Roxanna Guilford-Blake

SAVANNAH, GA. – Functional MRIs reveal neuroanatomical differences between normal worry and pathological worry in the elderly, and those differences might help explain why late-life anxiety often proves difficult to treat.

The amygdala and the subgenual anterior cingulate cortex (sACC) seem to be involved in the functional neuroanatomy of late-life anxiety disorders, Dr. Carmen Andreescu of the University of Pittsburgh reported at the meeting.

The findings, based on fMRIs of 10 nonanxious elderly people and 8 elderly people with anxiety, suggest a biological substrate for the persistent and uncontrollable characteristics of pathological worry, she said. The subjects were asked to worry while they were in the scanner, then they were asked to suppress the worry and think of “something nice” for a minute.

In the nonanxious subjects, worry induction increased activation of the amygdala and decreased activation of the sACC. During worry suppression, the scans revealed decreased activation of the amygdala and increased activation of the sACC.

Not so for the elderly subjects with generalized anxiety disorder (GAD). The fMRI revealed increased activation of the amygdala and the subgenual ACC during worry suppression, suggesting a delayed yet sustained amygdala involvement and the unsuccessful attempts of the subgenual ACC to modulate the worry process, she explained.

That the amygdala stays active during worry suppression is “the most yummy part,” Dr. Andreescu reported, explaining it this way: Tell a friend without anxiety to stop worrying, and they will. Tell someone with pathological anxiety to stop worrying, and the result might be increased amygdala activity.

“There is a paucity of data regarding late-life anxiety, but based on my preliminary data, it seems that these regions are involved in late-life anxiety, just as they are in mid-life anxiety,” she said in an interview. Significantly, when someone tries to modulate his or her worry, “the interplay between these two regions is different in healthy people and in pathologically anxious people.”

Dr. Andreescu reported no conflicts relevant to the study.

SAVANNAH, GA. – Functional MRIs reveal neuroanatomical differences between normal worry and pathological worry in the elderly, and those differences might help explain why late-life anxiety often proves difficult to treat.

The amygdala and the subgenual anterior cingulate cortex (sACC) seem to be involved in the functional neuroanatomy of late-life anxiety disorders, Dr. Carmen Andreescu of the University of Pittsburgh reported at the meeting.

The findings, based on fMRIs of 10 nonanxious elderly people and 8 elderly people with anxiety, suggest a biological substrate for the persistent and uncontrollable characteristics of pathological worry, she said. The subjects were asked to worry while they were in the scanner, then they were asked to suppress the worry and think of “something nice” for a minute.

In the nonanxious subjects, worry induction increased activation of the amygdala and decreased activation of the sACC. During worry suppression, the scans revealed decreased activation of the amygdala and increased activation of the sACC.

Not so for the elderly subjects with generalized anxiety disorder (GAD). The fMRI revealed increased activation of the amygdala and the subgenual ACC during worry suppression, suggesting a delayed yet sustained amygdala involvement and the unsuccessful attempts of the subgenual ACC to modulate the worry process, she explained.

That the amygdala stays active during worry suppression is “the most yummy part,” Dr. Andreescu reported, explaining it this way: Tell a friend without anxiety to stop worrying, and they will. Tell someone with pathological anxiety to stop worrying, and the result might be increased amygdala activity.

“There is a paucity of data regarding late-life anxiety, but based on my preliminary data, it seems that these regions are involved in late-life anxiety, just as they are in mid-life anxiety,” she said in an interview. Significantly, when someone tries to modulate his or her worry, “the interplay between these two regions is different in healthy people and in pathologically anxious people.”

Dr. Andreescu reported no conflicts relevant to the study.

SAVANNAH, GA. – Functional MRIs reveal neuroanatomical differences between normal worry and pathological worry in the elderly, and those differences might help explain why late-life anxiety often proves difficult to treat.

The amygdala and the subgenual anterior cingulate cortex (sACC) seem to be involved in the functional neuroanatomy of late-life anxiety disorders, Dr. Carmen Andreescu of the University of Pittsburgh reported at the meeting.

The findings, based on fMRIs of 10 nonanxious elderly people and 8 elderly people with anxiety, suggest a biological substrate for the persistent and uncontrollable characteristics of pathological worry, she said. The subjects were asked to worry while they were in the scanner, then they were asked to suppress the worry and think of “something nice” for a minute.

In the nonanxious subjects, worry induction increased activation of the amygdala and decreased activation of the sACC. During worry suppression, the scans revealed decreased activation of the amygdala and increased activation of the sACC.

Not so for the elderly subjects with generalized anxiety disorder (GAD). The fMRI revealed increased activation of the amygdala and the subgenual ACC during worry suppression, suggesting a delayed yet sustained amygdala involvement and the unsuccessful attempts of the subgenual ACC to modulate the worry process, she explained.

That the amygdala stays active during worry suppression is “the most yummy part,” Dr. Andreescu reported, explaining it this way: Tell a friend without anxiety to stop worrying, and they will. Tell someone with pathological anxiety to stop worrying, and the result might be increased amygdala activity.

“There is a paucity of data regarding late-life anxiety, but based on my preliminary data, it seems that these regions are involved in late-life anxiety, just as they are in mid-life anxiety,” she said in an interview. Significantly, when someone tries to modulate his or her worry, “the interplay between these two regions is different in healthy people and in pathologically anxious people.”

Dr. Andreescu reported no conflicts relevant to the study.

SAVANNAH, GA. – An innovative intervention combining exercise and exposure therapy addresses the outsized fear of falling that limits many seniors' activities.

Fear of falling, a debilitating but undertreated condition, is generally correlated more with anxiety than with physical disability. However, the proposed intervention called ABLE – Activity, Balance, Learning, and Exposure – might help solve the problem.

A quarter of the elderly report moderate to severe fear of falling; about 10% of those avoid activities as a result of that fear, Julie Wetherell, Ph.D., reported during a symposium on anxiety at the meeting. She noted that fear of falling has been described in many epidemiologic studies.

Fear of falling actually increases the risk of falls, she reported. In fact, those with no falls but high fear have a nearly fivefold increased risk of nursing home admission, even after controlling for age and disability. It also increases the risk of depression.

The condition often goes undetected and therefore untreated. Seniors are reluctant to discuss concerns about falling and they may be unwilling to seek help for the anxiety because of the stigmas related to mental health issues.

That the fear is rooted in an objective risk also makes identification and treatment more challenging. Nevertheless, Dr. Wetherell, who is with the department of psychiatry at the University of California, San Diego, noted that fear of falling is more closely correlated with symptoms of anxiety than with physical symptoms.

Community-based exercise and fall-education programs are available, but seniors who are unwilling to leave their homes as a result of their fear don't have access to them. Moreover, families often reinforce the avoidant behavior.

Dr. Wetherell offered a case study to illustrate some of these issues. An 85-year-old woman who had fallen twice in the past 3 years, once in the last year, was diagnosed with osteoporosis. The intervention consisted of her doctor telling her “don't fall.” She went online to find balance exercises, but she won't leave the house alone. Her daughter pays someone to accompany her when she goes out, which is reinforcing the avoidant behavior.

When Dr. Wetherell tried to discuss treatment, the woman turned her down because she was a psychologist. “My problem isn't in my head, it's real,” the woman said.

The woman did not receive an intervention.

Dr. Wetherell's proposed ABLE plan addresses several of those barriers. It includes exercise, a medication review, and a home safety evaluation. The intervention is delivered in the home by a physical therapist, not a mental health professional. Families and caregivers are encouraged to participate.

Delivery by the physical therapist is key: It helps avoid the “it's not in my head” reaction illustrated by the first case study. As part of the intervention, the patient creates a hierarchy of activities, such as walking to the driveway alone, walking with a full cart of groceries through a parking lot, getting in and out of a car alone, and so on. Then the patient rates, on a scale of 0-10, which of the activities are the most anxiety provoking.

The therapy starts with situations rated 5-6. The patient is asked to perform one of the activities in the presence of the therapist and then with a friend or family member between sessions. This is continued until the anxiety is only mild; then the process begins with the next items on the list.

Dr. Wetherell presented another case, this time one in which the ABLE intervention seemed to have been effective. A 79-year-old man had multiple medical problems and in addition to his fear of falling, he had symptoms of generalized anxiety disorder and depression. He wouldn't leave his home, nor would he use an assistive device.

After four sessions over 4 months, he showed marked improvement. (Sessions should be more frequent, but medical issues interfered in the case of this particular patient, Dr. Wetherell noted.) The man had fallen 10 times in past year, but fell only twice during treatment. His exercise capacity doubled, and his gait and balance improved. Moreover, he eventually started going out of his home.

As a result of the exposure therapy, the man, a 30-year Marine veteran, resumed a task he once loved: speaking to Marine recruits at Camp Pendleton. He now agrees to use a cane and let two younger Marines (“his honor guard”) escort him to and from the podium.

In an interview, Dr. Wetherell said that, pending funding, she hopes to start recruiting for a larger pilot soon.

Dr. Wetherell has received research support from Forest Laboratories.

SAVANNAH, GA. – An innovative intervention combining exercise and exposure therapy addresses the outsized fear of falling that limits many seniors' activities.

Fear of falling, a debilitating but undertreated condition, is generally correlated more with anxiety than with physical disability. However, the proposed intervention called ABLE – Activity, Balance, Learning, and Exposure – might help solve the problem.

A quarter of the elderly report moderate to severe fear of falling; about 10% of those avoid activities as a result of that fear, Julie Wetherell, Ph.D., reported during a symposium on anxiety at the meeting. She noted that fear of falling has been described in many epidemiologic studies.

Fear of falling actually increases the risk of falls, she reported. In fact, those with no falls but high fear have a nearly fivefold increased risk of nursing home admission, even after controlling for age and disability. It also increases the risk of depression.

The condition often goes undetected and therefore untreated. Seniors are reluctant to discuss concerns about falling and they may be unwilling to seek help for the anxiety because of the stigmas related to mental health issues.

That the fear is rooted in an objective risk also makes identification and treatment more challenging. Nevertheless, Dr. Wetherell, who is with the department of psychiatry at the University of California, San Diego, noted that fear of falling is more closely correlated with symptoms of anxiety than with physical symptoms.

Community-based exercise and fall-education programs are available, but seniors who are unwilling to leave their homes as a result of their fear don't have access to them. Moreover, families often reinforce the avoidant behavior.

Dr. Wetherell offered a case study to illustrate some of these issues. An 85-year-old woman who had fallen twice in the past 3 years, once in the last year, was diagnosed with osteoporosis. The intervention consisted of her doctor telling her “don't fall.” She went online to find balance exercises, but she won't leave the house alone. Her daughter pays someone to accompany her when she goes out, which is reinforcing the avoidant behavior.

When Dr. Wetherell tried to discuss treatment, the woman turned her down because she was a psychologist. “My problem isn't in my head, it's real,” the woman said.

The woman did not receive an intervention.

Dr. Wetherell's proposed ABLE plan addresses several of those barriers. It includes exercise, a medication review, and a home safety evaluation. The intervention is delivered in the home by a physical therapist, not a mental health professional. Families and caregivers are encouraged to participate.

Delivery by the physical therapist is key: It helps avoid the “it's not in my head” reaction illustrated by the first case study. As part of the intervention, the patient creates a hierarchy of activities, such as walking to the driveway alone, walking with a full cart of groceries through a parking lot, getting in and out of a car alone, and so on. Then the patient rates, on a scale of 0-10, which of the activities are the most anxiety provoking.

The therapy starts with situations rated 5-6. The patient is asked to perform one of the activities in the presence of the therapist and then with a friend or family member between sessions. This is continued until the anxiety is only mild; then the process begins with the next items on the list.

Dr. Wetherell presented another case, this time one in which the ABLE intervention seemed to have been effective. A 79-year-old man had multiple medical problems and in addition to his fear of falling, he had symptoms of generalized anxiety disorder and depression. He wouldn't leave his home, nor would he use an assistive device.

After four sessions over 4 months, he showed marked improvement. (Sessions should be more frequent, but medical issues interfered in the case of this particular patient, Dr. Wetherell noted.) The man had fallen 10 times in past year, but fell only twice during treatment. His exercise capacity doubled, and his gait and balance improved. Moreover, he eventually started going out of his home.

As a result of the exposure therapy, the man, a 30-year Marine veteran, resumed a task he once loved: speaking to Marine recruits at Camp Pendleton. He now agrees to use a cane and let two younger Marines (“his honor guard”) escort him to and from the podium.

In an interview, Dr. Wetherell said that, pending funding, she hopes to start recruiting for a larger pilot soon.

Dr. Wetherell has received research support from Forest Laboratories.

SAVANNAH, GA. – An innovative intervention combining exercise and exposure therapy addresses the outsized fear of falling that limits many seniors' activities.

Fear of falling, a debilitating but undertreated condition, is generally correlated more with anxiety than with physical disability. However, the proposed intervention called ABLE – Activity, Balance, Learning, and Exposure – might help solve the problem.

A quarter of the elderly report moderate to severe fear of falling; about 10% of those avoid activities as a result of that fear, Julie Wetherell, Ph.D., reported during a symposium on anxiety at the meeting. She noted that fear of falling has been described in many epidemiologic studies.

Fear of falling actually increases the risk of falls, she reported. In fact, those with no falls but high fear have a nearly fivefold increased risk of nursing home admission, even after controlling for age and disability. It also increases the risk of depression.

The condition often goes undetected and therefore untreated. Seniors are reluctant to discuss concerns about falling and they may be unwilling to seek help for the anxiety because of the stigmas related to mental health issues.

That the fear is rooted in an objective risk also makes identification and treatment more challenging. Nevertheless, Dr. Wetherell, who is with the department of psychiatry at the University of California, San Diego, noted that fear of falling is more closely correlated with symptoms of anxiety than with physical symptoms.

Community-based exercise and fall-education programs are available, but seniors who are unwilling to leave their homes as a result of their fear don't have access to them. Moreover, families often reinforce the avoidant behavior.

Dr. Wetherell offered a case study to illustrate some of these issues. An 85-year-old woman who had fallen twice in the past 3 years, once in the last year, was diagnosed with osteoporosis. The intervention consisted of her doctor telling her “don't fall.” She went online to find balance exercises, but she won't leave the house alone. Her daughter pays someone to accompany her when she goes out, which is reinforcing the avoidant behavior.

When Dr. Wetherell tried to discuss treatment, the woman turned her down because she was a psychologist. “My problem isn't in my head, it's real,” the woman said.

The woman did not receive an intervention.

Dr. Wetherell's proposed ABLE plan addresses several of those barriers. It includes exercise, a medication review, and a home safety evaluation. The intervention is delivered in the home by a physical therapist, not a mental health professional. Families and caregivers are encouraged to participate.

Delivery by the physical therapist is key: It helps avoid the “it's not in my head” reaction illustrated by the first case study. As part of the intervention, the patient creates a hierarchy of activities, such as walking to the driveway alone, walking with a full cart of groceries through a parking lot, getting in and out of a car alone, and so on. Then the patient rates, on a scale of 0-10, which of the activities are the most anxiety provoking.

The therapy starts with situations rated 5-6. The patient is asked to perform one of the activities in the presence of the therapist and then with a friend or family member between sessions. This is continued until the anxiety is only mild; then the process begins with the next items on the list.

Dr. Wetherell presented another case, this time one in which the ABLE intervention seemed to have been effective. A 79-year-old man had multiple medical problems and in addition to his fear of falling, he had symptoms of generalized anxiety disorder and depression. He wouldn't leave his home, nor would he use an assistive device.

After four sessions over 4 months, he showed marked improvement. (Sessions should be more frequent, but medical issues interfered in the case of this particular patient, Dr. Wetherell noted.) The man had fallen 10 times in past year, but fell only twice during treatment. His exercise capacity doubled, and his gait and balance improved. Moreover, he eventually started going out of his home.

As a result of the exposure therapy, the man, a 30-year Marine veteran, resumed a task he once loved: speaking to Marine recruits at Camp Pendleton. He now agrees to use a cane and let two younger Marines (“his honor guard”) escort him to and from the podium.

In an interview, Dr. Wetherell said that, pending funding, she hopes to start recruiting for a larger pilot soon.

Dr. Wetherell has received research support from Forest Laboratories.

SAVANNAH, GA. – Deep brain stimulation shows potential for treatment of geriatric psychiatric disorders, particularly treatment-resistant depression and obsessive-compulsive disorder.

Deep brain stimulation (DBS), an effective therapy for Parkinson's disease and essential tremor, may hold promise for treatment of geriatric psychiatric disorders, Dr. Paul Holtzheimer said in a symposium on neuromodulation therapies at the meeting.

Research into DBS for treatment-resistant depression (TRD) and for obsessive-compulsive disorder (OCD), as well as for other psychiatric disorders, has been advancing, noted Dr. Holtzheimer of the department of psychiatry and behavioral sciences at Emory University, Atlanta. But more studies into efficacy, mechanisms of action, and side-effect profile – and especially long-term effects – are needed.

DBS delivers targeted electrical stimulation into the brain through a device that consists of an electrode connected to an insulated wire, inserted through a small opening in the skull. The wire is run under the skin of the head, neck, and shoulder, connecting the electrode to an implantable pulse generator (a “pacemaker”), which is implanted near the collarbone.

One advantage of a DBS device is that it can be tuned, Dr. Holtzheimer said. The electrode has four contacts, allowing the stimulation level to be adjusted and revised.

Implantation is a relatively safe procedure – “as simple as it can be,” Dr. Holtzheimer said – with a low complication rate (around 10%). The most common complication is infection; stroke is a less common but far more worrisome one, he said.

Early research in TRD suggests efficacy and safety for subcallosal cingulate, ventral capsule/ventral striatum (VC/VS), and nucleus accumbens targets. Dr. Holtzheimer called the results so far “reasonably positive.” Multicenter trials are underway for the subcallosal cingulate and VC/VS targets.

The OCD data also suggest reasonable efficacy and safety for the VC/VS, inferior thalamic peduncle, and subthalamic nucleus targets, but not the nucleus accumbens.

In 2009, the Food and Drug Administration approved a humanitarian device exemption for the use of DBS to treat OCD (VC/VS target).

The progress is encouraging, but the lack of randomized, placebo-controlled data means that long-term safety and efficacy have yet to be established, Dr. Holtzheimer cautioned. Moreover, safety and efficacy have yet to be tested in geriatric populations, and those patients are not part of the ongoing trials.

There's no reason to believe that DBS would be less safe or effective in geriatric populations, observed another member of the neuromodulation panel, Dr. William McDonald, professor of psychiatry and behavioral sciences at Emory University.

Looking ahead, questions abound, Dr. Holtzheimer acknowledged: Is late-onset depression a completely different biology from depression in younger populations? Can clinicians extrapolate efficacy to an older population?

He also pointed out that it may take months of DBS therapy before it becomes effective. It does not replace medications or psychotherapy, but it may enhance other therapeutic approaches, such as cognitive-behavioral therapy, he said.

Meanwhile, researchers are starting to look at other psychiatric indications for DBS. For example, research is underway in Toronto to explore its use in dementia, Dr. Holtzheimer said.

Dr. Holtzheimer is a consultant for St. Jude Medical: Neuromodulation, a site of one of the trials for DBS in TRD.

SAVANNAH, GA. – Deep brain stimulation shows potential for treatment of geriatric psychiatric disorders, particularly treatment-resistant depression and obsessive-compulsive disorder.

Deep brain stimulation (DBS), an effective therapy for Parkinson's disease and essential tremor, may hold promise for treatment of geriatric psychiatric disorders, Dr. Paul Holtzheimer said in a symposium on neuromodulation therapies at the meeting.

Research into DBS for treatment-resistant depression (TRD) and for obsessive-compulsive disorder (OCD), as well as for other psychiatric disorders, has been advancing, noted Dr. Holtzheimer of the department of psychiatry and behavioral sciences at Emory University, Atlanta. But more studies into efficacy, mechanisms of action, and side-effect profile – and especially long-term effects – are needed.

DBS delivers targeted electrical stimulation into the brain through a device that consists of an electrode connected to an insulated wire, inserted through a small opening in the skull. The wire is run under the skin of the head, neck, and shoulder, connecting the electrode to an implantable pulse generator (a “pacemaker”), which is implanted near the collarbone.

One advantage of a DBS device is that it can be tuned, Dr. Holtzheimer said. The electrode has four contacts, allowing the stimulation level to be adjusted and revised.

Implantation is a relatively safe procedure – “as simple as it can be,” Dr. Holtzheimer said – with a low complication rate (around 10%). The most common complication is infection; stroke is a less common but far more worrisome one, he said.

Early research in TRD suggests efficacy and safety for subcallosal cingulate, ventral capsule/ventral striatum (VC/VS), and nucleus accumbens targets. Dr. Holtzheimer called the results so far “reasonably positive.” Multicenter trials are underway for the subcallosal cingulate and VC/VS targets.

The OCD data also suggest reasonable efficacy and safety for the VC/VS, inferior thalamic peduncle, and subthalamic nucleus targets, but not the nucleus accumbens.

In 2009, the Food and Drug Administration approved a humanitarian device exemption for the use of DBS to treat OCD (VC/VS target).

The progress is encouraging, but the lack of randomized, placebo-controlled data means that long-term safety and efficacy have yet to be established, Dr. Holtzheimer cautioned. Moreover, safety and efficacy have yet to be tested in geriatric populations, and those patients are not part of the ongoing trials.

There's no reason to believe that DBS would be less safe or effective in geriatric populations, observed another member of the neuromodulation panel, Dr. William McDonald, professor of psychiatry and behavioral sciences at Emory University.

Looking ahead, questions abound, Dr. Holtzheimer acknowledged: Is late-onset depression a completely different biology from depression in younger populations? Can clinicians extrapolate efficacy to an older population?

He also pointed out that it may take months of DBS therapy before it becomes effective. It does not replace medications or psychotherapy, but it may enhance other therapeutic approaches, such as cognitive-behavioral therapy, he said.

Meanwhile, researchers are starting to look at other psychiatric indications for DBS. For example, research is underway in Toronto to explore its use in dementia, Dr. Holtzheimer said.

Dr. Holtzheimer is a consultant for St. Jude Medical: Neuromodulation, a site of one of the trials for DBS in TRD.

SAVANNAH, GA. – Deep brain stimulation shows potential for treatment of geriatric psychiatric disorders, particularly treatment-resistant depression and obsessive-compulsive disorder.

Deep brain stimulation (DBS), an effective therapy for Parkinson's disease and essential tremor, may hold promise for treatment of geriatric psychiatric disorders, Dr. Paul Holtzheimer said in a symposium on neuromodulation therapies at the meeting.

Research into DBS for treatment-resistant depression (TRD) and for obsessive-compulsive disorder (OCD), as well as for other psychiatric disorders, has been advancing, noted Dr. Holtzheimer of the department of psychiatry and behavioral sciences at Emory University, Atlanta. But more studies into efficacy, mechanisms of action, and side-effect profile – and especially long-term effects – are needed.

DBS delivers targeted electrical stimulation into the brain through a device that consists of an electrode connected to an insulated wire, inserted through a small opening in the skull. The wire is run under the skin of the head, neck, and shoulder, connecting the electrode to an implantable pulse generator (a “pacemaker”), which is implanted near the collarbone.

One advantage of a DBS device is that it can be tuned, Dr. Holtzheimer said. The electrode has four contacts, allowing the stimulation level to be adjusted and revised.

Implantation is a relatively safe procedure – “as simple as it can be,” Dr. Holtzheimer said – with a low complication rate (around 10%). The most common complication is infection; stroke is a less common but far more worrisome one, he said.

Early research in TRD suggests efficacy and safety for subcallosal cingulate, ventral capsule/ventral striatum (VC/VS), and nucleus accumbens targets. Dr. Holtzheimer called the results so far “reasonably positive.” Multicenter trials are underway for the subcallosal cingulate and VC/VS targets.

The OCD data also suggest reasonable efficacy and safety for the VC/VS, inferior thalamic peduncle, and subthalamic nucleus targets, but not the nucleus accumbens.

In 2009, the Food and Drug Administration approved a humanitarian device exemption for the use of DBS to treat OCD (VC/VS target).

The progress is encouraging, but the lack of randomized, placebo-controlled data means that long-term safety and efficacy have yet to be established, Dr. Holtzheimer cautioned. Moreover, safety and efficacy have yet to be tested in geriatric populations, and those patients are not part of the ongoing trials.

There's no reason to believe that DBS would be less safe or effective in geriatric populations, observed another member of the neuromodulation panel, Dr. William McDonald, professor of psychiatry and behavioral sciences at Emory University.

Looking ahead, questions abound, Dr. Holtzheimer acknowledged: Is late-onset depression a completely different biology from depression in younger populations? Can clinicians extrapolate efficacy to an older population?

He also pointed out that it may take months of DBS therapy before it becomes effective. It does not replace medications or psychotherapy, but it may enhance other therapeutic approaches, such as cognitive-behavioral therapy, he said.

Meanwhile, researchers are starting to look at other psychiatric indications for DBS. For example, research is underway in Toronto to explore its use in dementia, Dr. Holtzheimer said.

Dr. Holtzheimer is a consultant for St. Jude Medical: Neuromodulation, a site of one of the trials for DBS in TRD.

Major Finding: Between the 2000 introduction of PCV7 and 2008, children younger than age 5 years experienced a 78% decline in penicillin-nonsusceptible IPD under the old, pre-2008 break points, and a 64% decline under the new break points.

Data Source: Analysis of 7,272 cases of serious pneumococcal infections in U.S. children younger than age 5 years in 10 ABC areas in 1998–2008.

Disclosures: Dr. Hampton reported that he had no conflicts of interest.

ATLANTA — Introduction of the 7-valent pneumococcal conjugate vaccine led to a major decline in penicillin-nonsusceptible invasive pneumococcal disease among children younger than age 5 years, according to research from the Centers for Disease Control and Prevention and other public health groups.

These findings were consistent regardless of which definition of susceptibility was used, which illustrates how changing case definitions can affect measured vaccine effects, reported Dr. Lee Hampton of the CDC's Epidemic Intelligence Service.

Using the ABC (Active Bacterial Core) surveillance system, Dr. Hampton and his colleagues analyzed 7,272 cases of serious pneumococcal infections in children younger than age 5 years in 10 ABC areas throughout the United States in 1998–2008.

Isolates were classified as susceptible or nonsusceptible; “nonsusceptibles” were further classified as intermediate or resistant based on both the old and new CLSI (Clinical and Laboratory Standards Institute) standards. CLSI issued new intravenous penicillin resistance break point standards in 2008.

Among cases of all types of IPD in children younger than age 5 years, 10% had intermediate susceptibility and 4% were fully resistant under the new break points. Under the old break points, 14% had intermediate susceptibility and 20% had full resistance, Dr. Hampton and his colleagues found.

Between the 2000 introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and 2008, children younger than age 5 years experienced a 78% decline in penicillin-nonsusceptible IPD under the old, pre-2008 break points, and a 64% decline under the new break points.

Rates of penicillin-nonsusceptible IPD in 2008 were higher under the old break points (7.4 cases per 100,000 children) than under the new break points (4.4 cases per 100,000).

“We conclude that the introduction of PCV7 was associated with dramatic reductions in penicillin-nonsusceptible invasive pneumococcal disease incidents,” regardless of which break point was used, he said. Abruptly switching from the old to the new penicillin break points can create the appearance of a sudden drop in penicillin nonsusceptibility, he added.

Six additional serotypes found in PCV13, but not PCV7, now account for 97% of all penicillin-nonsusceptible IPD under the new break points and 83% of penicillin-nonsusceptible IPD under the old break points, he said. If PCV13 is effective against these additional serotypes, rates of penicillin-nonsusceptible IPD should decrease.

Dr. Hampton identified several limitations to the research, including that the finding may not be generalizable outside the ABC system.

He emphasized the results are preliminary, but that they have significant implications for clinicians. “PCV7 has done a terrific job of reducing penicillin-resistant pneumococcal disease, no matter how you look at it. But doctors still need to avoid prescribing antibiotics when they're not needed, because unnecessary antibiotic use is one of the greatest driving forces behind resistance,” he said in an interview.

“Clinicians should understand that more of their patients who need intravenous therapy for nonmeningitis pneumococcal disease can now be treated with penicillin. This is great, because penicillin works very well against susceptible pneumococci and promotes less antibiotic resistance than many alternatives,” he said.

Major Finding: Between the 2000 introduction of PCV7 and 2008, children younger than age 5 years experienced a 78% decline in penicillin-nonsusceptible IPD under the old, pre-2008 break points, and a 64% decline under the new break points.

Data Source: Analysis of 7,272 cases of serious pneumococcal infections in U.S. children younger than age 5 years in 10 ABC areas in 1998–2008.

Disclosures: Dr. Hampton reported that he had no conflicts of interest.

ATLANTA — Introduction of the 7-valent pneumococcal conjugate vaccine led to a major decline in penicillin-nonsusceptible invasive pneumococcal disease among children younger than age 5 years, according to research from the Centers for Disease Control and Prevention and other public health groups.

These findings were consistent regardless of which definition of susceptibility was used, which illustrates how changing case definitions can affect measured vaccine effects, reported Dr. Lee Hampton of the CDC's Epidemic Intelligence Service.

Using the ABC (Active Bacterial Core) surveillance system, Dr. Hampton and his colleagues analyzed 7,272 cases of serious pneumococcal infections in children younger than age 5 years in 10 ABC areas throughout the United States in 1998–2008.

Isolates were classified as susceptible or nonsusceptible; “nonsusceptibles” were further classified as intermediate or resistant based on both the old and new CLSI (Clinical and Laboratory Standards Institute) standards. CLSI issued new intravenous penicillin resistance break point standards in 2008.

Among cases of all types of IPD in children younger than age 5 years, 10% had intermediate susceptibility and 4% were fully resistant under the new break points. Under the old break points, 14% had intermediate susceptibility and 20% had full resistance, Dr. Hampton and his colleagues found.

Between the 2000 introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and 2008, children younger than age 5 years experienced a 78% decline in penicillin-nonsusceptible IPD under the old, pre-2008 break points, and a 64% decline under the new break points.

Rates of penicillin-nonsusceptible IPD in 2008 were higher under the old break points (7.4 cases per 100,000 children) than under the new break points (4.4 cases per 100,000).

“We conclude that the introduction of PCV7 was associated with dramatic reductions in penicillin-nonsusceptible invasive pneumococcal disease incidents,” regardless of which break point was used, he said. Abruptly switching from the old to the new penicillin break points can create the appearance of a sudden drop in penicillin nonsusceptibility, he added.

Six additional serotypes found in PCV13, but not PCV7, now account for 97% of all penicillin-nonsusceptible IPD under the new break points and 83% of penicillin-nonsusceptible IPD under the old break points, he said. If PCV13 is effective against these additional serotypes, rates of penicillin-nonsusceptible IPD should decrease.

Dr. Hampton identified several limitations to the research, including that the finding may not be generalizable outside the ABC system.

He emphasized the results are preliminary, but that they have significant implications for clinicians. “PCV7 has done a terrific job of reducing penicillin-resistant pneumococcal disease, no matter how you look at it. But doctors still need to avoid prescribing antibiotics when they're not needed, because unnecessary antibiotic use is one of the greatest driving forces behind resistance,” he said in an interview.

“Clinicians should understand that more of their patients who need intravenous therapy for nonmeningitis pneumococcal disease can now be treated with penicillin. This is great, because penicillin works very well against susceptible pneumococci and promotes less antibiotic resistance than many alternatives,” he said.

Major Finding: Between the 2000 introduction of PCV7 and 2008, children younger than age 5 years experienced a 78% decline in penicillin-nonsusceptible IPD under the old, pre-2008 break points, and a 64% decline under the new break points.

Data Source: Analysis of 7,272 cases of serious pneumococcal infections in U.S. children younger than age 5 years in 10 ABC areas in 1998–2008.

Disclosures: Dr. Hampton reported that he had no conflicts of interest.

ATLANTA — Introduction of the 7-valent pneumococcal conjugate vaccine led to a major decline in penicillin-nonsusceptible invasive pneumococcal disease among children younger than age 5 years, according to research from the Centers for Disease Control and Prevention and other public health groups.

These findings were consistent regardless of which definition of susceptibility was used, which illustrates how changing case definitions can affect measured vaccine effects, reported Dr. Lee Hampton of the CDC's Epidemic Intelligence Service.

Using the ABC (Active Bacterial Core) surveillance system, Dr. Hampton and his colleagues analyzed 7,272 cases of serious pneumococcal infections in children younger than age 5 years in 10 ABC areas throughout the United States in 1998–2008.

Isolates were classified as susceptible or nonsusceptible; “nonsusceptibles” were further classified as intermediate or resistant based on both the old and new CLSI (Clinical and Laboratory Standards Institute) standards. CLSI issued new intravenous penicillin resistance break point standards in 2008.

Among cases of all types of IPD in children younger than age 5 years, 10% had intermediate susceptibility and 4% were fully resistant under the new break points. Under the old break points, 14% had intermediate susceptibility and 20% had full resistance, Dr. Hampton and his colleagues found.

Between the 2000 introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and 2008, children younger than age 5 years experienced a 78% decline in penicillin-nonsusceptible IPD under the old, pre-2008 break points, and a 64% decline under the new break points.

Rates of penicillin-nonsusceptible IPD in 2008 were higher under the old break points (7.4 cases per 100,000 children) than under the new break points (4.4 cases per 100,000).

“We conclude that the introduction of PCV7 was associated with dramatic reductions in penicillin-nonsusceptible invasive pneumococcal disease incidents,” regardless of which break point was used, he said. Abruptly switching from the old to the new penicillin break points can create the appearance of a sudden drop in penicillin nonsusceptibility, he added.

Six additional serotypes found in PCV13, but not PCV7, now account for 97% of all penicillin-nonsusceptible IPD under the new break points and 83% of penicillin-nonsusceptible IPD under the old break points, he said. If PCV13 is effective against these additional serotypes, rates of penicillin-nonsusceptible IPD should decrease.

Dr. Hampton identified several limitations to the research, including that the finding may not be generalizable outside the ABC system.

He emphasized the results are preliminary, but that they have significant implications for clinicians. “PCV7 has done a terrific job of reducing penicillin-resistant pneumococcal disease, no matter how you look at it. But doctors still need to avoid prescribing antibiotics when they're not needed, because unnecessary antibiotic use is one of the greatest driving forces behind resistance,” he said in an interview.

“Clinicians should understand that more of their patients who need intravenous therapy for nonmeningitis pneumococcal disease can now be treated with penicillin. This is great, because penicillin works very well against susceptible pneumococci and promotes less antibiotic resistance than many alternatives,” he said.

Major Finding: Seventy-three percent of postpartum women received the Tdap vaccine prior to discharge.

Data Source: A medically underserved, uninsured, predominantly Hispanic population of 11,174 postpartum women.

Disclosures: Sanofi Pasteur donated the vaccines. Dr. Healy said that she has served on an advisory board for Novartis.

ATLANTA — A Texas hospital's cocooning program demonstrates such efforts can be successful, but it also highlights the challenges and barriers to implementation, according to Dr. C. Mary Healy.

Using standing orders and on-site immunization, Houston's Ben Taub General Hospital successfully implemented cocooning in a high-risk population, said Dr. Healy, director of vaccinology and maternal immunization at the center for vaccine awareness and research, Texas Children's Hospital, Houston.

In 2006, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended Tdap booster immunizations for infant caregivers, but the approach has not been widely implemented, she reported at the conference sponsored by the CDC.

Cocooning involves vaccinating the baby's mother and other adults and adolescents (including health care providers) who have contact with the newborn. As a result, the baby is surrounded by those who cannot spread pertussis.

Infants under 6 months old are too young to have received all three doses of the pertussis vaccine, and most pertussis-related complications and deaths occur in this age group, she said.

More than 75% of infected babies get pertussis from family members; some regions of the country are experiencing an increase in pertussis because of waning immunity, she noted.

Dr. Healy reported on Ben Taub General Hospital's program to implement cocooning in a medically underserved, uninsured, predominantly Hispanic population.

Hispanic infants are at increased risk, accounting for 70% of the pertussis-related deaths in the United States in 2007, she said.

In phase 1 (launched January 2008), postpartum Tdap was provided.

In phase 2 (launched June 2009), infant caregivers were immunized on-site before the infant was discharged.

The effort began with pertussis education for health care personnel and mothers, and a standing order for postpartum Tdap immunization. From Jan. 7, 2008, to Jan. 31, 2010, 8,138 of 11,174 postpartum women (73%) received the Tdap vaccine prior to discharge.

When women who believed themselves ineligible for the vaccine were excluded, the rate rose to 96.2%.

Postpartum Tdap uptake increased 17% after the required 2-year interval from a previous tetanus-containing vaccine was eliminated, Dr. Healy reported.

Vaccine refusal was three times more common among black women. She noted that her team will be conducting additional research on this finding; the hospital's demographic data didn't distinguish between African Americans and recent immigrants from Africa.

In phase 2, 1,860 other infant caregivers received Tdap. The median number of Tdap-eligible caregivers per infant was three; a median of two were immunized.

Fifty-eight percent of the families had one or more infant contacts (other than the mother) vaccinated.

Overall, Tdap immunization was well accepted; no significant adverse events were reported.

Hospital restrictions imposed because of 2009 H1N1 influenza likely depressed the number of caregiver vaccinations, Dr. Healy said.

For much of the study period, mothers could select only one visitor during their stay; other friends and family – potential caregivers – could come to the hospital to receive the Tdap, but they were barred from visiting the mother or the infant. That had an understandably negative effect, she said.

The program is ongoing, and it has revealed many of the barriers to adequate cocooning, Dr. Healy said. They include the need for targeted education; convenient, out-of-hours service; and accurate, easily accessible immunization records.

The critical issues, she said, are how to develop the infrastructure and finding the funding for such a program. What made her program feasible, she noted, is that the vaccines were donated.

Reimbursement issues make cocooning more difficult because the cost of Tdap for infant caregivers isn't bundled into neonatal or perinatal care.

Dr. Healy said she and her team didn't estimate potential cost, but in terms of staffing it required one full-time nurse, one who spent 40%-50% of her time on the project, and one who spent about 25% of her time primarily managing operational issues and the database.

Dr. Healy estimated she spent about 20%-30% of her work hours on the project.

Education for families and health care professionals is critical, she said.

Family, pediatric, and obstetric and midwife practices all can play roles in helping reach caregivers.

Moreover, any clinician working with adults needs to think about these issues when talking to patients, especially those who have contact with young infants, Dr. Healy said in an interview.

Major Finding: Seventy-three percent of postpartum women received the Tdap vaccine prior to discharge.

Data Source: A medically underserved, uninsured, predominantly Hispanic population of 11,174 postpartum women.

Disclosures: Sanofi Pasteur donated the vaccines. Dr. Healy said that she has served on an advisory board for Novartis.

ATLANTA — A Texas hospital's cocooning program demonstrates such efforts can be successful, but it also highlights the challenges and barriers to implementation, according to Dr. C. Mary Healy.

Using standing orders and on-site immunization, Houston's Ben Taub General Hospital successfully implemented cocooning in a high-risk population, said Dr. Healy, director of vaccinology and maternal immunization at the center for vaccine awareness and research, Texas Children's Hospital, Houston.

In 2006, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended Tdap booster immunizations for infant caregivers, but the approach has not been widely implemented, she reported at the conference sponsored by the CDC.

Cocooning involves vaccinating the baby's mother and other adults and adolescents (including health care providers) who have contact with the newborn. As a result, the baby is surrounded by those who cannot spread pertussis.

Infants under 6 months old are too young to have received all three doses of the pertussis vaccine, and most pertussis-related complications and deaths occur in this age group, she said.

More than 75% of infected babies get pertussis from family members; some regions of the country are experiencing an increase in pertussis because of waning immunity, she noted.

Dr. Healy reported on Ben Taub General Hospital's program to implement cocooning in a medically underserved, uninsured, predominantly Hispanic population.

Hispanic infants are at increased risk, accounting for 70% of the pertussis-related deaths in the United States in 2007, she said.

In phase 1 (launched January 2008), postpartum Tdap was provided.

In phase 2 (launched June 2009), infant caregivers were immunized on-site before the infant was discharged.

The effort began with pertussis education for health care personnel and mothers, and a standing order for postpartum Tdap immunization. From Jan. 7, 2008, to Jan. 31, 2010, 8,138 of 11,174 postpartum women (73%) received the Tdap vaccine prior to discharge.

When women who believed themselves ineligible for the vaccine were excluded, the rate rose to 96.2%.

Postpartum Tdap uptake increased 17% after the required 2-year interval from a previous tetanus-containing vaccine was eliminated, Dr. Healy reported.

Vaccine refusal was three times more common among black women. She noted that her team will be conducting additional research on this finding; the hospital's demographic data didn't distinguish between African Americans and recent immigrants from Africa.

In phase 2, 1,860 other infant caregivers received Tdap. The median number of Tdap-eligible caregivers per infant was three; a median of two were immunized.

Fifty-eight percent of the families had one or more infant contacts (other than the mother) vaccinated.

Overall, Tdap immunization was well accepted; no significant adverse events were reported.

Hospital restrictions imposed because of 2009 H1N1 influenza likely depressed the number of caregiver vaccinations, Dr. Healy said.

For much of the study period, mothers could select only one visitor during their stay; other friends and family – potential caregivers – could come to the hospital to receive the Tdap, but they were barred from visiting the mother or the infant. That had an understandably negative effect, she said.

The program is ongoing, and it has revealed many of the barriers to adequate cocooning, Dr. Healy said. They include the need for targeted education; convenient, out-of-hours service; and accurate, easily accessible immunization records.

The critical issues, she said, are how to develop the infrastructure and finding the funding for such a program. What made her program feasible, she noted, is that the vaccines were donated.

Reimbursement issues make cocooning more difficult because the cost of Tdap for infant caregivers isn't bundled into neonatal or perinatal care.

Dr. Healy said she and her team didn't estimate potential cost, but in terms of staffing it required one full-time nurse, one who spent 40%-50% of her time on the project, and one who spent about 25% of her time primarily managing operational issues and the database.

Dr. Healy estimated she spent about 20%-30% of her work hours on the project.

Education for families and health care professionals is critical, she said.

Family, pediatric, and obstetric and midwife practices all can play roles in helping reach caregivers.

Moreover, any clinician working with adults needs to think about these issues when talking to patients, especially those who have contact with young infants, Dr. Healy said in an interview.

Major Finding: Seventy-three percent of postpartum women received the Tdap vaccine prior to discharge.

Data Source: A medically underserved, uninsured, predominantly Hispanic population of 11,174 postpartum women.

Disclosures: Sanofi Pasteur donated the vaccines. Dr. Healy said that she has served on an advisory board for Novartis.

ATLANTA — A Texas hospital's cocooning program demonstrates such efforts can be successful, but it also highlights the challenges and barriers to implementation, according to Dr. C. Mary Healy.

Using standing orders and on-site immunization, Houston's Ben Taub General Hospital successfully implemented cocooning in a high-risk population, said Dr. Healy, director of vaccinology and maternal immunization at the center for vaccine awareness and research, Texas Children's Hospital, Houston.

In 2006, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended Tdap booster immunizations for infant caregivers, but the approach has not been widely implemented, she reported at the conference sponsored by the CDC.

Cocooning involves vaccinating the baby's mother and other adults and adolescents (including health care providers) who have contact with the newborn. As a result, the baby is surrounded by those who cannot spread pertussis.

Infants under 6 months old are too young to have received all three doses of the pertussis vaccine, and most pertussis-related complications and deaths occur in this age group, she said.

More than 75% of infected babies get pertussis from family members; some regions of the country are experiencing an increase in pertussis because of waning immunity, she noted.

Dr. Healy reported on Ben Taub General Hospital's program to implement cocooning in a medically underserved, uninsured, predominantly Hispanic population.

Hispanic infants are at increased risk, accounting for 70% of the pertussis-related deaths in the United States in 2007, she said.

In phase 1 (launched January 2008), postpartum Tdap was provided.

In phase 2 (launched June 2009), infant caregivers were immunized on-site before the infant was discharged.

The effort began with pertussis education for health care personnel and mothers, and a standing order for postpartum Tdap immunization. From Jan. 7, 2008, to Jan. 31, 2010, 8,138 of 11,174 postpartum women (73%) received the Tdap vaccine prior to discharge.

When women who believed themselves ineligible for the vaccine were excluded, the rate rose to 96.2%.

Postpartum Tdap uptake increased 17% after the required 2-year interval from a previous tetanus-containing vaccine was eliminated, Dr. Healy reported.

Vaccine refusal was three times more common among black women. She noted that her team will be conducting additional research on this finding; the hospital's demographic data didn't distinguish between African Americans and recent immigrants from Africa.

In phase 2, 1,860 other infant caregivers received Tdap. The median number of Tdap-eligible caregivers per infant was three; a median of two were immunized.

Fifty-eight percent of the families had one or more infant contacts (other than the mother) vaccinated.

Overall, Tdap immunization was well accepted; no significant adverse events were reported.

Hospital restrictions imposed because of 2009 H1N1 influenza likely depressed the number of caregiver vaccinations, Dr. Healy said.

For much of the study period, mothers could select only one visitor during their stay; other friends and family – potential caregivers – could come to the hospital to receive the Tdap, but they were barred from visiting the mother or the infant. That had an understandably negative effect, she said.

The program is ongoing, and it has revealed many of the barriers to adequate cocooning, Dr. Healy said. They include the need for targeted education; convenient, out-of-hours service; and accurate, easily accessible immunization records.

The critical issues, she said, are how to develop the infrastructure and finding the funding for such a program. What made her program feasible, she noted, is that the vaccines were donated.

Reimbursement issues make cocooning more difficult because the cost of Tdap for infant caregivers isn't bundled into neonatal or perinatal care.

Dr. Healy said she and her team didn't estimate potential cost, but in terms of staffing it required one full-time nurse, one who spent 40%-50% of her time on the project, and one who spent about 25% of her time primarily managing operational issues and the database.

Dr. Healy estimated she spent about 20%-30% of her work hours on the project.

Education for families and health care professionals is critical, she said.

Family, pediatric, and obstetric and midwife practices all can play roles in helping reach caregivers.

Moreover, any clinician working with adults needs to think about these issues when talking to patients, especially those who have contact with young infants, Dr. Healy said in an interview.

ATLANTA — New influenza vaccine development is evolving rapidly, with approximately 75 different technologies currently in various stages, said Rick Bright, Ph.D., scientific director for the influenza vaccine project at Program for Appropriate Technology in Health, a global nonprofit health group.

They are desperately needed: Current seasonal vaccines are only 30%-50% effective in older adults, and candidate vaccines for pandemics “are poorly immunogenic in clinical studies,” he said.

Current vaccines may be safe and immunogenic, but they are highly vulnerable to antigenic drift and shift, which compromise efficacy and require reformulation and repeated immunization. Vaccine development is costly, complicated, and time consuming. As the H1N1 influenza outbreak demonstrates, the conventional production process is poorly equipped to respond to a pandemic, Dr. Bright said.

He discussed three promising types of influenza vaccines, each of which holds promise, he said. But all involve significant challenges such as safety, immunogenicity, scalability, and regulatory issues:

LAIV: Innovative Yet Decades Old

Live attenuated influenza viruses have been used to combat seasonal influenza for decades in some parts of the world, but Dr. Bright nevertheless characterized them as innovative. They have yet to be widely accepted or distributed, despite a strong safety record and low cost. It's easy to produce and purify; it has a broad immune response, including some mucosal and cellular immunity; and it is efficacious in naive populations, he said.

There are challenges, however. LAIV “doesn't follow the known, established correlates of immunity,” which can lead to regulatory and licensing hurdles. LAIVs are less effective in nonnaive adults, and there are current limitations on their use in children and some high-risk groups. But some of those limitations are based on “unfounded fears of the risk of reassortment,” he said.

Over the last few years, LAIV technology has expanded into development of both seasonal and pandemic vaccines.

VLP: Dealing With Vectors

Recombinant viruslike particles vaccines, with many varieties in early-stage development, show promise of being both low cost and high yield, with a rapid (12-week) production cycle, he said. Although VLPs contain multiple influenza proteins to resemble virions, they contain no genetic material, and therefore they do not replicate or cause infection.

Animal and early clinical studies suggest a broad immune response, but low immunogenicity may be an issue, he said; VLPs may need adjuvants.

Safety is an issue because all VLPs “rely on some sort of vector.” The challenge is to remove, or demonstrate the safety of, the residual vectors, Dr. Bright said.

Plant-Based: Speedy Development

Plant-based vaccines have been advancing steadily since 2000. They can be produced very rapidly, at about 8 weeks from sequencing to release. New approaches to plant-based expression create high yields with low production costs. Moreover, he said, the approach is “suitable for mixing and matching constantly emerging strains.”

Safety is less of a concern than it is for VLPs because plant-based vaccines are free of animal cells, microbial pathogens, and animal viruses. “It's all in plants, so that implies a safe host cell system.”

Dr. Bright disclosed financial ties with Novavax Inc.

The conventional production process is poorly equipped to respond to a pandemic.

Source DR. BRIGHT

ATLANTA — New influenza vaccine development is evolving rapidly, with approximately 75 different technologies currently in various stages, said Rick Bright, Ph.D., scientific director for the influenza vaccine project at Program for Appropriate Technology in Health, a global nonprofit health group.

They are desperately needed: Current seasonal vaccines are only 30%-50% effective in older adults, and candidate vaccines for pandemics “are poorly immunogenic in clinical studies,” he said.

Current vaccines may be safe and immunogenic, but they are highly vulnerable to antigenic drift and shift, which compromise efficacy and require reformulation and repeated immunization. Vaccine development is costly, complicated, and time consuming. As the H1N1 influenza outbreak demonstrates, the conventional production process is poorly equipped to respond to a pandemic, Dr. Bright said.

He discussed three promising types of influenza vaccines, each of which holds promise, he said. But all involve significant challenges such as safety, immunogenicity, scalability, and regulatory issues:

LAIV: Innovative Yet Decades Old

Live attenuated influenza viruses have been used to combat seasonal influenza for decades in some parts of the world, but Dr. Bright nevertheless characterized them as innovative. They have yet to be widely accepted or distributed, despite a strong safety record and low cost. It's easy to produce and purify; it has a broad immune response, including some mucosal and cellular immunity; and it is efficacious in naive populations, he said.

There are challenges, however. LAIV “doesn't follow the known, established correlates of immunity,” which can lead to regulatory and licensing hurdles. LAIVs are less effective in nonnaive adults, and there are current limitations on their use in children and some high-risk groups. But some of those limitations are based on “unfounded fears of the risk of reassortment,” he said.

Over the last few years, LAIV technology has expanded into development of both seasonal and pandemic vaccines.

VLP: Dealing With Vectors

Recombinant viruslike particles vaccines, with many varieties in early-stage development, show promise of being both low cost and high yield, with a rapid (12-week) production cycle, he said. Although VLPs contain multiple influenza proteins to resemble virions, they contain no genetic material, and therefore they do not replicate or cause infection.

Animal and early clinical studies suggest a broad immune response, but low immunogenicity may be an issue, he said; VLPs may need adjuvants.

Safety is an issue because all VLPs “rely on some sort of vector.” The challenge is to remove, or demonstrate the safety of, the residual vectors, Dr. Bright said.

Plant-Based: Speedy Development

Plant-based vaccines have been advancing steadily since 2000. They can be produced very rapidly, at about 8 weeks from sequencing to release. New approaches to plant-based expression create high yields with low production costs. Moreover, he said, the approach is “suitable for mixing and matching constantly emerging strains.”

Safety is less of a concern than it is for VLPs because plant-based vaccines are free of animal cells, microbial pathogens, and animal viruses. “It's all in plants, so that implies a safe host cell system.”

Dr. Bright disclosed financial ties with Novavax Inc.

The conventional production process is poorly equipped to respond to a pandemic.

Source DR. BRIGHT

ATLANTA — New influenza vaccine development is evolving rapidly, with approximately 75 different technologies currently in various stages, said Rick Bright, Ph.D., scientific director for the influenza vaccine project at Program for Appropriate Technology in Health, a global nonprofit health group.

They are desperately needed: Current seasonal vaccines are only 30%-50% effective in older adults, and candidate vaccines for pandemics “are poorly immunogenic in clinical studies,” he said.

Current vaccines may be safe and immunogenic, but they are highly vulnerable to antigenic drift and shift, which compromise efficacy and require reformulation and repeated immunization. Vaccine development is costly, complicated, and time consuming. As the H1N1 influenza outbreak demonstrates, the conventional production process is poorly equipped to respond to a pandemic, Dr. Bright said.

He discussed three promising types of influenza vaccines, each of which holds promise, he said. But all involve significant challenges such as safety, immunogenicity, scalability, and regulatory issues:

LAIV: Innovative Yet Decades Old

Live attenuated influenza viruses have been used to combat seasonal influenza for decades in some parts of the world, but Dr. Bright nevertheless characterized them as innovative. They have yet to be widely accepted or distributed, despite a strong safety record and low cost. It's easy to produce and purify; it has a broad immune response, including some mucosal and cellular immunity; and it is efficacious in naive populations, he said.

There are challenges, however. LAIV “doesn't follow the known, established correlates of immunity,” which can lead to regulatory and licensing hurdles. LAIVs are less effective in nonnaive adults, and there are current limitations on their use in children and some high-risk groups. But some of those limitations are based on “unfounded fears of the risk of reassortment,” he said.

Over the last few years, LAIV technology has expanded into development of both seasonal and pandemic vaccines.

VLP: Dealing With Vectors

Recombinant viruslike particles vaccines, with many varieties in early-stage development, show promise of being both low cost and high yield, with a rapid (12-week) production cycle, he said. Although VLPs contain multiple influenza proteins to resemble virions, they contain no genetic material, and therefore they do not replicate or cause infection.

Animal and early clinical studies suggest a broad immune response, but low immunogenicity may be an issue, he said; VLPs may need adjuvants.

Safety is an issue because all VLPs “rely on some sort of vector.” The challenge is to remove, or demonstrate the safety of, the residual vectors, Dr. Bright said.

Plant-Based: Speedy Development

Plant-based vaccines have been advancing steadily since 2000. They can be produced very rapidly, at about 8 weeks from sequencing to release. New approaches to plant-based expression create high yields with low production costs. Moreover, he said, the approach is “suitable for mixing and matching constantly emerging strains.”

Safety is less of a concern than it is for VLPs because plant-based vaccines are free of animal cells, microbial pathogens, and animal viruses. “It's all in plants, so that implies a safe host cell system.”

Dr. Bright disclosed financial ties with Novavax Inc.

The conventional production process is poorly equipped to respond to a pandemic.

Source DR. BRIGHT

ATLANTA — An intervention to administer a third dose of the MMR vaccine during a mumps outbreak appears to have slowed transmission of the virus, but more data are needed before such a strategy can be recommended, preliminary findings suggest.

For 2 months beginning in January 2010, public health officials offered a third dose of the measles-mumps-rubella (MMR) vaccine in three schools in Orange County, N.Y., where, despite a high level of two-dose coverage among students, viral transmission had continued for more than 2 months, said Dr. Ikechukwu Ogbuanu of the Centers for Disease Control and Prevention.

The Northeastern outbreak—the largest in the United States since 2006—began in June 2009 and was traced to a fully vaccinated 11-year-old Hasidic boy from Orange County, N.Y., who had recently returned from the United Kingdom. He subsequently spent time at summer camp and then traveled to Brooklyn.

From June 17, 2009 to May 7, 2010, a total of 3,341 outbreak-related mumps cases were reported from four sites in the New York and New Jersey area, predominantly among members of Jewish communities. Multiple factors might have fueled the outbreak in this community, including high population density and prolonged exposure, Dr. Ogbuanu said.

For their study, the researchers focused on records from the three Orange County schools where most of the cases occurred and conducted a survey of 6th-12th graders to assess risk factors related to mumps viral transmissions.

In those three schools, a third dose of MMR vaccine had been offered to eligible 6th-12th graders between Jan. 19 and Feb. 2, 2010; uptake occurred among 83% (1,863 of the 2,255) of those eligible.

“Preliminary data suggest a positive benefit,” Dr. Ogbuanu said. As of June 2010, of the 108 cases of mumps reported after the intervention, only four of the patients had received the third dose.

Dr. Ogbuanu, however, was adamant about not offering recommendations. The efficacy of a third MMR dose in controlling mumps outbreaks has not been previously reported and, he emphasized, researchers are still assessing the impact of this intervention.

The only adverse effects reported were pain, redness, and swelling at the injection site; there were no life-threatening adverse reactions.

Disclosures: Dr. Ogbuanu reported having no conflicts of interest.

'Preliminary data suggest a positive benefit,' but further testing will be needed.

Source DR. OGBUANU

ATLANTA — An intervention to administer a third dose of the MMR vaccine during a mumps outbreak appears to have slowed transmission of the virus, but more data are needed before such a strategy can be recommended, preliminary findings suggest.

For 2 months beginning in January 2010, public health officials offered a third dose of the measles-mumps-rubella (MMR) vaccine in three schools in Orange County, N.Y., where, despite a high level of two-dose coverage among students, viral transmission had continued for more than 2 months, said Dr. Ikechukwu Ogbuanu of the Centers for Disease Control and Prevention.

The Northeastern outbreak—the largest in the United States since 2006—began in June 2009 and was traced to a fully vaccinated 11-year-old Hasidic boy from Orange County, N.Y., who had recently returned from the United Kingdom. He subsequently spent time at summer camp and then traveled to Brooklyn.

From June 17, 2009 to May 7, 2010, a total of 3,341 outbreak-related mumps cases were reported from four sites in the New York and New Jersey area, predominantly among members of Jewish communities. Multiple factors might have fueled the outbreak in this community, including high population density and prolonged exposure, Dr. Ogbuanu said.

For their study, the researchers focused on records from the three Orange County schools where most of the cases occurred and conducted a survey of 6th-12th graders to assess risk factors related to mumps viral transmissions.

In those three schools, a third dose of MMR vaccine had been offered to eligible 6th-12th graders between Jan. 19 and Feb. 2, 2010; uptake occurred among 83% (1,863 of the 2,255) of those eligible.

“Preliminary data suggest a positive benefit,” Dr. Ogbuanu said. As of June 2010, of the 108 cases of mumps reported after the intervention, only four of the patients had received the third dose.

Dr. Ogbuanu, however, was adamant about not offering recommendations. The efficacy of a third MMR dose in controlling mumps outbreaks has not been previously reported and, he emphasized, researchers are still assessing the impact of this intervention.

The only adverse effects reported were pain, redness, and swelling at the injection site; there were no life-threatening adverse reactions.

Disclosures: Dr. Ogbuanu reported having no conflicts of interest.

'Preliminary data suggest a positive benefit,' but further testing will be needed.

Source DR. OGBUANU

ATLANTA — An intervention to administer a third dose of the MMR vaccine during a mumps outbreak appears to have slowed transmission of the virus, but more data are needed before such a strategy can be recommended, preliminary findings suggest.

For 2 months beginning in January 2010, public health officials offered a third dose of the measles-mumps-rubella (MMR) vaccine in three schools in Orange County, N.Y., where, despite a high level of two-dose coverage among students, viral transmission had continued for more than 2 months, said Dr. Ikechukwu Ogbuanu of the Centers for Disease Control and Prevention.

The Northeastern outbreak—the largest in the United States since 2006—began in June 2009 and was traced to a fully vaccinated 11-year-old Hasidic boy from Orange County, N.Y., who had recently returned from the United Kingdom. He subsequently spent time at summer camp and then traveled to Brooklyn.

From June 17, 2009 to May 7, 2010, a total of 3,341 outbreak-related mumps cases were reported from four sites in the New York and New Jersey area, predominantly among members of Jewish communities. Multiple factors might have fueled the outbreak in this community, including high population density and prolonged exposure, Dr. Ogbuanu said.

For their study, the researchers focused on records from the three Orange County schools where most of the cases occurred and conducted a survey of 6th-12th graders to assess risk factors related to mumps viral transmissions.

In those three schools, a third dose of MMR vaccine had been offered to eligible 6th-12th graders between Jan. 19 and Feb. 2, 2010; uptake occurred among 83% (1,863 of the 2,255) of those eligible.

“Preliminary data suggest a positive benefit,” Dr. Ogbuanu said. As of June 2010, of the 108 cases of mumps reported after the intervention, only four of the patients had received the third dose.

Dr. Ogbuanu, however, was adamant about not offering recommendations. The efficacy of a third MMR dose in controlling mumps outbreaks has not been previously reported and, he emphasized, researchers are still assessing the impact of this intervention.

The only adverse effects reported were pain, redness, and swelling at the injection site; there were no life-threatening adverse reactions.

Disclosures: Dr. Ogbuanu reported having no conflicts of interest.

'Preliminary data suggest a positive benefit,' but further testing will be needed.

Source DR. OGBUANU

ATLANTA — An estimated 5% of the Key West, Fla., population—more that 1,000 people—showed evidence of recent exposure to dengue virus in 2009, according to the Centers for Disease Control and Prevention and the Florida Department of Health.

Dengue is the most common mosquito-transmitted virus and causes 25,000 deaths each year, according to the CDC. From 1946 to 1980, no cases of dengue acquired in the continental United States were reported, and there has not been an outbreak in Florida since 1934.

These cases represent the reemergence of dengue fever in Florida (and elsewhere in the United States) after 75 years, Dr. Harold Margolis, chief of the dengue branch at CDC, said at the conference.

After three locally-acquired cases of dengue fever were initially reported in 2009, scientists from the CDC and the Florida Department of Health conducted a study to estimate the potential exposure of the Key West population to dengue virus.

Since 1980, a few locally acquired U.S. cases have been confirmed along the Texas-Mexico border, which coincided with large outbreaks in neighboring Mexican cities. In recent years, there has been an increase in epidemic dengue in the tropics and subtropics, including in Puerto Rico, the CDC reported. On Sept. 1, 2009, a New York state physician notified the Monroe County (Fla.) Health Department and FDH of a suspected dengue case in a New York state resident whose only recent travel had been to Key West. In the next 2 weeks, two dengue infections in Key West residents without recent travel were confirmed. By the end of 2009, 27 cases had been identified.

In a poster presented at the conference, a total of 240 blood samples were collected from randomly selected households in Key West and tested for the presence of virus or evidence of a previous dengue infection. Among the samples, 4.95% had dengue active in their systems or had dengue antibodies. The strain was similar to strains from Mexico, according to study investigator, Glen Gallagher, of the CDC's dengue branch in Puerto Rico.

The take-away for physicians is that dengue fever can be a potential diagnosis even in patients without a history of travel, he said in an interview.

The CDC and the FDH continue to monitor cases in and around Key West. As of the end of June 2010, there had been 12 additional cases of locally-acquired dengue infections, bringing the total to 39.

Disclosures: Mr. Gallagher reported that he had no conflicts.

Evidence of dengue or its antibodies was detected in 4.95% of 240 blood samples in Key West.

Source DR. MARGOLIS

The dengue virus, transmitted by the Aedes aegypti mosquito, causes 25,000 deaths annually.

Source Courtesy CDC/James Gathany

ATLANTA — An estimated 5% of the Key West, Fla., population—more that 1,000 people—showed evidence of recent exposure to dengue virus in 2009, according to the Centers for Disease Control and Prevention and the Florida Department of Health.

Dengue is the most common mosquito-transmitted virus and causes 25,000 deaths each year, according to the CDC. From 1946 to 1980, no cases of dengue acquired in the continental United States were reported, and there has not been an outbreak in Florida since 1934.

These cases represent the reemergence of dengue fever in Florida (and elsewhere in the United States) after 75 years, Dr. Harold Margolis, chief of the dengue branch at CDC, said at the conference.

After three locally-acquired cases of dengue fever were initially reported in 2009, scientists from the CDC and the Florida Department of Health conducted a study to estimate the potential exposure of the Key West population to dengue virus.

Since 1980, a few locally acquired U.S. cases have been confirmed along the Texas-Mexico border, which coincided with large outbreaks in neighboring Mexican cities. In recent years, there has been an increase in epidemic dengue in the tropics and subtropics, including in Puerto Rico, the CDC reported. On Sept. 1, 2009, a New York state physician notified the Monroe County (Fla.) Health Department and FDH of a suspected dengue case in a New York state resident whose only recent travel had been to Key West. In the next 2 weeks, two dengue infections in Key West residents without recent travel were confirmed. By the end of 2009, 27 cases had been identified.

In a poster presented at the conference, a total of 240 blood samples were collected from randomly selected households in Key West and tested for the presence of virus or evidence of a previous dengue infection. Among the samples, 4.95% had dengue active in their systems or had dengue antibodies. The strain was similar to strains from Mexico, according to study investigator, Glen Gallagher, of the CDC's dengue branch in Puerto Rico.

The take-away for physicians is that dengue fever can be a potential diagnosis even in patients without a history of travel, he said in an interview.

The CDC and the FDH continue to monitor cases in and around Key West. As of the end of June 2010, there had been 12 additional cases of locally-acquired dengue infections, bringing the total to 39.

Disclosures: Mr. Gallagher reported that he had no conflicts.

Evidence of dengue or its antibodies was detected in 4.95% of 240 blood samples in Key West.

Source DR. MARGOLIS

The dengue virus, transmitted by the Aedes aegypti mosquito, causes 25,000 deaths annually.

Source Courtesy CDC/James Gathany

ATLANTA — An estimated 5% of the Key West, Fla., population—more that 1,000 people—showed evidence of recent exposure to dengue virus in 2009, according to the Centers for Disease Control and Prevention and the Florida Department of Health.

Dengue is the most common mosquito-transmitted virus and causes 25,000 deaths each year, according to the CDC. From 1946 to 1980, no cases of dengue acquired in the continental United States were reported, and there has not been an outbreak in Florida since 1934.

These cases represent the reemergence of dengue fever in Florida (and elsewhere in the United States) after 75 years, Dr. Harold Margolis, chief of the dengue branch at CDC, said at the conference.

After three locally-acquired cases of dengue fever were initially reported in 2009, scientists from the CDC and the Florida Department of Health conducted a study to estimate the potential exposure of the Key West population to dengue virus.

Since 1980, a few locally acquired U.S. cases have been confirmed along the Texas-Mexico border, which coincided with large outbreaks in neighboring Mexican cities. In recent years, there has been an increase in epidemic dengue in the tropics and subtropics, including in Puerto Rico, the CDC reported. On Sept. 1, 2009, a New York state physician notified the Monroe County (Fla.) Health Department and FDH of a suspected dengue case in a New York state resident whose only recent travel had been to Key West. In the next 2 weeks, two dengue infections in Key West residents without recent travel were confirmed. By the end of 2009, 27 cases had been identified.

In a poster presented at the conference, a total of 240 blood samples were collected from randomly selected households in Key West and tested for the presence of virus or evidence of a previous dengue infection. Among the samples, 4.95% had dengue active in their systems or had dengue antibodies. The strain was similar to strains from Mexico, according to study investigator, Glen Gallagher, of the CDC's dengue branch in Puerto Rico.

The take-away for physicians is that dengue fever can be a potential diagnosis even in patients without a history of travel, he said in an interview.

The CDC and the FDH continue to monitor cases in and around Key West. As of the end of June 2010, there had been 12 additional cases of locally-acquired dengue infections, bringing the total to 39.

Disclosures: Mr. Gallagher reported that he had no conflicts.

Evidence of dengue or its antibodies was detected in 4.95% of 240 blood samples in Key West.

Source DR. MARGOLIS

The dengue virus, transmitted by the Aedes aegypti mosquito, causes 25,000 deaths annually.

Source Courtesy CDC/James Gathany

Major Finding: 32% of parents preferred only primary care providers, 14% would accept any of the settings, 11% would accept any setting except retail locations, and 10% would accept only PCPs or schools.

Data Source: A survey of 1,678 parents asked if they would consider getting their child's 2009 H1N1 influenza shot in one of four settings: health departments, schools, local retail locations, or primary care providers.

Disclosures: None was reported.

ATLANTA — Parents prefer to have their children receive the 2009 H1N1 flu vaccine in the primary care setting, but many are open to schools and other venues, according to an August 2009 national survey.

The findings have implications for vaccine delivery in general and, in particular, for future mass immunization efforts, said Sarah Clark of the division of general pediatrics at the University of Michigan, Ann Arbor.

The survey of parents—the C.S. Mott Children's Hospital National Poll on Children's Health—may be the first assessment of public acceptance of various settings for H1N1 flu vaccination for children.

The survey included the following question: “In which of these settings would you consider getting your child(ren) vaccinated against H1N1 influenza?” The 1,678 respondents chose from the following options: health departments, schools, local retail locations, and primary care providers. All respondents were asked the question, including the 29% who indicated they definitely or probably would not vaccinate their child against H1N1 flu.

The most preferred setting was the primary care provider's office, with 82% responding “yes,” 11% “not sure,” and 7% “no.” School vaccination clinics were the second most preferred venue: 43% said “yes”; 23%, “not sure”; and 34%, “no.”

Health department clinics came in third (34% “yes,” 21% “not sure,” 45% “no”), and retail settings were last (24% “yes,” 27% “not sure,” 49% “no”).

When responses were aggregated across the settings, they revealed that 32% preferred only primary care providers, 14% would accept any of the settings, 11% would accept any setting except retail locations, and 10% would accept only the primary care setting or schools.

Ms. Clark emphasized that the survey identified only intentions, which can change. Moreover, it did not capture other settings, such as emergency departments.

Models for vaccinating in alternative settings exist in several states, Ms. Clark said at the conference sponsored by the Centers for Disease Control and Prevention. For example, Rhode Island and Hawaii developed a system for H1N1 flu vaccination whereby school-aged children were vaccinated at school, and pediatricians were asked not to vaccinate them in the office setting. (They did vaccinate children not yet in school.)

“The definition of the school versus pediatrician role worked well in both states, and this model is a nice example of how public health and medicine can work together to provide broad access to vaccines for all children, without sacrificing clinical capacity,” she said.

Major Finding: 32% of parents preferred only primary care providers, 14% would accept any of the settings, 11% would accept any setting except retail locations, and 10% would accept only PCPs or schools.

Data Source: A survey of 1,678 parents asked if they would consider getting their child's 2009 H1N1 influenza shot in one of four settings: health departments, schools, local retail locations, or primary care providers.

Disclosures: None was reported.

ATLANTA — Parents prefer to have their children receive the 2009 H1N1 flu vaccine in the primary care setting, but many are open to schools and other venues, according to an August 2009 national survey.

The findings have implications for vaccine delivery in general and, in particular, for future mass immunization efforts, said Sarah Clark of the division of general pediatrics at the University of Michigan, Ann Arbor.

The survey of parents—the C.S. Mott Children's Hospital National Poll on Children's Health—may be the first assessment of public acceptance of various settings for H1N1 flu vaccination for children.

The survey included the following question: “In which of these settings would you consider getting your child(ren) vaccinated against H1N1 influenza?” The 1,678 respondents chose from the following options: health departments, schools, local retail locations, and primary care providers. All respondents were asked the question, including the 29% who indicated they definitely or probably would not vaccinate their child against H1N1 flu.

The most preferred setting was the primary care provider's office, with 82% responding “yes,” 11% “not sure,” and 7% “no.” School vaccination clinics were the second most preferred venue: 43% said “yes”; 23%, “not sure”; and 34%, “no.”

Health department clinics came in third (34% “yes,” 21% “not sure,” 45% “no”), and retail settings were last (24% “yes,” 27% “not sure,” 49% “no”).

When responses were aggregated across the settings, they revealed that 32% preferred only primary care providers, 14% would accept any of the settings, 11% would accept any setting except retail locations, and 10% would accept only the primary care setting or schools.

Ms. Clark emphasized that the survey identified only intentions, which can change. Moreover, it did not capture other settings, such as emergency departments.

Models for vaccinating in alternative settings exist in several states, Ms. Clark said at the conference sponsored by the Centers for Disease Control and Prevention. For example, Rhode Island and Hawaii developed a system for H1N1 flu vaccination whereby school-aged children were vaccinated at school, and pediatricians were asked not to vaccinate them in the office setting. (They did vaccinate children not yet in school.)

“The definition of the school versus pediatrician role worked well in both states, and this model is a nice example of how public health and medicine can work together to provide broad access to vaccines for all children, without sacrificing clinical capacity,” she said.

Major Finding: 32% of parents preferred only primary care providers, 14% would accept any of the settings, 11% would accept any setting except retail locations, and 10% would accept only PCPs or schools.

Data Source: A survey of 1,678 parents asked if they would consider getting their child's 2009 H1N1 influenza shot in one of four settings: health departments, schools, local retail locations, or primary care providers.

Disclosures: None was reported.

ATLANTA — Parents prefer to have their children receive the 2009 H1N1 flu vaccine in the primary care setting, but many are open to schools and other venues, according to an August 2009 national survey.

The findings have implications for vaccine delivery in general and, in particular, for future mass immunization efforts, said Sarah Clark of the division of general pediatrics at the University of Michigan, Ann Arbor.

The survey of parents—the C.S. Mott Children's Hospital National Poll on Children's Health—may be the first assessment of public acceptance of various settings for H1N1 flu vaccination for children.

The survey included the following question: “In which of these settings would you consider getting your child(ren) vaccinated against H1N1 influenza?” The 1,678 respondents chose from the following options: health departments, schools, local retail locations, and primary care providers. All respondents were asked the question, including the 29% who indicated they definitely or probably would not vaccinate their child against H1N1 flu.

The most preferred setting was the primary care provider's office, with 82% responding “yes,” 11% “not sure,” and 7% “no.” School vaccination clinics were the second most preferred venue: 43% said “yes”; 23%, “not sure”; and 34%, “no.”

Health department clinics came in third (34% “yes,” 21% “not sure,” 45% “no”), and retail settings were last (24% “yes,” 27% “not sure,” 49% “no”).

When responses were aggregated across the settings, they revealed that 32% preferred only primary care providers, 14% would accept any of the settings, 11% would accept any setting except retail locations, and 10% would accept only the primary care setting or schools.

Ms. Clark emphasized that the survey identified only intentions, which can change. Moreover, it did not capture other settings, such as emergency departments.

Models for vaccinating in alternative settings exist in several states, Ms. Clark said at the conference sponsored by the Centers for Disease Control and Prevention. For example, Rhode Island and Hawaii developed a system for H1N1 flu vaccination whereby school-aged children were vaccinated at school, and pediatricians were asked not to vaccinate them in the office setting. (They did vaccinate children not yet in school.)

“The definition of the school versus pediatrician role worked well in both states, and this model is a nice example of how public health and medicine can work together to provide broad access to vaccines for all children, without sacrificing clinical capacity,” she said.

ATLANTA — New influenza vaccine development is evolving rapidly, with approximately 75 different technologies currently in various stages, said Rick Bright, Ph.D., scientific director for the influenza vaccine project at Program for Appropriate Technology in Health, a global nonprofit health group.

And new vaccines are desperately needed: Current seasonal vaccines are only 30%-50% effective in older adults, and candidate vaccines for pandemics “are poorly immunogenic in clinical studies,” Dr. Bright said at the meeting.

Current influenza vaccines may be safe and immunogenic, but they are highly vulnerable to antigenic drift and shift, which compromise efficacy and require reformulation and repeated immunization.

In addition, vaccine development is costly, complicated, and time consuming. As the recent 2009 H1N1 influenza outbreak demonstrates, the conventional production process is poorly equipped to respond to a pandemic, Dr. Bright said.

He discussed three promising types of influenza vaccines: live attenuated influenza viruses (LAIV), recombinant viruslike particles (VLP), and plant-based production of vaccines. Each holds promise, but all involve significant challenges.

LAIV: Innovative Yet Decades Old

LAIVs have been used to combat seasonal influenza for decades in some parts of the world, including the United States and Russia, but Dr. Bright nevertheless characterized them as innovative. They have yet to be widely accepted or distributed, despite a strong safety record and low cost. In fact, he said, LAIV is the lowest-cost influenza vaccine available today. It's easy to produce and purify; it has a broad immune response, including some mucosal and cellular immunity; and it is efficacious in naive populations, Dr. Bright said.

There are challenges, however. LAIV “doesn't follow the known, established correlates of immunity,” which can lead to regulatory and licensing hurdles.

Moreover, LAIVs are less effective in nonnaive adults, and there are current limitations on their use in children and some high-risk groups. But, he added, some of those limitations are based on “unfounded fears of the risk of reassortment.”

VLP: Dealing With Vectors

VLP vaccines, with many varieties in early-stage development, show promise of being both low cost and high yield, with a rapid (12-week) production cycle, he said. Dr. Bright explained that although VLPs contain multiple influenza proteins to resemble virions, they contain no genetic material, and therefore they do not replicate or cause infection.

Safety is an issue because all VLPs “rely on some sort of vector.” The challenge is to remove—or demonstrate the safety of—the residual vectors, he said, noting that such concerns could lead to regulatory challenges.

Plant-Based Vaccines: Speedy Development

Plant-based vaccines have been advancing steadily since 2000, he reported. Such vaccines can be produced very rapidly, at about 8 weeks from sequencing to release. New approaches to plant-based expression create high yields with low production costs. Moreover, he said, the approach is “suitable for mixing and matching constantly emerging strains.”

Safety appears to be less of a concern than it is for VLPs, according to Dr. Bright, because plant-based vaccines are free of animal cells, microbial pathogens, and animal viruses. But “there are many things we don't know about the safety of plant-based proteins,” he cautioned.

Researchers are exploring the issue of low immunogenicity with plant-based vaccines, he said. Like the VLPs, plant-based vaccines will likely benefit from an adjuvant.

Disclosures: Dr. Bright disclosed receiving stock as part of a management position in 2006 from Novavax Inc.

The conventional influenza vaccine production process is poorly equipped to respond to a pandemic.

Source DR. BRIGHT

ATLANTA — New influenza vaccine development is evolving rapidly, with approximately 75 different technologies currently in various stages, said Rick Bright, Ph.D., scientific director for the influenza vaccine project at Program for Appropriate Technology in Health, a global nonprofit health group.

And new vaccines are desperately needed: Current seasonal vaccines are only 30%-50% effective in older adults, and candidate vaccines for pandemics “are poorly immunogenic in clinical studies,” Dr. Bright said at the meeting.

Current influenza vaccines may be safe and immunogenic, but they are highly vulnerable to antigenic drift and shift, which compromise efficacy and require reformulation and repeated immunization.

In addition, vaccine development is costly, complicated, and time consuming. As the recent 2009 H1N1 influenza outbreak demonstrates, the conventional production process is poorly equipped to respond to a pandemic, Dr. Bright said.

He discussed three promising types of influenza vaccines: live attenuated influenza viruses (LAIV), recombinant viruslike particles (VLP), and plant-based production of vaccines. Each holds promise, but all involve significant challenges.

LAIV: Innovative Yet Decades Old

LAIVs have been used to combat seasonal influenza for decades in some parts of the world, including the United States and Russia, but Dr. Bright nevertheless characterized them as innovative. They have yet to be widely accepted or distributed, despite a strong safety record and low cost. In fact, he said, LAIV is the lowest-cost influenza vaccine available today. It's easy to produce and purify; it has a broad immune response, including some mucosal and cellular immunity; and it is efficacious in naive populations, Dr. Bright said.

There are challenges, however. LAIV “doesn't follow the known, established correlates of immunity,” which can lead to regulatory and licensing hurdles.

Moreover, LAIVs are less effective in nonnaive adults, and there are current limitations on their use in children and some high-risk groups. But, he added, some of those limitations are based on “unfounded fears of the risk of reassortment.”

VLP: Dealing With Vectors

VLP vaccines, with many varieties in early-stage development, show promise of being both low cost and high yield, with a rapid (12-week) production cycle, he said. Dr. Bright explained that although VLPs contain multiple influenza proteins to resemble virions, they contain no genetic material, and therefore they do not replicate or cause infection.

Safety is an issue because all VLPs “rely on some sort of vector.” The challenge is to remove—or demonstrate the safety of—the residual vectors, he said, noting that such concerns could lead to regulatory challenges.

Plant-Based Vaccines: Speedy Development

Plant-based vaccines have been advancing steadily since 2000, he reported. Such vaccines can be produced very rapidly, at about 8 weeks from sequencing to release. New approaches to plant-based expression create high yields with low production costs. Moreover, he said, the approach is “suitable for mixing and matching constantly emerging strains.”

Safety appears to be less of a concern than it is for VLPs, according to Dr. Bright, because plant-based vaccines are free of animal cells, microbial pathogens, and animal viruses. But “there are many things we don't know about the safety of plant-based proteins,” he cautioned.

Researchers are exploring the issue of low immunogenicity with plant-based vaccines, he said. Like the VLPs, plant-based vaccines will likely benefit from an adjuvant.

Disclosures: Dr. Bright disclosed receiving stock as part of a management position in 2006 from Novavax Inc.

The conventional influenza vaccine production process is poorly equipped to respond to a pandemic.

Source DR. BRIGHT

ATLANTA — New influenza vaccine development is evolving rapidly, with approximately 75 different technologies currently in various stages, said Rick Bright, Ph.D., scientific director for the influenza vaccine project at Program for Appropriate Technology in Health, a global nonprofit health group.

And new vaccines are desperately needed: Current seasonal vaccines are only 30%-50% effective in older adults, and candidate vaccines for pandemics “are poorly immunogenic in clinical studies,” Dr. Bright said at the meeting.

Current influenza vaccines may be safe and immunogenic, but they are highly vulnerable to antigenic drift and shift, which compromise efficacy and require reformulation and repeated immunization.

In addition, vaccine development is costly, complicated, and time consuming. As the recent 2009 H1N1 influenza outbreak demonstrates, the conventional production process is poorly equipped to respond to a pandemic, Dr. Bright said.

He discussed three promising types of influenza vaccines: live attenuated influenza viruses (LAIV), recombinant viruslike particles (VLP), and plant-based production of vaccines. Each holds promise, but all involve significant challenges.

LAIV: Innovative Yet Decades Old

LAIVs have been used to combat seasonal influenza for decades in some parts of the world, including the United States and Russia, but Dr. Bright nevertheless characterized them as innovative. They have yet to be widely accepted or distributed, despite a strong safety record and low cost. In fact, he said, LAIV is the lowest-cost influenza vaccine available today. It's easy to produce and purify; it has a broad immune response, including some mucosal and cellular immunity; and it is efficacious in naive populations, Dr. Bright said.

There are challenges, however. LAIV “doesn't follow the known, established correlates of immunity,” which can lead to regulatory and licensing hurdles.

Moreover, LAIVs are less effective in nonnaive adults, and there are current limitations on their use in children and some high-risk groups. But, he added, some of those limitations are based on “unfounded fears of the risk of reassortment.”

VLP: Dealing With Vectors

VLP vaccines, with many varieties in early-stage development, show promise of being both low cost and high yield, with a rapid (12-week) production cycle, he said. Dr. Bright explained that although VLPs contain multiple influenza proteins to resemble virions, they contain no genetic material, and therefore they do not replicate or cause infection.

Safety is an issue because all VLPs “rely on some sort of vector.” The challenge is to remove—or demonstrate the safety of—the residual vectors, he said, noting that such concerns could lead to regulatory challenges.

Plant-Based Vaccines: Speedy Development

Plant-based vaccines have been advancing steadily since 2000, he reported. Such vaccines can be produced very rapidly, at about 8 weeks from sequencing to release. New approaches to plant-based expression create high yields with low production costs. Moreover, he said, the approach is “suitable for mixing and matching constantly emerging strains.”

Safety appears to be less of a concern than it is for VLPs, according to Dr. Bright, because plant-based vaccines are free of animal cells, microbial pathogens, and animal viruses. But “there are many things we don't know about the safety of plant-based proteins,” he cautioned.

Researchers are exploring the issue of low immunogenicity with plant-based vaccines, he said. Like the VLPs, plant-based vaccines will likely benefit from an adjuvant.

Disclosures: Dr. Bright disclosed receiving stock as part of a management position in 2006 from Novavax Inc.

The conventional influenza vaccine production process is poorly equipped to respond to a pandemic.

Source DR. BRIGHT