ACIP Meeting

A federal vaccine advisory panel is weighing options for a three-dose pneumococcal conjugate vaccination schedule for healthy infants and toddlers.

At least 34 developed countries, including most provinces in Canada, are already using a three-dose schedule for the 13-valent pneumococcal conjugate (PCV13) vaccine (Prevnar) as part of routine immunization programs. The three doses can be delivered either as a two-dose primary series followed by a booster (2+1) or a three-dose primary series without a booster (3+0).

Current Centers for Disease Control and Prevention (CDC) recommendations call for routine immunization of generally healthy infants, aged 2-59 months, using a four-dose schedule at 2, 4, 6, and 12-15 months (3+1).

An exhaustive GRADE (Grading of Recommendations Assessment, Development & Evaluation) review of the evidence strongly supports all of the schedules (3+1, 3+0, and 2+1) compared with no vaccination. There was high-quality evidence that shows each schedule is effective against invasive pneumococcal disease and pneumonia in children, in addition to demonstrating large indirect herd effects among adults.

In the absence of randomized trials with clinical outcomes directly comparing three- and four-dose schedules, evidence supporting three-dose schedules was limited to immunogenicity studies, Sara Tomczyk, R.N., of the CDC National Center for Immunization and Respiratory Diseases (NCIRD), said at a meeting of the CDC’s Advisory Committee on Immunization Practices (ACIP).

The pneumococcal working group concluded that the GRADE review suggests that "three-dose schedules are likely equivalent to a four-dose schedule," strong evidence from countries using three-dose schedules is reassuring, and a three-dose schedule for infants is "likely appropriate to maintain already observed benefits from 13 years of PCV use in the U.S."

Dr. Michael T. Brady, chair of the American Academy of Pediatrics infectious diseases committee and an ACIP liaison representative, pointed out that vaccine efficacy against invasive pneumococcal disease with the 3+0 schedule was only about 74%, while it was in the mid-90s with the 2+1 and 3+1 schedules.

"I don’t think you can say they’re equivalent," he said. "If you’re looking at whether 3+0 prevents pneumococcal disease, yes, but is it equivalent to the other ones, no."

Dr. Brady also expressed concerns about the generalizability of the results to the U.S. population, as most of the 3+0 studies were conducted in African countries, and that use of a three-dose schedule could reintroduce disparities in pneumococcal disease rates among African American children observed prior to PCV introduction.

"I would hate to find that we actually do need higher levels of antibody to protect African American children," said Dr Brady, who is professor and chair of pediatrics at Ohio State University, Columbus. "If we went to a schedule that was either 2+1 or 3+0, and we now returned to having a disparity, I would be very uncomfortable. I think that’s one of the issues that needs to be addressed."

The working group is not prepared to make a specific policy recommendation at this time, but it is considering the following policy options:

• Option 1. 2+1 for routine use, 3+1 for high-risk groups, to be defined.

• Option 2. 3+0 for routine use, 3+1 for high-risk groups, to be defined

• Option 3. Three-dose schedules (2+1 or 3+0) for routine use, 3+1 recommended at provider discretion for healthy infants, 3+1 for high-risk groups, to be defined.

• Option 4. 3+1 for routine use, three-dose schedules (2+1 or 3+0) optional for healthy infants, 3+1 for high-risk groups.

• Option 5. Status quo.

Unpublished 2012 National Immunization Survey data, also presented at the meeting, show that only a small proportion (10.4%) of U.S. children receive a total of three PCV doses and that coverage decreases with increasing poverty for all schedules. In all, 89.5% of children living in families with an annual income of more than $75,000 received at least three PCV doses before 12 months versus 80.3% of children living below poverty. Within each poverty level, coverage was lowest for the 3+1 schedule, said Dr. Tamara Pilishvili, CDC/NCIRD liaison to the ACIP pneumococcal working group.

Although most parents follow the recommended vaccine schedules, evidence suggests that a large proportion of parents may be "at risk" of switching to an alternative schedule, she said.

A recent cross-sectional survey of 748 parents found that more than 1 in 10 parents of young children, aged 6 months to 6 years, already follow an alternative vaccination schedule, with nonblack race and not having a regular provider increasing the odds of doing so. Further, 28% of parents surveyed thought delaying vaccine doses was safer than the schedule they used (Pediatrics 2011;128:848-56).

Data are unclear, however, whether removing a PCV dose at 6 months (2+1) or at 12-15 months (3+0) will help reduce refusals or delays of other recommended vaccines, Dr. Pilishvili said.

Several attendees who were ACIP liaison representatives expressed concern about the interval between PCV13 doses in the various schedules. Dr. Ruth Karron, director of the Center for Immunization Research and the Johns Hopkins Vaccine Initiative, Baltimore, was troubled by the 2+1 schedule, observing that if parents delay too long, there is invasive disease that occurs in the 12- to 18-month age range.

"I’m wondering if the data we already have are telling us something about a 2+1 versus a 3+0 schedule," she added.

Dr. Mark Netoskie of America’s Health Insurance Plans, reminded the committee about the "quagmire" that occurred with permissive recommendations for human papillomavirus vaccinations.

"I speak against options 3 and 4 [i.e., permissive recommendations], as it will open a quagmire, and I foresee a potential for scattered coverage across the country," he said. "The data’s either strong enough to recommend it or the data’s not strong enough to recommend it, or it’s strong enough to recommend it or recommend it for certain groups."

Dr. Pilishvili responded, "I appreciate your comment. There were several on the working group who shared your concerns."

Among its conclusions, the working group stated that a three-dose PCV13 schedule for routine use among infants requires careful consideration of implementation issues, and that further discussion is needed to define groups to be excluded from potential policy change and on the potential impact on nonadherence.

Dr. Pilishvili and Ms. Tomczyk reported having no financial disclosures.

pwendling@frontlinemedcom.com

A federal vaccine advisory panel is weighing options for a three-dose pneumococcal conjugate vaccination schedule for healthy infants and toddlers.

At least 34 developed countries, including most provinces in Canada, are already using a three-dose schedule for the 13-valent pneumococcal conjugate (PCV13) vaccine (Prevnar) as part of routine immunization programs. The three doses can be delivered either as a two-dose primary series followed by a booster (2+1) or a three-dose primary series without a booster (3+0).

Current Centers for Disease Control and Prevention (CDC) recommendations call for routine immunization of generally healthy infants, aged 2-59 months, using a four-dose schedule at 2, 4, 6, and 12-15 months (3+1).

An exhaustive GRADE (Grading of Recommendations Assessment, Development & Evaluation) review of the evidence strongly supports all of the schedules (3+1, 3+0, and 2+1) compared with no vaccination. There was high-quality evidence that shows each schedule is effective against invasive pneumococcal disease and pneumonia in children, in addition to demonstrating large indirect herd effects among adults.

In the absence of randomized trials with clinical outcomes directly comparing three- and four-dose schedules, evidence supporting three-dose schedules was limited to immunogenicity studies, Sara Tomczyk, R.N., of the CDC National Center for Immunization and Respiratory Diseases (NCIRD), said at a meeting of the CDC’s Advisory Committee on Immunization Practices (ACIP).

The pneumococcal working group concluded that the GRADE review suggests that "three-dose schedules are likely equivalent to a four-dose schedule," strong evidence from countries using three-dose schedules is reassuring, and a three-dose schedule for infants is "likely appropriate to maintain already observed benefits from 13 years of PCV use in the U.S."

Dr. Michael T. Brady, chair of the American Academy of Pediatrics infectious diseases committee and an ACIP liaison representative, pointed out that vaccine efficacy against invasive pneumococcal disease with the 3+0 schedule was only about 74%, while it was in the mid-90s with the 2+1 and 3+1 schedules.

"I don’t think you can say they’re equivalent," he said. "If you’re looking at whether 3+0 prevents pneumococcal disease, yes, but is it equivalent to the other ones, no."

Dr. Brady also expressed concerns about the generalizability of the results to the U.S. population, as most of the 3+0 studies were conducted in African countries, and that use of a three-dose schedule could reintroduce disparities in pneumococcal disease rates among African American children observed prior to PCV introduction.

"I would hate to find that we actually do need higher levels of antibody to protect African American children," said Dr Brady, who is professor and chair of pediatrics at Ohio State University, Columbus. "If we went to a schedule that was either 2+1 or 3+0, and we now returned to having a disparity, I would be very uncomfortable. I think that’s one of the issues that needs to be addressed."

The working group is not prepared to make a specific policy recommendation at this time, but it is considering the following policy options:

• Option 1. 2+1 for routine use, 3+1 for high-risk groups, to be defined.

• Option 2. 3+0 for routine use, 3+1 for high-risk groups, to be defined

• Option 3. Three-dose schedules (2+1 or 3+0) for routine use, 3+1 recommended at provider discretion for healthy infants, 3+1 for high-risk groups, to be defined.

• Option 4. 3+1 for routine use, three-dose schedules (2+1 or 3+0) optional for healthy infants, 3+1 for high-risk groups.

• Option 5. Status quo.

Unpublished 2012 National Immunization Survey data, also presented at the meeting, show that only a small proportion (10.4%) of U.S. children receive a total of three PCV doses and that coverage decreases with increasing poverty for all schedules. In all, 89.5% of children living in families with an annual income of more than $75,000 received at least three PCV doses before 12 months versus 80.3% of children living below poverty. Within each poverty level, coverage was lowest for the 3+1 schedule, said Dr. Tamara Pilishvili, CDC/NCIRD liaison to the ACIP pneumococcal working group.

Although most parents follow the recommended vaccine schedules, evidence suggests that a large proportion of parents may be "at risk" of switching to an alternative schedule, she said.

A recent cross-sectional survey of 748 parents found that more than 1 in 10 parents of young children, aged 6 months to 6 years, already follow an alternative vaccination schedule, with nonblack race and not having a regular provider increasing the odds of doing so. Further, 28% of parents surveyed thought delaying vaccine doses was safer than the schedule they used (Pediatrics 2011;128:848-56).

Data are unclear, however, whether removing a PCV dose at 6 months (2+1) or at 12-15 months (3+0) will help reduce refusals or delays of other recommended vaccines, Dr. Pilishvili said.

Several attendees who were ACIP liaison representatives expressed concern about the interval between PCV13 doses in the various schedules. Dr. Ruth Karron, director of the Center for Immunization Research and the Johns Hopkins Vaccine Initiative, Baltimore, was troubled by the 2+1 schedule, observing that if parents delay too long, there is invasive disease that occurs in the 12- to 18-month age range.

"I’m wondering if the data we already have are telling us something about a 2+1 versus a 3+0 schedule," she added.

Dr. Mark Netoskie of America’s Health Insurance Plans, reminded the committee about the "quagmire" that occurred with permissive recommendations for human papillomavirus vaccinations.

"I speak against options 3 and 4 [i.e., permissive recommendations], as it will open a quagmire, and I foresee a potential for scattered coverage across the country," he said. "The data’s either strong enough to recommend it or the data’s not strong enough to recommend it, or it’s strong enough to recommend it or recommend it for certain groups."

Dr. Pilishvili responded, "I appreciate your comment. There were several on the working group who shared your concerns."

Among its conclusions, the working group stated that a three-dose PCV13 schedule for routine use among infants requires careful consideration of implementation issues, and that further discussion is needed to define groups to be excluded from potential policy change and on the potential impact on nonadherence.

Dr. Pilishvili and Ms. Tomczyk reported having no financial disclosures.

pwendling@frontlinemedcom.com

A federal vaccine advisory panel is weighing options for a three-dose pneumococcal conjugate vaccination schedule for healthy infants and toddlers.

At least 34 developed countries, including most provinces in Canada, are already using a three-dose schedule for the 13-valent pneumococcal conjugate (PCV13) vaccine (Prevnar) as part of routine immunization programs. The three doses can be delivered either as a two-dose primary series followed by a booster (2+1) or a three-dose primary series without a booster (3+0).

Current Centers for Disease Control and Prevention (CDC) recommendations call for routine immunization of generally healthy infants, aged 2-59 months, using a four-dose schedule at 2, 4, 6, and 12-15 months (3+1).

An exhaustive GRADE (Grading of Recommendations Assessment, Development & Evaluation) review of the evidence strongly supports all of the schedules (3+1, 3+0, and 2+1) compared with no vaccination. There was high-quality evidence that shows each schedule is effective against invasive pneumococcal disease and pneumonia in children, in addition to demonstrating large indirect herd effects among adults.

In the absence of randomized trials with clinical outcomes directly comparing three- and four-dose schedules, evidence supporting three-dose schedules was limited to immunogenicity studies, Sara Tomczyk, R.N., of the CDC National Center for Immunization and Respiratory Diseases (NCIRD), said at a meeting of the CDC’s Advisory Committee on Immunization Practices (ACIP).

The pneumococcal working group concluded that the GRADE review suggests that "three-dose schedules are likely equivalent to a four-dose schedule," strong evidence from countries using three-dose schedules is reassuring, and a three-dose schedule for infants is "likely appropriate to maintain already observed benefits from 13 years of PCV use in the U.S."

Dr. Michael T. Brady, chair of the American Academy of Pediatrics infectious diseases committee and an ACIP liaison representative, pointed out that vaccine efficacy against invasive pneumococcal disease with the 3+0 schedule was only about 74%, while it was in the mid-90s with the 2+1 and 3+1 schedules.

"I don’t think you can say they’re equivalent," he said. "If you’re looking at whether 3+0 prevents pneumococcal disease, yes, but is it equivalent to the other ones, no."

Dr. Brady also expressed concerns about the generalizability of the results to the U.S. population, as most of the 3+0 studies were conducted in African countries, and that use of a three-dose schedule could reintroduce disparities in pneumococcal disease rates among African American children observed prior to PCV introduction.

"I would hate to find that we actually do need higher levels of antibody to protect African American children," said Dr Brady, who is professor and chair of pediatrics at Ohio State University, Columbus. "If we went to a schedule that was either 2+1 or 3+0, and we now returned to having a disparity, I would be very uncomfortable. I think that’s one of the issues that needs to be addressed."

The working group is not prepared to make a specific policy recommendation at this time, but it is considering the following policy options:

• Option 1. 2+1 for routine use, 3+1 for high-risk groups, to be defined.

• Option 2. 3+0 for routine use, 3+1 for high-risk groups, to be defined

• Option 3. Three-dose schedules (2+1 or 3+0) for routine use, 3+1 recommended at provider discretion for healthy infants, 3+1 for high-risk groups, to be defined.

• Option 4. 3+1 for routine use, three-dose schedules (2+1 or 3+0) optional for healthy infants, 3+1 for high-risk groups.

• Option 5. Status quo.

Unpublished 2012 National Immunization Survey data, also presented at the meeting, show that only a small proportion (10.4%) of U.S. children receive a total of three PCV doses and that coverage decreases with increasing poverty for all schedules. In all, 89.5% of children living in families with an annual income of more than $75,000 received at least three PCV doses before 12 months versus 80.3% of children living below poverty. Within each poverty level, coverage was lowest for the 3+1 schedule, said Dr. Tamara Pilishvili, CDC/NCIRD liaison to the ACIP pneumococcal working group.

Although most parents follow the recommended vaccine schedules, evidence suggests that a large proportion of parents may be "at risk" of switching to an alternative schedule, she said.

A recent cross-sectional survey of 748 parents found that more than 1 in 10 parents of young children, aged 6 months to 6 years, already follow an alternative vaccination schedule, with nonblack race and not having a regular provider increasing the odds of doing so. Further, 28% of parents surveyed thought delaying vaccine doses was safer than the schedule they used (Pediatrics 2011;128:848-56).

Data are unclear, however, whether removing a PCV dose at 6 months (2+1) or at 12-15 months (3+0) will help reduce refusals or delays of other recommended vaccines, Dr. Pilishvili said.

Several attendees who were ACIP liaison representatives expressed concern about the interval between PCV13 doses in the various schedules. Dr. Ruth Karron, director of the Center for Immunization Research and the Johns Hopkins Vaccine Initiative, Baltimore, was troubled by the 2+1 schedule, observing that if parents delay too long, there is invasive disease that occurs in the 12- to 18-month age range.

"I’m wondering if the data we already have are telling us something about a 2+1 versus a 3+0 schedule," she added.

Dr. Mark Netoskie of America’s Health Insurance Plans, reminded the committee about the "quagmire" that occurred with permissive recommendations for human papillomavirus vaccinations.

"I speak against options 3 and 4 [i.e., permissive recommendations], as it will open a quagmire, and I foresee a potential for scattered coverage across the country," he said. "The data’s either strong enough to recommend it or the data’s not strong enough to recommend it, or it’s strong enough to recommend it or recommend it for certain groups."

Dr. Pilishvili responded, "I appreciate your comment. There were several on the working group who shared your concerns."

Among its conclusions, the working group stated that a three-dose PCV13 schedule for routine use among infants requires careful consideration of implementation issues, and that further discussion is needed to define groups to be excluded from potential policy change and on the potential impact on nonadherence.

Dr. Pilishvili and Ms. Tomczyk reported having no financial disclosures.

pwendling@frontlinemedcom.com

U.S. surveillance data show that half of high-grade cervical lesions are caused by human papillomavirus 16 and 18.

Another 25% are attributable to the five additional HPV types 31/33/45/52/58 included in the investigational 9-valent vaccine.

National Cancer Institute

The analysis fills in some knowledge gaps regarding U.S. women and was based on 5,189 specimens drawn from women, aged 21-39 years, diagnosed with cervical intraepithelial neoplasia (CIN) 2 and 3 and adenocarcinoma in situ (AIS) (CIN2+) from 2008 through 2011 at five U.S. sites in the HPV-IMPACT sentinel surveillance project.

HPV 16 was the most commonly detected type among all lesions, while type 18 was relatively uncommon, accounting for only about 5% of lesions, Dr. Susan Hariri said at a meeting of the Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP).

HPV 16 and 18 increased with lesion severity from 40% in CIN2 to 66% in CIN3/AIS.

Type 31 was the most common of the five additional HPV types in the 9-valent vaccine, followed by types 52 and 58, both of which are more frequent in CIN2 than CIN3. Types 33 and 45 were detected in less than 5% of specimens across all histologic types.

The most common other high-risk, oncogenic types not found in any vaccine were 35 and 51, identified in 7% and 9% of CIN2 lesions, said Dr. Hariri of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

American Nurses Association representative Carol Hayes, M.P.H., a certified nurse-midwife, questioned this finding and asked why types 33 and 45 were included in the 9-valent vaccine, but 35 and 51 were not.

A representative from Merck responded that the five additional types in the 9-valent vaccine were selected based on their attribution to cervical cancer lesions, not precancers.

Proportional type attribution data analyses by race and age revealed HPV 16 and 18 were most common across all age and racial/ethnic groups, although some differences were identified. Types 16 and 18 declined from 50% for all groups to about 44% among the oldest age group (55-99 years), where the five additional HPV vaccine types were on the rise.

Types 31/33/45/52/58 were more common in racial and ethnic groups (28%-32%) than in whites (22%), while other high-risk HPV types were more common in blacks (20%) than other racial groups (14%-16%).

"The reasons for these differences are not clear and are probably multifactorial, but may be due to differences in the underlying prevalence of HPV in the subpopulations or to differences in screening and treatment," Dr. Hariri said.

Dr. Alain Luxembourg of Merck, the vaccine developer, said the 9-valent vaccine has the potential not only to prevent cancer, but to prevent a lot of "precancerous lesions, which in countries with cervical cancer screening programs, means a lower need for invasive procedures."

He presented a summary of 9-valent clinical data including the pivotal efficacy trial among females, aged 16-26 years, which showed noninferior immunogenicity for HPV 16 and 18 compared with the quadrivalent vaccine, and about 97% protection against disease related to the five additional strains. An immunobridging study also showed noninferior immunogenicity in adolescents compared with adults.

Regulatory action is expected by the Food and Drug Administration on the 9-valent vaccine within the next 3 months, he said.

ACIP is not expected to vote on whether to recommend the 9-valent vaccine until February 2015 at the earliest, following further review of clinical and health economics data and regulatory approval, said Dr. Lauri Markowitz of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

Considerations for the candidate vaccine include routine vaccination at age 11 or 12 years, vaccination of older females and males who were not vaccinated at the recommended age, vaccination of persons fully or partially vaccinated with quadrivalent vaccine, and the timing for consideration of males, aged 16-26 years, because it’s anticipated that the vaccine will not be licensed in this age group at the time of first licensure.

ACIP’s HPV work group also plans to review reduced-dose vaccination schedules in more detail. Some jurisdictions are already using two-dose schedules in their national or provincial immunization programs, and GlaxoSmithKline’s Cervarix received European marketing approval in December 2013 as a two-dose schedule (0, 6 months) for girls aged 9-14 years, Dr. Markowitz said.

As ACIP members met, Sanofi Pasteur announced that its quadrivalent HPV vaccine, Gardasil, was one step closer to receiving European approval for a two-dose schedule (0, 6 months) in girls and boys aged 9-13 years.

Finally, ACIP’s members unanimously affirmed efforts to update its 2007 HPV vaccine statement. The new statement, which still needs to go through editing before a final vote, consolidates and clarifies existing recommendations and updates background and clinical trial data. It also adds a variety of new sections including postlicensure safety data, areas of ongoing research, and future priorities, including the 9-valent vaccine and reduced-dose schedules, she said.

Dr. Hariri and Dr. Markowitz reported having no financial disclosures. Dr. Luxembourg is an employee of Merck.

pwendling@frontlinemedcom.com

U.S. surveillance data show that half of high-grade cervical lesions are caused by human papillomavirus 16 and 18.

Another 25% are attributable to the five additional HPV types 31/33/45/52/58 included in the investigational 9-valent vaccine.

National Cancer Institute

The analysis fills in some knowledge gaps regarding U.S. women and was based on 5,189 specimens drawn from women, aged 21-39 years, diagnosed with cervical intraepithelial neoplasia (CIN) 2 and 3 and adenocarcinoma in situ (AIS) (CIN2+) from 2008 through 2011 at five U.S. sites in the HPV-IMPACT sentinel surveillance project.

HPV 16 was the most commonly detected type among all lesions, while type 18 was relatively uncommon, accounting for only about 5% of lesions, Dr. Susan Hariri said at a meeting of the Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP).

HPV 16 and 18 increased with lesion severity from 40% in CIN2 to 66% in CIN3/AIS.

Type 31 was the most common of the five additional HPV types in the 9-valent vaccine, followed by types 52 and 58, both of which are more frequent in CIN2 than CIN3. Types 33 and 45 were detected in less than 5% of specimens across all histologic types.

The most common other high-risk, oncogenic types not found in any vaccine were 35 and 51, identified in 7% and 9% of CIN2 lesions, said Dr. Hariri of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

American Nurses Association representative Carol Hayes, M.P.H., a certified nurse-midwife, questioned this finding and asked why types 33 and 45 were included in the 9-valent vaccine, but 35 and 51 were not.

A representative from Merck responded that the five additional types in the 9-valent vaccine were selected based on their attribution to cervical cancer lesions, not precancers.

Proportional type attribution data analyses by race and age revealed HPV 16 and 18 were most common across all age and racial/ethnic groups, although some differences were identified. Types 16 and 18 declined from 50% for all groups to about 44% among the oldest age group (55-99 years), where the five additional HPV vaccine types were on the rise.

Types 31/33/45/52/58 were more common in racial and ethnic groups (28%-32%) than in whites (22%), while other high-risk HPV types were more common in blacks (20%) than other racial groups (14%-16%).

"The reasons for these differences are not clear and are probably multifactorial, but may be due to differences in the underlying prevalence of HPV in the subpopulations or to differences in screening and treatment," Dr. Hariri said.

Dr. Alain Luxembourg of Merck, the vaccine developer, said the 9-valent vaccine has the potential not only to prevent cancer, but to prevent a lot of "precancerous lesions, which in countries with cervical cancer screening programs, means a lower need for invasive procedures."

He presented a summary of 9-valent clinical data including the pivotal efficacy trial among females, aged 16-26 years, which showed noninferior immunogenicity for HPV 16 and 18 compared with the quadrivalent vaccine, and about 97% protection against disease related to the five additional strains. An immunobridging study also showed noninferior immunogenicity in adolescents compared with adults.

Regulatory action is expected by the Food and Drug Administration on the 9-valent vaccine within the next 3 months, he said.

ACIP is not expected to vote on whether to recommend the 9-valent vaccine until February 2015 at the earliest, following further review of clinical and health economics data and regulatory approval, said Dr. Lauri Markowitz of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

Considerations for the candidate vaccine include routine vaccination at age 11 or 12 years, vaccination of older females and males who were not vaccinated at the recommended age, vaccination of persons fully or partially vaccinated with quadrivalent vaccine, and the timing for consideration of males, aged 16-26 years, because it’s anticipated that the vaccine will not be licensed in this age group at the time of first licensure.

ACIP’s HPV work group also plans to review reduced-dose vaccination schedules in more detail. Some jurisdictions are already using two-dose schedules in their national or provincial immunization programs, and GlaxoSmithKline’s Cervarix received European marketing approval in December 2013 as a two-dose schedule (0, 6 months) for girls aged 9-14 years, Dr. Markowitz said.

As ACIP members met, Sanofi Pasteur announced that its quadrivalent HPV vaccine, Gardasil, was one step closer to receiving European approval for a two-dose schedule (0, 6 months) in girls and boys aged 9-13 years.

Finally, ACIP’s members unanimously affirmed efforts to update its 2007 HPV vaccine statement. The new statement, which still needs to go through editing before a final vote, consolidates and clarifies existing recommendations and updates background and clinical trial data. It also adds a variety of new sections including postlicensure safety data, areas of ongoing research, and future priorities, including the 9-valent vaccine and reduced-dose schedules, she said.

Dr. Hariri and Dr. Markowitz reported having no financial disclosures. Dr. Luxembourg is an employee of Merck.

pwendling@frontlinemedcom.com

U.S. surveillance data show that half of high-grade cervical lesions are caused by human papillomavirus 16 and 18.

Another 25% are attributable to the five additional HPV types 31/33/45/52/58 included in the investigational 9-valent vaccine.

National Cancer Institute

The analysis fills in some knowledge gaps regarding U.S. women and was based on 5,189 specimens drawn from women, aged 21-39 years, diagnosed with cervical intraepithelial neoplasia (CIN) 2 and 3 and adenocarcinoma in situ (AIS) (CIN2+) from 2008 through 2011 at five U.S. sites in the HPV-IMPACT sentinel surveillance project.

HPV 16 was the most commonly detected type among all lesions, while type 18 was relatively uncommon, accounting for only about 5% of lesions, Dr. Susan Hariri said at a meeting of the Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP).

HPV 16 and 18 increased with lesion severity from 40% in CIN2 to 66% in CIN3/AIS.

Type 31 was the most common of the five additional HPV types in the 9-valent vaccine, followed by types 52 and 58, both of which are more frequent in CIN2 than CIN3. Types 33 and 45 were detected in less than 5% of specimens across all histologic types.

The most common other high-risk, oncogenic types not found in any vaccine were 35 and 51, identified in 7% and 9% of CIN2 lesions, said Dr. Hariri of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

American Nurses Association representative Carol Hayes, M.P.H., a certified nurse-midwife, questioned this finding and asked why types 33 and 45 were included in the 9-valent vaccine, but 35 and 51 were not.

A representative from Merck responded that the five additional types in the 9-valent vaccine were selected based on their attribution to cervical cancer lesions, not precancers.

Proportional type attribution data analyses by race and age revealed HPV 16 and 18 were most common across all age and racial/ethnic groups, although some differences were identified. Types 16 and 18 declined from 50% for all groups to about 44% among the oldest age group (55-99 years), where the five additional HPV vaccine types were on the rise.

Types 31/33/45/52/58 were more common in racial and ethnic groups (28%-32%) than in whites (22%), while other high-risk HPV types were more common in blacks (20%) than other racial groups (14%-16%).

"The reasons for these differences are not clear and are probably multifactorial, but may be due to differences in the underlying prevalence of HPV in the subpopulations or to differences in screening and treatment," Dr. Hariri said.

Dr. Alain Luxembourg of Merck, the vaccine developer, said the 9-valent vaccine has the potential not only to prevent cancer, but to prevent a lot of "precancerous lesions, which in countries with cervical cancer screening programs, means a lower need for invasive procedures."

He presented a summary of 9-valent clinical data including the pivotal efficacy trial among females, aged 16-26 years, which showed noninferior immunogenicity for HPV 16 and 18 compared with the quadrivalent vaccine, and about 97% protection against disease related to the five additional strains. An immunobridging study also showed noninferior immunogenicity in adolescents compared with adults.

Regulatory action is expected by the Food and Drug Administration on the 9-valent vaccine within the next 3 months, he said.

ACIP is not expected to vote on whether to recommend the 9-valent vaccine until February 2015 at the earliest, following further review of clinical and health economics data and regulatory approval, said Dr. Lauri Markowitz of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

Considerations for the candidate vaccine include routine vaccination at age 11 or 12 years, vaccination of older females and males who were not vaccinated at the recommended age, vaccination of persons fully or partially vaccinated with quadrivalent vaccine, and the timing for consideration of males, aged 16-26 years, because it’s anticipated that the vaccine will not be licensed in this age group at the time of first licensure.

ACIP’s HPV work group also plans to review reduced-dose vaccination schedules in more detail. Some jurisdictions are already using two-dose schedules in their national or provincial immunization programs, and GlaxoSmithKline’s Cervarix received European marketing approval in December 2013 as a two-dose schedule (0, 6 months) for girls aged 9-14 years, Dr. Markowitz said.

As ACIP members met, Sanofi Pasteur announced that its quadrivalent HPV vaccine, Gardasil, was one step closer to receiving European approval for a two-dose schedule (0, 6 months) in girls and boys aged 9-13 years.

Finally, ACIP’s members unanimously affirmed efforts to update its 2007 HPV vaccine statement. The new statement, which still needs to go through editing before a final vote, consolidates and clarifies existing recommendations and updates background and clinical trial data. It also adds a variety of new sections including postlicensure safety data, areas of ongoing research, and future priorities, including the 9-valent vaccine and reduced-dose schedules, she said.

Dr. Hariri and Dr. Markowitz reported having no financial disclosures. Dr. Luxembourg is an employee of Merck.

pwendling@frontlinemedcom.com

No unexpected adverse events were seen with the administration of Tdap vaccine during pregnancy, although vaccine surveillance data show a shift toward later pregnancy administration.

Serious adverse events, defined as death, life threatening, hospitalization, prolonged hospitalization, and permanent disability, occurred in 6 of 132 (5%) Tdap pregnancies before the recommendation for routine Tdap vaccination during pregnancy and in 14 of 90 (16%) Tdap pregnancies after the recommendation.

The proportion of preterm births (2 vs. 5) and stillbirths (2 vs. 4) increased after the recommendation, while spontaneous abortions decreased (22 vs. 4), Dr. Pedro L. Moro reported at the winter meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

There was one major birth defect before and two after ACIP’s October 2011 recommendation for routine Tdap vaccination during pregnancy.

One of the biggest changes observed in the Vaccine Adverse Event Reporting System (VAERS) reports was the number of women receiving Tdap during the third trimester, up from just 4% to 55% now, said Dr. Moro, an epidemiologist with the CDC.

The most common non–pregnancy-related outcome in the postrecommendation cohort (Oct. 11, 2011-Jan. 31, 2014) was injection site reactions in 19, compared with 6 reported in the prerecommendation cohort (January 2005-June 2010).

"Changes in reporting patterns are likely due to the new routine Tdap recommendation, increased awareness, and differences in the trimester of vaccination," he said.

Pediatric infectious disease specialist and vaccine developer Dr. Stanley Plotkin said he was troubled that 45% of women are still receiving Tdap before the third trimester because this fails to derive maximum benefit from the vaccine in terms of transmitting passive antibodies to the infant.

"It seems to me the recommendation should be stronger for a third-trimester vaccination than for early [vaccination]," he said. "Also, the issue of confusion with congenital anomalies if the vaccine is given in the first trimester, could damage the idea of safety of vaccinations during pregnancy."

The issue of high antibody levels at birth is important, but "We shouldn’t assume that 45% of the Tdap doses are being given before the third trimester because that is not what this VAERS can tell us," commented Dr. Anne Schuchat, director of the CDC’s National Center for Immunization and Respiratory Diseases.

During his presentation, Dr. Moro emphasized that VAERS looks for safety signals and generates hypotheses, but has inconsistent data quality and completeness and was not designed to assess whether a vaccine caused an adverse event.

Dr. Moro reported having no financial disclosures.

pwendling@frontlinemedcom.com

No unexpected adverse events were seen with the administration of Tdap vaccine during pregnancy, although vaccine surveillance data show a shift toward later pregnancy administration.

Serious adverse events, defined as death, life threatening, hospitalization, prolonged hospitalization, and permanent disability, occurred in 6 of 132 (5%) Tdap pregnancies before the recommendation for routine Tdap vaccination during pregnancy and in 14 of 90 (16%) Tdap pregnancies after the recommendation.

The proportion of preterm births (2 vs. 5) and stillbirths (2 vs. 4) increased after the recommendation, while spontaneous abortions decreased (22 vs. 4), Dr. Pedro L. Moro reported at the winter meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

There was one major birth defect before and two after ACIP’s October 2011 recommendation for routine Tdap vaccination during pregnancy.

One of the biggest changes observed in the Vaccine Adverse Event Reporting System (VAERS) reports was the number of women receiving Tdap during the third trimester, up from just 4% to 55% now, said Dr. Moro, an epidemiologist with the CDC.

The most common non–pregnancy-related outcome in the postrecommendation cohort (Oct. 11, 2011-Jan. 31, 2014) was injection site reactions in 19, compared with 6 reported in the prerecommendation cohort (January 2005-June 2010).

"Changes in reporting patterns are likely due to the new routine Tdap recommendation, increased awareness, and differences in the trimester of vaccination," he said.

Pediatric infectious disease specialist and vaccine developer Dr. Stanley Plotkin said he was troubled that 45% of women are still receiving Tdap before the third trimester because this fails to derive maximum benefit from the vaccine in terms of transmitting passive antibodies to the infant.

"It seems to me the recommendation should be stronger for a third-trimester vaccination than for early [vaccination]," he said. "Also, the issue of confusion with congenital anomalies if the vaccine is given in the first trimester, could damage the idea of safety of vaccinations during pregnancy."

The issue of high antibody levels at birth is important, but "We shouldn’t assume that 45% of the Tdap doses are being given before the third trimester because that is not what this VAERS can tell us," commented Dr. Anne Schuchat, director of the CDC’s National Center for Immunization and Respiratory Diseases.

During his presentation, Dr. Moro emphasized that VAERS looks for safety signals and generates hypotheses, but has inconsistent data quality and completeness and was not designed to assess whether a vaccine caused an adverse event.

Dr. Moro reported having no financial disclosures.

pwendling@frontlinemedcom.com

No unexpected adverse events were seen with the administration of Tdap vaccine during pregnancy, although vaccine surveillance data show a shift toward later pregnancy administration.

Serious adverse events, defined as death, life threatening, hospitalization, prolonged hospitalization, and permanent disability, occurred in 6 of 132 (5%) Tdap pregnancies before the recommendation for routine Tdap vaccination during pregnancy and in 14 of 90 (16%) Tdap pregnancies after the recommendation.

The proportion of preterm births (2 vs. 5) and stillbirths (2 vs. 4) increased after the recommendation, while spontaneous abortions decreased (22 vs. 4), Dr. Pedro L. Moro reported at the winter meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

There was one major birth defect before and two after ACIP’s October 2011 recommendation for routine Tdap vaccination during pregnancy.

One of the biggest changes observed in the Vaccine Adverse Event Reporting System (VAERS) reports was the number of women receiving Tdap during the third trimester, up from just 4% to 55% now, said Dr. Moro, an epidemiologist with the CDC.

The most common non–pregnancy-related outcome in the postrecommendation cohort (Oct. 11, 2011-Jan. 31, 2014) was injection site reactions in 19, compared with 6 reported in the prerecommendation cohort (January 2005-June 2010).

"Changes in reporting patterns are likely due to the new routine Tdap recommendation, increased awareness, and differences in the trimester of vaccination," he said.

Pediatric infectious disease specialist and vaccine developer Dr. Stanley Plotkin said he was troubled that 45% of women are still receiving Tdap before the third trimester because this fails to derive maximum benefit from the vaccine in terms of transmitting passive antibodies to the infant.

"It seems to me the recommendation should be stronger for a third-trimester vaccination than for early [vaccination]," he said. "Also, the issue of confusion with congenital anomalies if the vaccine is given in the first trimester, could damage the idea of safety of vaccinations during pregnancy."

The issue of high antibody levels at birth is important, but "We shouldn’t assume that 45% of the Tdap doses are being given before the third trimester because that is not what this VAERS can tell us," commented Dr. Anne Schuchat, director of the CDC’s National Center for Immunization and Respiratory Diseases.

During his presentation, Dr. Moro emphasized that VAERS looks for safety signals and generates hypotheses, but has inconsistent data quality and completeness and was not designed to assess whether a vaccine caused an adverse event.

Dr. Moro reported having no financial disclosures.

pwendling@frontlinemedcom.com

Receipt of the Tdap vaccine during pregnancy was not associated with increased risks for adverse birth outcomes in a safety study, although there was a weak association with chorioamnionitis.

In a separate study, tetanus, diphtheria, and pertussis coverage during pregnancy increased eightfold among women in five states in 2012, while dipping slightly in California.

©AvailableLight/iStockphoto.com

The safety cohort included 26,224 women who received Tdap in pregnancy and 97,265 unvaccinated women with live births during 2010-2012 at two California sites in the Vaccine Safety Datalink (VSD) program.

Inpatient chorioamnionitis was diagnosed in 6.1% of vaccinated women and 5.5% of unvaccinated women (adjusted relative risk, 1.19; 95% confidence interval, 1.13-1.27), Dr. Elyse Olshen Kharbanda reported at the winter meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

In contrast, rates of preterm birth (less than 37 weeks’ gestation) were lower with receipt of Tdap (6.3% vs. 7.8%; hazard ratio, 0.88; 95% CI, 0.83-0.93), while rates were similar for small for gestational age births (8.4% vs. 8.3%; RR, 1.00; 95% CI, 0.96-1.06).

A new diagnosis of hypertensive disorders, examined only in those vaccinated before 20 weeks’ gestation, occurred in 8.2% of vaccinated and 8.0% of unvaccinated women (RR, 1.00; 95% CI, 0.99-1.20), she said.

Secondary analyses restricted to women vaccinated between 27 and 36 weeks’ gestation, consistent with the preferential timing for Tdap vaccination, appeared to confirm the results. Chorioamnionitis occurred in 5.6% of vaccinated and 5.5% of unvaccinated women (RR, 1.11; 95% CI, 1.03-1.21), preterm birth in 5.3% vs. 7.8% (HR, 0.83; 95% CI, 0.77-0.90), and small for gestational age births in 8.6% vs. 8.3% (RR, 1.03; 95% CI, 0.96-1.10).

"The chorioamnionitis findings merit further discussion and possibly further investigation," said Dr. Kharbanda of the HealthPartners Institute for Education and Research, Minneapolis.

The findings in the current study persisted after researchers adjusted for risk factors such as maternal age and comorbidities, although data were not available for many of the most important chorioamnionitis risk factors, she said. Dr. Kharbanda went on to say that the magnitude of the potential risk detected was small, the risk was largely attributable to differences in chorioamnionitis rates seen only for the year 2012, and that there was no associated risk for preterm birth.

Several ACIP representatives questioned the choice of chorioamnionitis as a safety outcome, including American College of Obstetricians and Gynecologists representative Dr. Laura Riley of Harvard Medical School, Boston, who said, "It’s probably one of the messiest diagnoses there is, and it’s really hard to make any sense out of what it really means."

Carol Hayes, MPH, a certified nurse-midwife and a representative from the American Nurses Association, suggested the data be stratified by gestational age at birth because chorioamnionitis is a link for preterm birth, adding "What made you pick chorioamnionitis? It’s such a bizarre thing to look at with a vaccine."

Dr. Kharbanda said chorioamnionitis previously had been studied in relation to trivalent inactivated influenza vaccine, where the risk was slightly increased among pregnant women (Obstet. Gynecol. 2013;1211:519-25). She acknowledged that their obstetrical consultant had also "brought up that in maternal-fetal medicine, often chorioamnionitis is on the pathway for preterm delivery, but not considered an outcome in itself. I think we were sort of trying to look at common diagnoses that occur in women, and it is a common diagnosis."

Tdap coverage

Tdap coverage estimates were based on pregnancies ending between Jan. 1, 2007, and Nov. 15, 2012 at seven sites in the VSD, a collaboration between the CDC and nine managed-care organizations. Among 371,539 live births from 2007 to 2012, overall, 9.5% of women received Tdap during pregnancy and 14.4% post partum. In 2012, the corresponding rates were 13.7% and 8.8%.

In Colorado, Minnesota, Oregon, Washington, and Wisconsin, 16% of women were vaccinated with Tdap during pregnancy in 2012, compared with 2.2% in 2011, Dr. Kharbanda said. Prepregnancy Tdap vaccination rates were 46% and 56.2%, respectively

The increase in Tdap coverage during pregnancy is likely in response to ACIP’s June 2011 recommendation that health care providers administer Tdap to pregnant women who had not previously been vaccinated, preferably after 20 weeks’ gestation, she said.

ACIP updated its guidelines again in October 2012 because of persistent increases in whooping cough in the United States, this time calling for Tdap administration during each pregnancy, irrespective of prior vaccination history, and preferably between 27 and 36 weeks’ gestation.

In California, Tdap coverage during pregnancy increased substantially in 2010 and 2011, but decreased in 2012 (16% vs. 30% vs. 19.5%), likely because many women had received Tdap prepregnancy, she said. Prepregnancy vaccinations climbed steadily from 21.5% in 2010 and 35.3% in 2011 to 53.8% in 2012.

In 2010, the California Department of Public Health began recommending that all women of childbearing age be vaccinated with Tdap.

A protocol looking at repeat Tdap vaccinations and repeat pregnancies has already been written and is being led by CDC investigators, Dr. Kharbanda said.

Dr. Kharbanda reported study support from the CDC VSD project.

pwendling@frontlinemedcom.com

Receipt of the Tdap vaccine during pregnancy was not associated with increased risks for adverse birth outcomes in a safety study, although there was a weak association with chorioamnionitis.

In a separate study, tetanus, diphtheria, and pertussis coverage during pregnancy increased eightfold among women in five states in 2012, while dipping slightly in California.

©AvailableLight/iStockphoto.com

The safety cohort included 26,224 women who received Tdap in pregnancy and 97,265 unvaccinated women with live births during 2010-2012 at two California sites in the Vaccine Safety Datalink (VSD) program.

Inpatient chorioamnionitis was diagnosed in 6.1% of vaccinated women and 5.5% of unvaccinated women (adjusted relative risk, 1.19; 95% confidence interval, 1.13-1.27), Dr. Elyse Olshen Kharbanda reported at the winter meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

In contrast, rates of preterm birth (less than 37 weeks’ gestation) were lower with receipt of Tdap (6.3% vs. 7.8%; hazard ratio, 0.88; 95% CI, 0.83-0.93), while rates were similar for small for gestational age births (8.4% vs. 8.3%; RR, 1.00; 95% CI, 0.96-1.06).

A new diagnosis of hypertensive disorders, examined only in those vaccinated before 20 weeks’ gestation, occurred in 8.2% of vaccinated and 8.0% of unvaccinated women (RR, 1.00; 95% CI, 0.99-1.20), she said.

Secondary analyses restricted to women vaccinated between 27 and 36 weeks’ gestation, consistent with the preferential timing for Tdap vaccination, appeared to confirm the results. Chorioamnionitis occurred in 5.6% of vaccinated and 5.5% of unvaccinated women (RR, 1.11; 95% CI, 1.03-1.21), preterm birth in 5.3% vs. 7.8% (HR, 0.83; 95% CI, 0.77-0.90), and small for gestational age births in 8.6% vs. 8.3% (RR, 1.03; 95% CI, 0.96-1.10).

"The chorioamnionitis findings merit further discussion and possibly further investigation," said Dr. Kharbanda of the HealthPartners Institute for Education and Research, Minneapolis.

The findings in the current study persisted after researchers adjusted for risk factors such as maternal age and comorbidities, although data were not available for many of the most important chorioamnionitis risk factors, she said. Dr. Kharbanda went on to say that the magnitude of the potential risk detected was small, the risk was largely attributable to differences in chorioamnionitis rates seen only for the year 2012, and that there was no associated risk for preterm birth.

Several ACIP representatives questioned the choice of chorioamnionitis as a safety outcome, including American College of Obstetricians and Gynecologists representative Dr. Laura Riley of Harvard Medical School, Boston, who said, "It’s probably one of the messiest diagnoses there is, and it’s really hard to make any sense out of what it really means."

Carol Hayes, MPH, a certified nurse-midwife and a representative from the American Nurses Association, suggested the data be stratified by gestational age at birth because chorioamnionitis is a link for preterm birth, adding "What made you pick chorioamnionitis? It’s such a bizarre thing to look at with a vaccine."

Dr. Kharbanda said chorioamnionitis previously had been studied in relation to trivalent inactivated influenza vaccine, where the risk was slightly increased among pregnant women (Obstet. Gynecol. 2013;1211:519-25). She acknowledged that their obstetrical consultant had also "brought up that in maternal-fetal medicine, often chorioamnionitis is on the pathway for preterm delivery, but not considered an outcome in itself. I think we were sort of trying to look at common diagnoses that occur in women, and it is a common diagnosis."

Tdap coverage

Tdap coverage estimates were based on pregnancies ending between Jan. 1, 2007, and Nov. 15, 2012 at seven sites in the VSD, a collaboration between the CDC and nine managed-care organizations. Among 371,539 live births from 2007 to 2012, overall, 9.5% of women received Tdap during pregnancy and 14.4% post partum. In 2012, the corresponding rates were 13.7% and 8.8%.

In Colorado, Minnesota, Oregon, Washington, and Wisconsin, 16% of women were vaccinated with Tdap during pregnancy in 2012, compared with 2.2% in 2011, Dr. Kharbanda said. Prepregnancy Tdap vaccination rates were 46% and 56.2%, respectively

The increase in Tdap coverage during pregnancy is likely in response to ACIP’s June 2011 recommendation that health care providers administer Tdap to pregnant women who had not previously been vaccinated, preferably after 20 weeks’ gestation, she said.

ACIP updated its guidelines again in October 2012 because of persistent increases in whooping cough in the United States, this time calling for Tdap administration during each pregnancy, irrespective of prior vaccination history, and preferably between 27 and 36 weeks’ gestation.

In California, Tdap coverage during pregnancy increased substantially in 2010 and 2011, but decreased in 2012 (16% vs. 30% vs. 19.5%), likely because many women had received Tdap prepregnancy, she said. Prepregnancy vaccinations climbed steadily from 21.5% in 2010 and 35.3% in 2011 to 53.8% in 2012.

In 2010, the California Department of Public Health began recommending that all women of childbearing age be vaccinated with Tdap.

A protocol looking at repeat Tdap vaccinations and repeat pregnancies has already been written and is being led by CDC investigators, Dr. Kharbanda said.

Dr. Kharbanda reported study support from the CDC VSD project.

pwendling@frontlinemedcom.com

Receipt of the Tdap vaccine during pregnancy was not associated with increased risks for adverse birth outcomes in a safety study, although there was a weak association with chorioamnionitis.

In a separate study, tetanus, diphtheria, and pertussis coverage during pregnancy increased eightfold among women in five states in 2012, while dipping slightly in California.

©AvailableLight/iStockphoto.com

The safety cohort included 26,224 women who received Tdap in pregnancy and 97,265 unvaccinated women with live births during 2010-2012 at two California sites in the Vaccine Safety Datalink (VSD) program.

Inpatient chorioamnionitis was diagnosed in 6.1% of vaccinated women and 5.5% of unvaccinated women (adjusted relative risk, 1.19; 95% confidence interval, 1.13-1.27), Dr. Elyse Olshen Kharbanda reported at the winter meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

In contrast, rates of preterm birth (less than 37 weeks’ gestation) were lower with receipt of Tdap (6.3% vs. 7.8%; hazard ratio, 0.88; 95% CI, 0.83-0.93), while rates were similar for small for gestational age births (8.4% vs. 8.3%; RR, 1.00; 95% CI, 0.96-1.06).

A new diagnosis of hypertensive disorders, examined only in those vaccinated before 20 weeks’ gestation, occurred in 8.2% of vaccinated and 8.0% of unvaccinated women (RR, 1.00; 95% CI, 0.99-1.20), she said.

Secondary analyses restricted to women vaccinated between 27 and 36 weeks’ gestation, consistent with the preferential timing for Tdap vaccination, appeared to confirm the results. Chorioamnionitis occurred in 5.6% of vaccinated and 5.5% of unvaccinated women (RR, 1.11; 95% CI, 1.03-1.21), preterm birth in 5.3% vs. 7.8% (HR, 0.83; 95% CI, 0.77-0.90), and small for gestational age births in 8.6% vs. 8.3% (RR, 1.03; 95% CI, 0.96-1.10).

"The chorioamnionitis findings merit further discussion and possibly further investigation," said Dr. Kharbanda of the HealthPartners Institute for Education and Research, Minneapolis.

The findings in the current study persisted after researchers adjusted for risk factors such as maternal age and comorbidities, although data were not available for many of the most important chorioamnionitis risk factors, she said. Dr. Kharbanda went on to say that the magnitude of the potential risk detected was small, the risk was largely attributable to differences in chorioamnionitis rates seen only for the year 2012, and that there was no associated risk for preterm birth.

Several ACIP representatives questioned the choice of chorioamnionitis as a safety outcome, including American College of Obstetricians and Gynecologists representative Dr. Laura Riley of Harvard Medical School, Boston, who said, "It’s probably one of the messiest diagnoses there is, and it’s really hard to make any sense out of what it really means."

Carol Hayes, MPH, a certified nurse-midwife and a representative from the American Nurses Association, suggested the data be stratified by gestational age at birth because chorioamnionitis is a link for preterm birth, adding "What made you pick chorioamnionitis? It’s such a bizarre thing to look at with a vaccine."

Dr. Kharbanda said chorioamnionitis previously had been studied in relation to trivalent inactivated influenza vaccine, where the risk was slightly increased among pregnant women (Obstet. Gynecol. 2013;1211:519-25). She acknowledged that their obstetrical consultant had also "brought up that in maternal-fetal medicine, often chorioamnionitis is on the pathway for preterm delivery, but not considered an outcome in itself. I think we were sort of trying to look at common diagnoses that occur in women, and it is a common diagnosis."

Tdap coverage

Tdap coverage estimates were based on pregnancies ending between Jan. 1, 2007, and Nov. 15, 2012 at seven sites in the VSD, a collaboration between the CDC and nine managed-care organizations. Among 371,539 live births from 2007 to 2012, overall, 9.5% of women received Tdap during pregnancy and 14.4% post partum. In 2012, the corresponding rates were 13.7% and 8.8%.

In Colorado, Minnesota, Oregon, Washington, and Wisconsin, 16% of women were vaccinated with Tdap during pregnancy in 2012, compared with 2.2% in 2011, Dr. Kharbanda said. Prepregnancy Tdap vaccination rates were 46% and 56.2%, respectively

The increase in Tdap coverage during pregnancy is likely in response to ACIP’s June 2011 recommendation that health care providers administer Tdap to pregnant women who had not previously been vaccinated, preferably after 20 weeks’ gestation, she said.

ACIP updated its guidelines again in October 2012 because of persistent increases in whooping cough in the United States, this time calling for Tdap administration during each pregnancy, irrespective of prior vaccination history, and preferably between 27 and 36 weeks’ gestation.

In California, Tdap coverage during pregnancy increased substantially in 2010 and 2011, but decreased in 2012 (16% vs. 30% vs. 19.5%), likely because many women had received Tdap prepregnancy, she said. Prepregnancy vaccinations climbed steadily from 21.5% in 2010 and 35.3% in 2011 to 53.8% in 2012.

In 2010, the California Department of Public Health began recommending that all women of childbearing age be vaccinated with Tdap.

A protocol looking at repeat Tdap vaccinations and repeat pregnancies has already been written and is being led by CDC investigators, Dr. Kharbanda said.

Dr. Kharbanda reported study support from the CDC VSD project.

pwendling@frontlinemedcom.com

The incidence of all meningococcal serotypes is in decline, except for the spike in serogroup B on college campuses.

"Although we do not expect an increase in MenB outbreaks on college campuses, the CDC has recently formed a meningococcal outbreak work group," said Dr. Manisha Patel, medical officer with the Centers for Disease Control and Prevention’s Meningitis and Vaccine Preventable Diseases Branch.

Five school-based meningitis B (MenB) outbreaks have been reported since 2009, involving four undergraduates at the University of California–Santa Barbara (UCSB) since November 2013 and eight cases from March to November 2013 among students or persons with links to Princeton University.

© Ingram Publishing/Thinkstock

There is no licensed MenB vaccine in the United States, but the Princeton isolates expressed two of the four antigens (fHBP and NHBA) in sufficient quantities to suggest protection with Bexsero, a recombinant MenB vaccine (Novartis) recently licensed in Europe, Australia, and Canada, Dr. Patel said at the CDC’s most recent Advisory Committee on Immunization Practices meeting.

An on-campus vaccination campaign that continued through Feb. 20, 2014, resulted in 95% coverage for dose 1 and 88% coverage for dose 2 among 5,772 at-risk persons.

Based on mandatory follow-up reporting to the Food and Drug Administration, the serious adverse event rate was 2.0/1,000 vaccinees following the first dose and 0.2/1,000 vaccinees after the second. None of these events have been determined to be causally related to the vaccine, and there have been no concerning patterns among other types of reported adverse events, she said.

The target population at Princeton includes all undergraduates, graduate students living in dormitories, at-risk students, faculty, and staff, as well as spouses or parents living with undergraduates in dorms.

The attack rate during the outbreak was 134/100,000 among undergraduates. No deaths occurred, but two cases had sequelae of neurocognitive deficit or hearing loss, Dr. Patel said.

The attack rate at UCSB was 21.1/100,000 among 17-22 years olds, or 234-fold higher than the incidence rate for this age group in the general population. All four students recovered, but one had bilateral foot amputation.

Procurement of the Bexsero vaccine began in August 2013 with the initial proposal to the FDA to explore its use in an outbreak under an expanded access Investigational New Drug (IND) protocol, Dr. Patel explained. Other steps along the way included isolate testing by Novartis, epidemiologic investigations, CDC Institutional Review Board approval, and issuance of an FDA safe to proceed letter before contractual agreements between the CDC, Novartis, and Princeton University were finalized in December 2013.

A CDC-sponsored expanded–access IND protocol was subsequently approved by the FDA for Bexsero use at UCSB. First-dose vaccinations began Feb. 24 – this time with an estimated 20,000 persons eligible for vaccination, Dr. Patel said.

"Vaccination is now possible in response to meningococcal B outbreaks," she said.

Dr. Peter Dull, head of meningitis cluster, Novartis Vaccines and Diagnostics, Cambridge, Mass., agreed that the vaccinations are a great example of collaboration among entities, but he cautioned ACIP members to take a step back.

"If you look at the timeline Dr. Patel laid out as to how long it took to walk through the steps, yes, there’s work with the FDA approving the IND, and yes, there’s set up of the implementation campaign," he said. "But also on the company side, we’re not in surge capacity that you can pick up the phone, and we can label and ship unlicensed vaccines in the U.S.A. very quickly.

"These outbreaks clearly happen fast, and we do have to have a more sustained solution to this."

Dr. Patel pointed to the challenges of using an unlicensed vaccine including the logistics of vaccine procurement and implementation, with the mandate to meet safety follow-up requirements. Plus the IND preparation process must address specifics of the outbreak.

The new meningococcal outbreak work group will bring together federal vaccine experts, state public and college health officials, university administrators, and insurance industry representatives. The group is tasked with reviewing recent epidemiology data of meningococcal disease and outbreaks, considering options for updating the current meningococcal outbreak guidelines, and developing guidance for the use of meningococcal vaccines, both licensed and unlicensed in an outbreak, she said.

Dr. Patel reported having no financial disclosures.

pwendling@frontlinemedcom.com

The incidence of all meningococcal serotypes is in decline, except for the spike in serogroup B on college campuses.

"Although we do not expect an increase in MenB outbreaks on college campuses, the CDC has recently formed a meningococcal outbreak work group," said Dr. Manisha Patel, medical officer with the Centers for Disease Control and Prevention’s Meningitis and Vaccine Preventable Diseases Branch.

Five school-based meningitis B (MenB) outbreaks have been reported since 2009, involving four undergraduates at the University of California–Santa Barbara (UCSB) since November 2013 and eight cases from March to November 2013 among students or persons with links to Princeton University.

© Ingram Publishing/Thinkstock

There is no licensed MenB vaccine in the United States, but the Princeton isolates expressed two of the four antigens (fHBP and NHBA) in sufficient quantities to suggest protection with Bexsero, a recombinant MenB vaccine (Novartis) recently licensed in Europe, Australia, and Canada, Dr. Patel said at the CDC’s most recent Advisory Committee on Immunization Practices meeting.

An on-campus vaccination campaign that continued through Feb. 20, 2014, resulted in 95% coverage for dose 1 and 88% coverage for dose 2 among 5,772 at-risk persons.

Based on mandatory follow-up reporting to the Food and Drug Administration, the serious adverse event rate was 2.0/1,000 vaccinees following the first dose and 0.2/1,000 vaccinees after the second. None of these events have been determined to be causally related to the vaccine, and there have been no concerning patterns among other types of reported adverse events, she said.

The target population at Princeton includes all undergraduates, graduate students living in dormitories, at-risk students, faculty, and staff, as well as spouses or parents living with undergraduates in dorms.

The attack rate during the outbreak was 134/100,000 among undergraduates. No deaths occurred, but two cases had sequelae of neurocognitive deficit or hearing loss, Dr. Patel said.

The attack rate at UCSB was 21.1/100,000 among 17-22 years olds, or 234-fold higher than the incidence rate for this age group in the general population. All four students recovered, but one had bilateral foot amputation.

Procurement of the Bexsero vaccine began in August 2013 with the initial proposal to the FDA to explore its use in an outbreak under an expanded access Investigational New Drug (IND) protocol, Dr. Patel explained. Other steps along the way included isolate testing by Novartis, epidemiologic investigations, CDC Institutional Review Board approval, and issuance of an FDA safe to proceed letter before contractual agreements between the CDC, Novartis, and Princeton University were finalized in December 2013.

A CDC-sponsored expanded–access IND protocol was subsequently approved by the FDA for Bexsero use at UCSB. First-dose vaccinations began Feb. 24 – this time with an estimated 20,000 persons eligible for vaccination, Dr. Patel said.

"Vaccination is now possible in response to meningococcal B outbreaks," she said.

Dr. Peter Dull, head of meningitis cluster, Novartis Vaccines and Diagnostics, Cambridge, Mass., agreed that the vaccinations are a great example of collaboration among entities, but he cautioned ACIP members to take a step back.

"If you look at the timeline Dr. Patel laid out as to how long it took to walk through the steps, yes, there’s work with the FDA approving the IND, and yes, there’s set up of the implementation campaign," he said. "But also on the company side, we’re not in surge capacity that you can pick up the phone, and we can label and ship unlicensed vaccines in the U.S.A. very quickly.

"These outbreaks clearly happen fast, and we do have to have a more sustained solution to this."

Dr. Patel pointed to the challenges of using an unlicensed vaccine including the logistics of vaccine procurement and implementation, with the mandate to meet safety follow-up requirements. Plus the IND preparation process must address specifics of the outbreak.

The new meningococcal outbreak work group will bring together federal vaccine experts, state public and college health officials, university administrators, and insurance industry representatives. The group is tasked with reviewing recent epidemiology data of meningococcal disease and outbreaks, considering options for updating the current meningococcal outbreak guidelines, and developing guidance for the use of meningococcal vaccines, both licensed and unlicensed in an outbreak, she said.

Dr. Patel reported having no financial disclosures.

pwendling@frontlinemedcom.com

The incidence of all meningococcal serotypes is in decline, except for the spike in serogroup B on college campuses.

"Although we do not expect an increase in MenB outbreaks on college campuses, the CDC has recently formed a meningococcal outbreak work group," said Dr. Manisha Patel, medical officer with the Centers for Disease Control and Prevention’s Meningitis and Vaccine Preventable Diseases Branch.

Five school-based meningitis B (MenB) outbreaks have been reported since 2009, involving four undergraduates at the University of California–Santa Barbara (UCSB) since November 2013 and eight cases from March to November 2013 among students or persons with links to Princeton University.

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There is no licensed MenB vaccine in the United States, but the Princeton isolates expressed two of the four antigens (fHBP and NHBA) in sufficient quantities to suggest protection with Bexsero, a recombinant MenB vaccine (Novartis) recently licensed in Europe, Australia, and Canada, Dr. Patel said at the CDC’s most recent Advisory Committee on Immunization Practices meeting.

An on-campus vaccination campaign that continued through Feb. 20, 2014, resulted in 95% coverage for dose 1 and 88% coverage for dose 2 among 5,772 at-risk persons.

Based on mandatory follow-up reporting to the Food and Drug Administration, the serious adverse event rate was 2.0/1,000 vaccinees following the first dose and 0.2/1,000 vaccinees after the second. None of these events have been determined to be causally related to the vaccine, and there have been no concerning patterns among other types of reported adverse events, she said.

The target population at Princeton includes all undergraduates, graduate students living in dormitories, at-risk students, faculty, and staff, as well as spouses or parents living with undergraduates in dorms.

The attack rate during the outbreak was 134/100,000 among undergraduates. No deaths occurred, but two cases had sequelae of neurocognitive deficit or hearing loss, Dr. Patel said.

The attack rate at UCSB was 21.1/100,000 among 17-22 years olds, or 234-fold higher than the incidence rate for this age group in the general population. All four students recovered, but one had bilateral foot amputation.

Procurement of the Bexsero vaccine began in August 2013 with the initial proposal to the FDA to explore its use in an outbreak under an expanded access Investigational New Drug (IND) protocol, Dr. Patel explained. Other steps along the way included isolate testing by Novartis, epidemiologic investigations, CDC Institutional Review Board approval, and issuance of an FDA safe to proceed letter before contractual agreements between the CDC, Novartis, and Princeton University were finalized in December 2013.

A CDC-sponsored expanded–access IND protocol was subsequently approved by the FDA for Bexsero use at UCSB. First-dose vaccinations began Feb. 24 – this time with an estimated 20,000 persons eligible for vaccination, Dr. Patel said.

"Vaccination is now possible in response to meningococcal B outbreaks," she said.

Dr. Peter Dull, head of meningitis cluster, Novartis Vaccines and Diagnostics, Cambridge, Mass., agreed that the vaccinations are a great example of collaboration among entities, but he cautioned ACIP members to take a step back.

"If you look at the timeline Dr. Patel laid out as to how long it took to walk through the steps, yes, there’s work with the FDA approving the IND, and yes, there’s set up of the implementation campaign," he said. "But also on the company side, we’re not in surge capacity that you can pick up the phone, and we can label and ship unlicensed vaccines in the U.S.A. very quickly.

"These outbreaks clearly happen fast, and we do have to have a more sustained solution to this."

Dr. Patel pointed to the challenges of using an unlicensed vaccine including the logistics of vaccine procurement and implementation, with the mandate to meet safety follow-up requirements. Plus the IND preparation process must address specifics of the outbreak.

The new meningococcal outbreak work group will bring together federal vaccine experts, state public and college health officials, university administrators, and insurance industry representatives. The group is tasked with reviewing recent epidemiology data of meningococcal disease and outbreaks, considering options for updating the current meningococcal outbreak guidelines, and developing guidance for the use of meningococcal vaccines, both licensed and unlicensed in an outbreak, she said.

Dr. Patel reported having no financial disclosures.

pwendling@frontlinemedcom.com

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted to retain its current recommendations and patient populations for annual influenza vaccination Feb. 26 at its meeting.

The vote was unanimous, but it belies the desire by some for ACIP to call for vote on whether live-attenuated influenza vaccine (LAIV) should be recommended preferentially over inactivated influenza vaccine (IIV) for healthy children.

"Many of us feel it’s long overdue," said Dr. Jeff Duchin, a member of the ACIP influenza working group. "We have a vaccine that even the CDC has acknowledged on a public Web page is superior in young children. Yet we haven’t made that step to make that recommendation, which does influence a lot of health care providers."

LAIV is recommended preferentially for various age groups in the United Kingdom, Canada, Israel, and Germany, as well as in the states of Oregon and Washington.

Several studies indicate that LAIV may have advantages over IIV in younger populations, but this is not clear in older populations, said influenza work group member Dr. Lisa Grohskopf of the influenza division in the CDC National Center for Immunization and Respiratory Diseases (NCIRD). The work group also struggled with the lower age limit for children when evaluating the efficacy and safety evidence because LAIV is not licensed for children under 2 years of age.

Based on review of the efficacy data, LAIV was associated with a decreased risk of lab-confirmed influenza among 2- to 8-year-olds based on high-quality randomized evidence, but it showed no difference over IIV among 9- to 18-year-olds based on very-low-quality observational data, Dr. Grohskopf said. Among 2- to 8-year-olds, LAIV also was associated with a decreased risk of otitis media, but there was no difference between vaccines with regard to hospitalization, medically attended acute respiratory illness, or influenzalike illness.

As ACIP goes forward, it will need to "harmonize" any possible changes to its recommendations with the American Academy of Pediatrics, which doesn’t meet on the issue until April, Dr. Grohskopf said. It also will have to consider the LAIV supply and the safety of quadrivalent vaccines since all of the studies in the evidence review were done when only trivalent vaccines were available.

Four new, recently licensed vaccines are now available for the 2013-1014 flu season, including FluMist Quadrivalent nasal LAIV (LAIV4) from MedImmune for persons aged 2-49 years; Fluarix Quadrivalent inactivated influenza vaccine (IIV4) from GlaxoSmithKline for those 3 years and older; Flucelvax, a cell culture–based inactivated influenza vaccine (ccIIV3) from Novartis for patients aged 18 years and older; and Flublok, a recombinant hemagglutinin vaccine (RIV3) from Protein Sciences for adults aged 18-49 years.

No new safety concerns have been detected for LAIV4, IIV4, or IIV3 vaccines during the 2013-14 influenza season in patients less than 18 years of age based on interim Vaccine Adverse Event Reporting System surveillance data and Vaccine Safety Datalink data, said Dr. Maria Cano of the CDC National Center for Emerging and Infectious Zoonotic Diseases. Uptake has been limited for the IIV4, cell culture–based IIV3, and recombinant IIV3 vaccines, compared with 194,080 LAIV4 doses and 3.1 million IIV3 doses.

The influenza work group also assessed influenza vaccine safety data in children aged 2-8 years and found no evidence for an increased risk of serious adverse events or medically attended wheezing after LAIV vs. trivalent influenza vaccine (TIV), reported Dr. Emmanuel Walter, director of the Duke Translational Medicine Institute’s clinical vaccine unit at Duke University Medical Center, Durham, N.C. There was evidence for a transient increased risk of mild fever after LAIV vs. TIV, but it was seen only in one study during a single influenza season.

In a pooled safety analysis of LAIV vs. IIV in healthy children, there was no difference between vaccines in medically attended wheezing, fever, or vaccine-related serious adverse events, Dr. Grohskopf said. Both she and Dr. Walter observed that the analyses were limited by several factors, including few studies directly comparing LAIV and IIV, lack of standardized outcome definitions across studies, and difficulty judging the risk of serious rare adverse events.

This led some in attendance to call for additional data on adverse events like seizures at the June meeting, while others tasked the work group with clarifying and separating contraindications from precautions before opening up use of the LAIV to a wider population.

Dr. Walter reported previously serving as a clinical investigator within the last 12 months for GlaxoSmithKline, Merck, and Pfizer and as a data monitoring board member and consultant for Novartis. No other presenters reported having financial disclosures.

pwendling@frontlinemedcom.com

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted to retain its current recommendations and patient populations for annual influenza vaccination Feb. 26 at its meeting.

The vote was unanimous, but it belies the desire by some for ACIP to call for vote on whether live-attenuated influenza vaccine (LAIV) should be recommended preferentially over inactivated influenza vaccine (IIV) for healthy children.

"Many of us feel it’s long overdue," said Dr. Jeff Duchin, a member of the ACIP influenza working group. "We have a vaccine that even the CDC has acknowledged on a public Web page is superior in young children. Yet we haven’t made that step to make that recommendation, which does influence a lot of health care providers."

LAIV is recommended preferentially for various age groups in the United Kingdom, Canada, Israel, and Germany, as well as in the states of Oregon and Washington.

Several studies indicate that LAIV may have advantages over IIV in younger populations, but this is not clear in older populations, said influenza work group member Dr. Lisa Grohskopf of the influenza division in the CDC National Center for Immunization and Respiratory Diseases (NCIRD). The work group also struggled with the lower age limit for children when evaluating the efficacy and safety evidence because LAIV is not licensed for children under 2 years of age.

Based on review of the efficacy data, LAIV was associated with a decreased risk of lab-confirmed influenza among 2- to 8-year-olds based on high-quality randomized evidence, but it showed no difference over IIV among 9- to 18-year-olds based on very-low-quality observational data, Dr. Grohskopf said. Among 2- to 8-year-olds, LAIV also was associated with a decreased risk of otitis media, but there was no difference between vaccines with regard to hospitalization, medically attended acute respiratory illness, or influenzalike illness.

As ACIP goes forward, it will need to "harmonize" any possible changes to its recommendations with the American Academy of Pediatrics, which doesn’t meet on the issue until April, Dr. Grohskopf said. It also will have to consider the LAIV supply and the safety of quadrivalent vaccines since all of the studies in the evidence review were done when only trivalent vaccines were available.

Four new, recently licensed vaccines are now available for the 2013-1014 flu season, including FluMist Quadrivalent nasal LAIV (LAIV4) from MedImmune for persons aged 2-49 years; Fluarix Quadrivalent inactivated influenza vaccine (IIV4) from GlaxoSmithKline for those 3 years and older; Flucelvax, a cell culture–based inactivated influenza vaccine (ccIIV3) from Novartis for patients aged 18 years and older; and Flublok, a recombinant hemagglutinin vaccine (RIV3) from Protein Sciences for adults aged 18-49 years.

No new safety concerns have been detected for LAIV4, IIV4, or IIV3 vaccines during the 2013-14 influenza season in patients less than 18 years of age based on interim Vaccine Adverse Event Reporting System surveillance data and Vaccine Safety Datalink data, said Dr. Maria Cano of the CDC National Center for Emerging and Infectious Zoonotic Diseases. Uptake has been limited for the IIV4, cell culture–based IIV3, and recombinant IIV3 vaccines, compared with 194,080 LAIV4 doses and 3.1 million IIV3 doses.

The influenza work group also assessed influenza vaccine safety data in children aged 2-8 years and found no evidence for an increased risk of serious adverse events or medically attended wheezing after LAIV vs. trivalent influenza vaccine (TIV), reported Dr. Emmanuel Walter, director of the Duke Translational Medicine Institute’s clinical vaccine unit at Duke University Medical Center, Durham, N.C. There was evidence for a transient increased risk of mild fever after LAIV vs. TIV, but it was seen only in one study during a single influenza season.

In a pooled safety analysis of LAIV vs. IIV in healthy children, there was no difference between vaccines in medically attended wheezing, fever, or vaccine-related serious adverse events, Dr. Grohskopf said. Both she and Dr. Walter observed that the analyses were limited by several factors, including few studies directly comparing LAIV and IIV, lack of standardized outcome definitions across studies, and difficulty judging the risk of serious rare adverse events.

This led some in attendance to call for additional data on adverse events like seizures at the June meeting, while others tasked the work group with clarifying and separating contraindications from precautions before opening up use of the LAIV to a wider population.

Dr. Walter reported previously serving as a clinical investigator within the last 12 months for GlaxoSmithKline, Merck, and Pfizer and as a data monitoring board member and consultant for Novartis. No other presenters reported having financial disclosures.

pwendling@frontlinemedcom.com

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted to retain its current recommendations and patient populations for annual influenza vaccination Feb. 26 at its meeting.

The vote was unanimous, but it belies the desire by some for ACIP to call for vote on whether live-attenuated influenza vaccine (LAIV) should be recommended preferentially over inactivated influenza vaccine (IIV) for healthy children.

"Many of us feel it’s long overdue," said Dr. Jeff Duchin, a member of the ACIP influenza working group. "We have a vaccine that even the CDC has acknowledged on a public Web page is superior in young children. Yet we haven’t made that step to make that recommendation, which does influence a lot of health care providers."

LAIV is recommended preferentially for various age groups in the United Kingdom, Canada, Israel, and Germany, as well as in the states of Oregon and Washington.

Several studies indicate that LAIV may have advantages over IIV in younger populations, but this is not clear in older populations, said influenza work group member Dr. Lisa Grohskopf of the influenza division in the CDC National Center for Immunization and Respiratory Diseases (NCIRD). The work group also struggled with the lower age limit for children when evaluating the efficacy and safety evidence because LAIV is not licensed for children under 2 years of age.

Based on review of the efficacy data, LAIV was associated with a decreased risk of lab-confirmed influenza among 2- to 8-year-olds based on high-quality randomized evidence, but it showed no difference over IIV among 9- to 18-year-olds based on very-low-quality observational data, Dr. Grohskopf said. Among 2- to 8-year-olds, LAIV also was associated with a decreased risk of otitis media, but there was no difference between vaccines with regard to hospitalization, medically attended acute respiratory illness, or influenzalike illness.

As ACIP goes forward, it will need to "harmonize" any possible changes to its recommendations with the American Academy of Pediatrics, which doesn’t meet on the issue until April, Dr. Grohskopf said. It also will have to consider the LAIV supply and the safety of quadrivalent vaccines since all of the studies in the evidence review were done when only trivalent vaccines were available.

Four new, recently licensed vaccines are now available for the 2013-1014 flu season, including FluMist Quadrivalent nasal LAIV (LAIV4) from MedImmune for persons aged 2-49 years; Fluarix Quadrivalent inactivated influenza vaccine (IIV4) from GlaxoSmithKline for those 3 years and older; Flucelvax, a cell culture–based inactivated influenza vaccine (ccIIV3) from Novartis for patients aged 18 years and older; and Flublok, a recombinant hemagglutinin vaccine (RIV3) from Protein Sciences for adults aged 18-49 years.

No new safety concerns have been detected for LAIV4, IIV4, or IIV3 vaccines during the 2013-14 influenza season in patients less than 18 years of age based on interim Vaccine Adverse Event Reporting System surveillance data and Vaccine Safety Datalink data, said Dr. Maria Cano of the CDC National Center for Emerging and Infectious Zoonotic Diseases. Uptake has been limited for the IIV4, cell culture–based IIV3, and recombinant IIV3 vaccines, compared with 194,080 LAIV4 doses and 3.1 million IIV3 doses.

The influenza work group also assessed influenza vaccine safety data in children aged 2-8 years and found no evidence for an increased risk of serious adverse events or medically attended wheezing after LAIV vs. trivalent influenza vaccine (TIV), reported Dr. Emmanuel Walter, director of the Duke Translational Medicine Institute’s clinical vaccine unit at Duke University Medical Center, Durham, N.C. There was evidence for a transient increased risk of mild fever after LAIV vs. TIV, but it was seen only in one study during a single influenza season.

In a pooled safety analysis of LAIV vs. IIV in healthy children, there was no difference between vaccines in medically attended wheezing, fever, or vaccine-related serious adverse events, Dr. Grohskopf said. Both she and Dr. Walter observed that the analyses were limited by several factors, including few studies directly comparing LAIV and IIV, lack of standardized outcome definitions across studies, and difficulty judging the risk of serious rare adverse events.

This led some in attendance to call for additional data on adverse events like seizures at the June meeting, while others tasked the work group with clarifying and separating contraindications from precautions before opening up use of the LAIV to a wider population.

Dr. Walter reported previously serving as a clinical investigator within the last 12 months for GlaxoSmithKline, Merck, and Pfizer and as a data monitoring board member and consultant for Novartis. No other presenters reported having financial disclosures.

pwendling@frontlinemedcom.com