Dr. Anne Schuchat

Also, five months after the World Health Organization declared the end of the pandemic, the virus lives on as part of the seasonal flu. In the United Kingdom, the season geared up with an outbreak caused by the H1N1 virus that emerged in 2009.

With the flu season upon the U.S., Duke University invited Dr. Anne Schuchat, U.S. assistant surgeon general, to talk about influenza preparedness at its winter forum. The two-day forum starts at the beginning of the semester and allows about 100 undergraduate students to work through a global issue and what people can do about it.

Schuchat, who kicked off the forum Sunday, spoke about the intense media attention during the pandemic and how vital information sharing and transparency was in the public health response. Her talk inspired these questions and answers to test your flu preparedness.

“Everything is called the flu these days,” Schuchat said. But a cold is not the flu.

Question: What’s the difference?

Answer: The symptoms of a cold and the flu can be similar – sore throat, cough, runny or stuffy nose – but the viruses at work are different. A cold can be caused by a human coronavirus, a rhinovirus, an adenovirus and other viruses. The seasonal flu is caused by an influenza virus, such as H1N1, H3N2 or influenza virus B. A flu can worsen existing chronic conditions such as asthma and can be followed by pneumonia, dehydration and respiratory failure.

Question: How deadly is the flu?

Answer: U.S. public health officials estimated that the seasonal flu killed as few as 3,400 and as many as 49,000 per year from 1976 to 2007, according to a report the Centers for Disease Control and Prevention published last year. That compares to about 43,000 Americans who die in auto accidents per year.

The flu viruses can change from season to season, Schuchat said. Usually, these changes are minor. Sometimes, the changes are significant and an influenza A virus appears that causes serious illness in humans. The H1N1 virus that was first confirmed in April 2009 in a 10-year-old southern California boy had undergone such a significant shift.

H1N1 virus identified in 2009

Question: How was the virus different from the seasonal flu virus?

Answer: Wild birds are natural hosts for influenza A viruses, but pigs can also catch the flu. The H1N1 virus that caused the 2009 pandemic was created by bird, swine and human hosts. The genetic mix created a new strain to which humans had no immunity. During the pandemic, about 61 million Americans were infected by the new H1N1 strain and about 12,500 died, according to CDC estimates. Nearly 90 percent of the deaths were adults younger than 65 and children.

Question: Can pets catch the flu?

Answer: Yes, Schuchat said. Greyhounds are susceptible. Also, the H1N1 virus was confirmed in a Bengal tiger – not that tigers make good pets, but their cousins, the domestic cats, do.

Five vaccines to protect against the H1N1 flu were developed within months, according to a response history compiled by the CDC. Four of them received regulatory approval in September and a national vaccination campaign started in October. A fifth vaccine was approved in November.

Question: How many Americans got vaccinated?

Answer: More than 80 million, Schuchat said.

Measuring twice the size of a Super Wal-Mart store, the plant (photo below) will be the first in the U.S. to use millions of factory-grown cells rather than millions of fertilized chicken eggs to make seasonal and pandemic flu vaccine. With a production capacity of up to 150 million doses per year and room for expansions on the 167-acre site, the Novartis vaccine manufacturing plant in Holly Springs will also be one of the largest.

Company officials expect that the first dose made in Holly Springs will be sold in 2011 – a milestone in U.S. flu vaccine manufacturing, which has relied on fertilized chicken eggs since the end of World War II.

On Tuesday, Novartis offered a rare look inside the facility. Gov. Beverly Perdue, Congressman David Price and Kathleen Sebelius, U.S. secretary of health and human services, toured the facility. Daniel Vasella, chief executive of Novartis, and Dr. Andrin Oswald, head of Novartis’ vaccines and diagnostics division, were on hand to host the guests.

“It’s the beginning of modern cell-based flu manufacturing,” Oswald (photo at right) said during a media briefing. “This facility is a promise for the next 20 to 40 years.”

Cells cultured in the laboratory and grown in a series of ever larger tanks have been used to make biotech medicines for more than a decade. The Triangle, the center of the North Carolina biotech hub, got its first commercial biotech manufacturing facility in 1997, when Boston drugmaker Biogen Idec opened its cell-based production plant in RTP.

Cell cultures are also used to make some vaccines, including those protecting against polio, hepatitis B and types of the human papilloma virus that can cause cervical cancer. But the handful of companies that make flu vaccines have long been reluctant to switch from chicken eggs to cell cultures.

Flu vaccines aren’t profitable enough to justify the large investment necessary to build cell-based production facilities, said Novartis CEO Vasella. (Photo at right)

The Holly Springs plant required more than $1 billion in investments – about $600 million from Novartis and $487 million from the U.S. Department of Health and Human Services.

Without the public-private partnership, Vasella said, “a $1 billion investment would be a real stretch” for Novartis.

Announced about 10 months ago, the partnership followed four years after Swiss-based Novartis bought Chiron, the second largest supplier of U.S. flu vaccine, for about $5 billion.

Like other large pharmaceutical companies, Novartis wanted to beef up its vaccine business. But the company also saw the Chiron deal as an opportunity to pursue cell-based production technologies, Vasella said.

In 2004, quality problems with Chiron’s egg-based production method caused a shortage of seasonal flu vaccine supplies in the U.S. The same year, the first avian flu virus to infect people emerged in Asia. The virus, also known as H5N1, killed half of the about 250 people it infected over the next two years before its advance stopped in Europe.

The 2004 shortage of U.S. seasonal flu vaccine supplies and the threat of a deadly avian flu epidemic alarmed federal public health officials and led to the partnership that made construction of the Holly Springs facility possible, Vasella said.

Novartis officials said they hope the H1N1 virus (photo at left), which arrived in the U.S. in April and has killed nearly 4,000 nationwide, will help them with an immune response booster, or adjuvant, they want to make at the plant.

The adjuvant not only reduces the amount of H1N1 pandemic vaccine needed per shot by 75 percent, clinical tests have shown it also gives better protection for young children and the elderly.

Like the cell-based pandemic flu vaccine, Novartis’ adjuvant still requires regulatory approval in the U.S. Both are approved in Europe, the adjuvant for more than a decade.

The Food and Drug Administration, long reluctant to consider approving a vaccine adjuvant because of safety concerns, now is at least talking about what it would take to bring it to market, Oswald said.

In the past year, Novartis has tested pandemic flu vaccine with an adjuvant in the U.S. and started collecting data from the tests, said Russell Thirsk, head of Novartis’ U.K. vaccine manufacturing site in Liverpool.

While FDA approvals for the cell-based vaccine and the adjuvant are far from guaranteed, Novartis officials said there is a chance.

Last week, Protein Sciences was sent looking for more safety data for its cell-based seasonal flu vaccine. But the Connecticut biotech company uses insect cells to grow the one crucial protein that produces an immune response. Novartis’ approach is less experimental, using canine kidney cells the company has long cultured in the lab and inactivated virus.

The current shortage of H1N1 pandemic vaccine – brought on by the virus’ slower-than-expected growth in chicken eggs – could also become a factor.

Cell cultures grow much faster than chicken embryos, are available on demand and don’t pose the risk of allergic reactions to the vaccine. Also, the virus produced in eggs is slightly altered.

At the Holly Springs plant the steps of making flu vaccines with the help of cells is spread across three floors: from growing the cells in tanks holding up to 5,000 liters, about 1,250 gallons, to infecting the cells, harvesting and inactivating the virus and filling up to 600 vials per minute on a packaging line that is equipped with the latest technology available.

The plant already employs about 200. The work force is projected to increase to 350 by 2013.

How well has North Carolina responded to the H1N1 flu pandemic?

Infectious disease experts in the Triangle, home to two university medical centers, and state public health officials said they have struggled dealing with the virus (photo at right).

At the University of North Carolina at Chapel Hill, some medical students working with flu patients had a hard time getting the vaccine even though UNC hospitals at the time encouraged staff to get immunized, one of the students said at a gathering of public health experts Thursday at the N.C. Biotechnology Center.

It’s been difficult parceling out the limited supply of vaccine, said Dr. Megan Davies, the state’s epidemiologist.

But the Centers for Disease Control and Prevention suffered the brunt of the criticism.

The Atlanta-based federal agency monitors the H1N1 outbreak in the U.S., which started in April, and advises public health experts on how to treat patients. The CDC also helped identify the H1N1 virus and distributed tests to confirm an infection.

Dr. Myron Cohen, director of the UNC Institute for Global Health and Infectious Diseases, called the CDC an “ineffectual organization.”

“What they need is leadership. What they don’t have is a leader,” echoed Dr. Fred Sparling, a professor of microbiology and immunology at UNC-CH.

Cohen and Sparling were among about 40 people who attended the discussion group that was organized by the Triangle Global Health Consortium, an organization recently founded by Duke University, UNC-CH, N.C. State University, RTI International, Family Health International and IntraHealth International.

Critics have questioned CDC recommendations on protective gear for health care workers, testing guidelines to confirm the H1N1 virus and the way the agency has presented outbreak data to the public.

UNC hospitals developed a test to confirm H1N1 infections in-house shortly after the outbreak started, because shipments of the test the CDC distributed weren’t forthcoming, said Dr. David Weber, professor of medicine, pediatrics and epidemiology at UNC-CH.

A few months later, CDC advised states to limit testing for the H1N1 virus to patients with flu-like symptoms. The reason for the guideline change was the high cost of testing at a time when most tests came back positive, CDC spokesman Jeff Dimond wrote in an e-mail.

In September, the CDC changed the way the outbreak was tracked. Data reflected patients with flu-like symptoms rather than just cases where the H1N1 virus was confirmed. And on Nov. 16, the CDC revised the number of deaths for the first six months of the outbreak, raising the estimated number of Americans who have died from H1N1 to about 3,900. But only 23 percent of the cases were laboratory-confirmed H1N1 infections, according to numbers states reported to the CDC.

Indeed, the revised death toll doesn’t mean the outbreak is worse than thought, Dimond wrote. It just reflects a more accurate count of cases that couldn’t be quantified before.

The number of H1N1 deaths compare to an average 36,000 deaths every year from seasonal flu and related complications, according to CDC data.

In North Carolina, 58 deaths have been attributed to H1N1, but only 13 were lab-confirmed as of Sept. 26, when the reporting guidelines changed.

UNC had six deaths, Duke had 10.

So far, the virus has caused two waves of infections in the U.S. with a third expected to follow in two to three months.

The H1N1 virus is different from the virus that causes the seasonal flu, because it contains genetic material from European and Asian birds and pigs. Symptoms include fever, fatigue and diarrhea.

The H1N1 flu is also called the swine flu, even though it is not linked to American pigs. The name has had unfortunate repercussions for North Carolina’s hog growers, said Barrett Slenning, a veterinarian at N.C. State University.

North Carolina’s swine industry, with about 9 million animals the second largest in the nation, is losing about $20 per head right now, Slenning said. He attributed at least half of the loss to consumers’ misconceptions about the origin of the H1N1 virus.

MONDAY

10 a.m. to 11:30 a.m.
National Evolutionary Synthesis Center, 2024 W. Main Street, Durham
Panel discussion on how evolutionary theory can contribute new insights to regulatory problems such as financial reform, environmental regulation and the regulation of between-group conflict. Leading experts in the field of evolutionary biology, economics. law, psychology and political science will participate.
More information here.

11 a.m. to noon
National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Rodbell A
Seminar: Maternal control of fertilization and early development: Insights from mouse genetics
Speaker: Dr. Jurrien Dean, National Institute of Diabetes and Digestive and Kidney Diseases

11:15 a.m.
NCSU, 3503 Thomas Hall, Raleigh
Dept. of Entomology Seminar: Behavioral and ecological determinants of Argentine ant invasion success
Speaker: Jules Silverman, NCSU

1:30 p.m.
NCSU, 3503 Thomas Hall, Raleigh
Dept. of Genetics Seminar: How to get published in Science
Speaker: Dr. Laura Zahn, associate editor of Science

1:30 p.m. to 2:30 p.m.
NIEHS, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Rodbell A
Seminar: Post-diagnosis weight change, physical activity and survival among women with breast cancer: A longitudinal study with missing data
Speaker: Patrick Bradshaw, department of epidemiology, UNC-CH

3 p.m.
NCSU, Room 105 Schaub Hall, Raleigh
Dept. of Food, Bioprocessing and Nutrition Sciences: “Food Inc.,” the movie, will be shown

4 p.m.
NCSU, Stephens Room, Gardner 3503, Raleigh
Dept. of Plant Pathology: Analysis of selected parasitism genes of the root knot nematode
Speaker: Adrienne Smith, PhD candidate, NCSU

4 p.m.
NCSU, Riddick 301, Raleigh
Dept. of Physics Colloqium:Phase-change memory: Progress in development of a new computer data storage technology
Speaker: Stephen Hudgens, Santa Clara University

TUESDAY

Noon to 1:30 p.m.
Research Triangle Park headquarters, 12 Davis Drive, Research Triangle Park
Triangle Area Research Directors Council luncheon
Speaker: Rudy Juliano, Carolina Center for Cancer Nanotechnology

3:30 p.m.
Duke University, Physics 298, Durham
Triangle Nuclear Theory Colloqium: Universality in pion-less EFT with the resonating group model: Three, four and six nucleons
Speaker: Johannes Kirscher, George Washington University

4 p.m.
NCSU, 101 David Clark Labs, Raleigh
Dept. of Plant Biology Seminar: HD videoconferencing: opening doors to new research, collaboration and teaching between the David H. Murdock Research Institute and NCSU
Speakers: Eva Johannes and John Mackenzie, NCSU

WEDNESDAY

7 a.m. to 4 p.m.
Duke University Fuqua School of Business, 1 Towerview Drive, Durham
Duke MBA Health Care Conference: Defying uncertainty: Changing the future of health care
Cost: $150.
More information here.

8:30 a.m. to 9:45 a.m.
NCBIO, 100 Capitola Drive, Suite 106, Raleigh
NCBIO’s emerging companies forum.
More information here.

11 a.m. to noon
NIEHS, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Room F193
Seminar: Mechanisms of synaptic plasticity in the adult and developing nervous system
Speaker: Serena Dudek, NIEHS

Noon to 1:30 p.m.
CED Entrepreneurship Center, 100 Capitola Drive, Suite 106, Durham
Direct Connections: Technology trends and emerging issues in the technology sector, including the view from partners and investors
More information here.

3:30 p.m. to 5 p.m.
NCSU, Centennial Campus Center for Wildlife Education, 1751 Varsity Drive, Raleigh
Dept. of Forestry and Environmental Resources: Managing native warm-season grasses: Striking a balance between wildlife and livestock interests
Speaker: Craig Harper, professor at the University of Tennessee

5:30 p.m.
UNC, Maurice J. Koury Auditorium, Chapel Hill
Carolina Entrepreneurial Initiative: “The story of an entrepreneur”
Speaker: Ping Fu, CEO of Geomagic, shares her gripping story from Chinese prison to the Research Triangle Park

THURSDAY

7:30 a.m. to 9 a.m.
N.C. Biotechnology Center, 15 T.W. Alexander Drive, Research Triangle Park
Triangle Global Health Consortium breakfast discussion: Local response to the novel H1N1 pandemic
Facilitator: David Weber, professor of medicine and pediatrics, professor of epidemiology, UNC-CH
More information here.

10 a.m. to 2 p.m.
RTP headquarters, 12 Davis Drive, Research Triangle Park
Environment@rtp: Solid waste management vendor fair
Speaker: Scott Mouw, N.C. Division of Pollution Prevention and Environmental Assistance

10 a.m. to 11 a.m.
NIEHS, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Room D450
Seminar: The complex roles of IKK and NF-kappaB in oncogenesis
Speaker: Albert S. Baldwin, UNC Lineberger Comprehensive Cancer Center

1 p.m. to 2 p.m.
NIEHS, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Room F193
Seminar: Mass-spectrometry-based structural proteomics: HD amide exchange, chemical mapping and free-radical footprinting
Speaker: Michael Gross, professor of chemistry, Washington University

4 p.m.
NCSU, 101 David Clark Labs, Raleigh
Dept. of Biology Seminar: Understanding the behavioral context of ultrasound production by wild Peromyscus mice
Speaker: Matina Kalcounis-Rueppel, UNC-Greensboro

Salix soars on rifaximin data

Shares of Salix Pharmaceuticals are up more than 50 percent since the Morrisville company, which specializes in gastrointestinal treatments, announced results from two late-stage studies.

The studies showed rifaximin works better than placebo in treating non-constipation irritable bowel syndrome. Salix already sells rifaximin for traveler’s diarrhea under the name Xifaxan.

Treatments for non-constipation IBS generate about $2.2 billion in annual sales, but patients and doctors are looking for more choices with fewer side effects.

Salix stock dropped below $6 a year ago as the company struggled with generic competition. The day the rifaximin study results came out, Salix shares soared as high as $21.34. Since then, they’ve been close to $20 and attracting the attention of Credit Suisse pharmaceuticals analyst Catherine Arnold, who has tagged Salix an appetizing acquisition target for large drugmakers looking to boost revenue.

Pozen hires executive to broaden its scope

Pozen, a Chapel Hill drug development company, hired a chief commercial officer to develop licensing and marketing strategies for its drugs in development. Elizabeth Cermack, a former Johnson & Johnson executive, specializes in sales and marketing.

Founded in 1996, Pozen has long relied on partnerships with large drugmaker to help develop and market its medicines. Migraine pill Treximet, its first drug to receive regulatory approval, is sold by GlaxoSmithKline, which also helped develop it. Pozen also has a partnership with AstraZeneca to develop and bring to market Vimovo, an experimental painkiller that is easy on the stomach.

But the company, which never ventured into sales and marketing before, recently announced plans to broaden its scope and fly solo bringing to market its family of aspirins that promise to be gentler on the stomach.

GSK waits while competition gets ahead

GlaxoSmithKline, which has its U.S. headquarters in Research Triangle Park, hopes to get approval for Cervarix, a vaccine that blocks a major risk factor for cervical cancer, before the end of the month.

A Food and Drug Administration panel recently recommended the vaccine get cleared for sale after a series of delays. If the FDA follows the recommendation, Cervarix would become available in the U.S. three years after Merck’s version Gardasil was approved.

GSK is also still awaiting FDA approval of its H1N1 vaccine. Four competitors already got the regulatory nod.