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ACP roadmap to raise adult immunization rates
NEW ORLEANS – carried out in seven rural southwestern Georgia counties.
“We saw increases of 52%-93% in our pneumococcal vaccination rates in our nine adult medicine clinics,” Frances E. Ferguson, MD, said at the annual meeting of the American College of Physicians.
The project, conducted through the ACP’s quality improvement program, known as Quality Connect, with funding from the Centers for Disease Control and Prevention, has as its ultimate goal making adult immunization standard practice across the country in general internal medicine and primary care. One of the initial pilot projects was conducted at Albany (Ga.) Area Primary Health Care, a federally qualified community health center with 28 service delivery sites in seven mainly rural southwestern Georgia counties. The majority of the center’s patients are at or below the poverty level. The lessons learned from this and other successful local projects will be disseminated nationally, according to Dr. Ferguson, a general internist at the health center.
The project utilizes the ACP Quality Connect “Plan, Do, Study, Act” approach to implementing constructive changes in medical practice, coupled with an abundance of resources readily available from the nonprofit Immunization Action Coalition, which has been funded by the CDC for more than 20 years.
The coalition’s website includes easily downloadable and custom-modifiable standing orders, plain-language information handouts on pneumococcal pneumonia and other vaccine-preventable illnesses and possible vaccine side effects for patients to read in the waiting room before their office visit, concise CDC-standardized talking points for providers to use in convincing patients to get vaccinated, as well as a detailed 10-point action plan for medical practice leadership to make it all happen.
“You don’t have to reinvent the wheel with this. You just go to their website,” Dr. Ferguson explained.
She cited her personal experience as representative of that of her fellow general internists who got on board with the project’s goal. As of April 2016, just before rollout of the pilot project, Dr. Ferguson’s pneumococcal vaccination rate stood at 22.5%. One month into the project, her vaccination rate had zoomed to 60%. When the formal pilot project ended in February 2017, her rate was 88.2%, an absolute 65.7% increase in 10 months. And since the pilot project’s conclusion, adult pneumococcal vaccination rates across Albany Area Primary Health Care have continued to climb.
“We have continued to improve because our champions are still in place, and our standing orders are, too,” she noted.
Standing orders are at the core of the project’s success, according to Dr. Ferguson. They provide nurses with the legal authority to determine if a patient is eligible for a vaccine and to go ahead and give it before seeing the physician.
“The most important thing for me is that nurses are an essential and invaluable asset to your practice, especially when you empower them to function fully within the scope of their practice. They can do amazing things. I just feel like the nurses are the winners here. We are winners because of our nurses,” she said.
It wasn’t easy at first, Dr. Ferguson recalled.
“We had pushback from nurses because they were afraid to do anything without the doctor directly telling them to do it. And we had physicians who didn’t want to have standing orders because they didn’t want anybody to do anything until they told them to. But we managed to get all that straightened out in the first month,” according to the internist.
Other keys to the program’s success included designating champions of the project at every clinic. Often this was the director of nursing, who was appointed to be in charge of the standing orders program. This “champions” concept is detailed in the ACP Quality Connect website. The champion – Dr. Ferguson was one – gets staff buy in on promoting the importance of immunizations, teaches strategies, and engages in community outreach.
“They lead the practice in the quality improvement project. We found that was very important, to have someone at each site who could keep the fire under the staff, keep the project going even when it’s very busy and everybody’s running around. There has to be someone there who’s encouraging people to remember to keep giving immunizations in spite of everything that’s going on that day,” she explained.
A central principle of successful quality improvement programs is accurate performance data gathering and dissemination. “Doctors are very competitive people,” Dr. Ferguson observed. “When I tell you you’re not doing as well as your colleagues and I can show you a graph that shows how far you are lagging behind, you get the fire under you and get moving.”
Audience members were agog at the community health center’s stratospheric vaccination rates. What about all the vaccine skeptics? they asked.
“I think for us it’s a matter of trust,” she replied. “We are a community health center and many of our patients and our providers have been with us for a long time. The nursing staff live in those communities, so the patients know them well. The CDC’s cards with talking points are a big help. I take the time to talk to patients and explain how the vaccine is going to build an army of immunologic protection. There are always going to be the diehards who say, ‘My cousin’s foot fell off when he got the pneumonia vaccine,’ though. You can’t get past those people. There’s just nothing you can say to them that will change their mind.”
She reported having no financial conflicts regarding her presentation or the adult immunization initiative.
[email protected]
NEW ORLEANS – carried out in seven rural southwestern Georgia counties.
“We saw increases of 52%-93% in our pneumococcal vaccination rates in our nine adult medicine clinics,” Frances E. Ferguson, MD, said at the annual meeting of the American College of Physicians.
The project, conducted through the ACP’s quality improvement program, known as Quality Connect, with funding from the Centers for Disease Control and Prevention, has as its ultimate goal making adult immunization standard practice across the country in general internal medicine and primary care. One of the initial pilot projects was conducted at Albany (Ga.) Area Primary Health Care, a federally qualified community health center with 28 service delivery sites in seven mainly rural southwestern Georgia counties. The majority of the center’s patients are at or below the poverty level. The lessons learned from this and other successful local projects will be disseminated nationally, according to Dr. Ferguson, a general internist at the health center.
The project utilizes the ACP Quality Connect “Plan, Do, Study, Act” approach to implementing constructive changes in medical practice, coupled with an abundance of resources readily available from the nonprofit Immunization Action Coalition, which has been funded by the CDC for more than 20 years.
The coalition’s website includes easily downloadable and custom-modifiable standing orders, plain-language information handouts on pneumococcal pneumonia and other vaccine-preventable illnesses and possible vaccine side effects for patients to read in the waiting room before their office visit, concise CDC-standardized talking points for providers to use in convincing patients to get vaccinated, as well as a detailed 10-point action plan for medical practice leadership to make it all happen.
“You don’t have to reinvent the wheel with this. You just go to their website,” Dr. Ferguson explained.
She cited her personal experience as representative of that of her fellow general internists who got on board with the project’s goal. As of April 2016, just before rollout of the pilot project, Dr. Ferguson’s pneumococcal vaccination rate stood at 22.5%. One month into the project, her vaccination rate had zoomed to 60%. When the formal pilot project ended in February 2017, her rate was 88.2%, an absolute 65.7% increase in 10 months. And since the pilot project’s conclusion, adult pneumococcal vaccination rates across Albany Area Primary Health Care have continued to climb.
“We have continued to improve because our champions are still in place, and our standing orders are, too,” she noted.
Standing orders are at the core of the project’s success, according to Dr. Ferguson. They provide nurses with the legal authority to determine if a patient is eligible for a vaccine and to go ahead and give it before seeing the physician.
“The most important thing for me is that nurses are an essential and invaluable asset to your practice, especially when you empower them to function fully within the scope of their practice. They can do amazing things. I just feel like the nurses are the winners here. We are winners because of our nurses,” she said.
It wasn’t easy at first, Dr. Ferguson recalled.
“We had pushback from nurses because they were afraid to do anything without the doctor directly telling them to do it. And we had physicians who didn’t want to have standing orders because they didn’t want anybody to do anything until they told them to. But we managed to get all that straightened out in the first month,” according to the internist.
Other keys to the program’s success included designating champions of the project at every clinic. Often this was the director of nursing, who was appointed to be in charge of the standing orders program. This “champions” concept is detailed in the ACP Quality Connect website. The champion – Dr. Ferguson was one – gets staff buy in on promoting the importance of immunizations, teaches strategies, and engages in community outreach.
“They lead the practice in the quality improvement project. We found that was very important, to have someone at each site who could keep the fire under the staff, keep the project going even when it’s very busy and everybody’s running around. There has to be someone there who’s encouraging people to remember to keep giving immunizations in spite of everything that’s going on that day,” she explained.
A central principle of successful quality improvement programs is accurate performance data gathering and dissemination. “Doctors are very competitive people,” Dr. Ferguson observed. “When I tell you you’re not doing as well as your colleagues and I can show you a graph that shows how far you are lagging behind, you get the fire under you and get moving.”
Audience members were agog at the community health center’s stratospheric vaccination rates. What about all the vaccine skeptics? they asked.
“I think for us it’s a matter of trust,” she replied. “We are a community health center and many of our patients and our providers have been with us for a long time. The nursing staff live in those communities, so the patients know them well. The CDC’s cards with talking points are a big help. I take the time to talk to patients and explain how the vaccine is going to build an army of immunologic protection. There are always going to be the diehards who say, ‘My cousin’s foot fell off when he got the pneumonia vaccine,’ though. You can’t get past those people. There’s just nothing you can say to them that will change their mind.”
She reported having no financial conflicts regarding her presentation or the adult immunization initiative.
[email protected]
NEW ORLEANS – carried out in seven rural southwestern Georgia counties.
“We saw increases of 52%-93% in our pneumococcal vaccination rates in our nine adult medicine clinics,” Frances E. Ferguson, MD, said at the annual meeting of the American College of Physicians.
The project, conducted through the ACP’s quality improvement program, known as Quality Connect, with funding from the Centers for Disease Control and Prevention, has as its ultimate goal making adult immunization standard practice across the country in general internal medicine and primary care. One of the initial pilot projects was conducted at Albany (Ga.) Area Primary Health Care, a federally qualified community health center with 28 service delivery sites in seven mainly rural southwestern Georgia counties. The majority of the center’s patients are at or below the poverty level. The lessons learned from this and other successful local projects will be disseminated nationally, according to Dr. Ferguson, a general internist at the health center.
The project utilizes the ACP Quality Connect “Plan, Do, Study, Act” approach to implementing constructive changes in medical practice, coupled with an abundance of resources readily available from the nonprofit Immunization Action Coalition, which has been funded by the CDC for more than 20 years.
The coalition’s website includes easily downloadable and custom-modifiable standing orders, plain-language information handouts on pneumococcal pneumonia and other vaccine-preventable illnesses and possible vaccine side effects for patients to read in the waiting room before their office visit, concise CDC-standardized talking points for providers to use in convincing patients to get vaccinated, as well as a detailed 10-point action plan for medical practice leadership to make it all happen.
“You don’t have to reinvent the wheel with this. You just go to their website,” Dr. Ferguson explained.
She cited her personal experience as representative of that of her fellow general internists who got on board with the project’s goal. As of April 2016, just before rollout of the pilot project, Dr. Ferguson’s pneumococcal vaccination rate stood at 22.5%. One month into the project, her vaccination rate had zoomed to 60%. When the formal pilot project ended in February 2017, her rate was 88.2%, an absolute 65.7% increase in 10 months. And since the pilot project’s conclusion, adult pneumococcal vaccination rates across Albany Area Primary Health Care have continued to climb.
“We have continued to improve because our champions are still in place, and our standing orders are, too,” she noted.
Standing orders are at the core of the project’s success, according to Dr. Ferguson. They provide nurses with the legal authority to determine if a patient is eligible for a vaccine and to go ahead and give it before seeing the physician.
“The most important thing for me is that nurses are an essential and invaluable asset to your practice, especially when you empower them to function fully within the scope of their practice. They can do amazing things. I just feel like the nurses are the winners here. We are winners because of our nurses,” she said.
It wasn’t easy at first, Dr. Ferguson recalled.
“We had pushback from nurses because they were afraid to do anything without the doctor directly telling them to do it. And we had physicians who didn’t want to have standing orders because they didn’t want anybody to do anything until they told them to. But we managed to get all that straightened out in the first month,” according to the internist.
Other keys to the program’s success included designating champions of the project at every clinic. Often this was the director of nursing, who was appointed to be in charge of the standing orders program. This “champions” concept is detailed in the ACP Quality Connect website. The champion – Dr. Ferguson was one – gets staff buy in on promoting the importance of immunizations, teaches strategies, and engages in community outreach.
“They lead the practice in the quality improvement project. We found that was very important, to have someone at each site who could keep the fire under the staff, keep the project going even when it’s very busy and everybody’s running around. There has to be someone there who’s encouraging people to remember to keep giving immunizations in spite of everything that’s going on that day,” she explained.
A central principle of successful quality improvement programs is accurate performance data gathering and dissemination. “Doctors are very competitive people,” Dr. Ferguson observed. “When I tell you you’re not doing as well as your colleagues and I can show you a graph that shows how far you are lagging behind, you get the fire under you and get moving.”
Audience members were agog at the community health center’s stratospheric vaccination rates. What about all the vaccine skeptics? they asked.
“I think for us it’s a matter of trust,” she replied. “We are a community health center and many of our patients and our providers have been with us for a long time. The nursing staff live in those communities, so the patients know them well. The CDC’s cards with talking points are a big help. I take the time to talk to patients and explain how the vaccine is going to build an army of immunologic protection. There are always going to be the diehards who say, ‘My cousin’s foot fell off when he got the pneumonia vaccine,’ though. You can’t get past those people. There’s just nothing you can say to them that will change their mind.”
She reported having no financial conflicts regarding her presentation or the adult immunization initiative.
[email protected]
REPORTING FROM ACP INTERNAL MEDICINE
Study supports meningococcal B vaccine in children with rare diseases
A new study, the first of its kind, provided support for guidelines suggesting that the capsular meningococcal B vaccine be given to children with three rare conditions that boost infection risk.
For children with terminal chain complement deficiencies or who are undergoing treatment with eculizumab, “it is important that these patients are identified, receive education about sepsis management plans, and are prescribed prophylactic antibiotics according to local guidelines, along with vaccination, to provide every chance for them to be protected against this deadly disease,” the researchers wrote in Pediatrics.
While some countries suggest that the vaccine be given to all healthy infants, U.S. guidelines advise that the vaccine be given to preteenagers, teenagers, and adults who are considered at special risk. These include those with terminal chain complement deficiencies, who are believed to be up to 10,000 times more likely than healthy children to develop invasive meningococcal disease, and those who take eculizumab (Soliris). The risk groups recommended for vaccinations also include those with asplenia and splenic dysfunction, although their excess risk, if any, is unknown.
The new study of the capsular group meningococcal B vaccine, led by Federico Martinón-Torres, PhD, of the Hospital Clinico Universitario de Santiago de Compostela, Spain, adds to previous research that confirmed the effectiveness of vaccinating complement-deficient patients with capsular group A, C, W, and Y meningococcal vaccines.
For the open-label, phase 3b study, researchers in Italy, Spain, Poland, and Russia gave two doses of the vaccine 2 months apart to 239 children aged 2-17 years with an average age of 10 years. Nearly all were white, and 45% were female.
A total of 40 children had complement deficiency, 112 had asplenia or splenic dysfunction, and 87 children in the control group also received the vaccine.
Following vaccination, the percentages of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 to the four test strains were similar in the healthy children and those with asplenia/splenic dysfunction. “It is reasonable to expect that this vaccine will be as effective in children with asplenia or splenic deficiency as in children in the control category,” the researchers wrote.
However, these levels were lower in the complement-deficient children, particularly in those with terminal chain complement deficiency and those who took eculizumab.
The proportions of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 against the four test strains were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713) in complement-deficient children, compared with 98%, 99%, 83%, and 99%, respectively, in the healthy controls.
“Ongoing surveillance for vaccine failures is required to determine the significance of the trend to reduced immune response in children with terminal chain complement deficiencies or undergoing treatment with eculizumab,” the researchers wrote.
Eculizumab’s manufacturer has noted the risk of serious meningococcal infections and warned physicians to “immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection,” according to the website.
The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
SOURCE: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
The Centers for Disease Control and Prevention reported an annual average of 792 cases of meningococcal disease and 98 deaths in the United States from 2006 to 2015 with serotype B isolates causing the highest numbers of cases. In a recent development, two vaccines against this strain have become available in the United States in the past 3 years for people aged 10-25 years. But officials don’t recommend their routine use, instead, guidelines suggest they be given to those at high risk only.
There’s a gap in knowledge because vaccine researchers didn’t include people with complement deficiency (either congenital or related to eculizumab), asplenia, or splenic dysfunction in studies that led to approval. Now, the new study offers reassuring findings regarding the latter two conditions, as bactericidal antibody responses were equal to those in healthy controls.
The findings regarding complement deficiency aren’t surprising, and suggest that vaccine strength in children with the condition only reached the levels in healthy children when an exogenous complement was added.
The study supports guidelines suggesting antibiotic prophylaxis in patients receiving eculizumab even if they already underwent meningococcal vaccination. It’s not clear if this approach also will be effective in those with congenital complement deficiencies (except for complement component 6 deficiency).
It is hoped that surveillance studies will show that use of serogroup B vaccines will prevent invasive meningococcal infections in these high-risk populations for which they are recommended.
Sheldon L. Kaplan, MD, is a pediatrician at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. These comments are summarized from an editorial accompanying the article by Martinón-Torres et al. (Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2018-0554).
The Centers for Disease Control and Prevention reported an annual average of 792 cases of meningococcal disease and 98 deaths in the United States from 2006 to 2015 with serotype B isolates causing the highest numbers of cases. In a recent development, two vaccines against this strain have become available in the United States in the past 3 years for people aged 10-25 years. But officials don’t recommend their routine use, instead, guidelines suggest they be given to those at high risk only.
There’s a gap in knowledge because vaccine researchers didn’t include people with complement deficiency (either congenital or related to eculizumab), asplenia, or splenic dysfunction in studies that led to approval. Now, the new study offers reassuring findings regarding the latter two conditions, as bactericidal antibody responses were equal to those in healthy controls.
The findings regarding complement deficiency aren’t surprising, and suggest that vaccine strength in children with the condition only reached the levels in healthy children when an exogenous complement was added.
The study supports guidelines suggesting antibiotic prophylaxis in patients receiving eculizumab even if they already underwent meningococcal vaccination. It’s not clear if this approach also will be effective in those with congenital complement deficiencies (except for complement component 6 deficiency).
It is hoped that surveillance studies will show that use of serogroup B vaccines will prevent invasive meningococcal infections in these high-risk populations for which they are recommended.
Sheldon L. Kaplan, MD, is a pediatrician at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. These comments are summarized from an editorial accompanying the article by Martinón-Torres et al. (Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2018-0554).
The Centers for Disease Control and Prevention reported an annual average of 792 cases of meningococcal disease and 98 deaths in the United States from 2006 to 2015 with serotype B isolates causing the highest numbers of cases. In a recent development, two vaccines against this strain have become available in the United States in the past 3 years for people aged 10-25 years. But officials don’t recommend their routine use, instead, guidelines suggest they be given to those at high risk only.
There’s a gap in knowledge because vaccine researchers didn’t include people with complement deficiency (either congenital or related to eculizumab), asplenia, or splenic dysfunction in studies that led to approval. Now, the new study offers reassuring findings regarding the latter two conditions, as bactericidal antibody responses were equal to those in healthy controls.
The findings regarding complement deficiency aren’t surprising, and suggest that vaccine strength in children with the condition only reached the levels in healthy children when an exogenous complement was added.
The study supports guidelines suggesting antibiotic prophylaxis in patients receiving eculizumab even if they already underwent meningococcal vaccination. It’s not clear if this approach also will be effective in those with congenital complement deficiencies (except for complement component 6 deficiency).
It is hoped that surveillance studies will show that use of serogroup B vaccines will prevent invasive meningococcal infections in these high-risk populations for which they are recommended.
Sheldon L. Kaplan, MD, is a pediatrician at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. These comments are summarized from an editorial accompanying the article by Martinón-Torres et al. (Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2018-0554).
A new study, the first of its kind, provided support for guidelines suggesting that the capsular meningococcal B vaccine be given to children with three rare conditions that boost infection risk.
For children with terminal chain complement deficiencies or who are undergoing treatment with eculizumab, “it is important that these patients are identified, receive education about sepsis management plans, and are prescribed prophylactic antibiotics according to local guidelines, along with vaccination, to provide every chance for them to be protected against this deadly disease,” the researchers wrote in Pediatrics.
While some countries suggest that the vaccine be given to all healthy infants, U.S. guidelines advise that the vaccine be given to preteenagers, teenagers, and adults who are considered at special risk. These include those with terminal chain complement deficiencies, who are believed to be up to 10,000 times more likely than healthy children to develop invasive meningococcal disease, and those who take eculizumab (Soliris). The risk groups recommended for vaccinations also include those with asplenia and splenic dysfunction, although their excess risk, if any, is unknown.
The new study of the capsular group meningococcal B vaccine, led by Federico Martinón-Torres, PhD, of the Hospital Clinico Universitario de Santiago de Compostela, Spain, adds to previous research that confirmed the effectiveness of vaccinating complement-deficient patients with capsular group A, C, W, and Y meningococcal vaccines.
For the open-label, phase 3b study, researchers in Italy, Spain, Poland, and Russia gave two doses of the vaccine 2 months apart to 239 children aged 2-17 years with an average age of 10 years. Nearly all were white, and 45% were female.
A total of 40 children had complement deficiency, 112 had asplenia or splenic dysfunction, and 87 children in the control group also received the vaccine.
Following vaccination, the percentages of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 to the four test strains were similar in the healthy children and those with asplenia/splenic dysfunction. “It is reasonable to expect that this vaccine will be as effective in children with asplenia or splenic deficiency as in children in the control category,” the researchers wrote.
However, these levels were lower in the complement-deficient children, particularly in those with terminal chain complement deficiency and those who took eculizumab.
The proportions of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 against the four test strains were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713) in complement-deficient children, compared with 98%, 99%, 83%, and 99%, respectively, in the healthy controls.
“Ongoing surveillance for vaccine failures is required to determine the significance of the trend to reduced immune response in children with terminal chain complement deficiencies or undergoing treatment with eculizumab,” the researchers wrote.
Eculizumab’s manufacturer has noted the risk of serious meningococcal infections and warned physicians to “immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection,” according to the website.
The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
SOURCE: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
A new study, the first of its kind, provided support for guidelines suggesting that the capsular meningococcal B vaccine be given to children with three rare conditions that boost infection risk.
For children with terminal chain complement deficiencies or who are undergoing treatment with eculizumab, “it is important that these patients are identified, receive education about sepsis management plans, and are prescribed prophylactic antibiotics according to local guidelines, along with vaccination, to provide every chance for them to be protected against this deadly disease,” the researchers wrote in Pediatrics.
While some countries suggest that the vaccine be given to all healthy infants, U.S. guidelines advise that the vaccine be given to preteenagers, teenagers, and adults who are considered at special risk. These include those with terminal chain complement deficiencies, who are believed to be up to 10,000 times more likely than healthy children to develop invasive meningococcal disease, and those who take eculizumab (Soliris). The risk groups recommended for vaccinations also include those with asplenia and splenic dysfunction, although their excess risk, if any, is unknown.
The new study of the capsular group meningococcal B vaccine, led by Federico Martinón-Torres, PhD, of the Hospital Clinico Universitario de Santiago de Compostela, Spain, adds to previous research that confirmed the effectiveness of vaccinating complement-deficient patients with capsular group A, C, W, and Y meningococcal vaccines.
For the open-label, phase 3b study, researchers in Italy, Spain, Poland, and Russia gave two doses of the vaccine 2 months apart to 239 children aged 2-17 years with an average age of 10 years. Nearly all were white, and 45% were female.
A total of 40 children had complement deficiency, 112 had asplenia or splenic dysfunction, and 87 children in the control group also received the vaccine.
Following vaccination, the percentages of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 to the four test strains were similar in the healthy children and those with asplenia/splenic dysfunction. “It is reasonable to expect that this vaccine will be as effective in children with asplenia or splenic deficiency as in children in the control category,” the researchers wrote.
However, these levels were lower in the complement-deficient children, particularly in those with terminal chain complement deficiency and those who took eculizumab.
The proportions of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 against the four test strains were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713) in complement-deficient children, compared with 98%, 99%, 83%, and 99%, respectively, in the healthy controls.
“Ongoing surveillance for vaccine failures is required to determine the significance of the trend to reduced immune response in children with terminal chain complement deficiencies or undergoing treatment with eculizumab,” the researchers wrote.
Eculizumab’s manufacturer has noted the risk of serious meningococcal infections and warned physicians to “immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection,” according to the website.
The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
SOURCE: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
FROM PEDIATRICS
Key clinical point: The meningococcal B vaccine retained its strength in kids with two rare immunosuppressive diseases, but may be weaker in a third group.
Major finding: The vaccine’s effectiveness was roughly the same in healthy controls and in those with asplenia and splenic dysfunction, but it dipped in those with complement deficiency.
Study details: An open-label, multicenter analysis of children aged 2-17 years who received two doses over 2 months.
Disclosures: The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
Source: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
Pertussis vaccination: We can do better
Resources
Liang JL, Tiwari T, Moro P, et al. Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2018;67:1-44.
Centers for Disease Control and Prevention. Pertussis (whooping cough). Available at: https://www.cdc.gov/pertussis/index.html. Accessed July 6, 2018.
Resources
Liang JL, Tiwari T, Moro P, et al. Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2018;67:1-44.
Centers for Disease Control and Prevention. Pertussis (whooping cough). Available at: https://www.cdc.gov/pertussis/index.html. Accessed July 6, 2018.
Resources
Liang JL, Tiwari T, Moro P, et al. Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2018;67:1-44.
Centers for Disease Control and Prevention. Pertussis (whooping cough). Available at: https://www.cdc.gov/pertussis/index.html. Accessed July 6, 2018.
DTPa-HBV-IPV/Hib in infancy maintains lasting immune memory against HBV in teens
MALMO, SWEDEN – Four doses of hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b vaccine given in infancy provides reassuringly long-lasting immune memory against hepatitis B among 14- to 15-year-olds, Tino F. Schwarz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
He presented the fourth and final study in a series evaluating the antibody persistence and immune memory against hepatitis B (HBV) in recipients of the complete four-dose series of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy. Because exposure to HBV can increase during adolescence, it was essential to determine whether antibody persistence is maintained, explained Dr. Schwarz of Juliusspital Hospital in Wurzburg, Germany.
“As expected, we saw a decrease in anti-HBs [hepatitis B surface antigen] antibody levels over the years, with persistent seroprotection in 85% of children at age 4-5 years, 72% at 7-8 years, 61% at 12-13 years, and now 54% of adolescents at 14-15 years. But we could demonstrate a very strong anamnestic response in the trial. This is good information. It clearly shows that, in patients who are exposed to hepatitis B, we can certainly guarantee that they are protected. It’s a good result for public health. The vaccine is a very robust vaccine which induces a very strong response over the years. It can be boosted, but from an immunologic point of view it is not required,” he said.
The multicenter study included 268 adolescents aged 14-15 years who had received the four-dose hexavalent vaccine series in infancy. Their antibody persistence against anti-HBs was measured, then measured once again 1 month after receiving a challenge dose of monovalent HBV vaccine.
Prechallenge, 105 of the teens were seronegative, 144 were seroprotected as defined by an anti-HBs concentration of at least 10 mIU/mL, and 19 had low seropositivity marked by an antibody level of 6 to less than 10 mIU/mL. Yet 1 month after the booster, which was intended to mimic the impact of real-world exposure to HBV, 83% of the initially seronegative subjects had an anti-HBs concentration of 10 mIU/mL or more, and 67% of them had a level of at least 100 mIU/mL.
“We saw a clear fantastic anamnestic response,” Dr. Schwarz declared.
Overall, 93% of study participants seroconverted, and 87% of them had anti-HBs titers of 100 mIU/mL, “which is the level we’d like to achieve in vaccinees,” he observed.
The booster monovalent HBV vaccine was well tolerated, with one-third of subjects complaining of mild local injection site pain and 30% noting fatigue. But in response to a question posed by session chair Ronald de Groot, MD, emeritus professor of pediatrics at Radboud University in Nijmegen, the Netherlands, Dr. Schwarz said these study results indicate there’s no need for routine boosting in healthy adolescents such as those in the trial. Immunocompromised individuals might be a different story, but they weren’t investigated.
But what about in physicians and surgeons, where protection against HBV infection is essential? Dr. de Groot asked.
“In Germany, we require a titer of 100 mIU/mL or more in medical staff, but we’re quite alone in Europe. Other countries do not require booster vaccination for medical staff. The data we’ve shown here is quite reassuring: If you get exposed, you in effect get a booster. It’s complicated to test surgeons in their offices; better to just rely on the anamnestic response that we’ve demonstrated,” Dr. Schwarz replied.
He reported serving as a consultant to GlaxoSmithKline, which funded the study, as well as to Pfizer and Sanofi Pasteur.
MALMO, SWEDEN – Four doses of hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b vaccine given in infancy provides reassuringly long-lasting immune memory against hepatitis B among 14- to 15-year-olds, Tino F. Schwarz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
He presented the fourth and final study in a series evaluating the antibody persistence and immune memory against hepatitis B (HBV) in recipients of the complete four-dose series of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy. Because exposure to HBV can increase during adolescence, it was essential to determine whether antibody persistence is maintained, explained Dr. Schwarz of Juliusspital Hospital in Wurzburg, Germany.
“As expected, we saw a decrease in anti-HBs [hepatitis B surface antigen] antibody levels over the years, with persistent seroprotection in 85% of children at age 4-5 years, 72% at 7-8 years, 61% at 12-13 years, and now 54% of adolescents at 14-15 years. But we could demonstrate a very strong anamnestic response in the trial. This is good information. It clearly shows that, in patients who are exposed to hepatitis B, we can certainly guarantee that they are protected. It’s a good result for public health. The vaccine is a very robust vaccine which induces a very strong response over the years. It can be boosted, but from an immunologic point of view it is not required,” he said.
The multicenter study included 268 adolescents aged 14-15 years who had received the four-dose hexavalent vaccine series in infancy. Their antibody persistence against anti-HBs was measured, then measured once again 1 month after receiving a challenge dose of monovalent HBV vaccine.
Prechallenge, 105 of the teens were seronegative, 144 were seroprotected as defined by an anti-HBs concentration of at least 10 mIU/mL, and 19 had low seropositivity marked by an antibody level of 6 to less than 10 mIU/mL. Yet 1 month after the booster, which was intended to mimic the impact of real-world exposure to HBV, 83% of the initially seronegative subjects had an anti-HBs concentration of 10 mIU/mL or more, and 67% of them had a level of at least 100 mIU/mL.
“We saw a clear fantastic anamnestic response,” Dr. Schwarz declared.
Overall, 93% of study participants seroconverted, and 87% of them had anti-HBs titers of 100 mIU/mL, “which is the level we’d like to achieve in vaccinees,” he observed.
The booster monovalent HBV vaccine was well tolerated, with one-third of subjects complaining of mild local injection site pain and 30% noting fatigue. But in response to a question posed by session chair Ronald de Groot, MD, emeritus professor of pediatrics at Radboud University in Nijmegen, the Netherlands, Dr. Schwarz said these study results indicate there’s no need for routine boosting in healthy adolescents such as those in the trial. Immunocompromised individuals might be a different story, but they weren’t investigated.
But what about in physicians and surgeons, where protection against HBV infection is essential? Dr. de Groot asked.
“In Germany, we require a titer of 100 mIU/mL or more in medical staff, but we’re quite alone in Europe. Other countries do not require booster vaccination for medical staff. The data we’ve shown here is quite reassuring: If you get exposed, you in effect get a booster. It’s complicated to test surgeons in their offices; better to just rely on the anamnestic response that we’ve demonstrated,” Dr. Schwarz replied.
He reported serving as a consultant to GlaxoSmithKline, which funded the study, as well as to Pfizer and Sanofi Pasteur.
MALMO, SWEDEN – Four doses of hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b vaccine given in infancy provides reassuringly long-lasting immune memory against hepatitis B among 14- to 15-year-olds, Tino F. Schwarz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
He presented the fourth and final study in a series evaluating the antibody persistence and immune memory against hepatitis B (HBV) in recipients of the complete four-dose series of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy. Because exposure to HBV can increase during adolescence, it was essential to determine whether antibody persistence is maintained, explained Dr. Schwarz of Juliusspital Hospital in Wurzburg, Germany.
“As expected, we saw a decrease in anti-HBs [hepatitis B surface antigen] antibody levels over the years, with persistent seroprotection in 85% of children at age 4-5 years, 72% at 7-8 years, 61% at 12-13 years, and now 54% of adolescents at 14-15 years. But we could demonstrate a very strong anamnestic response in the trial. This is good information. It clearly shows that, in patients who are exposed to hepatitis B, we can certainly guarantee that they are protected. It’s a good result for public health. The vaccine is a very robust vaccine which induces a very strong response over the years. It can be boosted, but from an immunologic point of view it is not required,” he said.
The multicenter study included 268 adolescents aged 14-15 years who had received the four-dose hexavalent vaccine series in infancy. Their antibody persistence against anti-HBs was measured, then measured once again 1 month after receiving a challenge dose of monovalent HBV vaccine.
Prechallenge, 105 of the teens were seronegative, 144 were seroprotected as defined by an anti-HBs concentration of at least 10 mIU/mL, and 19 had low seropositivity marked by an antibody level of 6 to less than 10 mIU/mL. Yet 1 month after the booster, which was intended to mimic the impact of real-world exposure to HBV, 83% of the initially seronegative subjects had an anti-HBs concentration of 10 mIU/mL or more, and 67% of them had a level of at least 100 mIU/mL.
“We saw a clear fantastic anamnestic response,” Dr. Schwarz declared.
Overall, 93% of study participants seroconverted, and 87% of them had anti-HBs titers of 100 mIU/mL, “which is the level we’d like to achieve in vaccinees,” he observed.
The booster monovalent HBV vaccine was well tolerated, with one-third of subjects complaining of mild local injection site pain and 30% noting fatigue. But in response to a question posed by session chair Ronald de Groot, MD, emeritus professor of pediatrics at Radboud University in Nijmegen, the Netherlands, Dr. Schwarz said these study results indicate there’s no need for routine boosting in healthy adolescents such as those in the trial. Immunocompromised individuals might be a different story, but they weren’t investigated.
But what about in physicians and surgeons, where protection against HBV infection is essential? Dr. de Groot asked.
“In Germany, we require a titer of 100 mIU/mL or more in medical staff, but we’re quite alone in Europe. Other countries do not require booster vaccination for medical staff. The data we’ve shown here is quite reassuring: If you get exposed, you in effect get a booster. It’s complicated to test surgeons in their offices; better to just rely on the anamnestic response that we’ve demonstrated,” Dr. Schwarz replied.
He reported serving as a consultant to GlaxoSmithKline, which funded the study, as well as to Pfizer and Sanofi Pasteur.
REPORTING FROM ESPID 2018
Key clinical point:
Major finding: Ninety-three percent of recipients of four doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy were seroprotected against HBV at age 14-15 years.
Study details: This was a prospective study of antibody persistence and immune memory in 268 teens aged 14-15 before and 1 month after receiving a booster challenge HBV monovalent vaccine.
Disclosures: The presenter reported serving as a consultant to GlaxoSmithKline, which funded the study, as well as to Pfizer and Sanofi Pasteur.
Reducing risk of febrile convulsion after first dose of MMRV
MALMO, SWEDEN – Giving a combined MMR vaccine and a varicella vaccine separately on the same day in children with personal or family history of febrile convulsions while utilizing the more convenient MMRV vaccine in those without such a history showed promise as a means of reducing the overall risk of febrile convulsions attributable to vaccination, Corinne Willame said at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a post hoc analysis of an enormous, German observational study that demonstrated an increased risk of hospitalization for febrile convulsions 5-12 days after receiving the first dose of the Priorix-Tetra MMRV vaccine, with no alternative plausible cause of the convulsions (Vaccine. 2014 Feb 3;32[6]:645-50).
The original study was conducted in more than 180,000 children under the age of 5 years, 90% of whom were 11- 23 months. The increased risk associated with MMRV, compared with MMR alone or MMR plus V separately on the same day, was similar in magnitude to what had previously been reported for the ProQuad MMRV vaccine, suggesting a class effect for the quadrivalent vaccines.
Because genetic predisposition is known to be associated with increased risk of febrile convulsions, Ms. Willame of GlaxoSmithKline in Wavre, Belgium, and her coinvestigators conducted an exploratory analysis investigating whether the presence of a personal or first-degree family history of febrile convulsions impacted the risk of developing febrile convulsions following a first dose of MMRV, compared with MMR alone or MMR and V administered separately on the same day. They found that indeed it did, according to Ms. Willame.
They analyzed the data in multiple ways. The first scenario compared the risk of febrile convulsions in 74,631 children 5-12 days after receiving the MMRV vaccine with a roughly equal number of children who received the MMR vaccine. Study subjects were matched for age, sex, month of vaccination, and insurance provider. The febrile convulsion incidence rate was 6.03 cases per 10,000 children in MMRV recipients and 2.55 per 10,000 in those who got MMR. Then they reanalyzed the data after subtracting all children with a baseline personal history of febrile convulsions from the pool of MMRV recipients: The febrile convulsion rate in the MMRV group dropped to 5.27 cases per 10,000.
Next, they did the same analysis in more than 64,000 matched children who got either MMRV or MMR plus V separately. For the whole cohort of MMRV recipients, the febrile convulsion rate was 6.53 cases per 10,000 vaccine recipients, dropping to 5.95 per 10,000 if children with a personal history of febrile convulsions were removed. The relative risk of febrile convulsions was 150% greater in the overall MMRV group than with MMR plus V, but only 58% greater when the children with a personal history of febrile seizures were excluded from the MMRV population.
Unfortunately, the parent study didn’t record whether a history of febrile convulsions was present in first-degree family members. The investigators therefore turned to the published literature on the subject and constructed conditional probability analyses based upon a 20%-40% likelihood of a positive family history in children with a personal history, and a 5% likelihood in those children without such a history. In this scenario, when children with a personal or hypothetical family history of febrile convulsions were subtracted from the MMRV group, the result was a febrile convulsion incidence rate of 3.27-4.41 cases per 10,000 MMRV recipients in the comparison with MMR and 3.63-4.95 per 10,000 in the comparison with MMR plus V.
Ms. Willame emphasized that her analysis must be considered hypothesis generating because it’s post hoc and relies upon published estimates of the prevalence of a positive family history of febrile convulsions. The febrile convulsion risk differences she found with the different vaccination strategies should be confirmed in studies that collect family history data of febrile seizures at an individual level.
Her study was funded by her employer, GlaxoSmithKline.
MALMO, SWEDEN – Giving a combined MMR vaccine and a varicella vaccine separately on the same day in children with personal or family history of febrile convulsions while utilizing the more convenient MMRV vaccine in those without such a history showed promise as a means of reducing the overall risk of febrile convulsions attributable to vaccination, Corinne Willame said at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a post hoc analysis of an enormous, German observational study that demonstrated an increased risk of hospitalization for febrile convulsions 5-12 days after receiving the first dose of the Priorix-Tetra MMRV vaccine, with no alternative plausible cause of the convulsions (Vaccine. 2014 Feb 3;32[6]:645-50).
The original study was conducted in more than 180,000 children under the age of 5 years, 90% of whom were 11- 23 months. The increased risk associated with MMRV, compared with MMR alone or MMR plus V separately on the same day, was similar in magnitude to what had previously been reported for the ProQuad MMRV vaccine, suggesting a class effect for the quadrivalent vaccines.
Because genetic predisposition is known to be associated with increased risk of febrile convulsions, Ms. Willame of GlaxoSmithKline in Wavre, Belgium, and her coinvestigators conducted an exploratory analysis investigating whether the presence of a personal or first-degree family history of febrile convulsions impacted the risk of developing febrile convulsions following a first dose of MMRV, compared with MMR alone or MMR and V administered separately on the same day. They found that indeed it did, according to Ms. Willame.
They analyzed the data in multiple ways. The first scenario compared the risk of febrile convulsions in 74,631 children 5-12 days after receiving the MMRV vaccine with a roughly equal number of children who received the MMR vaccine. Study subjects were matched for age, sex, month of vaccination, and insurance provider. The febrile convulsion incidence rate was 6.03 cases per 10,000 children in MMRV recipients and 2.55 per 10,000 in those who got MMR. Then they reanalyzed the data after subtracting all children with a baseline personal history of febrile convulsions from the pool of MMRV recipients: The febrile convulsion rate in the MMRV group dropped to 5.27 cases per 10,000.
Next, they did the same analysis in more than 64,000 matched children who got either MMRV or MMR plus V separately. For the whole cohort of MMRV recipients, the febrile convulsion rate was 6.53 cases per 10,000 vaccine recipients, dropping to 5.95 per 10,000 if children with a personal history of febrile convulsions were removed. The relative risk of febrile convulsions was 150% greater in the overall MMRV group than with MMR plus V, but only 58% greater when the children with a personal history of febrile seizures were excluded from the MMRV population.
Unfortunately, the parent study didn’t record whether a history of febrile convulsions was present in first-degree family members. The investigators therefore turned to the published literature on the subject and constructed conditional probability analyses based upon a 20%-40% likelihood of a positive family history in children with a personal history, and a 5% likelihood in those children without such a history. In this scenario, when children with a personal or hypothetical family history of febrile convulsions were subtracted from the MMRV group, the result was a febrile convulsion incidence rate of 3.27-4.41 cases per 10,000 MMRV recipients in the comparison with MMR and 3.63-4.95 per 10,000 in the comparison with MMR plus V.
Ms. Willame emphasized that her analysis must be considered hypothesis generating because it’s post hoc and relies upon published estimates of the prevalence of a positive family history of febrile convulsions. The febrile convulsion risk differences she found with the different vaccination strategies should be confirmed in studies that collect family history data of febrile seizures at an individual level.
Her study was funded by her employer, GlaxoSmithKline.
MALMO, SWEDEN – Giving a combined MMR vaccine and a varicella vaccine separately on the same day in children with personal or family history of febrile convulsions while utilizing the more convenient MMRV vaccine in those without such a history showed promise as a means of reducing the overall risk of febrile convulsions attributable to vaccination, Corinne Willame said at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a post hoc analysis of an enormous, German observational study that demonstrated an increased risk of hospitalization for febrile convulsions 5-12 days after receiving the first dose of the Priorix-Tetra MMRV vaccine, with no alternative plausible cause of the convulsions (Vaccine. 2014 Feb 3;32[6]:645-50).
The original study was conducted in more than 180,000 children under the age of 5 years, 90% of whom were 11- 23 months. The increased risk associated with MMRV, compared with MMR alone or MMR plus V separately on the same day, was similar in magnitude to what had previously been reported for the ProQuad MMRV vaccine, suggesting a class effect for the quadrivalent vaccines.
Because genetic predisposition is known to be associated with increased risk of febrile convulsions, Ms. Willame of GlaxoSmithKline in Wavre, Belgium, and her coinvestigators conducted an exploratory analysis investigating whether the presence of a personal or first-degree family history of febrile convulsions impacted the risk of developing febrile convulsions following a first dose of MMRV, compared with MMR alone or MMR and V administered separately on the same day. They found that indeed it did, according to Ms. Willame.
They analyzed the data in multiple ways. The first scenario compared the risk of febrile convulsions in 74,631 children 5-12 days after receiving the MMRV vaccine with a roughly equal number of children who received the MMR vaccine. Study subjects were matched for age, sex, month of vaccination, and insurance provider. The febrile convulsion incidence rate was 6.03 cases per 10,000 children in MMRV recipients and 2.55 per 10,000 in those who got MMR. Then they reanalyzed the data after subtracting all children with a baseline personal history of febrile convulsions from the pool of MMRV recipients: The febrile convulsion rate in the MMRV group dropped to 5.27 cases per 10,000.
Next, they did the same analysis in more than 64,000 matched children who got either MMRV or MMR plus V separately. For the whole cohort of MMRV recipients, the febrile convulsion rate was 6.53 cases per 10,000 vaccine recipients, dropping to 5.95 per 10,000 if children with a personal history of febrile convulsions were removed. The relative risk of febrile convulsions was 150% greater in the overall MMRV group than with MMR plus V, but only 58% greater when the children with a personal history of febrile seizures were excluded from the MMRV population.
Unfortunately, the parent study didn’t record whether a history of febrile convulsions was present in first-degree family members. The investigators therefore turned to the published literature on the subject and constructed conditional probability analyses based upon a 20%-40% likelihood of a positive family history in children with a personal history, and a 5% likelihood in those children without such a history. In this scenario, when children with a personal or hypothetical family history of febrile convulsions were subtracted from the MMRV group, the result was a febrile convulsion incidence rate of 3.27-4.41 cases per 10,000 MMRV recipients in the comparison with MMR and 3.63-4.95 per 10,000 in the comparison with MMR plus V.
Ms. Willame emphasized that her analysis must be considered hypothesis generating because it’s post hoc and relies upon published estimates of the prevalence of a positive family history of febrile convulsions. The febrile convulsion risk differences she found with the different vaccination strategies should be confirmed in studies that collect family history data of febrile seizures at an individual level.
Her study was funded by her employer, GlaxoSmithKline.
REPORTING FROM ESPID 2018
Key clinical point: The increased risk of febrile seizures associated with MMRV vaccine can probably be reduced by administering the MMR and varicella vaccines separately on the same day in children with a personal or family history of febrile seizures.
Major finding: The incidence rate of febrile seizures 5-12 days post MMRV vaccination was reduced from 6.53 to 3.63-4.95 cases per 10,000 vaccine recipients.
Study details: This was a post hoc analysis of an observational study of more than 180,000 German children.
Disclosures: The study was sponsored by GlaxoSmithKline and presented by a company employee.
European experts envy U.S. pediatric flu vaccination approach
MALMO, SWEDEN – When American physicians think about health care in Europe, what typically comes to mind are government-funded, single-payer national health services with cradle-to-grave coverage of essential services, a strong public health bent, and perhaps some queuing.
“It’s complicated. There is no common strategic approach,” Hanna Nohynek, MD, PhD, observed at a session on childhood immunization against flu held during the annual meeting of the European Society for Paediatric Infectious Diseases.
“In real life, influenza coverage among [European] children is either not known or quite low. Impact assessments in children are done in only a few countries,” said Dr. Nohynek, chief physician in the infectious diseases control and vaccinations unit of the National Institute for Health and Welfare in Helsinki, Finland.
“The only country doing as well coverage-wise as the U.S. is the U.K., with rates of 50%-65%. In Finland it’s less than 40%,” according to Dr. Nohynek.
“We have 28 countries today in the E.U. [European Union], and we have 28 different recommendations in Europe. So where do we go from here? It’s really not easy,” observed session cochair Alberticus Osterhaus, DVM, PhD, emeritus professor of virology at Erasmus University in Rotterdam, the Netherlands.
For all the oft-cited shortcomings of health care in the United States, That’s why Jon S. Abramson, MD, a former chair of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP), was invited to explain how the U.S. strategy was accomplished.
The U.S. approach
The current U.S. policy, implemented in 2010, is to recommend an annual flu shot for all persons older than 6 months of age.
Influenza vaccination has been part of the U.S. public health program since 1960. Children aged 6-23 months, as well as their household contacts and women who will be pregnant during flu season, were added in 2004. In 2006, the flu vaccine recommendation was expanded to include children aged 6-59 months as a result of persuasive data showing that the rate of flu-associated hospitalizations and deaths in children up to 4 years old was second only to the rate in the elderly population.
The rationale for expanding the recommendation to include all school-age children and adolescents stemmed from evidence that the highest average flu-related illness rate in the United States was in that age group, which confirmed that schools are a powerful vector for the spread of influenza. Vaccinating this age-group also was seen as having an indirect benefit for their household contacts.
The current policy of recommending vaccination of everyone over age 6 months was adopted because it checked off a lot of boxes: “It’s a single recommendation, easy to apply; it eliminates the need to look for indications and risk factors; it increases vaccination coverage rates; annual vaccination is safe and effective; and flu-related morbidity and mortality occur in all age groups,” Dr. Abramson continued.
The rate of influenza vaccine coverage in pregnant women has improved over time from less than 15% to about 50%. To place that in perspective, however, the rate in Argentina is 95%, the pediatrician noted.
“We’re doing better in children than we are in adults in terms of seasonal coverage rates,” he added. “In 2015, it was 59%, versus 42% in adults.”
Dr. Abramson said there remains some skepticism in the United States regarding the effectiveness of flu vaccines in preventing flu-related illness. That’s because of the difficulty in communicating that vaccine effectiveness varies from year to year, sometimes substantially, depending upon two factors: the transmission characteristics of the circulating strains and how well the vaccines match up against those strains.
“I think we have to learn to live with that. I don’t think we’ll see a universal flu vaccine that we can give once every 10 years,” he said.
“The bottom line is, even if a vaccine is only 50% efficacious overall, we’re still impacting huge numbers,” the pediatrician added.
Dr. Abramson cited a CDC estimate that, for the 2012-2013 season, where the vaccine was 49% efficacious, the result of vaccination was 6.6 million fewer cases of influenza-associated illnesses nationally, 3.2 million fewer flu-associated medical visits, and 79,000 hospitalizations avoided.
“I think we have a fairly good program in the United States. We’re doing well in children. We certainly could be doing better. Not having FluMist for the past 2 seasons probably hurt us some,” according to Dr. Abramson.
The FluMist experience
The FluMist episode is viewed by many European pediatric infectious disease experts as a debacle. Europeans eager to develop a pan-European strategy for seasonal immunization against influenza in children and adolescents viewed the U.S. FluMist episode with dismay. For the 2016-2017 and 2017-2018 flu seasons, the ACIP recommended against FluMist, a previously approved intranasally administered quadrivalent live attenuated virus vaccine, on the basis of a single study showing subpar effectiveness against influenza A H1NI. Then at its October 2017 meeting, ACIP reversed itself and reinstated FluMist for the 2018-2019 season after viewing data from Finland and several other countries demonstrating that, in countries where it hadn’t been taken off the market, the vaccine had performed as well as injectable inactivated influenza vaccines in the 2016-2017 flu season.
“I think from the European side, it’s been a bit of a sorry spectacle,” commented Dr. Osterhaus, referring to the ACIP’s waffling. After all, authorities in Canada and European countries where FluMist was available had looked at the same data that caused ACIP to derecommend the vaccine but hadn’t found it convincing.
“We’re very happy to see ACIP has reinstated the vaccine,” Dr. Nohynek said.
Dr. Abramson declined to defend the ACIP decision to drop FluMist.
“From my standpoint, knowing that influenza B kills more children than A does, if I had been on the ACIP committee – and I’m not anymore – that would not have been my vote,” he said. “Whatever you want to say about the live attenuated influenza vaccine, about how good it is against some A strains or not, it’s better than other vaccines against influenza B. And the death rate is higher from B than A in children, although that is not true in adults.”
Plus, FluMist was an important option for people avoiding immunization because they dislike shots.
“The vast majority of deaths due to flu in children in 2010-2016 have been in kids who didn’t get vaccinated,” he noted.
Dr. Nohynek said the Finnish real-world experience recorded in comprehensive national registries for the 2017-2018 flu season – a bad year for vaccine/virus mismatch in Europe – confirmed Dr. Abramson’s comments about the superiority of quadrivalent live attenuated influenza vaccine against influenza B. Among 54,611 Finnish children aged 24-35 months, the laboratory-confirmed vaccine effectiveness of trivalent inactivated virus vaccine, with 9% coverage, was 4.5% for influenza A and 12.2% for influenza B. In contrast, the vaccine effectiveness for the intranasal quadrivalent live attenuated influenza vaccine was 32% for A and a whopping 80% for B.
“It’s quite amazing, at least to me, to see figures like this in real world data,” she commented.
Session cochair Adam Finn, MD, PhD, said he has found it instructive to take a closer look at the U.K. data for the past several flu seasons.
“We’ve seen greater control of the epidemic in Scotland and Northern Ireland, where coverage in primary school kids was higher, in the 60%-70% area, and lower in England and Wales, where it was more like 50%. So we’re beginning to think that’s the kind of level of annual coverage in children we might need to suppress an epidemic. I think that’s a really important message that people should understand: We’re not looking for 95% coverage,” observed Dr. Finn, aprofessor of pediatrics at the University of Bristol (England).
Vaccine effectiveness will improve
Dr. Osterhaus predicted better times are coming in terms of vaccine effectiveness. Vaccine production times will become shorter as recombinant technologies replace the traditional lengthy chicken egg-based vaccine production; as a result, there will be less drift-associated mismatch. Improved surveillance, including the ability to follow strain mobility patterns and population-based antibody landscapes, are another important advance.
“We’ve always been looking at one side of the coin: the virus. Once or twice a year eminent gray people sitting together in Geneva at WHO decide which strains should be selected for the next vaccine. But if you know what antibodies are present in the population, this can be quite important information as well,” he said.
Dr. Nohynek reported receiving research funding from GlaxoSmithKline and Pfizer. The other speakers reported having no relevant financial conflicts of interest.
MALMO, SWEDEN – When American physicians think about health care in Europe, what typically comes to mind are government-funded, single-payer national health services with cradle-to-grave coverage of essential services, a strong public health bent, and perhaps some queuing.
“It’s complicated. There is no common strategic approach,” Hanna Nohynek, MD, PhD, observed at a session on childhood immunization against flu held during the annual meeting of the European Society for Paediatric Infectious Diseases.
“In real life, influenza coverage among [European] children is either not known or quite low. Impact assessments in children are done in only a few countries,” said Dr. Nohynek, chief physician in the infectious diseases control and vaccinations unit of the National Institute for Health and Welfare in Helsinki, Finland.
“The only country doing as well coverage-wise as the U.S. is the U.K., with rates of 50%-65%. In Finland it’s less than 40%,” according to Dr. Nohynek.
“We have 28 countries today in the E.U. [European Union], and we have 28 different recommendations in Europe. So where do we go from here? It’s really not easy,” observed session cochair Alberticus Osterhaus, DVM, PhD, emeritus professor of virology at Erasmus University in Rotterdam, the Netherlands.
For all the oft-cited shortcomings of health care in the United States, That’s why Jon S. Abramson, MD, a former chair of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP), was invited to explain how the U.S. strategy was accomplished.
The U.S. approach
The current U.S. policy, implemented in 2010, is to recommend an annual flu shot for all persons older than 6 months of age.
Influenza vaccination has been part of the U.S. public health program since 1960. Children aged 6-23 months, as well as their household contacts and women who will be pregnant during flu season, were added in 2004. In 2006, the flu vaccine recommendation was expanded to include children aged 6-59 months as a result of persuasive data showing that the rate of flu-associated hospitalizations and deaths in children up to 4 years old was second only to the rate in the elderly population.
The rationale for expanding the recommendation to include all school-age children and adolescents stemmed from evidence that the highest average flu-related illness rate in the United States was in that age group, which confirmed that schools are a powerful vector for the spread of influenza. Vaccinating this age-group also was seen as having an indirect benefit for their household contacts.
The current policy of recommending vaccination of everyone over age 6 months was adopted because it checked off a lot of boxes: “It’s a single recommendation, easy to apply; it eliminates the need to look for indications and risk factors; it increases vaccination coverage rates; annual vaccination is safe and effective; and flu-related morbidity and mortality occur in all age groups,” Dr. Abramson continued.
The rate of influenza vaccine coverage in pregnant women has improved over time from less than 15% to about 50%. To place that in perspective, however, the rate in Argentina is 95%, the pediatrician noted.
“We’re doing better in children than we are in adults in terms of seasonal coverage rates,” he added. “In 2015, it was 59%, versus 42% in adults.”
Dr. Abramson said there remains some skepticism in the United States regarding the effectiveness of flu vaccines in preventing flu-related illness. That’s because of the difficulty in communicating that vaccine effectiveness varies from year to year, sometimes substantially, depending upon two factors: the transmission characteristics of the circulating strains and how well the vaccines match up against those strains.
“I think we have to learn to live with that. I don’t think we’ll see a universal flu vaccine that we can give once every 10 years,” he said.
“The bottom line is, even if a vaccine is only 50% efficacious overall, we’re still impacting huge numbers,” the pediatrician added.
Dr. Abramson cited a CDC estimate that, for the 2012-2013 season, where the vaccine was 49% efficacious, the result of vaccination was 6.6 million fewer cases of influenza-associated illnesses nationally, 3.2 million fewer flu-associated medical visits, and 79,000 hospitalizations avoided.
“I think we have a fairly good program in the United States. We’re doing well in children. We certainly could be doing better. Not having FluMist for the past 2 seasons probably hurt us some,” according to Dr. Abramson.
The FluMist experience
The FluMist episode is viewed by many European pediatric infectious disease experts as a debacle. Europeans eager to develop a pan-European strategy for seasonal immunization against influenza in children and adolescents viewed the U.S. FluMist episode with dismay. For the 2016-2017 and 2017-2018 flu seasons, the ACIP recommended against FluMist, a previously approved intranasally administered quadrivalent live attenuated virus vaccine, on the basis of a single study showing subpar effectiveness against influenza A H1NI. Then at its October 2017 meeting, ACIP reversed itself and reinstated FluMist for the 2018-2019 season after viewing data from Finland and several other countries demonstrating that, in countries where it hadn’t been taken off the market, the vaccine had performed as well as injectable inactivated influenza vaccines in the 2016-2017 flu season.
“I think from the European side, it’s been a bit of a sorry spectacle,” commented Dr. Osterhaus, referring to the ACIP’s waffling. After all, authorities in Canada and European countries where FluMist was available had looked at the same data that caused ACIP to derecommend the vaccine but hadn’t found it convincing.
“We’re very happy to see ACIP has reinstated the vaccine,” Dr. Nohynek said.
Dr. Abramson declined to defend the ACIP decision to drop FluMist.
“From my standpoint, knowing that influenza B kills more children than A does, if I had been on the ACIP committee – and I’m not anymore – that would not have been my vote,” he said. “Whatever you want to say about the live attenuated influenza vaccine, about how good it is against some A strains or not, it’s better than other vaccines against influenza B. And the death rate is higher from B than A in children, although that is not true in adults.”
Plus, FluMist was an important option for people avoiding immunization because they dislike shots.
“The vast majority of deaths due to flu in children in 2010-2016 have been in kids who didn’t get vaccinated,” he noted.
Dr. Nohynek said the Finnish real-world experience recorded in comprehensive national registries for the 2017-2018 flu season – a bad year for vaccine/virus mismatch in Europe – confirmed Dr. Abramson’s comments about the superiority of quadrivalent live attenuated influenza vaccine against influenza B. Among 54,611 Finnish children aged 24-35 months, the laboratory-confirmed vaccine effectiveness of trivalent inactivated virus vaccine, with 9% coverage, was 4.5% for influenza A and 12.2% for influenza B. In contrast, the vaccine effectiveness for the intranasal quadrivalent live attenuated influenza vaccine was 32% for A and a whopping 80% for B.
“It’s quite amazing, at least to me, to see figures like this in real world data,” she commented.
Session cochair Adam Finn, MD, PhD, said he has found it instructive to take a closer look at the U.K. data for the past several flu seasons.
“We’ve seen greater control of the epidemic in Scotland and Northern Ireland, where coverage in primary school kids was higher, in the 60%-70% area, and lower in England and Wales, where it was more like 50%. So we’re beginning to think that’s the kind of level of annual coverage in children we might need to suppress an epidemic. I think that’s a really important message that people should understand: We’re not looking for 95% coverage,” observed Dr. Finn, aprofessor of pediatrics at the University of Bristol (England).
Vaccine effectiveness will improve
Dr. Osterhaus predicted better times are coming in terms of vaccine effectiveness. Vaccine production times will become shorter as recombinant technologies replace the traditional lengthy chicken egg-based vaccine production; as a result, there will be less drift-associated mismatch. Improved surveillance, including the ability to follow strain mobility patterns and population-based antibody landscapes, are another important advance.
“We’ve always been looking at one side of the coin: the virus. Once or twice a year eminent gray people sitting together in Geneva at WHO decide which strains should be selected for the next vaccine. But if you know what antibodies are present in the population, this can be quite important information as well,” he said.
Dr. Nohynek reported receiving research funding from GlaxoSmithKline and Pfizer. The other speakers reported having no relevant financial conflicts of interest.
MALMO, SWEDEN – When American physicians think about health care in Europe, what typically comes to mind are government-funded, single-payer national health services with cradle-to-grave coverage of essential services, a strong public health bent, and perhaps some queuing.
“It’s complicated. There is no common strategic approach,” Hanna Nohynek, MD, PhD, observed at a session on childhood immunization against flu held during the annual meeting of the European Society for Paediatric Infectious Diseases.
“In real life, influenza coverage among [European] children is either not known or quite low. Impact assessments in children are done in only a few countries,” said Dr. Nohynek, chief physician in the infectious diseases control and vaccinations unit of the National Institute for Health and Welfare in Helsinki, Finland.
“The only country doing as well coverage-wise as the U.S. is the U.K., with rates of 50%-65%. In Finland it’s less than 40%,” according to Dr. Nohynek.
“We have 28 countries today in the E.U. [European Union], and we have 28 different recommendations in Europe. So where do we go from here? It’s really not easy,” observed session cochair Alberticus Osterhaus, DVM, PhD, emeritus professor of virology at Erasmus University in Rotterdam, the Netherlands.
For all the oft-cited shortcomings of health care in the United States, That’s why Jon S. Abramson, MD, a former chair of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP), was invited to explain how the U.S. strategy was accomplished.
The U.S. approach
The current U.S. policy, implemented in 2010, is to recommend an annual flu shot for all persons older than 6 months of age.
Influenza vaccination has been part of the U.S. public health program since 1960. Children aged 6-23 months, as well as their household contacts and women who will be pregnant during flu season, were added in 2004. In 2006, the flu vaccine recommendation was expanded to include children aged 6-59 months as a result of persuasive data showing that the rate of flu-associated hospitalizations and deaths in children up to 4 years old was second only to the rate in the elderly population.
The rationale for expanding the recommendation to include all school-age children and adolescents stemmed from evidence that the highest average flu-related illness rate in the United States was in that age group, which confirmed that schools are a powerful vector for the spread of influenza. Vaccinating this age-group also was seen as having an indirect benefit for their household contacts.
The current policy of recommending vaccination of everyone over age 6 months was adopted because it checked off a lot of boxes: “It’s a single recommendation, easy to apply; it eliminates the need to look for indications and risk factors; it increases vaccination coverage rates; annual vaccination is safe and effective; and flu-related morbidity and mortality occur in all age groups,” Dr. Abramson continued.
The rate of influenza vaccine coverage in pregnant women has improved over time from less than 15% to about 50%. To place that in perspective, however, the rate in Argentina is 95%, the pediatrician noted.
“We’re doing better in children than we are in adults in terms of seasonal coverage rates,” he added. “In 2015, it was 59%, versus 42% in adults.”
Dr. Abramson said there remains some skepticism in the United States regarding the effectiveness of flu vaccines in preventing flu-related illness. That’s because of the difficulty in communicating that vaccine effectiveness varies from year to year, sometimes substantially, depending upon two factors: the transmission characteristics of the circulating strains and how well the vaccines match up against those strains.
“I think we have to learn to live with that. I don’t think we’ll see a universal flu vaccine that we can give once every 10 years,” he said.
“The bottom line is, even if a vaccine is only 50% efficacious overall, we’re still impacting huge numbers,” the pediatrician added.
Dr. Abramson cited a CDC estimate that, for the 2012-2013 season, where the vaccine was 49% efficacious, the result of vaccination was 6.6 million fewer cases of influenza-associated illnesses nationally, 3.2 million fewer flu-associated medical visits, and 79,000 hospitalizations avoided.
“I think we have a fairly good program in the United States. We’re doing well in children. We certainly could be doing better. Not having FluMist for the past 2 seasons probably hurt us some,” according to Dr. Abramson.
The FluMist experience
The FluMist episode is viewed by many European pediatric infectious disease experts as a debacle. Europeans eager to develop a pan-European strategy for seasonal immunization against influenza in children and adolescents viewed the U.S. FluMist episode with dismay. For the 2016-2017 and 2017-2018 flu seasons, the ACIP recommended against FluMist, a previously approved intranasally administered quadrivalent live attenuated virus vaccine, on the basis of a single study showing subpar effectiveness against influenza A H1NI. Then at its October 2017 meeting, ACIP reversed itself and reinstated FluMist for the 2018-2019 season after viewing data from Finland and several other countries demonstrating that, in countries where it hadn’t been taken off the market, the vaccine had performed as well as injectable inactivated influenza vaccines in the 2016-2017 flu season.
“I think from the European side, it’s been a bit of a sorry spectacle,” commented Dr. Osterhaus, referring to the ACIP’s waffling. After all, authorities in Canada and European countries where FluMist was available had looked at the same data that caused ACIP to derecommend the vaccine but hadn’t found it convincing.
“We’re very happy to see ACIP has reinstated the vaccine,” Dr. Nohynek said.
Dr. Abramson declined to defend the ACIP decision to drop FluMist.
“From my standpoint, knowing that influenza B kills more children than A does, if I had been on the ACIP committee – and I’m not anymore – that would not have been my vote,” he said. “Whatever you want to say about the live attenuated influenza vaccine, about how good it is against some A strains or not, it’s better than other vaccines against influenza B. And the death rate is higher from B than A in children, although that is not true in adults.”
Plus, FluMist was an important option for people avoiding immunization because they dislike shots.
“The vast majority of deaths due to flu in children in 2010-2016 have been in kids who didn’t get vaccinated,” he noted.
Dr. Nohynek said the Finnish real-world experience recorded in comprehensive national registries for the 2017-2018 flu season – a bad year for vaccine/virus mismatch in Europe – confirmed Dr. Abramson’s comments about the superiority of quadrivalent live attenuated influenza vaccine against influenza B. Among 54,611 Finnish children aged 24-35 months, the laboratory-confirmed vaccine effectiveness of trivalent inactivated virus vaccine, with 9% coverage, was 4.5% for influenza A and 12.2% for influenza B. In contrast, the vaccine effectiveness for the intranasal quadrivalent live attenuated influenza vaccine was 32% for A and a whopping 80% for B.
“It’s quite amazing, at least to me, to see figures like this in real world data,” she commented.
Session cochair Adam Finn, MD, PhD, said he has found it instructive to take a closer look at the U.K. data for the past several flu seasons.
“We’ve seen greater control of the epidemic in Scotland and Northern Ireland, where coverage in primary school kids was higher, in the 60%-70% area, and lower in England and Wales, where it was more like 50%. So we’re beginning to think that’s the kind of level of annual coverage in children we might need to suppress an epidemic. I think that’s a really important message that people should understand: We’re not looking for 95% coverage,” observed Dr. Finn, aprofessor of pediatrics at the University of Bristol (England).
Vaccine effectiveness will improve
Dr. Osterhaus predicted better times are coming in terms of vaccine effectiveness. Vaccine production times will become shorter as recombinant technologies replace the traditional lengthy chicken egg-based vaccine production; as a result, there will be less drift-associated mismatch. Improved surveillance, including the ability to follow strain mobility patterns and population-based antibody landscapes, are another important advance.
“We’ve always been looking at one side of the coin: the virus. Once or twice a year eminent gray people sitting together in Geneva at WHO decide which strains should be selected for the next vaccine. But if you know what antibodies are present in the population, this can be quite important information as well,” he said.
Dr. Nohynek reported receiving research funding from GlaxoSmithKline and Pfizer. The other speakers reported having no relevant financial conflicts of interest.
EXPERT ANALYSIS FROM ESPID 2018
Bivalent HPV vaccine brings no significant increase in 38 potential adverse outcomes
MALMO, SWEDEN – in a nationwide, retrospective cohort study.
“Anxiety and fear regarding adverse events are still very much alive and are associated with lack of acceptance of HPV vaccination,” Jozica Skufca, DVM, MIPH, observed while presenting the study findings at the annual meeting of the European Society for Paediatric Infectious Diseases.
“These results contribute valid evidence to combat public skepticism, anxiety, fears of adverse events, and possible opposition to HPV vaccination and consequently can contribute to increase HPV vaccination coverage in Finland as well as elsewhere,” added Dr. Skufca, who conducted this research while at the Finnish National Institute for Health and Welfare but is now an epidemiologist at P95, a privately held epidemiology and pharmacovigilance consulting firm in Heverlee, Belgium.
Finland introduced the bivalent HPV vaccine known as Cervarix, which is directed against HPV types 16 and 18, into the nation’s vaccination program in November 2013. The target population were girls aged 11-13 years, with catch-up vaccination at ages 14-15 years until 2015.
Dr. Skufca utilized Finland’s comprehensive system of national health care registries to conduct a study of all 240,605 Finnish girls aged 11-15 years who were eligible for the bivalent HPV vaccine from November 2013 to December 2016. Only 56% of the target population, or 134,615 girls, were actually vaccinated. All were subsequently followed for more than a year.
The investigators compared vaccinated and unvaccinated groups in terms of the subsequent rates of 38 selected outcomes of national and international interest. These included celiac disease, chronic fatigue syndrome, type 1 diabetes, Guillain-Barré syndrome, postural orthostatic tachycardia syndrome, ulcerative colitis, venous thromboembolism, psoriasis, vitiligo, scleroderma, autism, poyarteritis nodosa, asthma, Raynaud’s disease, systemic lupus erythematosus, Bell’s palsy, polycystic ovaries, juvenile arthritis, Hashimoto’s disease, and many others.
HPV vaccination rates varied considerably between hospital districts, so the results were adjusted for that potential confounder. Risks also were adjusted for the number of hospital visits 1-2 years prior to vaccination, because healthier girls – those with fewer hospital visits – turned out to be more likely to get vaccinated.
The study’s main result was that HPV vaccination wasn’t associated with a significantly higher risk of any of the 38 adverse outcomes. To the contrary, vaccination was associated with significantly reduced risk of several of them: The risk of chronic fatigue syndrome was reduced by 25%, epilepsy and recurrent seizures were reduced by 28%, the risk of Henoch-Schönlein purpura was an adjusted 52% lower in children vaccinated against HPV, and the risk of malaise and fatigue was reduced by 24%.
Dr. Skufca drew particular attention to the 400% increased risk of Guillain-Barré syndrome in vaccinated children. While this may look impressive, it wasn’t a statistically significant difference. Guillain-Barré was a rare event, with only six cases occurring during 186,934 person-years of follow-up of vaccinated individuals and a single case in unvaccinated girls. Two cases occurred within 180 days after vaccination, for an adjusted 200% increase in risk, which was nonsignificant.
Another two cases occurred more than 365 days postvaccination, for a whopping 3100% increased risk, compared with unvaccinated children; however, this too was a nonstatistically significant finding, with extraordinarily broad confidence intervals of 1.59-652.4. And there is no plausible mechanism to account for a true association between HPV vaccination and a complication, such as this, occurring more than 1 year later. It appeared to be a matter of chance, she added.
However, session cochair Ron Dagan, MD, commented that vaccine skeptics won’t find the Guillain-Barré findings reassuring.
“With HPV vaccination, there are a lot of issues related to mass perception. You say it’s not statistically significant, but some people will say, ‘Forget about the statistics – look at the confidence intervals, the risk could be more than 600 times increased.’ How do you answer this? It’s not easy, especially when we’re talking about a vaccine which has a strong adjuvant,” said Dr. Dagan, director of the pediatric infectious disease unit at Soroka University Medical Center and professor of pediatrics and infectious diseases at the Ben-Gurion University of the Negev, both in Beer-Sheva, Israel.
“I completely agree, how to communicate results to the public is one of the most challenging things. They don’t understand about statistics,” Dr. Skufca replied.
The ball is now in the court of the Finnish health ministry, she added. These study results are brand new. Ministry officials are now going over the details and developing a strategy to communicate the results to the media, the public, and affected families.
The study was funded by the Finnish National Institute for Health and Welfare. Dr. Skufca reported receiving research grants from GlaxoSmithKline and Pfizer.
MALMO, SWEDEN – in a nationwide, retrospective cohort study.
“Anxiety and fear regarding adverse events are still very much alive and are associated with lack of acceptance of HPV vaccination,” Jozica Skufca, DVM, MIPH, observed while presenting the study findings at the annual meeting of the European Society for Paediatric Infectious Diseases.
“These results contribute valid evidence to combat public skepticism, anxiety, fears of adverse events, and possible opposition to HPV vaccination and consequently can contribute to increase HPV vaccination coverage in Finland as well as elsewhere,” added Dr. Skufca, who conducted this research while at the Finnish National Institute for Health and Welfare but is now an epidemiologist at P95, a privately held epidemiology and pharmacovigilance consulting firm in Heverlee, Belgium.
Finland introduced the bivalent HPV vaccine known as Cervarix, which is directed against HPV types 16 and 18, into the nation’s vaccination program in November 2013. The target population were girls aged 11-13 years, with catch-up vaccination at ages 14-15 years until 2015.
Dr. Skufca utilized Finland’s comprehensive system of national health care registries to conduct a study of all 240,605 Finnish girls aged 11-15 years who were eligible for the bivalent HPV vaccine from November 2013 to December 2016. Only 56% of the target population, or 134,615 girls, were actually vaccinated. All were subsequently followed for more than a year.
The investigators compared vaccinated and unvaccinated groups in terms of the subsequent rates of 38 selected outcomes of national and international interest. These included celiac disease, chronic fatigue syndrome, type 1 diabetes, Guillain-Barré syndrome, postural orthostatic tachycardia syndrome, ulcerative colitis, venous thromboembolism, psoriasis, vitiligo, scleroderma, autism, poyarteritis nodosa, asthma, Raynaud’s disease, systemic lupus erythematosus, Bell’s palsy, polycystic ovaries, juvenile arthritis, Hashimoto’s disease, and many others.
HPV vaccination rates varied considerably between hospital districts, so the results were adjusted for that potential confounder. Risks also were adjusted for the number of hospital visits 1-2 years prior to vaccination, because healthier girls – those with fewer hospital visits – turned out to be more likely to get vaccinated.
The study’s main result was that HPV vaccination wasn’t associated with a significantly higher risk of any of the 38 adverse outcomes. To the contrary, vaccination was associated with significantly reduced risk of several of them: The risk of chronic fatigue syndrome was reduced by 25%, epilepsy and recurrent seizures were reduced by 28%, the risk of Henoch-Schönlein purpura was an adjusted 52% lower in children vaccinated against HPV, and the risk of malaise and fatigue was reduced by 24%.
Dr. Skufca drew particular attention to the 400% increased risk of Guillain-Barré syndrome in vaccinated children. While this may look impressive, it wasn’t a statistically significant difference. Guillain-Barré was a rare event, with only six cases occurring during 186,934 person-years of follow-up of vaccinated individuals and a single case in unvaccinated girls. Two cases occurred within 180 days after vaccination, for an adjusted 200% increase in risk, which was nonsignificant.
Another two cases occurred more than 365 days postvaccination, for a whopping 3100% increased risk, compared with unvaccinated children; however, this too was a nonstatistically significant finding, with extraordinarily broad confidence intervals of 1.59-652.4. And there is no plausible mechanism to account for a true association between HPV vaccination and a complication, such as this, occurring more than 1 year later. It appeared to be a matter of chance, she added.
However, session cochair Ron Dagan, MD, commented that vaccine skeptics won’t find the Guillain-Barré findings reassuring.
“With HPV vaccination, there are a lot of issues related to mass perception. You say it’s not statistically significant, but some people will say, ‘Forget about the statistics – look at the confidence intervals, the risk could be more than 600 times increased.’ How do you answer this? It’s not easy, especially when we’re talking about a vaccine which has a strong adjuvant,” said Dr. Dagan, director of the pediatric infectious disease unit at Soroka University Medical Center and professor of pediatrics and infectious diseases at the Ben-Gurion University of the Negev, both in Beer-Sheva, Israel.
“I completely agree, how to communicate results to the public is one of the most challenging things. They don’t understand about statistics,” Dr. Skufca replied.
The ball is now in the court of the Finnish health ministry, she added. These study results are brand new. Ministry officials are now going over the details and developing a strategy to communicate the results to the media, the public, and affected families.
The study was funded by the Finnish National Institute for Health and Welfare. Dr. Skufca reported receiving research grants from GlaxoSmithKline and Pfizer.
MALMO, SWEDEN – in a nationwide, retrospective cohort study.
“Anxiety and fear regarding adverse events are still very much alive and are associated with lack of acceptance of HPV vaccination,” Jozica Skufca, DVM, MIPH, observed while presenting the study findings at the annual meeting of the European Society for Paediatric Infectious Diseases.
“These results contribute valid evidence to combat public skepticism, anxiety, fears of adverse events, and possible opposition to HPV vaccination and consequently can contribute to increase HPV vaccination coverage in Finland as well as elsewhere,” added Dr. Skufca, who conducted this research while at the Finnish National Institute for Health and Welfare but is now an epidemiologist at P95, a privately held epidemiology and pharmacovigilance consulting firm in Heverlee, Belgium.
Finland introduced the bivalent HPV vaccine known as Cervarix, which is directed against HPV types 16 and 18, into the nation’s vaccination program in November 2013. The target population were girls aged 11-13 years, with catch-up vaccination at ages 14-15 years until 2015.
Dr. Skufca utilized Finland’s comprehensive system of national health care registries to conduct a study of all 240,605 Finnish girls aged 11-15 years who were eligible for the bivalent HPV vaccine from November 2013 to December 2016. Only 56% of the target population, or 134,615 girls, were actually vaccinated. All were subsequently followed for more than a year.
The investigators compared vaccinated and unvaccinated groups in terms of the subsequent rates of 38 selected outcomes of national and international interest. These included celiac disease, chronic fatigue syndrome, type 1 diabetes, Guillain-Barré syndrome, postural orthostatic tachycardia syndrome, ulcerative colitis, venous thromboembolism, psoriasis, vitiligo, scleroderma, autism, poyarteritis nodosa, asthma, Raynaud’s disease, systemic lupus erythematosus, Bell’s palsy, polycystic ovaries, juvenile arthritis, Hashimoto’s disease, and many others.
HPV vaccination rates varied considerably between hospital districts, so the results were adjusted for that potential confounder. Risks also were adjusted for the number of hospital visits 1-2 years prior to vaccination, because healthier girls – those with fewer hospital visits – turned out to be more likely to get vaccinated.
The study’s main result was that HPV vaccination wasn’t associated with a significantly higher risk of any of the 38 adverse outcomes. To the contrary, vaccination was associated with significantly reduced risk of several of them: The risk of chronic fatigue syndrome was reduced by 25%, epilepsy and recurrent seizures were reduced by 28%, the risk of Henoch-Schönlein purpura was an adjusted 52% lower in children vaccinated against HPV, and the risk of malaise and fatigue was reduced by 24%.
Dr. Skufca drew particular attention to the 400% increased risk of Guillain-Barré syndrome in vaccinated children. While this may look impressive, it wasn’t a statistically significant difference. Guillain-Barré was a rare event, with only six cases occurring during 186,934 person-years of follow-up of vaccinated individuals and a single case in unvaccinated girls. Two cases occurred within 180 days after vaccination, for an adjusted 200% increase in risk, which was nonsignificant.
Another two cases occurred more than 365 days postvaccination, for a whopping 3100% increased risk, compared with unvaccinated children; however, this too was a nonstatistically significant finding, with extraordinarily broad confidence intervals of 1.59-652.4. And there is no plausible mechanism to account for a true association between HPV vaccination and a complication, such as this, occurring more than 1 year later. It appeared to be a matter of chance, she added.
However, session cochair Ron Dagan, MD, commented that vaccine skeptics won’t find the Guillain-Barré findings reassuring.
“With HPV vaccination, there are a lot of issues related to mass perception. You say it’s not statistically significant, but some people will say, ‘Forget about the statistics – look at the confidence intervals, the risk could be more than 600 times increased.’ How do you answer this? It’s not easy, especially when we’re talking about a vaccine which has a strong adjuvant,” said Dr. Dagan, director of the pediatric infectious disease unit at Soroka University Medical Center and professor of pediatrics and infectious diseases at the Ben-Gurion University of the Negev, both in Beer-Sheva, Israel.
“I completely agree, how to communicate results to the public is one of the most challenging things. They don’t understand about statistics,” Dr. Skufca replied.
The ball is now in the court of the Finnish health ministry, she added. These study results are brand new. Ministry officials are now going over the details and developing a strategy to communicate the results to the media, the public, and affected families.
The study was funded by the Finnish National Institute for Health and Welfare. Dr. Skufca reported receiving research grants from GlaxoSmithKline and Pfizer.
REPORTING FROM ESPID 2018
Key clinical point: Human papillomavirus vaccination poses no significant increased risk of numerous potential adverse outcomes.
Major finding: There was no significantly increased risk of any of 38 potential adverse outcomes in girls aged 11-15 years following administration of a bivalent HPV vaccine.
Study details: This was a retrospective cohort study including more than 240,000 Finnish girls eligible for HPV vaccination following its introduction into the national immunization program.
Disclosures: The study was sponsored by the Finnish National Institute for Health and Welfare. The presenter reported receiving research grants from GlaxoSmithKline and Pfizer.
CDC now offering CME course on HPV vaccination
The Centers for Disease Control and Prevention is now offering a CME course to educate clinicians about the importance of human papillomavirus (HPV) vaccination in protecting adolescents from certain types of cancer and to provide them with the skills and resources to make effective HPV vaccine recommendations.
The course is a Web-on-demand video that will teach clinicians how to be successful in making HPV vaccination recommendations, how to communicate HPV vaccination information to parents and patients, and how to properly answer parents’ questions. Currently, the CDC recommends the HPV vaccine for adolescents at 11- to 12-years-of-age. The CDC hopes this will reduce missed opportunities to protect patients against HPV.
Speakers in the video include Alix Casler, MD, of the Orlando Family Physician Association; Linda Fu, MD, MS, of Children’s National Health System in Washington; Todd Wolynn, MD, president and CEO of Kids Plus Pediatrics, Pittsburgh; and Wendy Sue Swanson, MD, MBE, a pediatrician who is chief of digital innovation at Seattle Children’s Hospital.
The course was initiated in Jan. 16, 2018, and will continue until Jan. 16, 2020. Anyone who provides immunization to patients can participate.
The course is called “Routinely Recommending Cancer Prevention: HPV Vaccination at 11 and 12 as a Standard of Care.” Read more about the course on and download it from the CDC’s website.
The Centers for Disease Control and Prevention is now offering a CME course to educate clinicians about the importance of human papillomavirus (HPV) vaccination in protecting adolescents from certain types of cancer and to provide them with the skills and resources to make effective HPV vaccine recommendations.
The course is a Web-on-demand video that will teach clinicians how to be successful in making HPV vaccination recommendations, how to communicate HPV vaccination information to parents and patients, and how to properly answer parents’ questions. Currently, the CDC recommends the HPV vaccine for adolescents at 11- to 12-years-of-age. The CDC hopes this will reduce missed opportunities to protect patients against HPV.
Speakers in the video include Alix Casler, MD, of the Orlando Family Physician Association; Linda Fu, MD, MS, of Children’s National Health System in Washington; Todd Wolynn, MD, president and CEO of Kids Plus Pediatrics, Pittsburgh; and Wendy Sue Swanson, MD, MBE, a pediatrician who is chief of digital innovation at Seattle Children’s Hospital.
The course was initiated in Jan. 16, 2018, and will continue until Jan. 16, 2020. Anyone who provides immunization to patients can participate.
The course is called “Routinely Recommending Cancer Prevention: HPV Vaccination at 11 and 12 as a Standard of Care.” Read more about the course on and download it from the CDC’s website.
The Centers for Disease Control and Prevention is now offering a CME course to educate clinicians about the importance of human papillomavirus (HPV) vaccination in protecting adolescents from certain types of cancer and to provide them with the skills and resources to make effective HPV vaccine recommendations.
The course is a Web-on-demand video that will teach clinicians how to be successful in making HPV vaccination recommendations, how to communicate HPV vaccination information to parents and patients, and how to properly answer parents’ questions. Currently, the CDC recommends the HPV vaccine for adolescents at 11- to 12-years-of-age. The CDC hopes this will reduce missed opportunities to protect patients against HPV.
Speakers in the video include Alix Casler, MD, of the Orlando Family Physician Association; Linda Fu, MD, MS, of Children’s National Health System in Washington; Todd Wolynn, MD, president and CEO of Kids Plus Pediatrics, Pittsburgh; and Wendy Sue Swanson, MD, MBE, a pediatrician who is chief of digital innovation at Seattle Children’s Hospital.
The course was initiated in Jan. 16, 2018, and will continue until Jan. 16, 2020. Anyone who provides immunization to patients can participate.
The course is called “Routinely Recommending Cancer Prevention: HPV Vaccination at 11 and 12 as a Standard of Care.” Read more about the course on and download it from the CDC’s website.
Immunogenicity of two-dose Gardasil 9 persists at 36 months
MALMO, SWEDEN – Robust human papillomavirus antibody responses persist through 36 months in boys and girls who received two doses of the 9-valent HPV vaccine known as Gardasil 9 at age 9-14 years, according to an open-label randomized immunogenicity study conducted in 15 countries.
This is reassuring news supportive of regulatory decisions made in 2016/2017 to license the more convenient two-dose schedule in the United States, European Union, Canada, and other countries, Rosybel Drury, PhD, observed in reporting the results at the annual meeting of the European Society for Paediatric Infectious Diseases.
Moreover, HPV type-specific antibody levels at 36 months post vaccination in boys and girls who received two doses were similar to or greater than in the 36-month follow-up of adolescent and young adult females who received three doses at ages 16-26 years.
“This result supports the bridging of efficacy findings in young women receiving three doses to girls and boys receiving two doses,” according to Dr. Drury, a vaccine scientist at Merck Sharp & Dohme in Lyon, France.
She presented an update of a five-cohort study including roughly 1,500 recipients of either two doses of the 9-valent HPV vaccine given 6 or 12 months apart or three doses administered at 0, 2, and 6 months. Four cohorts were composed of 9- to 14-year-olds. The fifth consisted of adolescent girls and young women who got three doses of Gardasil 9 over the course of 6 months at ages 16-26 years. The previous report from this major study provided only short-term data based upon measurements of immunogenicity obtained 1 month after the last dose of vaccine (JAMA. 2016 Dec. 13;316(22):2411-21).
Anti-HPV geometric mean titers were highest 1 month after completing a two- or three-dose series, dropped off sharply during the next 6-12 months, then declined more slowly through 36 months.
While the demonstration of persistent immunogenicity over 3 years of follow-up was reassuring overall, there was a potential hitch: Significantly lower antibody levels for some HPV types were observed in girls who received two doses of the vaccine than in those who got three. Specifically, levels of anti-HPV antibodies to HPV types 18, 31, 45, and 52 were significantly lower in the girls who got two doses of the 9-valent HPV vaccine than in those who got three doses at the same age. Antibody levels directed against HPV types 6, 11, 16, 33, and 58 were similar in the two patient populations.
“The clinical significance of this finding remains unknown,” Dr. Drury said.
Challenged as to why the study didn’t include a single-dose vaccine arm, which would be the preferred preventive strategy in low-income countries where the burden of anogenital cancers and warts due to HPV is greatest, she replied that while there is great interest in this approach, and some modeling studies suggest it would be beneficial, the study she presented was designed to evaluate immunogenicity over time, not clinical efficacy, which needs to be assessed before single-dose public health programs are implemented.
The study was funded by Merck and presented by a company employee.
MALMO, SWEDEN – Robust human papillomavirus antibody responses persist through 36 months in boys and girls who received two doses of the 9-valent HPV vaccine known as Gardasil 9 at age 9-14 years, according to an open-label randomized immunogenicity study conducted in 15 countries.
This is reassuring news supportive of regulatory decisions made in 2016/2017 to license the more convenient two-dose schedule in the United States, European Union, Canada, and other countries, Rosybel Drury, PhD, observed in reporting the results at the annual meeting of the European Society for Paediatric Infectious Diseases.
Moreover, HPV type-specific antibody levels at 36 months post vaccination in boys and girls who received two doses were similar to or greater than in the 36-month follow-up of adolescent and young adult females who received three doses at ages 16-26 years.
“This result supports the bridging of efficacy findings in young women receiving three doses to girls and boys receiving two doses,” according to Dr. Drury, a vaccine scientist at Merck Sharp & Dohme in Lyon, France.
She presented an update of a five-cohort study including roughly 1,500 recipients of either two doses of the 9-valent HPV vaccine given 6 or 12 months apart or three doses administered at 0, 2, and 6 months. Four cohorts were composed of 9- to 14-year-olds. The fifth consisted of adolescent girls and young women who got three doses of Gardasil 9 over the course of 6 months at ages 16-26 years. The previous report from this major study provided only short-term data based upon measurements of immunogenicity obtained 1 month after the last dose of vaccine (JAMA. 2016 Dec. 13;316(22):2411-21).
Anti-HPV geometric mean titers were highest 1 month after completing a two- or three-dose series, dropped off sharply during the next 6-12 months, then declined more slowly through 36 months.
While the demonstration of persistent immunogenicity over 3 years of follow-up was reassuring overall, there was a potential hitch: Significantly lower antibody levels for some HPV types were observed in girls who received two doses of the vaccine than in those who got three. Specifically, levels of anti-HPV antibodies to HPV types 18, 31, 45, and 52 were significantly lower in the girls who got two doses of the 9-valent HPV vaccine than in those who got three doses at the same age. Antibody levels directed against HPV types 6, 11, 16, 33, and 58 were similar in the two patient populations.
“The clinical significance of this finding remains unknown,” Dr. Drury said.
Challenged as to why the study didn’t include a single-dose vaccine arm, which would be the preferred preventive strategy in low-income countries where the burden of anogenital cancers and warts due to HPV is greatest, she replied that while there is great interest in this approach, and some modeling studies suggest it would be beneficial, the study she presented was designed to evaluate immunogenicity over time, not clinical efficacy, which needs to be assessed before single-dose public health programs are implemented.
The study was funded by Merck and presented by a company employee.
MALMO, SWEDEN – Robust human papillomavirus antibody responses persist through 36 months in boys and girls who received two doses of the 9-valent HPV vaccine known as Gardasil 9 at age 9-14 years, according to an open-label randomized immunogenicity study conducted in 15 countries.
This is reassuring news supportive of regulatory decisions made in 2016/2017 to license the more convenient two-dose schedule in the United States, European Union, Canada, and other countries, Rosybel Drury, PhD, observed in reporting the results at the annual meeting of the European Society for Paediatric Infectious Diseases.
Moreover, HPV type-specific antibody levels at 36 months post vaccination in boys and girls who received two doses were similar to or greater than in the 36-month follow-up of adolescent and young adult females who received three doses at ages 16-26 years.
“This result supports the bridging of efficacy findings in young women receiving three doses to girls and boys receiving two doses,” according to Dr. Drury, a vaccine scientist at Merck Sharp & Dohme in Lyon, France.
She presented an update of a five-cohort study including roughly 1,500 recipients of either two doses of the 9-valent HPV vaccine given 6 or 12 months apart or three doses administered at 0, 2, and 6 months. Four cohorts were composed of 9- to 14-year-olds. The fifth consisted of adolescent girls and young women who got three doses of Gardasil 9 over the course of 6 months at ages 16-26 years. The previous report from this major study provided only short-term data based upon measurements of immunogenicity obtained 1 month after the last dose of vaccine (JAMA. 2016 Dec. 13;316(22):2411-21).
Anti-HPV geometric mean titers were highest 1 month after completing a two- or three-dose series, dropped off sharply during the next 6-12 months, then declined more slowly through 36 months.
While the demonstration of persistent immunogenicity over 3 years of follow-up was reassuring overall, there was a potential hitch: Significantly lower antibody levels for some HPV types were observed in girls who received two doses of the vaccine than in those who got three. Specifically, levels of anti-HPV antibodies to HPV types 18, 31, 45, and 52 were significantly lower in the girls who got two doses of the 9-valent HPV vaccine than in those who got three doses at the same age. Antibody levels directed against HPV types 6, 11, 16, 33, and 58 were similar in the two patient populations.
“The clinical significance of this finding remains unknown,” Dr. Drury said.
Challenged as to why the study didn’t include a single-dose vaccine arm, which would be the preferred preventive strategy in low-income countries where the burden of anogenital cancers and warts due to HPV is greatest, she replied that while there is great interest in this approach, and some modeling studies suggest it would be beneficial, the study she presented was designed to evaluate immunogenicity over time, not clinical efficacy, which needs to be assessed before single-dose public health programs are implemented.
The study was funded by Merck and presented by a company employee.
REPORTING FROM ESPID 2018
Key clinical point:
Major finding: HPV type-specific antibody responses to two doses given at age 9-14 years were as good as or better than in 16- to 26-year-olds who got three doses.
Study details: This prospective open-label immunogenicity study included roughly 1,500 subjects in 15 countries who received either two or three doses of the 9-valent HPV vaccine.
Disclosures: The study was funded by Merck and presented by a company employee.
Primary efficacy not met by new M. tuberculosis vaccine strategies
Vaccination may have reduced the rate of sustained Mycobacterium tuberculosis infection in a recent randomized, placebo-controlled clinical trial conducted in a high-risk setting for tuberculosis transmission, despite not meeting the primary endpoint of the study.
In adolescents who had received the bacille Calmette-Guérin (BCG) vaccine in infancy, BCG revaccination reduced the rate of sustained conversion of QuantiFERON-TB Gold In-Tube assay (QFT), a test that is thought to reflect sustained M. tuberculosis infection.
The study also evaluated a candidate subunit vaccine, H4:IC31, which also reduced the rate of sustained QFT conversion, though the efficacy estimate did not reach statistical significance, investigators reported.
Neither H4:IC31 nor BCG revaccination prevented initial QFT conversion, the primary endpoint of the study; however, both vaccines were immunogenic, they said.
Moreover, the significantly reduced rate of sustained conversion with BCG revaccination provides a “promising signal,” study authors said in the New England Journal of Medicine.
“The durability of this important finding and potential public health significance for protection against tuberculosis disease warrants epidemiologic modeling and further clinical evaluation,” wrote Elisa Nemes, PhD, of the South African Tuberculosis Vaccine Initiative, which is part of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town (South Africa), and her coauthors.
Similarly, the nonsignificantly reduced rate of sustained QFT conversion seen with H4:IC31 suggested that subunit vaccines can have a biologic effect in this setting, which may inform development of new tuberculosis vaccines, Dr. Nemes and her colleagues added.
The phase 2 trial included 990 adolescents in South Africa who had undergone neonatal BCG vaccination. They were randomly assigned to receive BCG revaccination, H4:IC31 vaccine, or placebo.
Neither vaccine met the primary efficacy criterion based on initial QFT conversion rates, which were 13.1% for BCG revaccination, 14.3% for H4:IC31 vaccine, and 15.8% for placebo.
For the secondary endpoint of sustained QFT conversion, the efficacy of BCG revaccination was 45.4% (95% confidence interval, 6.4%-68.1%; P = .03), while the efficacy of H4:IC31 vaccine was 34.2% (95% CI, –10.4% to 60.7%; P = .11).
“These encouraging findings provide an impetus to reevaluate the use of BCG revaccination of populations that are free of M. tuberculosis infection for the prevention of disease,” Dr. Nemes and her coauthors wrote in their report.
Revaccination with BCG was associated with more adverse events, compared with the other groups, although adverse events in the trial were predominantly injection-site reactions that were mild to moderate in severity, investigators reported. There were no serious adverse events judged by investigators to be related to trial vaccine.
Taken together, these results raise important questions regarding the potential benefits of vaccine-mediated prevention of M. tuberculosis infection for control of tuberculosis disease, according to Dr. Nemes and her coauthors.
However, interpretation of the findings is limited because there is no definitive test for M. tuberculosis infection.
Recent infection diagnosed by tuberculin skin test or QFT conversion has been associated with higher risk of disease, compared with nonconversion, according to investigators, while reversion to a negative tuberculin skin test correlates with infection containment and lower risk of tuberculosis.
“Although the clinical significance of QFT reversion remains to be established, we propose that sustained QFT conversion more likely represents sustained M. tuberculosis infection and a higher risk of progression to disease than transient QFT conversion,” they wrote.
The study was supported by Aeras, Sanofi Pasteur, the Bill & Melinda Gates Foundation, the Government of the Netherlands Directorate-General for International Cooperation and Development, and the United Kingdom Department for International Development. Study authors reported disclosures related to GlaxoSmithKline, Sanofi Pasteur, and Aeras.
SOURCE: Nemes E et al. N Engl J Med. 2018;379:138-49.
Vaccination may have reduced the rate of sustained Mycobacterium tuberculosis infection in a recent randomized, placebo-controlled clinical trial conducted in a high-risk setting for tuberculosis transmission, despite not meeting the primary endpoint of the study.
In adolescents who had received the bacille Calmette-Guérin (BCG) vaccine in infancy, BCG revaccination reduced the rate of sustained conversion of QuantiFERON-TB Gold In-Tube assay (QFT), a test that is thought to reflect sustained M. tuberculosis infection.
The study also evaluated a candidate subunit vaccine, H4:IC31, which also reduced the rate of sustained QFT conversion, though the efficacy estimate did not reach statistical significance, investigators reported.
Neither H4:IC31 nor BCG revaccination prevented initial QFT conversion, the primary endpoint of the study; however, both vaccines were immunogenic, they said.
Moreover, the significantly reduced rate of sustained conversion with BCG revaccination provides a “promising signal,” study authors said in the New England Journal of Medicine.
“The durability of this important finding and potential public health significance for protection against tuberculosis disease warrants epidemiologic modeling and further clinical evaluation,” wrote Elisa Nemes, PhD, of the South African Tuberculosis Vaccine Initiative, which is part of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town (South Africa), and her coauthors.
Similarly, the nonsignificantly reduced rate of sustained QFT conversion seen with H4:IC31 suggested that subunit vaccines can have a biologic effect in this setting, which may inform development of new tuberculosis vaccines, Dr. Nemes and her colleagues added.
The phase 2 trial included 990 adolescents in South Africa who had undergone neonatal BCG vaccination. They were randomly assigned to receive BCG revaccination, H4:IC31 vaccine, or placebo.
Neither vaccine met the primary efficacy criterion based on initial QFT conversion rates, which were 13.1% for BCG revaccination, 14.3% for H4:IC31 vaccine, and 15.8% for placebo.
For the secondary endpoint of sustained QFT conversion, the efficacy of BCG revaccination was 45.4% (95% confidence interval, 6.4%-68.1%; P = .03), while the efficacy of H4:IC31 vaccine was 34.2% (95% CI, –10.4% to 60.7%; P = .11).
“These encouraging findings provide an impetus to reevaluate the use of BCG revaccination of populations that are free of M. tuberculosis infection for the prevention of disease,” Dr. Nemes and her coauthors wrote in their report.
Revaccination with BCG was associated with more adverse events, compared with the other groups, although adverse events in the trial were predominantly injection-site reactions that were mild to moderate in severity, investigators reported. There were no serious adverse events judged by investigators to be related to trial vaccine.
Taken together, these results raise important questions regarding the potential benefits of vaccine-mediated prevention of M. tuberculosis infection for control of tuberculosis disease, according to Dr. Nemes and her coauthors.
However, interpretation of the findings is limited because there is no definitive test for M. tuberculosis infection.
Recent infection diagnosed by tuberculin skin test or QFT conversion has been associated with higher risk of disease, compared with nonconversion, according to investigators, while reversion to a negative tuberculin skin test correlates with infection containment and lower risk of tuberculosis.
“Although the clinical significance of QFT reversion remains to be established, we propose that sustained QFT conversion more likely represents sustained M. tuberculosis infection and a higher risk of progression to disease than transient QFT conversion,” they wrote.
The study was supported by Aeras, Sanofi Pasteur, the Bill & Melinda Gates Foundation, the Government of the Netherlands Directorate-General for International Cooperation and Development, and the United Kingdom Department for International Development. Study authors reported disclosures related to GlaxoSmithKline, Sanofi Pasteur, and Aeras.
SOURCE: Nemes E et al. N Engl J Med. 2018;379:138-49.
Vaccination may have reduced the rate of sustained Mycobacterium tuberculosis infection in a recent randomized, placebo-controlled clinical trial conducted in a high-risk setting for tuberculosis transmission, despite not meeting the primary endpoint of the study.
In adolescents who had received the bacille Calmette-Guérin (BCG) vaccine in infancy, BCG revaccination reduced the rate of sustained conversion of QuantiFERON-TB Gold In-Tube assay (QFT), a test that is thought to reflect sustained M. tuberculosis infection.
The study also evaluated a candidate subunit vaccine, H4:IC31, which also reduced the rate of sustained QFT conversion, though the efficacy estimate did not reach statistical significance, investigators reported.
Neither H4:IC31 nor BCG revaccination prevented initial QFT conversion, the primary endpoint of the study; however, both vaccines were immunogenic, they said.
Moreover, the significantly reduced rate of sustained conversion with BCG revaccination provides a “promising signal,” study authors said in the New England Journal of Medicine.
“The durability of this important finding and potential public health significance for protection against tuberculosis disease warrants epidemiologic modeling and further clinical evaluation,” wrote Elisa Nemes, PhD, of the South African Tuberculosis Vaccine Initiative, which is part of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town (South Africa), and her coauthors.
Similarly, the nonsignificantly reduced rate of sustained QFT conversion seen with H4:IC31 suggested that subunit vaccines can have a biologic effect in this setting, which may inform development of new tuberculosis vaccines, Dr. Nemes and her colleagues added.
The phase 2 trial included 990 adolescents in South Africa who had undergone neonatal BCG vaccination. They were randomly assigned to receive BCG revaccination, H4:IC31 vaccine, or placebo.
Neither vaccine met the primary efficacy criterion based on initial QFT conversion rates, which were 13.1% for BCG revaccination, 14.3% for H4:IC31 vaccine, and 15.8% for placebo.
For the secondary endpoint of sustained QFT conversion, the efficacy of BCG revaccination was 45.4% (95% confidence interval, 6.4%-68.1%; P = .03), while the efficacy of H4:IC31 vaccine was 34.2% (95% CI, –10.4% to 60.7%; P = .11).
“These encouraging findings provide an impetus to reevaluate the use of BCG revaccination of populations that are free of M. tuberculosis infection for the prevention of disease,” Dr. Nemes and her coauthors wrote in their report.
Revaccination with BCG was associated with more adverse events, compared with the other groups, although adverse events in the trial were predominantly injection-site reactions that were mild to moderate in severity, investigators reported. There were no serious adverse events judged by investigators to be related to trial vaccine.
Taken together, these results raise important questions regarding the potential benefits of vaccine-mediated prevention of M. tuberculosis infection for control of tuberculosis disease, according to Dr. Nemes and her coauthors.
However, interpretation of the findings is limited because there is no definitive test for M. tuberculosis infection.
Recent infection diagnosed by tuberculin skin test or QFT conversion has been associated with higher risk of disease, compared with nonconversion, according to investigators, while reversion to a negative tuberculin skin test correlates with infection containment and lower risk of tuberculosis.
“Although the clinical significance of QFT reversion remains to be established, we propose that sustained QFT conversion more likely represents sustained M. tuberculosis infection and a higher risk of progression to disease than transient QFT conversion,” they wrote.
The study was supported by Aeras, Sanofi Pasteur, the Bill & Melinda Gates Foundation, the Government of the Netherlands Directorate-General for International Cooperation and Development, and the United Kingdom Department for International Development. Study authors reported disclosures related to GlaxoSmithKline, Sanofi Pasteur, and Aeras.
SOURCE: Nemes E et al. N Engl J Med. 2018;379:138-49.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Neither H4:IC31 nor BCG revaccination prevented initial QFT conversion, the primary endpoint; however, both vaccines were immunogenic.
Major finding: For the secondary endpoint of sustained QuantiFERON-TB Gold In-Tube Assay (QFT) conversion, efficacy was 45.4% (P = .03) for BCG revaccination and 34.2% (P = .11) for H4:IC31, a candidate subunit vaccine.
Study details: A phase 2, randomized, placebo-controlled trial including 990 adolescents in South Africa who had received BCG vaccine in infancy.
Disclosures: The study was supported by Aeras, Sanofi Pasteur, the Bill & Melinda Gates Foundation, the Government of the Netherlands Directorate-General for International Cooperation and Development, and the United Kingdom Department for International Development. Study authors reported disclosures related to GlaxoSmithKline, Sanofi Pasteur, and Aeras.
Source: Nemes E et al. N Engl J Med. 2018;379:138-49.
