NF-kappa-B ? the "master regulator" of genes that encode mediators of inflammation ? might make a good target.

The researchers knew that NF-kappa-B moves from the cell cytoplasm to the nucleus (where it is active) in response to cellular injury or microbial agents, and they decided to try to block this nuclear translocation.

They designed a small protein fragment ? a peptide ? that mimicked the nuclear transport "signal," hoping that it would compete with, and block, NF-kappa-B's movement to the nucleus. To get the peptide into cells, the team took advantage of the cellular mechanism that proteins use to cross membranes and engineered a membrane-crossing motif onto the therapeutic peptide.

"To our delight, we found that this peptide crossed the cell membrane and stopped NF-kappa-B in its tracks, blocking it from going to the nucleus in response to conditions which cause inflammation," Hawiger said.

It turned out that the inhibitor worked even more broadly than the researchers expected. The peptide blocks a "shuttle" that ferries not only NF-kappa-B to the nucleus, but also a group of additional stress-responsive proteins. The nuclear shuttle protein represents a new intracellular target for anti-inflammatory therapy, Hawiger said.

The researchers tested the effectiveness of this cell-penetrating peptide therapy against inflammation in a mouse model of acute lung injury.

They exposed mice to staphylococcal enterotoxin B (SEB), an immunotoxin produced by methicillin-resistant S. aureus (MRSA). SEB generates a "storm" of inflammatory signals that damages the lungs and causes ARDS and multiple organ dysfunction. Airborne SEB caused fatal ARDS in non-human primates.

Treatment of SEB-exposed mice with the nuclear transport inhibitor suppressed the inflammatory storm in the lungs. Inflammatory cells, whose numbers increase 2.5-fold after SEB exposure, remained normal in peptide-treated mice. Peptide therapy also suppressed the levels of chemokines and cytokines and prevented injury to the lung's blood vessels.

"It's very reassuring to us that this single agent, which targets the nuclear import shuttle, suppressed the production of all of these harmful mediators of excessive inflammation," Hawiger said.

The investigators are pursuing pre-clinical studies of the peptide therapy with hopes that it will lead to improved adjunctive therapies for life-threatening pneumonia caused by multiple germs.

###

Danya Liu, M.D., Jozef Zienkiewicz, Ph.D., and Antonio DiGiandomenico, Ph.D., performed the studies, which were supported by research and fellowship grants from the National Heart, Lung, and Blood Institute.
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<cite cite="http://www.eurekalert.org/pub_releases/2009-03/vumc-ntp031109.php">New therapy protects lungs from runaway inflammation</cite>

 

[Giuseppe]

Re: Influenza and Pandemic Influenza: Are New Vaccines and Therapeuticals coming as current defense waning?

Proc Natl Acad Sci U S A. 2009 Mar 11. [Epub ahead of print]

TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection.

Aldridge JR Jr, Moseley CE, Boltz DA, Negovetich NJ, Reynolds C, Franks J, Brown SA, Doherty PC, Webster RG, Thomas PG. - Division of Virology, Department of Infectious Diseases, and.

Respiratory infection with highly pathogenic influenza A viruses is characterized by the exuberant production of cytokines and chemokines and the enhanced recruitment of innate inflammatory cells.
Here, we show that challenging mice with virulent influenza A viruses, including currently circulating H5N1 strains, causes the increased selective accumulation of a particular dendritic cell subset, the tipDCs, in the pneumonic airways.
These tipDCs are required for the further proliferation of influenza-specific CD8(+) T cells in the infected lung, because blocking their recruitment in CCR2(-/-) mice decreases the numbers of CD8(+) effectors and ultimately compromises virus clearance.
However, diminution rather than total elimination of tipDC trafficking by treatment with the peroxisome proliferator-activated receptor-gamma agonist pioglitazone moderates the potentially lethal consequences of excessive tipDC recruitment without abrogating CD8(+) T cell expansion or compromising virus control.
Targeting the tipDCs in this way thus offers possibilities for therapeutic intervention in the face of a catastrophic pandemic.

PMID: 19279209 [PubMed - as supplied by publisher]
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[sharon sanders]

Re: Influenza and Pandemic Influenza: Are New Vaccines and Therapeuticals coming as current defense waning?

China and Egypt are using plasma anti-body treatment to cure bird flu cases:


http://www.flutrackers.com/forum/showthread.php?t=96932