Roxanna Guilford-Blake

ATLANTA — Cryptococcus gattii, a fungal pathogen previously found only in tropical and subtropical areas, is emerging as a serious infection in the U.S. Pacific Northwest, according to the Centers for Disease Control and Prevention.

It has infected at least 60 people and 52 animals in Washington, Oregon, Idaho, and California, according to Julie R. Harris, Ph.D., a CDC epidemiologist. This is “one of the most interesting emerging infectious diseases in the United States today,” she said.

In September 2009, the CDC and various organizations in the affected states began passive surveillance for human and veterinary cases in the Pacific Northwest to understand the extent of the pathogen's spread and its epidemiology.

Twenty cases were identified in 2009, and she expects that even more cases will be identified this year.

Of the 39 patients on which researchers have data, 89% were hospitalized; 33% died of or with the C. gattii infection, she said. The mean age of infected patients is 52 years (range, 15–95 years); C. gattii appears to affect men and women equally. It's rarely a pediatric disease. Moreover, it appears to infect both immunocompetent and immunocompromised patients, most of whom were not infected with HIV.

The most common symptoms are cough, shortness of breath, headache, nausea and vomiting, fever, and weight loss. The patients developed pneumonia (57%), meningitis (44%), encephalitis (21%), and cryptococcomas in the lung (34%) and the brain (25%).

Emilio DeBess, D.M.V., of the Oregon Department of Human Services, noted that C. gattii spores appear to live in association with certain trees and the soil around those trees. Humans can become infected by inhalation of the airborne fungi. “As far as we know, there is no human-to-human or animal-to-human transmission,” he said.

Before 1999, reports of infection were generally limited to tropical and subtropical areas and were most prevalent in Australia. In 1999, it was identified in Vancouver Island, B.C., and then jumped to the mainland in 2004, and spread to the U.S. Pacific Northwest. Most cases are in Washington and Oregon, but reports of infection also have been identified in Idaho and California, Dr. DeBess said.

One explanation for the recent transmissions is that the spores are carried by trucks on the I-5 corridor, which stretches from British Columbia to San Diego. “There are a lot of theories out there. That's the one we are working with at this point,” he said. “Marion County [Oregon] along the I-5 corridor is the Petri dish of C. gattii.”

Then again, Dr. DeBess acknowledged that “it's hard to say” whether C. gattii is truly spreading or if more cases are being identified as a result of more intense surveillance.

C. gattii may be underdiagnosed and, as a result, the mortality rate may be inflated, he added. Both he and Dr. Harris noted the U.S. mortality rate is higher than that reported in British Columbia. He hopes to improve surveillance and promote awareness among physicians and veterinarians.

One of the clinical challenges, Dr. Harris noted, is that most labs cannot distinguish between Cryptococcus neoformans and C. gattii.

“We want all physicians to be aware that this is a new possible etiology of cryptococcal infections in the United States, and if infected with C. gattii, their patients might require prolonged therapy with antifungal drugs, or special procedures and follow-up that normally aren't warranted with C. neoformans infections,” she said in an interview.

“Although most patients either live in or have visited the Pacific Northwest, we would encourage all physicians to keep Cryptococcus gattii in mind when they see an atypical patient with cryptococcal infection, as we don't yet know the extent of the endemic area,” she said.

Because C. neoformans is so much more common than C. gattii, at this point she is not suggesting submission and speciation of every Cryptococcus isolate. “However, for patients with suspected C. gattii infection, we encourage clinicians to report the cases to their states and submit isolates as requested for further speciation,” she said.

Risk factors are poorly defined at this point, she added. “We know anecdotally that many patients live in or near wooded areas or have occupations that involve contact with soil or wood, but we don't have a good group with which to compare these types of exposures. We do plan to conduct a study on this in the near future.”

Disclosures: Dr. DeBess and Dr. Harris reported that they had no conflicts.

ATLANTA — Cryptococcus gattii, a fungal pathogen previously found only in tropical and subtropical areas, is emerging as a serious infection in the U.S. Pacific Northwest, according to the Centers for Disease Control and Prevention.

It has infected at least 60 people and 52 animals in Washington, Oregon, Idaho, and California, according to Julie R. Harris, Ph.D., a CDC epidemiologist. This is “one of the most interesting emerging infectious diseases in the United States today,” she said.

In September 2009, the CDC and various organizations in the affected states began passive surveillance for human and veterinary cases in the Pacific Northwest to understand the extent of the pathogen's spread and its epidemiology.

Twenty cases were identified in 2009, and she expects that even more cases will be identified this year.

Of the 39 patients on which researchers have data, 89% were hospitalized; 33% died of or with the C. gattii infection, she said. The mean age of infected patients is 52 years (range, 15–95 years); C. gattii appears to affect men and women equally. It's rarely a pediatric disease. Moreover, it appears to infect both immunocompetent and immunocompromised patients, most of whom were not infected with HIV.

The most common symptoms are cough, shortness of breath, headache, nausea and vomiting, fever, and weight loss. The patients developed pneumonia (57%), meningitis (44%), encephalitis (21%), and cryptococcomas in the lung (34%) and the brain (25%).

Emilio DeBess, D.M.V., of the Oregon Department of Human Services, noted that C. gattii spores appear to live in association with certain trees and the soil around those trees. Humans can become infected by inhalation of the airborne fungi. “As far as we know, there is no human-to-human or animal-to-human transmission,” he said.

Before 1999, reports of infection were generally limited to tropical and subtropical areas and were most prevalent in Australia. In 1999, it was identified in Vancouver Island, B.C., and then jumped to the mainland in 2004, and spread to the U.S. Pacific Northwest. Most cases are in Washington and Oregon, but reports of infection also have been identified in Idaho and California, Dr. DeBess said.

One explanation for the recent transmissions is that the spores are carried by trucks on the I-5 corridor, which stretches from British Columbia to San Diego. “There are a lot of theories out there. That's the one we are working with at this point,” he said. “Marion County [Oregon] along the I-5 corridor is the Petri dish of C. gattii.”

Then again, Dr. DeBess acknowledged that “it's hard to say” whether C. gattii is truly spreading or if more cases are being identified as a result of more intense surveillance.

C. gattii may be underdiagnosed and, as a result, the mortality rate may be inflated, he added. Both he and Dr. Harris noted the U.S. mortality rate is higher than that reported in British Columbia. He hopes to improve surveillance and promote awareness among physicians and veterinarians.

One of the clinical challenges, Dr. Harris noted, is that most labs cannot distinguish between Cryptococcus neoformans and C. gattii.

“We want all physicians to be aware that this is a new possible etiology of cryptococcal infections in the United States, and if infected with C. gattii, their patients might require prolonged therapy with antifungal drugs, or special procedures and follow-up that normally aren't warranted with C. neoformans infections,” she said in an interview.

“Although most patients either live in or have visited the Pacific Northwest, we would encourage all physicians to keep Cryptococcus gattii in mind when they see an atypical patient with cryptococcal infection, as we don't yet know the extent of the endemic area,” she said.

Because C. neoformans is so much more common than C. gattii, at this point she is not suggesting submission and speciation of every Cryptococcus isolate. “However, for patients with suspected C. gattii infection, we encourage clinicians to report the cases to their states and submit isolates as requested for further speciation,” she said.

Risk factors are poorly defined at this point, she added. “We know anecdotally that many patients live in or near wooded areas or have occupations that involve contact with soil or wood, but we don't have a good group with which to compare these types of exposures. We do plan to conduct a study on this in the near future.”

Disclosures: Dr. DeBess and Dr. Harris reported that they had no conflicts.

ATLANTA — Cryptococcus gattii, a fungal pathogen previously found only in tropical and subtropical areas, is emerging as a serious infection in the U.S. Pacific Northwest, according to the Centers for Disease Control and Prevention.

It has infected at least 60 people and 52 animals in Washington, Oregon, Idaho, and California, according to Julie R. Harris, Ph.D., a CDC epidemiologist. This is “one of the most interesting emerging infectious diseases in the United States today,” she said.

In September 2009, the CDC and various organizations in the affected states began passive surveillance for human and veterinary cases in the Pacific Northwest to understand the extent of the pathogen's spread and its epidemiology.

Twenty cases were identified in 2009, and she expects that even more cases will be identified this year.

Of the 39 patients on which researchers have data, 89% were hospitalized; 33% died of or with the C. gattii infection, she said. The mean age of infected patients is 52 years (range, 15–95 years); C. gattii appears to affect men and women equally. It's rarely a pediatric disease. Moreover, it appears to infect both immunocompetent and immunocompromised patients, most of whom were not infected with HIV.

The most common symptoms are cough, shortness of breath, headache, nausea and vomiting, fever, and weight loss. The patients developed pneumonia (57%), meningitis (44%), encephalitis (21%), and cryptococcomas in the lung (34%) and the brain (25%).

Emilio DeBess, D.M.V., of the Oregon Department of Human Services, noted that C. gattii spores appear to live in association with certain trees and the soil around those trees. Humans can become infected by inhalation of the airborne fungi. “As far as we know, there is no human-to-human or animal-to-human transmission,” he said.

Before 1999, reports of infection were generally limited to tropical and subtropical areas and were most prevalent in Australia. In 1999, it was identified in Vancouver Island, B.C., and then jumped to the mainland in 2004, and spread to the U.S. Pacific Northwest. Most cases are in Washington and Oregon, but reports of infection also have been identified in Idaho and California, Dr. DeBess said.

One explanation for the recent transmissions is that the spores are carried by trucks on the I-5 corridor, which stretches from British Columbia to San Diego. “There are a lot of theories out there. That's the one we are working with at this point,” he said. “Marion County [Oregon] along the I-5 corridor is the Petri dish of C. gattii.”

Then again, Dr. DeBess acknowledged that “it's hard to say” whether C. gattii is truly spreading or if more cases are being identified as a result of more intense surveillance.

C. gattii may be underdiagnosed and, as a result, the mortality rate may be inflated, he added. Both he and Dr. Harris noted the U.S. mortality rate is higher than that reported in British Columbia. He hopes to improve surveillance and promote awareness among physicians and veterinarians.

One of the clinical challenges, Dr. Harris noted, is that most labs cannot distinguish between Cryptococcus neoformans and C. gattii.

“We want all physicians to be aware that this is a new possible etiology of cryptococcal infections in the United States, and if infected with C. gattii, their patients might require prolonged therapy with antifungal drugs, or special procedures and follow-up that normally aren't warranted with C. neoformans infections,” she said in an interview.

“Although most patients either live in or have visited the Pacific Northwest, we would encourage all physicians to keep Cryptococcus gattii in mind when they see an atypical patient with cryptococcal infection, as we don't yet know the extent of the endemic area,” she said.

Because C. neoformans is so much more common than C. gattii, at this point she is not suggesting submission and speciation of every Cryptococcus isolate. “However, for patients with suspected C. gattii infection, we encourage clinicians to report the cases to their states and submit isolates as requested for further speciation,” she said.

Risk factors are poorly defined at this point, she added. “We know anecdotally that many patients live in or near wooded areas or have occupations that involve contact with soil or wood, but we don't have a good group with which to compare these types of exposures. We do plan to conduct a study on this in the near future.”

Disclosures: Dr. DeBess and Dr. Harris reported that they had no conflicts.

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, the researchers noted.

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).

“The introduction of PCV7 was associated with dramatic reductions in penicillin-nonsusceptible invasive pneumococcal disease incidents,” regardless of which break point was used, Dr. Hampton 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.

The findings may not be generalizable outside the ABC system, Dr. Hampton said.

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,” 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.”

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, the researchers noted.

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).

“The introduction of PCV7 was associated with dramatic reductions in penicillin-nonsusceptible invasive pneumococcal disease incidents,” regardless of which break point was used, Dr. Hampton 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.

The findings may not be generalizable outside the ABC system, Dr. Hampton said.

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,” 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.”

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, the researchers noted.

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).

“The introduction of PCV7 was associated with dramatic reductions in penicillin-nonsusceptible invasive pneumococcal disease incidents,” regardless of which break point was used, Dr. Hampton 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.

The findings may not be generalizable outside the ABC system, Dr. Hampton said.

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,” 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.”

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 told attendees.

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 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, including safety, immunogenicity, scalability, and regulatory issues.

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, he 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.”

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

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, Dr. Bright 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 said.

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

Current seasonal influenza vaccines are only 30%-50% effective in older adults.

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 told attendees.

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 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, including safety, immunogenicity, scalability, and regulatory issues.

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, he 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.”

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

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, Dr. Bright 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 said.

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

Current seasonal influenza vaccines are only 30%-50% effective in older adults.

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 told attendees.

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 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, including safety, immunogenicity, scalability, and regulatory issues.

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, he 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.”

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

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, Dr. Bright 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 said.

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

Current seasonal influenza vaccines are only 30%-50% effective in older adults.

Source DR. BRIGHT

ATLANTA — Cryptococcus gattii, a fungal pathogen previously found only in tropical and subtropical areas, is emerging as a serious infection in the Pacific Northwestern United States, according to a report from the Centers for Disease Control and Prevention.

It has infected at least 60 people and 52 animals in Washington, Oregon, Idaho, and California, according to Julie R. Harris, Ph.D., a CDC epidemiologist. This is “one of the most interesting emerging infectious diseases in the United States today,” she said.

In September 2009, the CDC and various organizations in the affected states began passive surveillance for human and veterinary cases in the Pacific Northwest to understand the extent of the pathogen's spread and its epidemiology.

Twenty cases were identified in 2009, and she expects that even more cases will be identified this year.

Of the 39 patients on which researchers have data, 89% were hospitalized; 33% died of or with the C. gattii infection, she said. The mean age of infected patients is 52 years (range, 15-95 years); C. gattii appears to affect men and women equally. It's rarely a pediatric disease. Moreover, it appears to infect both immunocompetent and immunocompromised patients, most of whom were not infected with HIV.

The most common symptoms are cough, shortness of breath, headache, nausea and vomiting, fever, and weight loss. The patients developed pneumonia (57%), meningitis (44%), encephalitis (21%), and cryptococcomas in the lung (34%) and the brain (25%).

Emilio DeBess, D.M.V., of the Oregon Department of Human Services, noted that C. gattii spores appear to live in association with certain trees and the soil around those trees. Humans can become infected by inhalation of the airborne fungi. “As far as we know, there is no human-to-human or animal-to-human transmission,” he said.

Before 1999, reports of infection were generally limited to tropical and subtropical areas and were most prevalent in Australia. In 1999, it was identified in Vancouver Island, British Columbia and then jumped to the mainland in 2004, and spread to the U.S. Pacific Northwest. Most cases are in Washington and Oregon, but reports of infection also have been identified in Idaho and California, Dr. DeBess said.

One explanation for the recent transmissions is that the spores are carried by trucks on the I-5 corridor, which stretches from British Columbia to San Diego. “There are a lot of theories out there. That's the one we are working with at this point,” he said. “Marion County [Oregon] along the I-5 corridor is the Petri dish of C. gattii.”

Then again, Dr. DeBess acknowledged that “it's hard to say” whether C. gattii is truly spreading or if more cases are being identified as a result of more intense surveillance.

C. gattii may be underdiagnosed and, as a result, the mortality rate may be inflated, he added. He and Dr. Harris noted the U.S. mortality rate is higher than that reported in British Columbia. He hopes to improve surveillance and promote awareness among physicians and veterinarians.

One of the clinical challenges, Dr. Harris noted, is that most labs cannot distinguish between Cryptococcus neoformans and C. gattii.

“We want all physicians to be aware that this is a new possible etiology of cryptococcal infections in the United States, and if infected with C. gattii, their patients might require prolonged therapy with antifungal drugs, or special procedures and follow-up,” she said in an interview.

Because C. neoformans is so much more common than C. gattii, at this point she is not suggesting submission and speciation of every Cryptococcus isolate. “However, for patients with suspected C. gattii infection, we encourage clinicians to report the cases to their states and submit isolates as requested for further speciation,” she said.

Dr. DeBess and Dr. Harris reported that they had no conflicts of interest.

ATLANTA — Cryptococcus gattii, a fungal pathogen previously found only in tropical and subtropical areas, is emerging as a serious infection in the Pacific Northwestern United States, according to a report from the Centers for Disease Control and Prevention.

It has infected at least 60 people and 52 animals in Washington, Oregon, Idaho, and California, according to Julie R. Harris, Ph.D., a CDC epidemiologist. This is “one of the most interesting emerging infectious diseases in the United States today,” she said.

In September 2009, the CDC and various organizations in the affected states began passive surveillance for human and veterinary cases in the Pacific Northwest to understand the extent of the pathogen's spread and its epidemiology.

Twenty cases were identified in 2009, and she expects that even more cases will be identified this year.

Of the 39 patients on which researchers have data, 89% were hospitalized; 33% died of or with the C. gattii infection, she said. The mean age of infected patients is 52 years (range, 15-95 years); C. gattii appears to affect men and women equally. It's rarely a pediatric disease. Moreover, it appears to infect both immunocompetent and immunocompromised patients, most of whom were not infected with HIV.

The most common symptoms are cough, shortness of breath, headache, nausea and vomiting, fever, and weight loss. The patients developed pneumonia (57%), meningitis (44%), encephalitis (21%), and cryptococcomas in the lung (34%) and the brain (25%).

Emilio DeBess, D.M.V., of the Oregon Department of Human Services, noted that C. gattii spores appear to live in association with certain trees and the soil around those trees. Humans can become infected by inhalation of the airborne fungi. “As far as we know, there is no human-to-human or animal-to-human transmission,” he said.

Before 1999, reports of infection were generally limited to tropical and subtropical areas and were most prevalent in Australia. In 1999, it was identified in Vancouver Island, British Columbia and then jumped to the mainland in 2004, and spread to the U.S. Pacific Northwest. Most cases are in Washington and Oregon, but reports of infection also have been identified in Idaho and California, Dr. DeBess said.

One explanation for the recent transmissions is that the spores are carried by trucks on the I-5 corridor, which stretches from British Columbia to San Diego. “There are a lot of theories out there. That's the one we are working with at this point,” he said. “Marion County [Oregon] along the I-5 corridor is the Petri dish of C. gattii.”

Then again, Dr. DeBess acknowledged that “it's hard to say” whether C. gattii is truly spreading or if more cases are being identified as a result of more intense surveillance.

C. gattii may be underdiagnosed and, as a result, the mortality rate may be inflated, he added. He and Dr. Harris noted the U.S. mortality rate is higher than that reported in British Columbia. He hopes to improve surveillance and promote awareness among physicians and veterinarians.

One of the clinical challenges, Dr. Harris noted, is that most labs cannot distinguish between Cryptococcus neoformans and C. gattii.

“We want all physicians to be aware that this is a new possible etiology of cryptococcal infections in the United States, and if infected with C. gattii, their patients might require prolonged therapy with antifungal drugs, or special procedures and follow-up,” she said in an interview.

Because C. neoformans is so much more common than C. gattii, at this point she is not suggesting submission and speciation of every Cryptococcus isolate. “However, for patients with suspected C. gattii infection, we encourage clinicians to report the cases to their states and submit isolates as requested for further speciation,” she said.

Dr. DeBess and Dr. Harris reported that they had no conflicts of interest.

ATLANTA — Cryptococcus gattii, a fungal pathogen previously found only in tropical and subtropical areas, is emerging as a serious infection in the Pacific Northwestern United States, according to a report from the Centers for Disease Control and Prevention.

It has infected at least 60 people and 52 animals in Washington, Oregon, Idaho, and California, according to Julie R. Harris, Ph.D., a CDC epidemiologist. This is “one of the most interesting emerging infectious diseases in the United States today,” she said.

In September 2009, the CDC and various organizations in the affected states began passive surveillance for human and veterinary cases in the Pacific Northwest to understand the extent of the pathogen's spread and its epidemiology.

Twenty cases were identified in 2009, and she expects that even more cases will be identified this year.

Of the 39 patients on which researchers have data, 89% were hospitalized; 33% died of or with the C. gattii infection, she said. The mean age of infected patients is 52 years (range, 15-95 years); C. gattii appears to affect men and women equally. It's rarely a pediatric disease. Moreover, it appears to infect both immunocompetent and immunocompromised patients, most of whom were not infected with HIV.

The most common symptoms are cough, shortness of breath, headache, nausea and vomiting, fever, and weight loss. The patients developed pneumonia (57%), meningitis (44%), encephalitis (21%), and cryptococcomas in the lung (34%) and the brain (25%).

Emilio DeBess, D.M.V., of the Oregon Department of Human Services, noted that C. gattii spores appear to live in association with certain trees and the soil around those trees. Humans can become infected by inhalation of the airborne fungi. “As far as we know, there is no human-to-human or animal-to-human transmission,” he said.

Before 1999, reports of infection were generally limited to tropical and subtropical areas and were most prevalent in Australia. In 1999, it was identified in Vancouver Island, British Columbia and then jumped to the mainland in 2004, and spread to the U.S. Pacific Northwest. Most cases are in Washington and Oregon, but reports of infection also have been identified in Idaho and California, Dr. DeBess said.

One explanation for the recent transmissions is that the spores are carried by trucks on the I-5 corridor, which stretches from British Columbia to San Diego. “There are a lot of theories out there. That's the one we are working with at this point,” he said. “Marion County [Oregon] along the I-5 corridor is the Petri dish of C. gattii.”

Then again, Dr. DeBess acknowledged that “it's hard to say” whether C. gattii is truly spreading or if more cases are being identified as a result of more intense surveillance.

C. gattii may be underdiagnosed and, as a result, the mortality rate may be inflated, he added. He and Dr. Harris noted the U.S. mortality rate is higher than that reported in British Columbia. He hopes to improve surveillance and promote awareness among physicians and veterinarians.

One of the clinical challenges, Dr. Harris noted, is that most labs cannot distinguish between Cryptococcus neoformans and C. gattii.

“We want all physicians to be aware that this is a new possible etiology of cryptococcal infections in the United States, and if infected with C. gattii, their patients might require prolonged therapy with antifungal drugs, or special procedures and follow-up,” she said in an interview.

Because C. neoformans is so much more common than C. gattii, at this point she is not suggesting submission and speciation of every Cryptococcus isolate. “However, for patients with suspected C. gattii infection, we encourage clinicians to report the cases to their states and submit isolates as requested for further speciation,” she said.

Dr. DeBess and Dr. Harris reported that they had no conflicts of interest.

ATLANTA - Cryptococcus gattii, a fungal pathogen previously found only in tropical and subtropical areas, is emerging as a serious infection in the Pacific Northwestern United States, according to the Centers for Disease Control and Prevention.

It has infected at least 60 people and 52 animals in Washington, Oregon, Idaho, and California, according to Julie R. Harris, Ph.D., a CDC epidemiologist. This is "one of the most interesting emerging infectious diseases in the United States today," she said.

In September 2009, the CDC and various organizations in the affected states began passive surveillance for human and veterinary cases in the Pacific Northwest to understand the extent of the pathogen’s spread and its epidemiology.

Twenty cases were identified in 2009, and she expects that even more cases will be identified this year.

Of the 39 patients on which researchers have data, 89% were hospitalized; 33% died of or with the C. gattii infection, she said. The mean age of infected patients is 52 years (range, 15-95 years); C. gattii appears to affect men and women equally. It's rarely a pediatric disease. Moreover, it appears to infect both immunocompetent and immunocompromised patients, most of whom were not infected with HIV.

The most common symptoms are cough, shortness of breath, headache, nausea and vomiting, fever, and weight loss. The patients developed pneumonia (57%), meningitis (44%), encephalitis (21%), and cryptococcomas in the lung (34%) and the brain (25%).

Emilio DeBess, D.M.V., of the Oregon Department of Human Services, noted that C. gattii spores appear to live in association with certain trees and the soil around those trees. Humans can become infected by inhalation of the airborne fungi. "As far as we know, there is no human-to-human or animal-to-human transmission," he said.

Before 1999, reports of infection were generally limited to tropical and subtropical areas and were most prevalent in Australia. In 1999, it was identified in Vancouver Island, British Columbia and then jumped to the mainland in 2004, and spread to the U.S. Pacific Northwest. Most cases are in Washington and Oregon, but reports of infection also have been identified in Idaho and California, Dr. DeBess said.

One explanation for the recent transmissions is that the spores are carried by trucks on the I-5 corridor, which stretches from British Columbia to San Diego. "There are a lot of theories out there. That's the one we are working with at this point," he said. "Marion County [Oregon] along the I-5 corridor is the Petri dish of C. gattii."

Then again, Dr. DeBess acknowledged that "it's hard to say" whether C. gattii is truly spreading or if more cases are being identified as a result of more intense surveillance.

C. gattii may be underdiagnosed and, as a result, the mortality rate may be inflated, he added. Both he and Dr. Harris noted the U.S. mortality rate is higher than that reported in British Columbia. He hopes to improve surveillance and promote awareness among physicians and veterinarians.

One of the clinical challenges, Dr. Harris noted, is that most labs cannot distinguish between Cryptococcus neoformans and C. gattii.

"We want all physicians to be aware that this is a new possible etiology of cryptococcal infections in the United States, and if infected with C. gattii, their patients might require prolonged therapy with antifungal drugs, or special procedures and follow-up that normally aren't warranted with C. neoformans infections," she said in an interview.

"Although most patients either live in or have visited the Pacific Northwest, we would encourage all physicians to keep Cryptococcus gattii in mind when they see an atypical patient with cryptococcal infection, as we don’t yet know the extent of the endemic area," she said.

Because C. neoformans is so much more common than C. gattii, at this point she is not suggesting submission and speciation of every Cryptococcus isolate. "However, for patients with suspected C. gattii infection, we encourage clinicians to report the cases to their states and submit isolates as requested for further speciation," she said.

Risk factors are poorly defined at this point, she added. "We know anecdotally that many patients live in or near wooded areas or have occupations that involve contact with soil or wood, but we don't have a good group with which to compare these types of exposures. We do plan to conduct a study on this in the near future."

Dr. DeBess and Dr. Harris reported that they had no conflicts.

ATLANTA - Cryptococcus gattii, a fungal pathogen previously found only in tropical and subtropical areas, is emerging as a serious infection in the Pacific Northwestern United States, according to the Centers for Disease Control and Prevention.

It has infected at least 60 people and 52 animals in Washington, Oregon, Idaho, and California, according to Julie R. Harris, Ph.D., a CDC epidemiologist. This is "one of the most interesting emerging infectious diseases in the United States today," she said.

In September 2009, the CDC and various organizations in the affected states began passive surveillance for human and veterinary cases in the Pacific Northwest to understand the extent of the pathogen’s spread and its epidemiology.

Twenty cases were identified in 2009, and she expects that even more cases will be identified this year.

Of the 39 patients on which researchers have data, 89% were hospitalized; 33% died of or with the C. gattii infection, she said. The mean age of infected patients is 52 years (range, 15-95 years); C. gattii appears to affect men and women equally. It's rarely a pediatric disease. Moreover, it appears to infect both immunocompetent and immunocompromised patients, most of whom were not infected with HIV.

The most common symptoms are cough, shortness of breath, headache, nausea and vomiting, fever, and weight loss. The patients developed pneumonia (57%), meningitis (44%), encephalitis (21%), and cryptococcomas in the lung (34%) and the brain (25%).

Emilio DeBess, D.M.V., of the Oregon Department of Human Services, noted that C. gattii spores appear to live in association with certain trees and the soil around those trees. Humans can become infected by inhalation of the airborne fungi. "As far as we know, there is no human-to-human or animal-to-human transmission," he said.

Before 1999, reports of infection were generally limited to tropical and subtropical areas and were most prevalent in Australia. In 1999, it was identified in Vancouver Island, British Columbia and then jumped to the mainland in 2004, and spread to the U.S. Pacific Northwest. Most cases are in Washington and Oregon, but reports of infection also have been identified in Idaho and California, Dr. DeBess said.

One explanation for the recent transmissions is that the spores are carried by trucks on the I-5 corridor, which stretches from British Columbia to San Diego. "There are a lot of theories out there. That's the one we are working with at this point," he said. "Marion County [Oregon] along the I-5 corridor is the Petri dish of C. gattii."

Then again, Dr. DeBess acknowledged that "it's hard to say" whether C. gattii is truly spreading or if more cases are being identified as a result of more intense surveillance.

C. gattii may be underdiagnosed and, as a result, the mortality rate may be inflated, he added. Both he and Dr. Harris noted the U.S. mortality rate is higher than that reported in British Columbia. He hopes to improve surveillance and promote awareness among physicians and veterinarians.

One of the clinical challenges, Dr. Harris noted, is that most labs cannot distinguish between Cryptococcus neoformans and C. gattii.

"We want all physicians to be aware that this is a new possible etiology of cryptococcal infections in the United States, and if infected with C. gattii, their patients might require prolonged therapy with antifungal drugs, or special procedures and follow-up that normally aren't warranted with C. neoformans infections," she said in an interview.

"Although most patients either live in or have visited the Pacific Northwest, we would encourage all physicians to keep Cryptococcus gattii in mind when they see an atypical patient with cryptococcal infection, as we don’t yet know the extent of the endemic area," she said.

Because C. neoformans is so much more common than C. gattii, at this point she is not suggesting submission and speciation of every Cryptococcus isolate. "However, for patients with suspected C. gattii infection, we encourage clinicians to report the cases to their states and submit isolates as requested for further speciation," she said.

Risk factors are poorly defined at this point, she added. "We know anecdotally that many patients live in or near wooded areas or have occupations that involve contact with soil or wood, but we don't have a good group with which to compare these types of exposures. We do plan to conduct a study on this in the near future."

Dr. DeBess and Dr. Harris reported that they had no conflicts.

ATLANTA - Cryptococcus gattii, a fungal pathogen previously found only in tropical and subtropical areas, is emerging as a serious infection in the Pacific Northwestern United States, according to the Centers for Disease Control and Prevention.

It has infected at least 60 people and 52 animals in Washington, Oregon, Idaho, and California, according to Julie R. Harris, Ph.D., a CDC epidemiologist. This is "one of the most interesting emerging infectious diseases in the United States today," she said.

In September 2009, the CDC and various organizations in the affected states began passive surveillance for human and veterinary cases in the Pacific Northwest to understand the extent of the pathogen’s spread and its epidemiology.

Twenty cases were identified in 2009, and she expects that even more cases will be identified this year.

Of the 39 patients on which researchers have data, 89% were hospitalized; 33% died of or with the C. gattii infection, she said. The mean age of infected patients is 52 years (range, 15-95 years); C. gattii appears to affect men and women equally. It's rarely a pediatric disease. Moreover, it appears to infect both immunocompetent and immunocompromised patients, most of whom were not infected with HIV.

The most common symptoms are cough, shortness of breath, headache, nausea and vomiting, fever, and weight loss. The patients developed pneumonia (57%), meningitis (44%), encephalitis (21%), and cryptococcomas in the lung (34%) and the brain (25%).

Emilio DeBess, D.M.V., of the Oregon Department of Human Services, noted that C. gattii spores appear to live in association with certain trees and the soil around those trees. Humans can become infected by inhalation of the airborne fungi. "As far as we know, there is no human-to-human or animal-to-human transmission," he said.

Before 1999, reports of infection were generally limited to tropical and subtropical areas and were most prevalent in Australia. In 1999, it was identified in Vancouver Island, British Columbia and then jumped to the mainland in 2004, and spread to the U.S. Pacific Northwest. Most cases are in Washington and Oregon, but reports of infection also have been identified in Idaho and California, Dr. DeBess said.

One explanation for the recent transmissions is that the spores are carried by trucks on the I-5 corridor, which stretches from British Columbia to San Diego. "There are a lot of theories out there. That's the one we are working with at this point," he said. "Marion County [Oregon] along the I-5 corridor is the Petri dish of C. gattii."

Then again, Dr. DeBess acknowledged that "it's hard to say" whether C. gattii is truly spreading or if more cases are being identified as a result of more intense surveillance.

C. gattii may be underdiagnosed and, as a result, the mortality rate may be inflated, he added. Both he and Dr. Harris noted the U.S. mortality rate is higher than that reported in British Columbia. He hopes to improve surveillance and promote awareness among physicians and veterinarians.

One of the clinical challenges, Dr. Harris noted, is that most labs cannot distinguish between Cryptococcus neoformans and C. gattii.

"We want all physicians to be aware that this is a new possible etiology of cryptococcal infections in the United States, and if infected with C. gattii, their patients might require prolonged therapy with antifungal drugs, or special procedures and follow-up that normally aren't warranted with C. neoformans infections," she said in an interview.

"Although most patients either live in or have visited the Pacific Northwest, we would encourage all physicians to keep Cryptococcus gattii in mind when they see an atypical patient with cryptococcal infection, as we don’t yet know the extent of the endemic area," she said.

Because C. neoformans is so much more common than C. gattii, at this point she is not suggesting submission and speciation of every Cryptococcus isolate. "However, for patients with suspected C. gattii infection, we encourage clinicians to report the cases to their states and submit isolates as requested for further speciation," she said.

Risk factors are poorly defined at this point, she added. "We know anecdotally that many patients live in or near wooded areas or have occupations that involve contact with soil or wood, but we don't have a good group with which to compare these types of exposures. We do plan to conduct a study on this in the near future."

Dr. DeBess and Dr. Harris reported that they had no conflicts.

ATLANTA — The problem of how to reduce vaccine-related errors was raised during the lively question-and-answer session at the conference, which was sponsored by the Centers for Disease Control and Prevention.

The panelists—Dr. Iyabode Akinsanya-Beysolow, Dr. William Atkinson, Dr. Andrew Kroger, and Donna Weaver, R.N., all of the Centers for Disease Control and Prevention's National Center for Immunization and Respiratory Diseases—fielded a variety of vaccine-related questions from the audience.

One audience member reported that, in the last year, the number of vaccine errors she has seen had gone up fourfold, and there is no system to capture them. Without capturing the data, she added, it is difficult to make the case to manufacturers for label changes.

“Point well taken,” Dr. Atkinson replied. The Vaccine Adverse Event Reporting System is not built to capture administration errors, he noted. “We just don't have the kind of epidemiologic analysis we'd like to have.”

Ms. Weaver emphasized the importance of training and orientation for each new person and each time there is a new vaccine. And after training, she advised, test your office staff to make sure they indeed developed the proper knowledge and skills.

Convincing manufacturers to improve labeling can be helpful, but providers can make important changes in their own offices, she counseled. She cited several simple examples, including carefully labeling diluents and keeping each diluent with the right vaccine.

Educational programs, posters, and other resources are available from the CDC and other organizations to help enhance vaccine safety in the office, she said. In particular, she mentioned California's www.eziz.org

The other topics discussed included the following:

▸ Confusing the diphtheria, tetanus, acellular pertussis (DTaP) vaccine for children and the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine for adolescents and adults. Practices continue to make this mistake, one audience member reported. Dr. Akinsanya-Beysolow advised storing each vaccine on a different shelf. Label each shelf with the name of the vaccine and the age of the patient “in big, big neon letters.”

She also echoed Ms. Weaver's remarks about the importance of adequate training.

▸ More to come on pertussis, Tdap. The pertussis work group has started meeting again after taking about a year off, Dr. Atkinson reported, and he predicted a flurry of information “emerging from their discussions.” Another issue he expects the group to address is the use of Tdap in patients 65 and older.

An audience member asked if the CDC planned to refine its guidance regarding Tdap during pregnancy. It might. ACIP's recommendation to defer the vaccine until after pregnancy is based on data from 1945, Dr. Kroger said.

▸ Allaying fears about live attenuated influenza vaccine (LAIV). An audience member asked about the use of LAIV among health care providers, noting “no one would use it” because of the fears generated by the warning about using it around immunocompromised individuals. Dr. Atkinson explained that warning would be removed, and that it had been “a real distraction.” Compounding the concerns, noted an audience member, is that various professional groups issue “countermessages.”

Disclosures: None of the panelists reported any conflicts of interest.

ATLANTA — The problem of how to reduce vaccine-related errors was raised during the lively question-and-answer session at the conference, which was sponsored by the Centers for Disease Control and Prevention.

The panelists—Dr. Iyabode Akinsanya-Beysolow, Dr. William Atkinson, Dr. Andrew Kroger, and Donna Weaver, R.N., all of the Centers for Disease Control and Prevention's National Center for Immunization and Respiratory Diseases—fielded a variety of vaccine-related questions from the audience.

One audience member reported that, in the last year, the number of vaccine errors she has seen had gone up fourfold, and there is no system to capture them. Without capturing the data, she added, it is difficult to make the case to manufacturers for label changes.

“Point well taken,” Dr. Atkinson replied. The Vaccine Adverse Event Reporting System is not built to capture administration errors, he noted. “We just don't have the kind of epidemiologic analysis we'd like to have.”

Ms. Weaver emphasized the importance of training and orientation for each new person and each time there is a new vaccine. And after training, she advised, test your office staff to make sure they indeed developed the proper knowledge and skills.

Convincing manufacturers to improve labeling can be helpful, but providers can make important changes in their own offices, she counseled. She cited several simple examples, including carefully labeling diluents and keeping each diluent with the right vaccine.

Educational programs, posters, and other resources are available from the CDC and other organizations to help enhance vaccine safety in the office, she said. In particular, she mentioned California's www.eziz.org

The other topics discussed included the following:

▸ Confusing the diphtheria, tetanus, acellular pertussis (DTaP) vaccine for children and the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine for adolescents and adults. Practices continue to make this mistake, one audience member reported. Dr. Akinsanya-Beysolow advised storing each vaccine on a different shelf. Label each shelf with the name of the vaccine and the age of the patient “in big, big neon letters.”

She also echoed Ms. Weaver's remarks about the importance of adequate training.

▸ More to come on pertussis, Tdap. The pertussis work group has started meeting again after taking about a year off, Dr. Atkinson reported, and he predicted a flurry of information “emerging from their discussions.” Another issue he expects the group to address is the use of Tdap in patients 65 and older.

An audience member asked if the CDC planned to refine its guidance regarding Tdap during pregnancy. It might. ACIP's recommendation to defer the vaccine until after pregnancy is based on data from 1945, Dr. Kroger said.

▸ Allaying fears about live attenuated influenza vaccine (LAIV). An audience member asked about the use of LAIV among health care providers, noting “no one would use it” because of the fears generated by the warning about using it around immunocompromised individuals. Dr. Atkinson explained that warning would be removed, and that it had been “a real distraction.” Compounding the concerns, noted an audience member, is that various professional groups issue “countermessages.”

Disclosures: None of the panelists reported any conflicts of interest.

ATLANTA — The problem of how to reduce vaccine-related errors was raised during the lively question-and-answer session at the conference, which was sponsored by the Centers for Disease Control and Prevention.

The panelists—Dr. Iyabode Akinsanya-Beysolow, Dr. William Atkinson, Dr. Andrew Kroger, and Donna Weaver, R.N., all of the Centers for Disease Control and Prevention's National Center for Immunization and Respiratory Diseases—fielded a variety of vaccine-related questions from the audience.

One audience member reported that, in the last year, the number of vaccine errors she has seen had gone up fourfold, and there is no system to capture them. Without capturing the data, she added, it is difficult to make the case to manufacturers for label changes.

“Point well taken,” Dr. Atkinson replied. The Vaccine Adverse Event Reporting System is not built to capture administration errors, he noted. “We just don't have the kind of epidemiologic analysis we'd like to have.”

Ms. Weaver emphasized the importance of training and orientation for each new person and each time there is a new vaccine. And after training, she advised, test your office staff to make sure they indeed developed the proper knowledge and skills.

Convincing manufacturers to improve labeling can be helpful, but providers can make important changes in their own offices, she counseled. She cited several simple examples, including carefully labeling diluents and keeping each diluent with the right vaccine.

Educational programs, posters, and other resources are available from the CDC and other organizations to help enhance vaccine safety in the office, she said. In particular, she mentioned California's www.eziz.org

The other topics discussed included the following:

▸ Confusing the diphtheria, tetanus, acellular pertussis (DTaP) vaccine for children and the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine for adolescents and adults. Practices continue to make this mistake, one audience member reported. Dr. Akinsanya-Beysolow advised storing each vaccine on a different shelf. Label each shelf with the name of the vaccine and the age of the patient “in big, big neon letters.”

She also echoed Ms. Weaver's remarks about the importance of adequate training.

▸ More to come on pertussis, Tdap. The pertussis work group has started meeting again after taking about a year off, Dr. Atkinson reported, and he predicted a flurry of information “emerging from their discussions.” Another issue he expects the group to address is the use of Tdap in patients 65 and older.

An audience member asked if the CDC planned to refine its guidance regarding Tdap during pregnancy. It might. ACIP's recommendation to defer the vaccine until after pregnancy is based on data from 1945, Dr. Kroger said.

▸ Allaying fears about live attenuated influenza vaccine (LAIV). An audience member asked about the use of LAIV among health care providers, noting “no one would use it” because of the fears generated by the warning about using it around immunocompromised individuals. Dr. Atkinson explained that warning would be removed, and that it had been “a real distraction.” Compounding the concerns, noted an audience member, is that various professional groups issue “countermessages.”

Disclosures: None of the panelists reported any conflicts of interest.

Major Finding: Seventy-seven percent of pediatricians and family physicians reported being very or somewhat willing to participate with public health organizations to set up community clinics where their patients could be vaccinated, and 76% reported being very or somewhat willing to refer certain patients to public clinics or pharmacies.

Data Source: A national survey of 628 pediatricians and family physicians conducted July through October 2009.

Disclosures: None was reported.

ATLANTA — Although they would rather vaccinate children in their own offices, pediatricians and family physicians appear willing to collaborate with other practices and public health clinics to facilitate influenza vaccine delivery, based on a national survey.

They have significant concerns, however, including potential records-transfer problems and being left with surplus vaccine, reported Dr. Allison Kempe, director of the children's outcomes research program at the University of Colorado at Denver.

In the survey of pediatricians and family physicians conducted July through October 2009, a majority (78%) of the 628 physicians responded strongly or somewhat agreed that having multiple delivery sites increased vaccination rates among their patients.

The physicians reported being very or somewhat willing to:

▸ Participate with public health organizations to set up community clinics where their patients could be vaccinated: 77%.

▸ Refer certain patients to public clinics or pharmacies: 76%.

▸ Refer patients to other practices for vaccines: 50%.

▸ Vaccinate patients from other practices: 49%.

In addition, almost all indicated a willingness to sell vaccine to public health clinics (92%) or buy extra vaccine from them (90%).

This reflects the frustrations physicians have with vaccine supply and delivery problems, she said.

Among the frequently cited barriers are:

▸ Concerns about transfer of records of vaccines (“record scatter”): 57% (25% identified it as significant).

▸ Difficulty estimating the amount of vaccine to order: 56% (23% called it significant).

▸ Time and effort required: 31% (23% called it significant).

▸ Reluctance of families to use another site: 45% (11% called it significant).

In general, the responses of the pediatricians and family physicians were similar, Dr. Kempe said at the conference sponsored by the Centers for Disease Control and Prevention.

But she pointed out two important differences: Pediatricians were more likely to believe strongly that infants should be vaccinated in their medical home, and family physicians indicated a greater willingness to collaborate.

She noted the findings correspond with her observation that the willingness to collaborate on vaccine delivery has increased since the 2009 H1N1 flu outbreak.

Dr. Kempe cited a growing need for collaboration.

The CDC Advisory Committee on Immunization Practices's recommendations have been rapidly expanding over the last 5 years, which has been “somewhat difficult for primary care physicians to deal with,” she said, and noted, “If all the influenza vaccinations were given in the medical home, it is estimated that 42–49 million additional visits might be needed in a given year.”

Moreover, most primary care physicians are not actively re-calling all children, and if they did, they might be unable to handle the increased volume, she said.

“Clearly, collaboration between the different vaccine sectors may be very advantageous to this process,” Dr. Kempe said.

Major Finding: Seventy-seven percent of pediatricians and family physicians reported being very or somewhat willing to participate with public health organizations to set up community clinics where their patients could be vaccinated, and 76% reported being very or somewhat willing to refer certain patients to public clinics or pharmacies.

Data Source: A national survey of 628 pediatricians and family physicians conducted July through October 2009.

Disclosures: None was reported.

ATLANTA — Although they would rather vaccinate children in their own offices, pediatricians and family physicians appear willing to collaborate with other practices and public health clinics to facilitate influenza vaccine delivery, based on a national survey.

They have significant concerns, however, including potential records-transfer problems and being left with surplus vaccine, reported Dr. Allison Kempe, director of the children's outcomes research program at the University of Colorado at Denver.

In the survey of pediatricians and family physicians conducted July through October 2009, a majority (78%) of the 628 physicians responded strongly or somewhat agreed that having multiple delivery sites increased vaccination rates among their patients.

The physicians reported being very or somewhat willing to:

▸ Participate with public health organizations to set up community clinics where their patients could be vaccinated: 77%.

▸ Refer certain patients to public clinics or pharmacies: 76%.

▸ Refer patients to other practices for vaccines: 50%.

▸ Vaccinate patients from other practices: 49%.

In addition, almost all indicated a willingness to sell vaccine to public health clinics (92%) or buy extra vaccine from them (90%).

This reflects the frustrations physicians have with vaccine supply and delivery problems, she said.

Among the frequently cited barriers are:

▸ Concerns about transfer of records of vaccines (“record scatter”): 57% (25% identified it as significant).

▸ Difficulty estimating the amount of vaccine to order: 56% (23% called it significant).

▸ Time and effort required: 31% (23% called it significant).

▸ Reluctance of families to use another site: 45% (11% called it significant).

In general, the responses of the pediatricians and family physicians were similar, Dr. Kempe said at the conference sponsored by the Centers for Disease Control and Prevention.

But she pointed out two important differences: Pediatricians were more likely to believe strongly that infants should be vaccinated in their medical home, and family physicians indicated a greater willingness to collaborate.

She noted the findings correspond with her observation that the willingness to collaborate on vaccine delivery has increased since the 2009 H1N1 flu outbreak.

Dr. Kempe cited a growing need for collaboration.

The CDC Advisory Committee on Immunization Practices's recommendations have been rapidly expanding over the last 5 years, which has been “somewhat difficult for primary care physicians to deal with,” she said, and noted, “If all the influenza vaccinations were given in the medical home, it is estimated that 42–49 million additional visits might be needed in a given year.”

Moreover, most primary care physicians are not actively re-calling all children, and if they did, they might be unable to handle the increased volume, she said.

“Clearly, collaboration between the different vaccine sectors may be very advantageous to this process,” Dr. Kempe said.

Major Finding: Seventy-seven percent of pediatricians and family physicians reported being very or somewhat willing to participate with public health organizations to set up community clinics where their patients could be vaccinated, and 76% reported being very or somewhat willing to refer certain patients to public clinics or pharmacies.

Data Source: A national survey of 628 pediatricians and family physicians conducted July through October 2009.

Disclosures: None was reported.

ATLANTA — Although they would rather vaccinate children in their own offices, pediatricians and family physicians appear willing to collaborate with other practices and public health clinics to facilitate influenza vaccine delivery, based on a national survey.

They have significant concerns, however, including potential records-transfer problems and being left with surplus vaccine, reported Dr. Allison Kempe, director of the children's outcomes research program at the University of Colorado at Denver.

In the survey of pediatricians and family physicians conducted July through October 2009, a majority (78%) of the 628 physicians responded strongly or somewhat agreed that having multiple delivery sites increased vaccination rates among their patients.

The physicians reported being very or somewhat willing to:

▸ Participate with public health organizations to set up community clinics where their patients could be vaccinated: 77%.

▸ Refer certain patients to public clinics or pharmacies: 76%.

▸ Refer patients to other practices for vaccines: 50%.

▸ Vaccinate patients from other practices: 49%.

In addition, almost all indicated a willingness to sell vaccine to public health clinics (92%) or buy extra vaccine from them (90%).

This reflects the frustrations physicians have with vaccine supply and delivery problems, she said.

Among the frequently cited barriers are:

▸ Concerns about transfer of records of vaccines (“record scatter”): 57% (25% identified it as significant).

▸ Difficulty estimating the amount of vaccine to order: 56% (23% called it significant).

▸ Time and effort required: 31% (23% called it significant).

▸ Reluctance of families to use another site: 45% (11% called it significant).

In general, the responses of the pediatricians and family physicians were similar, Dr. Kempe said at the conference sponsored by the Centers for Disease Control and Prevention.

But she pointed out two important differences: Pediatricians were more likely to believe strongly that infants should be vaccinated in their medical home, and family physicians indicated a greater willingness to collaborate.

She noted the findings correspond with her observation that the willingness to collaborate on vaccine delivery has increased since the 2009 H1N1 flu outbreak.

Dr. Kempe cited a growing need for collaboration.

The CDC Advisory Committee on Immunization Practices's recommendations have been rapidly expanding over the last 5 years, which has been “somewhat difficult for primary care physicians to deal with,” she said, and noted, “If all the influenza vaccinations were given in the medical home, it is estimated that 42–49 million additional visits might be needed in a given year.”

Moreover, most primary care physicians are not actively re-calling all children, and if they did, they might be unable to handle the increased volume, she said.

“Clearly, collaboration between the different vaccine sectors may be very advantageous to this process,” Dr. Kempe said.

Major Finding: In the 7- to10-day postvaccination period, use of MMRV was associated with 4.3 additional febrile seizures per 10,000 doses, compared with separate administration of MMR and varicella vaccine.

Data Source: Vaccine Safety Datalink data on 83,107 MMRV vaccine recipients and 376,354 MMR+V recipients in 2000–2008.

Disclosures: Study funding came from the VSD contract with America's Health Insurance Plans, funded by the Centers for Disease Control and Prevention. Dr. Klein and Dr. Baxter have reported research support from Merck & Co, Novartis, GlaxoSmithKline, Wyeth, and Sanofi-Pasteur. The other authors reported no conflicts of interest.

Children aged 12–23 months old are at increased risk of febrile seizures 7–10 days after vaccination with the combination measles-mumps-rubella-varicella vaccine, compared with separate administration of the measles-mumps-rubella vaccine and the varicella vaccine, according to surveillance data from the United States.

The use of the combination measles-mumps-rubella-varicella (MMRV) vaccine instead of separate measles-mumps-rubella and varicella (MMR+V) vaccines accounted for one additional febrile seizure for every 2,300 MMRV vaccines administered—a nearly twofold increased risk, Dr. Nicola P. Klein of Kaiser Permanente Vaccine Study Center, Oakland, Calif., and her colleagues reported.

The researchers issued their preliminary findings to the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) in February 2008.

ACIP subsequently changed its recommendations from a stated preference for MMRV to no preference for either MMRV or separate MMR+V vaccination.

“We analyzed [more than] 459,000 12- to 23-month old children vaccinated with either MMRV or separate MMR and varicella vaccines and found the MMRV vaccine to be associated with increased fever and seizures 7–10 days after vaccination,” they wrote (Pediatrics 2010 June [doi:10.1542/peds.2010–0665]).

Researchers compared seizure risk following MMRV to that following MMR+V using regression analyses and by incorporating chart-reviewed febrile seizure cases.

They looked at Vaccine Safety Datalink (VSD) data on 83,107 MMRV vaccine recipients and 376,354 MMR+V recipients from 2000 to 2008. VSD's surveillance system monitors for potential associations between specific vaccines and adverse events using weekly data and sequential statistical analysis, according to investigators.

In the 7–10 days post vaccination, the MMRV vaccination was associated with 4.3 additional seizures per 10,000 doses. It was not associated with significantly elevated seizure risks during any of the five intervals outside that period, Dr. Klein and her colleagues said.

“Our study results show that both MMRV and MMR vaccines, but not varicella vaccine alone, are associated with increased outpatient fever visits and seizures 7–10 days after vaccination, with MMRV vaccine increasing fever and seizure twice as much as the MMR plus varicella vaccines,” the investigators reported.

“Providers who choose to use the combination vaccine should be aware of and clearly communicate this increased risk to the families and caregivers of their patients,” Dr. Klein and her colleagues said.

Major Finding: In the 7- to10-day postvaccination period, use of MMRV was associated with 4.3 additional febrile seizures per 10,000 doses, compared with separate administration of MMR and varicella vaccine.

Data Source: Vaccine Safety Datalink data on 83,107 MMRV vaccine recipients and 376,354 MMR+V recipients in 2000–2008.

Disclosures: Study funding came from the VSD contract with America's Health Insurance Plans, funded by the Centers for Disease Control and Prevention. Dr. Klein and Dr. Baxter have reported research support from Merck & Co, Novartis, GlaxoSmithKline, Wyeth, and Sanofi-Pasteur. The other authors reported no conflicts of interest.

Children aged 12–23 months old are at increased risk of febrile seizures 7–10 days after vaccination with the combination measles-mumps-rubella-varicella vaccine, compared with separate administration of the measles-mumps-rubella vaccine and the varicella vaccine, according to surveillance data from the United States.

The use of the combination measles-mumps-rubella-varicella (MMRV) vaccine instead of separate measles-mumps-rubella and varicella (MMR+V) vaccines accounted for one additional febrile seizure for every 2,300 MMRV vaccines administered—a nearly twofold increased risk, Dr. Nicola P. Klein of Kaiser Permanente Vaccine Study Center, Oakland, Calif., and her colleagues reported.

The researchers issued their preliminary findings to the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) in February 2008.

ACIP subsequently changed its recommendations from a stated preference for MMRV to no preference for either MMRV or separate MMR+V vaccination.

“We analyzed [more than] 459,000 12- to 23-month old children vaccinated with either MMRV or separate MMR and varicella vaccines and found the MMRV vaccine to be associated with increased fever and seizures 7–10 days after vaccination,” they wrote (Pediatrics 2010 June [doi:10.1542/peds.2010–0665]).

Researchers compared seizure risk following MMRV to that following MMR+V using regression analyses and by incorporating chart-reviewed febrile seizure cases.

They looked at Vaccine Safety Datalink (VSD) data on 83,107 MMRV vaccine recipients and 376,354 MMR+V recipients from 2000 to 2008. VSD's surveillance system monitors for potential associations between specific vaccines and adverse events using weekly data and sequential statistical analysis, according to investigators.

In the 7–10 days post vaccination, the MMRV vaccination was associated with 4.3 additional seizures per 10,000 doses. It was not associated with significantly elevated seizure risks during any of the five intervals outside that period, Dr. Klein and her colleagues said.

“Our study results show that both MMRV and MMR vaccines, but not varicella vaccine alone, are associated with increased outpatient fever visits and seizures 7–10 days after vaccination, with MMRV vaccine increasing fever and seizure twice as much as the MMR plus varicella vaccines,” the investigators reported.

“Providers who choose to use the combination vaccine should be aware of and clearly communicate this increased risk to the families and caregivers of their patients,” Dr. Klein and her colleagues said.

Major Finding: In the 7- to10-day postvaccination period, use of MMRV was associated with 4.3 additional febrile seizures per 10,000 doses, compared with separate administration of MMR and varicella vaccine.

Data Source: Vaccine Safety Datalink data on 83,107 MMRV vaccine recipients and 376,354 MMR+V recipients in 2000–2008.

Disclosures: Study funding came from the VSD contract with America's Health Insurance Plans, funded by the Centers for Disease Control and Prevention. Dr. Klein and Dr. Baxter have reported research support from Merck & Co, Novartis, GlaxoSmithKline, Wyeth, and Sanofi-Pasteur. The other authors reported no conflicts of interest.

Children aged 12–23 months old are at increased risk of febrile seizures 7–10 days after vaccination with the combination measles-mumps-rubella-varicella vaccine, compared with separate administration of the measles-mumps-rubella vaccine and the varicella vaccine, according to surveillance data from the United States.

The use of the combination measles-mumps-rubella-varicella (MMRV) vaccine instead of separate measles-mumps-rubella and varicella (MMR+V) vaccines accounted for one additional febrile seizure for every 2,300 MMRV vaccines administered—a nearly twofold increased risk, Dr. Nicola P. Klein of Kaiser Permanente Vaccine Study Center, Oakland, Calif., and her colleagues reported.

The researchers issued their preliminary findings to the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) in February 2008.

ACIP subsequently changed its recommendations from a stated preference for MMRV to no preference for either MMRV or separate MMR+V vaccination.

“We analyzed [more than] 459,000 12- to 23-month old children vaccinated with either MMRV or separate MMR and varicella vaccines and found the MMRV vaccine to be associated with increased fever and seizures 7–10 days after vaccination,” they wrote (Pediatrics 2010 June [doi:10.1542/peds.2010–0665]).

Researchers compared seizure risk following MMRV to that following MMR+V using regression analyses and by incorporating chart-reviewed febrile seizure cases.

They looked at Vaccine Safety Datalink (VSD) data on 83,107 MMRV vaccine recipients and 376,354 MMR+V recipients from 2000 to 2008. VSD's surveillance system monitors for potential associations between specific vaccines and adverse events using weekly data and sequential statistical analysis, according to investigators.

In the 7–10 days post vaccination, the MMRV vaccination was associated with 4.3 additional seizures per 10,000 doses. It was not associated with significantly elevated seizure risks during any of the five intervals outside that period, Dr. Klein and her colleagues said.

“Our study results show that both MMRV and MMR vaccines, but not varicella vaccine alone, are associated with increased outpatient fever visits and seizures 7–10 days after vaccination, with MMRV vaccine increasing fever and seizure twice as much as the MMR plus varicella vaccines,” the investigators reported.

“Providers who choose to use the combination vaccine should be aware of and clearly communicate this increased risk to the families and caregivers of their patients,” Dr. Klein and her colleagues said.

ATLANTA — Questions about varicella immunity and human papillomavirus vaccine logistics topped physicians' concerns during a Q&A session with an expert panel at the annual National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

The panelists included Dr. William Atkinson, Dr. Andrew Kroger, and Donna Weaver, R.N., of the CDC's National Center for Immunization and Respiratory Diseases.

Among the questions were the following:

Does an infant less than 1 year old who develops chickenpox still need the varicella vaccine?

"A few experts will say if you are absolutely sure it was chickenpox ... the child would have natural immunity in that circumstance and not need another dose," Dr. Kroger said. But it can be difficult to be certain. He advised clinicians to "play it safe" and follow the recommended ages for vaccination. A dose of the varicella vaccine won't hurt a child who had chickenpox as an infant, he said.

Is birth prior to 1980 evidence of varicella immunity?

Dr. Atkinson said that for health care workers and pregnant women, being born before 1980 is not considered evidence of varicella immunity. The CDC's Advisory Committee on Immunization Practices has a document forthcoming on health care workers later this year, he added.

When a private clinic sees teens who have begun their human papillomavirus (HPV) vaccine series elsewhere, can the series be finished with a vaccine different from the one with which they started the series?

Both the quadrivalent HPV vaccine Gardasil and the bivalent HPV vaccine Cervarix protect against HPV serotypes 16 and 18, but only Gardasil protects against HPV-6 and -11 as well. Ideally, said Ms. Weaver, you should use the same vaccine you started with. If you have to switch, you need to make it clear that there's no protection for HPV-6 and -11 if you're not using Gardasil. "It's preferred that you complete the series with the same vaccine if you can," she said.

Would the male HPV vaccine help protect females?

"The hope is certainly there, but ... we don't know at this point," said Ms. Weaver.

"That would be a very tough study to do," Dr. Atkinson observed. "What kind of study would you design ... to be able to show that transmission was less frequent from—or to—a vaccinated person compared to an unvaccinated person?"

Generally, immune people don't transmit and don't get infected, he reminded the audience, "so it's reasonable to hope ... that it will interfere with transmission."

None of the panelists reported any conflicts of interest.

ATLANTA — Questions about varicella immunity and human papillomavirus vaccine logistics topped physicians' concerns during a Q&A session with an expert panel at the annual National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

The panelists included Dr. William Atkinson, Dr. Andrew Kroger, and Donna Weaver, R.N., of the CDC's National Center for Immunization and Respiratory Diseases.

Among the questions were the following:

Does an infant less than 1 year old who develops chickenpox still need the varicella vaccine?

"A few experts will say if you are absolutely sure it was chickenpox ... the child would have natural immunity in that circumstance and not need another dose," Dr. Kroger said. But it can be difficult to be certain. He advised clinicians to "play it safe" and follow the recommended ages for vaccination. A dose of the varicella vaccine won't hurt a child who had chickenpox as an infant, he said.

Is birth prior to 1980 evidence of varicella immunity?

Dr. Atkinson said that for health care workers and pregnant women, being born before 1980 is not considered evidence of varicella immunity. The CDC's Advisory Committee on Immunization Practices has a document forthcoming on health care workers later this year, he added.

When a private clinic sees teens who have begun their human papillomavirus (HPV) vaccine series elsewhere, can the series be finished with a vaccine different from the one with which they started the series?

Both the quadrivalent HPV vaccine Gardasil and the bivalent HPV vaccine Cervarix protect against HPV serotypes 16 and 18, but only Gardasil protects against HPV-6 and -11 as well. Ideally, said Ms. Weaver, you should use the same vaccine you started with. If you have to switch, you need to make it clear that there's no protection for HPV-6 and -11 if you're not using Gardasil. "It's preferred that you complete the series with the same vaccine if you can," she said.

Would the male HPV vaccine help protect females?

"The hope is certainly there, but ... we don't know at this point," said Ms. Weaver.

"That would be a very tough study to do," Dr. Atkinson observed. "What kind of study would you design ... to be able to show that transmission was less frequent from—or to—a vaccinated person compared to an unvaccinated person?"

Generally, immune people don't transmit and don't get infected, he reminded the audience, "so it's reasonable to hope ... that it will interfere with transmission."

None of the panelists reported any conflicts of interest.

ATLANTA — Questions about varicella immunity and human papillomavirus vaccine logistics topped physicians' concerns during a Q&A session with an expert panel at the annual National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

The panelists included Dr. William Atkinson, Dr. Andrew Kroger, and Donna Weaver, R.N., of the CDC's National Center for Immunization and Respiratory Diseases.

Among the questions were the following:

Does an infant less than 1 year old who develops chickenpox still need the varicella vaccine?

"A few experts will say if you are absolutely sure it was chickenpox ... the child would have natural immunity in that circumstance and not need another dose," Dr. Kroger said. But it can be difficult to be certain. He advised clinicians to "play it safe" and follow the recommended ages for vaccination. A dose of the varicella vaccine won't hurt a child who had chickenpox as an infant, he said.

Is birth prior to 1980 evidence of varicella immunity?

Dr. Atkinson said that for health care workers and pregnant women, being born before 1980 is not considered evidence of varicella immunity. The CDC's Advisory Committee on Immunization Practices has a document forthcoming on health care workers later this year, he added.

When a private clinic sees teens who have begun their human papillomavirus (HPV) vaccine series elsewhere, can the series be finished with a vaccine different from the one with which they started the series?

Both the quadrivalent HPV vaccine Gardasil and the bivalent HPV vaccine Cervarix protect against HPV serotypes 16 and 18, but only Gardasil protects against HPV-6 and -11 as well. Ideally, said Ms. Weaver, you should use the same vaccine you started with. If you have to switch, you need to make it clear that there's no protection for HPV-6 and -11 if you're not using Gardasil. "It's preferred that you complete the series with the same vaccine if you can," she said.

Would the male HPV vaccine help protect females?

"The hope is certainly there, but ... we don't know at this point," said Ms. Weaver.

"That would be a very tough study to do," Dr. Atkinson observed. "What kind of study would you design ... to be able to show that transmission was less frequent from—or to—a vaccinated person compared to an unvaccinated person?"

Generally, immune people don't transmit and don't get infected, he reminded the audience, "so it's reasonable to hope ... that it will interfere with transmission."

None of the panelists reported any conflicts of interest.

ATLANTA — Vaccine safety is the most important consideration for parents in deciding whether their teens should receive recommended vaccines, a national survey of parents showed.

The 557 respondents came from Harris Poll Online's survey panel, and each identified himself or herself as being the parent of at least one child aged 11-17 years, Dr. Stanley Schaffer of the University of Rochester (N.Y.) reported in a poster at the National Immunization Conference.

Parents most commonly cited vaccine safety as their single most important consideration in deciding whether their children should be immunized. Concerns about potential side effects were most pronounced for the human papillomavirus (HPV) vaccine; it was cited by 66% of parents of girls aged 11-14 years and 63% of parents of girls aged 15-17 years.

"While parents consider a number of factors when deciding whether or not to have their adolescents immunized, vaccine safety is clearly their No. 1 concern," Dr. Schaffer said in an interview. "By addressing parental concerns about the safety of vaccines with credible information and thereby reassuring parents, physicians, and others, health care providers can have a significant impact on efforts to immunize their patients and the adolescent population as a whole."
Dr. Schaffer said he had no conflicts of interest.

ATLANTA — Vaccine safety is the most important consideration for parents in deciding whether their teens should receive recommended vaccines, a national survey of parents showed.

The 557 respondents came from Harris Poll Online's survey panel, and each identified himself or herself as being the parent of at least one child aged 11-17 years, Dr. Stanley Schaffer of the University of Rochester (N.Y.) reported in a poster at the National Immunization Conference.

Parents most commonly cited vaccine safety as their single most important consideration in deciding whether their children should be immunized. Concerns about potential side effects were most pronounced for the human papillomavirus (HPV) vaccine; it was cited by 66% of parents of girls aged 11-14 years and 63% of parents of girls aged 15-17 years.

"While parents consider a number of factors when deciding whether or not to have their adolescents immunized, vaccine safety is clearly their No. 1 concern," Dr. Schaffer said in an interview. "By addressing parental concerns about the safety of vaccines with credible information and thereby reassuring parents, physicians, and others, health care providers can have a significant impact on efforts to immunize their patients and the adolescent population as a whole."
Dr. Schaffer said he had no conflicts of interest.

ATLANTA — Vaccine safety is the most important consideration for parents in deciding whether their teens should receive recommended vaccines, a national survey of parents showed.

The 557 respondents came from Harris Poll Online's survey panel, and each identified himself or herself as being the parent of at least one child aged 11-17 years, Dr. Stanley Schaffer of the University of Rochester (N.Y.) reported in a poster at the National Immunization Conference.

Parents most commonly cited vaccine safety as their single most important consideration in deciding whether their children should be immunized. Concerns about potential side effects were most pronounced for the human papillomavirus (HPV) vaccine; it was cited by 66% of parents of girls aged 11-14 years and 63% of parents of girls aged 15-17 years.

"While parents consider a number of factors when deciding whether or not to have their adolescents immunized, vaccine safety is clearly their No. 1 concern," Dr. Schaffer said in an interview. "By addressing parental concerns about the safety of vaccines with credible information and thereby reassuring parents, physicians, and others, health care providers can have a significant impact on efforts to immunize their patients and the adolescent population as a whole."
Dr. Schaffer said he had no conflicts of interest.