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Baylor Flu Fighters Take On the Wily "Novel H1N1" (Swine) Flu Virusby Ruth SoRelle, M.P.H. 
Dr. Wendy A. Keitel, left, and Dr. Gail J. Demmler-Harrison Nothing has been easy about the stealth influenza virus, variously called novel H1N1 and swine flu, that attacked Mexico and then snuck across the U.S. and other borders to create a pandemic. When the news of the new influenza first became public last April, researchers at Baylor College of Medicine went into overdrive. In the Diagnostic Virology Laboratory at Texas Children's Hospital, the director, Dr. Gail Demmler-Harrison, a professor of pediatrics at BCM, immediately began the ticklish process of growing the virus in culture. Success in that endeavor enabled her to help public health experts across the world put together a genomic picture of the virus itself. In March, faint echoes of a possible new virus had filtered through to her from colleagues in Mexico, preparing her for the challenge that came to a head in April and May. Blue-masked faces from Mexico City dominated the headlines, and the public responded with alarm as it became clear the virus did not respect international borders. Cases cropped up across the United States and as far away as New Zealand. 
Demmler-Harrison checks a specimen through the microscope When the public's attention waned as school let out at the end of May, Demmler-Harrison and her colleagues in BCM's Vaccine and Treatment Evaluation Unit found no respite. While the numbers declined some, flu cases—primarily the new variety—continued during summer, when flu usually drops off the radar entirely. At the end of July, Demmler-Harrison was walking through her laboratory at the end of a day when she got a call from the Texas Children's emergency department. How many rapid flu test kits did she have? It appeared that there was a flu outbreak at a camp for children with chronic diseases, and many of them were coming in to be tested. As "ground zero" for viral diagnostics in this region, Demmler-Harrison's lab takes the brunt of any outbreak. Influenza is a regular visitor. She calls it "predictably unpredictable." Accounting for unpredictability is what flu experts hope to do each year as they try to figure out how to craft a vaccine that will protect against a form of the virus that has not yet hit. Everyone is prepared for the dramatic change that could set off a worldwide influenza deluge, but no one knows what it will be. That is why laboratories such as Demmler-Harrison's are so important. They are the world's sentinels against viral rampage. 
Demmler-Harrison confers with Marily Flores, a BCM virology research technician, over the results of a rapid flu test. Her experience with the virus gives her a certain familiarity with its quirks. "The virus is RNA (ribonucleic acid) and made up of little segmented pieces," she said. "You can be infected with two different strains of flu. If that happens, when the virus replicates in your body, it can get the strains to mix up. Add to that the fact that it does not correct the errors it makes during replication well. Those uncorrected errors add to the mix and can change the flu from year to year." Because flu can infect birds and swine, experts watch them carefully for signs that a new strain is emerging. Recently, avian flu has cropped up in small outbreaks in various places around the world, arousing concern among infectious disease experts. Because flu can infect birds and swine, experts watch them carefully for signs that a new strain is emerging. "Everyone was watching the birds, and the swine made a move," said Demmler-Harrison. She considers herself one of the point people for the vaccine studies being undertaken by Drs. Wendy Keitel, Pedro (Tony) Piedra, Hana El Sahly, Paul Glezen, Flor Munoz-Rivas, Shital Patel, Robert Atmar and Robert Couch, all members of the Vaccine and Treatment Evaluation Unit team at BCM. "We talk to the doctors and start the process of referring patients to the vaccine studies," she said. "We are a good place to start because we are on the front line in diagnosis." 
The racks of specimens are full as the flu outbreak grows. Many of the samples from patients are placed in "archives" and forwarded to the National Institutes of Health for further studies to determine if the virus is changing over time, with geography and as it moves through infected individuals. One concern is that it could become resistant to Tamiflu, the drug currently used to reduce the effects of the virus after a person is infected. "We already know it is going to change," she said. "We are already seeing minor resistance." They are also keeping close watch on the proteins on the surface and within the virus to see if any of those proteins change. Changes in those can also change the population affected by the influenza virus. 
More and more rapid flu tests come back positive. Demmler-Harrison provides a web page with a "flu-o-meter" that alerts physicians and members of the public about the level of flu infections in the community and about what kinds of flu are circulating. Novel H1N1 (swine) flu dominated in the summer of 2009, but Demmler expects that the flu season will have a mixture of seasonal flu for which a vaccine exists and the swine variety for which a vaccine has been developed. Keitel, professor of molecular virology and microbiology at BCM, and her colleagues are part of that national effort to test new vaccines in various populations to determine how effective they are at stimulating responses that are associated with protection against infection. It appears to hit young people the hardest, and pregnant women are at particular risk. Yet she and her colleagues are concerned that reserving vaccine for the highest risk populations could backfire, leaving a large part of the population unprotected because they hesitate to get vaccinated. Vaccination against both seasonal and novel H1N1 (swine) influenza viruses will be important, she said. In the Southern Hemisphere during that part of the world's winter, both kinds of influenza circulated in varying rates, depending on the country and time frame. She anticipates a similar pattern in this part of the world during flu season. Demmler-Harrison provides a web page with a "flu-o-meter" that alerts physicians and members of the public about the level of flu infections in the community. If, as she and Demmler-Harrison anticipate, the virus "drifts" into resistance against Tamiflu, the world may have to rely on another antiviral medication called Relenza. Keitel's days are spent in high gear as she takes part in the "rapid research response" to collect information about how the virus attacks people and how it changes over time. Her unit ran a study of the effect of the licensed seasonal flu vaccine in pregnant women. Information about their immune response to that vaccine helped inform the use of the vaccine against the swine flu. Another study in her unit is looking at how co-administering the two vaccines—one against seasonal influenza viruses and the other against the novel H1N1 swine virus—in different combinations and at different times will prompt an immune response against both vaccines. Different studies in adults and children will give important information for using both vaccines. 
Keitel confers with Research II Technicians Adrienne Guerrero (left) and Brittany Ellis as they continue their tests of the H1N1 vaccine. Signing up hundreds of people in a few weeks, giving them the vaccine and evaluating their responses is a monumental task that requires both administrative and clinical skill. Keitel spends much of her day negotiating via conference calls, meeting with colleagues and collaborators and planning for the trials that will help determine how best to fight the disease during its heaviest season. Collaboration with different sites such as Scott and White Healthcare in Temple, Texas, The University of Texas Medical Branch in Galveston, and Kelsey-Seybold Clinic will help her make sure that the vaccine is safe and effective and the best formulation to give. Like Demmler-Harrison, Keitel stresses that vigilance is key to fighting the influenza virus, which can change quickly and in different ways. Concerns with influenza viruses in birds were justified because they infected humans, but the swine component was unexpected. "The world needs to be prepared for whatever comes next," she said. Keitel's job is to make sure the vaccines produced work safely, and it takes a huge team—from the physicians to the nurses, physician assistants, regulatory specialists, and others. The development of the new vaccine, which was prepared in the same way as seasonal influenza vaccines, took the expected six months, she said. Research needs to go into more efficient ways to grow viruses, said Keitel. Licensed influenza vaccines are grown in eggs, a limited and vulnerable resource. Current research is looking at using biotechnology to produce vaccines in more readily available substrates. If proven effective, these techniques could speed the availability and increase the supply of vaccines, said Keitel. Understanding the pattern of infection could prove important, she said. Viruses of the H1N1 variety circulated frequently in the human population before 1957, and reappeared in the late 1970s. Many of the people born before 1957 have been exposed to viruses similar to the current "swine" variety. Limited studies show that older people are more likely to have pre-existing antibodies to the "swine" virus. 
Demmler-Harrison checks test tubes in a special storage area. Defining the immunization needs of vulnerable populations—those most likely to be infected and to suffer complications following influenza—is critical, she said. The studies being conducted at the Vaccine and Treatment Evaluation Unit could inform public health officials about the best way to immunize people of all ages. A form of vaccine called live attenuated vaccine extends immunization supplies. It is given to healthy people between the ages of 2 and 49 years, while the other inactivated, or killed, virus vaccine is reserved for those for whom the live attenuated vaccine is not indicated. That would include infants under age 2, children with underlying health conditions such as heart diseases or asthma, younger adults with such health conditions or who are at greatest risk for serious disease with the H1N1 (swine) flu, and the elderly. "We need to do better outreach to pregnant women to insure that they get the vaccine," said Keitel. "We also need to do a better job immunizing people under age 65 who have underlying health conditions and health care workers. They all should be protected against influenza." Her job is to make sure the vaccines produced work safely, and it takes a huge team—from the physicians to the nurses, physician assistants, regulatory specialists, data management people, technicians in the laboratory and pharmacists as well as research coordinators and administrative personnel. It is a lot of work, and Keitel puts in long hours with her team. "But if you win, you save a lot of lives," she said. |
FeaturesGiving Elephants a Fighting Chance Facilitating a Vision for Research Integrating Care Around the Patient Baylor Flu Fighters Take On the Wily "Novel H1N1" (Swine) Flu Virus NewsNew Board Chair has High Hopes for BCM Lynch: A Physician-Teacher with a Humanitarian Twist SpotlightDr. Sean McGuire: Translating Early Lessons into Tomorrow's Treatment Simulated Patient Program Important Part of Medical Training Adding Value to Medical School Training Catalyzing Innovative Research is Mantra for BCM Diabetes Center A Coordinated Effort to Improve Health Care BriefsBCM Researchers Top Texas List of Stimulus Funds Recipients Wang Recognized for Contributions to Genetic Research Dr. Brendan Lee Receives Director's Transformative R01 'Pioneer' Studies Bacteria to Understand Cancer Dr. Mark Kline Selected Chair of Pediatrics Herding DNA to a New Understanding of Cows Development/AlumniBaylor Alumni Help Ease the Financial Burdens of Current Students Development BriefsAlkek Eye Center Celebrates 20th Year Partnership Gala To Fund DeBakey Heart Center® of Baylor College of Medicine Breast Center Advisory Council Funds Imaging Fellow Bra Art Displayed as Fundraiser Promise of Research Solid in Baylor's Future
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Volume 5, Issue 1, Winter 2009 |
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| Last modified: December 7, 2009 |