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Flu activity takes another turn for the better
Outpatient influenza-like illness activity continues to drop, but pediatric deaths for 2017-2018 are already higher than either of the last two entire seasons, according to the Centers for Disease and Prevention.
An additional 17 influenza-like illness-related (ILI) pediatric deaths were reported during the week ending Feb. 24, eight of which occurred in previous weeks. That brings the total to 114 for the 2017-2018 flu season so far, compared with 110 for the entire 2016-2017 season and 93 for the 2015-2016 season, the CDC reported Mar. 2.
The proportion of outpatient visits for ILI took another big drop, falling to 5.0% for the week, which was down from 6.4% the previous week and the seasonal high of 7.4% the 2 weeks before that (Feb. 10 and Feb. 3), CDC data show.
Flu-related hospitalizations, however, continued to rise to new highs, as the cumulative rate hit 81.7 per 100,000 population. In 2014-2015, the season with the highest number of hospitalizations since the CDC started keeping track, the cumulative rate for the corresponding week was 55.9 per 100,000, according to the CDC’s Fluview website.
The map of state-reported ILI activity shows that 25 states are at level 10 on the CDC’s 1-10 scale, which is down from 33 the week before. Eight other states and the District of Columbia were in the “high” range with activity at levels 8 and 9 for the week ending Feb. 24, the CDC said.
Outpatient influenza-like illness activity continues to drop, but pediatric deaths for 2017-2018 are already higher than either of the last two entire seasons, according to the Centers for Disease and Prevention.
An additional 17 influenza-like illness-related (ILI) pediatric deaths were reported during the week ending Feb. 24, eight of which occurred in previous weeks. That brings the total to 114 for the 2017-2018 flu season so far, compared with 110 for the entire 2016-2017 season and 93 for the 2015-2016 season, the CDC reported Mar. 2.
The proportion of outpatient visits for ILI took another big drop, falling to 5.0% for the week, which was down from 6.4% the previous week and the seasonal high of 7.4% the 2 weeks before that (Feb. 10 and Feb. 3), CDC data show.
Flu-related hospitalizations, however, continued to rise to new highs, as the cumulative rate hit 81.7 per 100,000 population. In 2014-2015, the season with the highest number of hospitalizations since the CDC started keeping track, the cumulative rate for the corresponding week was 55.9 per 100,000, according to the CDC’s Fluview website.
The map of state-reported ILI activity shows that 25 states are at level 10 on the CDC’s 1-10 scale, which is down from 33 the week before. Eight other states and the District of Columbia were in the “high” range with activity at levels 8 and 9 for the week ending Feb. 24, the CDC said.
Outpatient influenza-like illness activity continues to drop, but pediatric deaths for 2017-2018 are already higher than either of the last two entire seasons, according to the Centers for Disease and Prevention.
An additional 17 influenza-like illness-related (ILI) pediatric deaths were reported during the week ending Feb. 24, eight of which occurred in previous weeks. That brings the total to 114 for the 2017-2018 flu season so far, compared with 110 for the entire 2016-2017 season and 93 for the 2015-2016 season, the CDC reported Mar. 2.
The proportion of outpatient visits for ILI took another big drop, falling to 5.0% for the week, which was down from 6.4% the previous week and the seasonal high of 7.4% the 2 weeks before that (Feb. 10 and Feb. 3), CDC data show.
Flu-related hospitalizations, however, continued to rise to new highs, as the cumulative rate hit 81.7 per 100,000 population. In 2014-2015, the season with the highest number of hospitalizations since the CDC started keeping track, the cumulative rate for the corresponding week was 55.9 per 100,000, according to the CDC’s Fluview website.
The map of state-reported ILI activity shows that 25 states are at level 10 on the CDC’s 1-10 scale, which is down from 33 the week before. Eight other states and the District of Columbia were in the “high” range with activity at levels 8 and 9 for the week ending Feb. 24, the CDC said.
2 new influenza strains recommended for next season
SILVER SPRING, MD. – In an effort to better match the vaccine to the virus, federal advisors have recommended two new strains be swapped into the 2018-2019 quadrivalent influenza vaccine.
Singapore A(H3N2) and the B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) are recommended be added to A/Michigan/45/2015 (H1N1)pdm09-like virus and B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) for the upcoming season, according to a near-unanimous vote at a meeting of the Food and Drug Administration Vaccines and Related Biological Products Advisory Committee.
Trivalent vaccines should include the same strains, with the exception of B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage), the committee recommended.
The panel voted separately on the strains, and all votes were unanimous, except for the vote on the B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) in the trivalent vaccine, which was supported with 11 positive votes with 1 abstention.
The advisory committee’s recommendation is identical to the recommendations recently made by the World Health Organization for next season’s influenza vaccines in the Northern Hemisphere. The WHO recommended that trivalent vaccines contain A/Michigan/45/2015 (H1N1)pdm09-like virus, A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage). WHO also recommended that quadrivalent vaccines contain all of the above strains and B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) as the second influenza B strain.
Most of the influenza activity in the United States this season is due to influenza A (H3N2) viruses (67%), according to Lisa Grohskopf, MD, associate chief for policy & liaison in the Influenza Division at the Centers for Disease Control and Prevention. Fortunately, the majority of circulating strains are similar to those contained in the 2017-2018 vaccine. Only strains with B/Victoria lineage displayed antigenic drift, but represented less than 1% of all circulating viruses.
Hospitalization rates for laboratory-confirmed influenza this season have been markedly higher among people aged 65 years and older, compared with younger age groups, and have increased since last season. As of Feb. 17, the preliminary estimate of hospitalizations in this age group was 322.7 cases per 100,000 people, compared with about 290.5 per 100,000 during the 2016-2017 season. There have been 97 pediatric deaths associated with influenza, compared with 110 reported during the 2016-2017 season, 93 during 2015-2016, and 148 during 2014-2015.
These data are not final because the flu season is still ongoing, but a full analysis will be provided at the end of the season, Dr. Grohskopf pointed out.With H3N2 strains of influenza A predominating, questions on the effectiveness of the newly recommended Singapore A(H3N2) were raised by the committee. Jacqueline Katz, PhD, director of the WHO Collaborating Center for Surveillance, Epidemiology, and Control of Influenza, reassured the committee.
“Yes, in fact, it does cover them very well. The majority of the viruses that we’ve tested at the CDC were that emerging 3C2a2 [clade of H3N2] group, and the Singapore virus covered those very well. In general, that’s why we went with Singapore,” she said.
Dr. Katz added that one of the reasons Singapore is so effective is because of its position in the lineage of these flu strains. “It’s at the base of the [phylogenetic] tree; it’s not on the tip of the tree where things are changing, so it’s a more conservative selection.”
The CDC estimate of current vaccine effectiveness (VE) against influenza A (H3N2) viruses is 25%, as of Feb. 3. Effectiveness is even higher for all influenza viruses, with an estimated VE of 36%, indicating that the flu vaccine reduced a person’s risk of having to seek medical care at a doctor’s office for flu illness by 36% (MMWR. 2018;67:180-5).
While the FDA usually follows the recommendations of its panel members, it is not obligated to do so. None of the committee members disclosed relevant financial conflicts of interest.
SILVER SPRING, MD. – In an effort to better match the vaccine to the virus, federal advisors have recommended two new strains be swapped into the 2018-2019 quadrivalent influenza vaccine.
Singapore A(H3N2) and the B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) are recommended be added to A/Michigan/45/2015 (H1N1)pdm09-like virus and B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) for the upcoming season, according to a near-unanimous vote at a meeting of the Food and Drug Administration Vaccines and Related Biological Products Advisory Committee.
Trivalent vaccines should include the same strains, with the exception of B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage), the committee recommended.
The panel voted separately on the strains, and all votes were unanimous, except for the vote on the B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) in the trivalent vaccine, which was supported with 11 positive votes with 1 abstention.
The advisory committee’s recommendation is identical to the recommendations recently made by the World Health Organization for next season’s influenza vaccines in the Northern Hemisphere. The WHO recommended that trivalent vaccines contain A/Michigan/45/2015 (H1N1)pdm09-like virus, A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage). WHO also recommended that quadrivalent vaccines contain all of the above strains and B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) as the second influenza B strain.
Most of the influenza activity in the United States this season is due to influenza A (H3N2) viruses (67%), according to Lisa Grohskopf, MD, associate chief for policy & liaison in the Influenza Division at the Centers for Disease Control and Prevention. Fortunately, the majority of circulating strains are similar to those contained in the 2017-2018 vaccine. Only strains with B/Victoria lineage displayed antigenic drift, but represented less than 1% of all circulating viruses.
Hospitalization rates for laboratory-confirmed influenza this season have been markedly higher among people aged 65 years and older, compared with younger age groups, and have increased since last season. As of Feb. 17, the preliminary estimate of hospitalizations in this age group was 322.7 cases per 100,000 people, compared with about 290.5 per 100,000 during the 2016-2017 season. There have been 97 pediatric deaths associated with influenza, compared with 110 reported during the 2016-2017 season, 93 during 2015-2016, and 148 during 2014-2015.
These data are not final because the flu season is still ongoing, but a full analysis will be provided at the end of the season, Dr. Grohskopf pointed out.With H3N2 strains of influenza A predominating, questions on the effectiveness of the newly recommended Singapore A(H3N2) were raised by the committee. Jacqueline Katz, PhD, director of the WHO Collaborating Center for Surveillance, Epidemiology, and Control of Influenza, reassured the committee.
“Yes, in fact, it does cover them very well. The majority of the viruses that we’ve tested at the CDC were that emerging 3C2a2 [clade of H3N2] group, and the Singapore virus covered those very well. In general, that’s why we went with Singapore,” she said.
Dr. Katz added that one of the reasons Singapore is so effective is because of its position in the lineage of these flu strains. “It’s at the base of the [phylogenetic] tree; it’s not on the tip of the tree where things are changing, so it’s a more conservative selection.”
The CDC estimate of current vaccine effectiveness (VE) against influenza A (H3N2) viruses is 25%, as of Feb. 3. Effectiveness is even higher for all influenza viruses, with an estimated VE of 36%, indicating that the flu vaccine reduced a person’s risk of having to seek medical care at a doctor’s office for flu illness by 36% (MMWR. 2018;67:180-5).
While the FDA usually follows the recommendations of its panel members, it is not obligated to do so. None of the committee members disclosed relevant financial conflicts of interest.
SILVER SPRING, MD. – In an effort to better match the vaccine to the virus, federal advisors have recommended two new strains be swapped into the 2018-2019 quadrivalent influenza vaccine.
Singapore A(H3N2) and the B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) are recommended be added to A/Michigan/45/2015 (H1N1)pdm09-like virus and B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) for the upcoming season, according to a near-unanimous vote at a meeting of the Food and Drug Administration Vaccines and Related Biological Products Advisory Committee.
Trivalent vaccines should include the same strains, with the exception of B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage), the committee recommended.
The panel voted separately on the strains, and all votes were unanimous, except for the vote on the B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) in the trivalent vaccine, which was supported with 11 positive votes with 1 abstention.
The advisory committee’s recommendation is identical to the recommendations recently made by the World Health Organization for next season’s influenza vaccines in the Northern Hemisphere. The WHO recommended that trivalent vaccines contain A/Michigan/45/2015 (H1N1)pdm09-like virus, A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage). WHO also recommended that quadrivalent vaccines contain all of the above strains and B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) as the second influenza B strain.
Most of the influenza activity in the United States this season is due to influenza A (H3N2) viruses (67%), according to Lisa Grohskopf, MD, associate chief for policy & liaison in the Influenza Division at the Centers for Disease Control and Prevention. Fortunately, the majority of circulating strains are similar to those contained in the 2017-2018 vaccine. Only strains with B/Victoria lineage displayed antigenic drift, but represented less than 1% of all circulating viruses.
Hospitalization rates for laboratory-confirmed influenza this season have been markedly higher among people aged 65 years and older, compared with younger age groups, and have increased since last season. As of Feb. 17, the preliminary estimate of hospitalizations in this age group was 322.7 cases per 100,000 people, compared with about 290.5 per 100,000 during the 2016-2017 season. There have been 97 pediatric deaths associated with influenza, compared with 110 reported during the 2016-2017 season, 93 during 2015-2016, and 148 during 2014-2015.
These data are not final because the flu season is still ongoing, but a full analysis will be provided at the end of the season, Dr. Grohskopf pointed out.With H3N2 strains of influenza A predominating, questions on the effectiveness of the newly recommended Singapore A(H3N2) were raised by the committee. Jacqueline Katz, PhD, director of the WHO Collaborating Center for Surveillance, Epidemiology, and Control of Influenza, reassured the committee.
“Yes, in fact, it does cover them very well. The majority of the viruses that we’ve tested at the CDC were that emerging 3C2a2 [clade of H3N2] group, and the Singapore virus covered those very well. In general, that’s why we went with Singapore,” she said.
Dr. Katz added that one of the reasons Singapore is so effective is because of its position in the lineage of these flu strains. “It’s at the base of the [phylogenetic] tree; it’s not on the tip of the tree where things are changing, so it’s a more conservative selection.”
The CDC estimate of current vaccine effectiveness (VE) against influenza A (H3N2) viruses is 25%, as of Feb. 3. Effectiveness is even higher for all influenza viruses, with an estimated VE of 36%, indicating that the flu vaccine reduced a person’s risk of having to seek medical care at a doctor’s office for flu illness by 36% (MMWR. 2018;67:180-5).
While the FDA usually follows the recommendations of its panel members, it is not obligated to do so. None of the committee members disclosed relevant financial conflicts of interest.
REPORTING FROM AN FDA ADVISORY COMMITTEE MEETING
Vaccines: Effectiveness vs. efficacy
During the influenza portion of the Feb. 21, 2018, Centers for Diseases Control and Prevention’s Advisory Committee on Immunization Practices meeting, two pleas from the audience asked the CDC/ACIP to make messages very clear about how protective influenza vaccine really is.
We hear apparently conflicting percentages from Australia, Canada, Europe, and the United States from the many stories/press releases in the news media and from official public health outlets. And the gloomiest ones get the most exposure.1 It can be confusing even for medical care providers who are supposed to advise families on such matters.
A key misunderstanding in many medical and lay news stories is about what vaccine effectiveness and vaccine efficacy really mean. What? Aren’t those the same thing? Nope. They are quite different. And are we sure of what those 95% confidence intervals (CI) mean? Let’s review the “math” so we can explain this to families.
Vaccine effectiveness (VE)2,3
The first thing to know is that the CDC and similar public health agencies in other countries do not report vaccine efficacy. Instead, the percentage reported is VE during (interim estimated VE) and just after (final adjusted VE) each influenza season. This means that VE is generally a retrospective analysis of data, most of which were collected prospectively. Further, VE is likely the worst case scenario. VE is a measure of real-world benefit to patients for whom vaccine is recommended, by analyzing specific geographically diverse populations (population-based) without excluding most underlying illness or comorbidities (note that immunosuppressed persons are excluded). Subjects in VE studies receive their vaccine in the real world and, therefore, vaccinees may receive their vaccines from any number of the usual outlets (e.g., primary care provider, urgent care or emergency department, public health department, pharmacy, school, or nursing home). There are multiple lots of multiple brands from multiple vaccine manufacturers. Children who need two doses of influenza vaccine do not necessarily receive those doses according to the package insert’s schedule. VE studies do not have the capability to confirm that vaccine was stored, handled, and administered in a precisely correct manner according to manufacturer’s and CDC’s recommendations.
VE is calculated using a “test-negative” (case-control) analysis of patients presenting with acute respiratory infections (ARIs). People who are not in vaccine research can find this methodology confusing. Briefly, the VE compares the odds of vaccination in ARIs due to confirmed influenza to the odds of vaccination in ARIs not due to influenza. Additional statistical tools can adjust VE for specific factors. VE is also calculated by factors of interest, such as age, gender, pregnancy, influenza type, region of the country, presence of asthma or other comorbidity, etc. Whether the VE value is the “truth in the universe” is related to having enough subjects in each analyzed group and the degree to which the studied populations actually represent the whole country. So, VE is more accurate when there are large subject numbers.
Remember also that VE is usually calculated from outpatients, so it does not really measure all the benefits of vaccination. Prevention rates for severe influenza (such as influenza hospitalizations) are higher but usually unavailable until after the entire season.
VE studies generally measure real-world and likely worst-case-scenario benefit for the overall population being protected against outpatient influenza medical visits.
Vaccine efficacy2,3
Vaccine efficacy measures how the vaccine performs under ideal circumstances in a regimented protocol in relatively normal hosts – likely the best-case-scenario benefit. Vaccine efficacy is the percent difference in confirmed influenza episodes in vaccinees getting the “experimental” vaccine vs. episodes in nonvaccinees (or vaccinees getting an established vaccine). Vaccine efficacy, therefore, is usually calculated based on prospective well-controlled studies under ideal circumstances in subjects who received their vaccines on time per the recommended schedule. Most such studies are performed on otherwise healthy children or adults, with most comorbidities excluded. The “experimental” vaccine is generally from a single manufacturer from a single lot, and chain-of-custody is well controlled. The vaccine is administered at selected research sites according to a strict protocol; vaccine storage is ensured to be as recommended.
Confidence intervals
To assess whether the “protection” is “significant,” the calculations derive 95% confidence intervals (CI). If the 95% CI range is wide, such as many tens of percents, then there is less confidence that the calculation is correct. And if the lower CI is less than 0, then the result is not significant. For example, a VE of 20% is not highly protective, but can be significant if the 95% CI ranges from 10 to 28 (the lower value of 10 is above zero). It would not be significant if the 95% CI lower limit was –10. Values for seasons 2004-2005 and 2005-2006 were similar to this. Consider however that a VE of 55% seems great, but may not be significant if the 95% CI range is –20 to 89 (the lower value is less than zero). In the ideal world, the VE would be greater than 50% and the 95% CI range would be tight with the lower CI value far above zero; for example, VE of 70% with 95% CI ranging from 60 to 80. The 2010-2011 season was close to this.
Type and age-specific VE
Aside from overall VE, there are subset analyses that can be revealing. This year there are the concerning mid-season VE estimates of approximately 25% for the United States and 17% in Canada, for one specific type, H3N2, which unfortunately has been the dominant circulating U.S. type. That number is what everybody seems to have focused on. But remember influenza B becomes dominant late in most seasons (increasing at the time of writing this article). Interim 2017-2018 VE for influenza B was in the mid 60% range, making the box plot near 40% overall.
Age-related VE analysis can show difference; for example, the best benefit for H3N2 this season has been in young children and the worst in elderly and 9- to 17-year-olds.
Take-home message
The simplest way to think of overall VE is that it is the real-world, worst-case-scenario value for influenza protection by vaccine against the several circulating types of influenza. While this year’s vaccine seems less protective than we hoped, we should still feel good recommending a vaccine that can prevent 40% of overall influenza cases and that provides an additional benefit of lessening severity in many breakthrough infections. That said, we still need a better and universal influenza vaccine.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Children’s Mercy Hospital receives grant funding for Dr. Harrison’s work as an investigator from GSK for MMR and rotavirus vaccine studies, from Merck for in vitro and clinical antibiotic studies, from Allergan for clinical antibiotic studies, from Pfizer for pneumococcal seroepidemiology studies, and from Regeneron for RSV studies. Dr. Harrison received support for travel and to present seroepidemiology data at one meeting. Email him at [email protected].
References
1. MMWR Weekly. 2017 Feb 17;66(6):167-71.
2. Dev Biol Stand. 1998;95:195-201.
3. Lancet Infect Dis. 2012 Jan;12(1):36-44.
During the influenza portion of the Feb. 21, 2018, Centers for Diseases Control and Prevention’s Advisory Committee on Immunization Practices meeting, two pleas from the audience asked the CDC/ACIP to make messages very clear about how protective influenza vaccine really is.
We hear apparently conflicting percentages from Australia, Canada, Europe, and the United States from the many stories/press releases in the news media and from official public health outlets. And the gloomiest ones get the most exposure.1 It can be confusing even for medical care providers who are supposed to advise families on such matters.
A key misunderstanding in many medical and lay news stories is about what vaccine effectiveness and vaccine efficacy really mean. What? Aren’t those the same thing? Nope. They are quite different. And are we sure of what those 95% confidence intervals (CI) mean? Let’s review the “math” so we can explain this to families.
Vaccine effectiveness (VE)2,3
The first thing to know is that the CDC and similar public health agencies in other countries do not report vaccine efficacy. Instead, the percentage reported is VE during (interim estimated VE) and just after (final adjusted VE) each influenza season. This means that VE is generally a retrospective analysis of data, most of which were collected prospectively. Further, VE is likely the worst case scenario. VE is a measure of real-world benefit to patients for whom vaccine is recommended, by analyzing specific geographically diverse populations (population-based) without excluding most underlying illness or comorbidities (note that immunosuppressed persons are excluded). Subjects in VE studies receive their vaccine in the real world and, therefore, vaccinees may receive their vaccines from any number of the usual outlets (e.g., primary care provider, urgent care or emergency department, public health department, pharmacy, school, or nursing home). There are multiple lots of multiple brands from multiple vaccine manufacturers. Children who need two doses of influenza vaccine do not necessarily receive those doses according to the package insert’s schedule. VE studies do not have the capability to confirm that vaccine was stored, handled, and administered in a precisely correct manner according to manufacturer’s and CDC’s recommendations.
VE is calculated using a “test-negative” (case-control) analysis of patients presenting with acute respiratory infections (ARIs). People who are not in vaccine research can find this methodology confusing. Briefly, the VE compares the odds of vaccination in ARIs due to confirmed influenza to the odds of vaccination in ARIs not due to influenza. Additional statistical tools can adjust VE for specific factors. VE is also calculated by factors of interest, such as age, gender, pregnancy, influenza type, region of the country, presence of asthma or other comorbidity, etc. Whether the VE value is the “truth in the universe” is related to having enough subjects in each analyzed group and the degree to which the studied populations actually represent the whole country. So, VE is more accurate when there are large subject numbers.
Remember also that VE is usually calculated from outpatients, so it does not really measure all the benefits of vaccination. Prevention rates for severe influenza (such as influenza hospitalizations) are higher but usually unavailable until after the entire season.
VE studies generally measure real-world and likely worst-case-scenario benefit for the overall population being protected against outpatient influenza medical visits.
Vaccine efficacy2,3
Vaccine efficacy measures how the vaccine performs under ideal circumstances in a regimented protocol in relatively normal hosts – likely the best-case-scenario benefit. Vaccine efficacy is the percent difference in confirmed influenza episodes in vaccinees getting the “experimental” vaccine vs. episodes in nonvaccinees (or vaccinees getting an established vaccine). Vaccine efficacy, therefore, is usually calculated based on prospective well-controlled studies under ideal circumstances in subjects who received their vaccines on time per the recommended schedule. Most such studies are performed on otherwise healthy children or adults, with most comorbidities excluded. The “experimental” vaccine is generally from a single manufacturer from a single lot, and chain-of-custody is well controlled. The vaccine is administered at selected research sites according to a strict protocol; vaccine storage is ensured to be as recommended.
Confidence intervals
To assess whether the “protection” is “significant,” the calculations derive 95% confidence intervals (CI). If the 95% CI range is wide, such as many tens of percents, then there is less confidence that the calculation is correct. And if the lower CI is less than 0, then the result is not significant. For example, a VE of 20% is not highly protective, but can be significant if the 95% CI ranges from 10 to 28 (the lower value of 10 is above zero). It would not be significant if the 95% CI lower limit was –10. Values for seasons 2004-2005 and 2005-2006 were similar to this. Consider however that a VE of 55% seems great, but may not be significant if the 95% CI range is –20 to 89 (the lower value is less than zero). In the ideal world, the VE would be greater than 50% and the 95% CI range would be tight with the lower CI value far above zero; for example, VE of 70% with 95% CI ranging from 60 to 80. The 2010-2011 season was close to this.
Type and age-specific VE
Aside from overall VE, there are subset analyses that can be revealing. This year there are the concerning mid-season VE estimates of approximately 25% for the United States and 17% in Canada, for one specific type, H3N2, which unfortunately has been the dominant circulating U.S. type. That number is what everybody seems to have focused on. But remember influenza B becomes dominant late in most seasons (increasing at the time of writing this article). Interim 2017-2018 VE for influenza B was in the mid 60% range, making the box plot near 40% overall.
Age-related VE analysis can show difference; for example, the best benefit for H3N2 this season has been in young children and the worst in elderly and 9- to 17-year-olds.
Take-home message
The simplest way to think of overall VE is that it is the real-world, worst-case-scenario value for influenza protection by vaccine against the several circulating types of influenza. While this year’s vaccine seems less protective than we hoped, we should still feel good recommending a vaccine that can prevent 40% of overall influenza cases and that provides an additional benefit of lessening severity in many breakthrough infections. That said, we still need a better and universal influenza vaccine.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Children’s Mercy Hospital receives grant funding for Dr. Harrison’s work as an investigator from GSK for MMR and rotavirus vaccine studies, from Merck for in vitro and clinical antibiotic studies, from Allergan for clinical antibiotic studies, from Pfizer for pneumococcal seroepidemiology studies, and from Regeneron for RSV studies. Dr. Harrison received support for travel and to present seroepidemiology data at one meeting. Email him at [email protected].
References
1. MMWR Weekly. 2017 Feb 17;66(6):167-71.
2. Dev Biol Stand. 1998;95:195-201.
3. Lancet Infect Dis. 2012 Jan;12(1):36-44.
During the influenza portion of the Feb. 21, 2018, Centers for Diseases Control and Prevention’s Advisory Committee on Immunization Practices meeting, two pleas from the audience asked the CDC/ACIP to make messages very clear about how protective influenza vaccine really is.
We hear apparently conflicting percentages from Australia, Canada, Europe, and the United States from the many stories/press releases in the news media and from official public health outlets. And the gloomiest ones get the most exposure.1 It can be confusing even for medical care providers who are supposed to advise families on such matters.
A key misunderstanding in many medical and lay news stories is about what vaccine effectiveness and vaccine efficacy really mean. What? Aren’t those the same thing? Nope. They are quite different. And are we sure of what those 95% confidence intervals (CI) mean? Let’s review the “math” so we can explain this to families.
Vaccine effectiveness (VE)2,3
The first thing to know is that the CDC and similar public health agencies in other countries do not report vaccine efficacy. Instead, the percentage reported is VE during (interim estimated VE) and just after (final adjusted VE) each influenza season. This means that VE is generally a retrospective analysis of data, most of which were collected prospectively. Further, VE is likely the worst case scenario. VE is a measure of real-world benefit to patients for whom vaccine is recommended, by analyzing specific geographically diverse populations (population-based) without excluding most underlying illness or comorbidities (note that immunosuppressed persons are excluded). Subjects in VE studies receive their vaccine in the real world and, therefore, vaccinees may receive their vaccines from any number of the usual outlets (e.g., primary care provider, urgent care or emergency department, public health department, pharmacy, school, or nursing home). There are multiple lots of multiple brands from multiple vaccine manufacturers. Children who need two doses of influenza vaccine do not necessarily receive those doses according to the package insert’s schedule. VE studies do not have the capability to confirm that vaccine was stored, handled, and administered in a precisely correct manner according to manufacturer’s and CDC’s recommendations.
VE is calculated using a “test-negative” (case-control) analysis of patients presenting with acute respiratory infections (ARIs). People who are not in vaccine research can find this methodology confusing. Briefly, the VE compares the odds of vaccination in ARIs due to confirmed influenza to the odds of vaccination in ARIs not due to influenza. Additional statistical tools can adjust VE for specific factors. VE is also calculated by factors of interest, such as age, gender, pregnancy, influenza type, region of the country, presence of asthma or other comorbidity, etc. Whether the VE value is the “truth in the universe” is related to having enough subjects in each analyzed group and the degree to which the studied populations actually represent the whole country. So, VE is more accurate when there are large subject numbers.
Remember also that VE is usually calculated from outpatients, so it does not really measure all the benefits of vaccination. Prevention rates for severe influenza (such as influenza hospitalizations) are higher but usually unavailable until after the entire season.
VE studies generally measure real-world and likely worst-case-scenario benefit for the overall population being protected against outpatient influenza medical visits.
Vaccine efficacy2,3
Vaccine efficacy measures how the vaccine performs under ideal circumstances in a regimented protocol in relatively normal hosts – likely the best-case-scenario benefit. Vaccine efficacy is the percent difference in confirmed influenza episodes in vaccinees getting the “experimental” vaccine vs. episodes in nonvaccinees (or vaccinees getting an established vaccine). Vaccine efficacy, therefore, is usually calculated based on prospective well-controlled studies under ideal circumstances in subjects who received their vaccines on time per the recommended schedule. Most such studies are performed on otherwise healthy children or adults, with most comorbidities excluded. The “experimental” vaccine is generally from a single manufacturer from a single lot, and chain-of-custody is well controlled. The vaccine is administered at selected research sites according to a strict protocol; vaccine storage is ensured to be as recommended.
Confidence intervals
To assess whether the “protection” is “significant,” the calculations derive 95% confidence intervals (CI). If the 95% CI range is wide, such as many tens of percents, then there is less confidence that the calculation is correct. And if the lower CI is less than 0, then the result is not significant. For example, a VE of 20% is not highly protective, but can be significant if the 95% CI ranges from 10 to 28 (the lower value of 10 is above zero). It would not be significant if the 95% CI lower limit was –10. Values for seasons 2004-2005 and 2005-2006 were similar to this. Consider however that a VE of 55% seems great, but may not be significant if the 95% CI range is –20 to 89 (the lower value is less than zero). In the ideal world, the VE would be greater than 50% and the 95% CI range would be tight with the lower CI value far above zero; for example, VE of 70% with 95% CI ranging from 60 to 80. The 2010-2011 season was close to this.
Type and age-specific VE
Aside from overall VE, there are subset analyses that can be revealing. This year there are the concerning mid-season VE estimates of approximately 25% for the United States and 17% in Canada, for one specific type, H3N2, which unfortunately has been the dominant circulating U.S. type. That number is what everybody seems to have focused on. But remember influenza B becomes dominant late in most seasons (increasing at the time of writing this article). Interim 2017-2018 VE for influenza B was in the mid 60% range, making the box plot near 40% overall.
Age-related VE analysis can show difference; for example, the best benefit for H3N2 this season has been in young children and the worst in elderly and 9- to 17-year-olds.
Take-home message
The simplest way to think of overall VE is that it is the real-world, worst-case-scenario value for influenza protection by vaccine against the several circulating types of influenza. While this year’s vaccine seems less protective than we hoped, we should still feel good recommending a vaccine that can prevent 40% of overall influenza cases and that provides an additional benefit of lessening severity in many breakthrough infections. That said, we still need a better and universal influenza vaccine.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Children’s Mercy Hospital receives grant funding for Dr. Harrison’s work as an investigator from GSK for MMR and rotavirus vaccine studies, from Merck for in vitro and clinical antibiotic studies, from Allergan for clinical antibiotic studies, from Pfizer for pneumococcal seroepidemiology studies, and from Regeneron for RSV studies. Dr. Harrison received support for travel and to present seroepidemiology data at one meeting. Email him at [email protected].
References
1. MMWR Weekly. 2017 Feb 17;66(6):167-71.
2. Dev Biol Stand. 1998;95:195-201.
3. Lancet Infect Dis. 2012 Jan;12(1):36-44.
Fluarix Quadrivalent effective in very young, simplifies flu shots for all ages
Fluarix Quadrivalent is highly effective against moderate and severe flu strains in children aged 6-35 months, and has the potential to simplify influenza vaccinations for all ages, according the results of a phase 3 clinical trial presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
“Fluarix Quadrivalent, at the 0.5-mL dose in young children 6 to 35 months of age, demonstrated efficacy of 63.2% against moderate to severe influenza and 49.8% against any severity influenza disease” stated Leonard Friedland, MD, director of scientific affairs and public health, Vaccines North America, GlaxoSmithKline. Dr. Friedland, a pediatrician in Pennsylvania, said that a standard 0.5-mL dose of Fluarix Quadrivalent has practice-changing implications for physicians. “The use of a 0.5-mL dose (15 mcg per strain) for all persons aged 6 months and older potentially simplifies influenza vaccination by allowing the same vaccine dose to be used for all eligible individuals.”
The high efficacy of Fluarix against almost half of all influenza strains, regardless of severity, and in preventing moderate to severe influenza, correlated with a reduction in health care utilization by pediatric influenza patients, he said. Visits to general practitioners and emergency departments decreased by 47% and 79%, respectively, in children aged 6-35 months. Influenza-associated antibiotic use in these pediatric influenza patients also decreased by 50%.
These findings were the result of D-QIV-004, a phase 3, observer-blinded, randomized trial of 12,018 children aged 6-35 months. These children were split into five cohorts, each in a different influenza season. The study spanned 13 countries and ran from October 2011 to December 2014. To determine the safety of Fluarix, the study utilized noninfluenza vaccine comparator vaccines that were age appropriate, including Prevnar 13, Havrix, and Varivax.
A majority of the children in the study (98%) were vaccine unprimed (had never received two doses of seasonal influenza vaccine) and received two doses of Fluarix. The remaining children received one dose.
On Jan. 11, 2018, the Food and Drug Administration expanded the indication of Fluarix Quadrivalent to include use in persons 6 months and older. Previously, it was approved only for persons 3 years and older.
“These study results support universal vaccination of all individuals from 6 months of age [with Fluarix] to prevent influenza.” Dr. Friedland concluded.
For live updates and information concerning influenza, visit the CDC website.
[email protected]
SOURCE: D-QIV-004.
Fluarix Quadrivalent is highly effective against moderate and severe flu strains in children aged 6-35 months, and has the potential to simplify influenza vaccinations for all ages, according the results of a phase 3 clinical trial presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
“Fluarix Quadrivalent, at the 0.5-mL dose in young children 6 to 35 months of age, demonstrated efficacy of 63.2% against moderate to severe influenza and 49.8% against any severity influenza disease” stated Leonard Friedland, MD, director of scientific affairs and public health, Vaccines North America, GlaxoSmithKline. Dr. Friedland, a pediatrician in Pennsylvania, said that a standard 0.5-mL dose of Fluarix Quadrivalent has practice-changing implications for physicians. “The use of a 0.5-mL dose (15 mcg per strain) for all persons aged 6 months and older potentially simplifies influenza vaccination by allowing the same vaccine dose to be used for all eligible individuals.”
The high efficacy of Fluarix against almost half of all influenza strains, regardless of severity, and in preventing moderate to severe influenza, correlated with a reduction in health care utilization by pediatric influenza patients, he said. Visits to general practitioners and emergency departments decreased by 47% and 79%, respectively, in children aged 6-35 months. Influenza-associated antibiotic use in these pediatric influenza patients also decreased by 50%.
These findings were the result of D-QIV-004, a phase 3, observer-blinded, randomized trial of 12,018 children aged 6-35 months. These children were split into five cohorts, each in a different influenza season. The study spanned 13 countries and ran from October 2011 to December 2014. To determine the safety of Fluarix, the study utilized noninfluenza vaccine comparator vaccines that were age appropriate, including Prevnar 13, Havrix, and Varivax.
A majority of the children in the study (98%) were vaccine unprimed (had never received two doses of seasonal influenza vaccine) and received two doses of Fluarix. The remaining children received one dose.
On Jan. 11, 2018, the Food and Drug Administration expanded the indication of Fluarix Quadrivalent to include use in persons 6 months and older. Previously, it was approved only for persons 3 years and older.
“These study results support universal vaccination of all individuals from 6 months of age [with Fluarix] to prevent influenza.” Dr. Friedland concluded.
For live updates and information concerning influenza, visit the CDC website.
[email protected]
SOURCE: D-QIV-004.
Fluarix Quadrivalent is highly effective against moderate and severe flu strains in children aged 6-35 months, and has the potential to simplify influenza vaccinations for all ages, according the results of a phase 3 clinical trial presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
“Fluarix Quadrivalent, at the 0.5-mL dose in young children 6 to 35 months of age, demonstrated efficacy of 63.2% against moderate to severe influenza and 49.8% against any severity influenza disease” stated Leonard Friedland, MD, director of scientific affairs and public health, Vaccines North America, GlaxoSmithKline. Dr. Friedland, a pediatrician in Pennsylvania, said that a standard 0.5-mL dose of Fluarix Quadrivalent has practice-changing implications for physicians. “The use of a 0.5-mL dose (15 mcg per strain) for all persons aged 6 months and older potentially simplifies influenza vaccination by allowing the same vaccine dose to be used for all eligible individuals.”
The high efficacy of Fluarix against almost half of all influenza strains, regardless of severity, and in preventing moderate to severe influenza, correlated with a reduction in health care utilization by pediatric influenza patients, he said. Visits to general practitioners and emergency departments decreased by 47% and 79%, respectively, in children aged 6-35 months. Influenza-associated antibiotic use in these pediatric influenza patients also decreased by 50%.
These findings were the result of D-QIV-004, a phase 3, observer-blinded, randomized trial of 12,018 children aged 6-35 months. These children were split into five cohorts, each in a different influenza season. The study spanned 13 countries and ran from October 2011 to December 2014. To determine the safety of Fluarix, the study utilized noninfluenza vaccine comparator vaccines that were age appropriate, including Prevnar 13, Havrix, and Varivax.
A majority of the children in the study (98%) were vaccine unprimed (had never received two doses of seasonal influenza vaccine) and received two doses of Fluarix. The remaining children received one dose.
On Jan. 11, 2018, the Food and Drug Administration expanded the indication of Fluarix Quadrivalent to include use in persons 6 months and older. Previously, it was approved only for persons 3 years and older.
“These study results support universal vaccination of all individuals from 6 months of age [with Fluarix] to prevent influenza.” Dr. Friedland concluded.
For live updates and information concerning influenza, visit the CDC website.
[email protected]
SOURCE: D-QIV-004.
FROM AN ACIP MEETING
Key clinical point: The high efficacy of Fluarix against almost half of all influenza strains, regardless of severity, as well as preventing moderate to severe influenza, reduced health care utilization by pediatric influenza patients.
Major finding: Fluarix Quadrivalent was effective against moderate to severe influenza in 63.2% and against any severity of influenza in 49.8% of children aged 6-35 months.
Study details: A phase 3, observer-blinded, randomized trial of 12,018 children aged 6-35 months, in which the children were split into five cohorts, each in a different influenza season from October 2011 to December 2014.
Disclosures: No disclosures were reported.
Source: The D-QIV-004 study.
Flu season shows signs of slowing
Flu-related outpatient activity dropped for the second week in a row as the cumulative hospitalization rate continues to rise, according to data from the Centers for Disease Control and Prevention.
For the week ending Feb. 17, the proportion of outpatient visits for influenza-like illness (ILI) was 6.4%, which was down from 7.4% the previous week (Feb. 10) and down from the seasonal high of 7.5% set 2 weeks earlier, the CDC said in its weekly flu surveillance report. The rate for the week ending Feb. 10 was reported last week as 7.5%, but it has been revised downward.
State reports of ILI activity support the decreases seen in the national outpatient rate. There were 33 states at level 10 on the CDC’s 1-10 scale for the week ending Feb. 17 – down from 39 the week before – and a total of 41 states in the “high” range from levels 8-10, compared with 45 the previous week, CDC’s FluView website shows.
Reports of flu-related pediatric deaths continued: 13 deaths were reported during the week, although 9 occurred in previous weeks. The total for the 2017-2018 season is now 97. There were 110 pediatric deaths in the entire 2016-2017 season, 93 during the 2015-2016 season, and 149 in 2014-2015, the CDC said.
Flu-related outpatient activity dropped for the second week in a row as the cumulative hospitalization rate continues to rise, according to data from the Centers for Disease Control and Prevention.
For the week ending Feb. 17, the proportion of outpatient visits for influenza-like illness (ILI) was 6.4%, which was down from 7.4% the previous week (Feb. 10) and down from the seasonal high of 7.5% set 2 weeks earlier, the CDC said in its weekly flu surveillance report. The rate for the week ending Feb. 10 was reported last week as 7.5%, but it has been revised downward.
State reports of ILI activity support the decreases seen in the national outpatient rate. There were 33 states at level 10 on the CDC’s 1-10 scale for the week ending Feb. 17 – down from 39 the week before – and a total of 41 states in the “high” range from levels 8-10, compared with 45 the previous week, CDC’s FluView website shows.
Reports of flu-related pediatric deaths continued: 13 deaths were reported during the week, although 9 occurred in previous weeks. The total for the 2017-2018 season is now 97. There were 110 pediatric deaths in the entire 2016-2017 season, 93 during the 2015-2016 season, and 149 in 2014-2015, the CDC said.
Flu-related outpatient activity dropped for the second week in a row as the cumulative hospitalization rate continues to rise, according to data from the Centers for Disease Control and Prevention.
For the week ending Feb. 17, the proportion of outpatient visits for influenza-like illness (ILI) was 6.4%, which was down from 7.4% the previous week (Feb. 10) and down from the seasonal high of 7.5% set 2 weeks earlier, the CDC said in its weekly flu surveillance report. The rate for the week ending Feb. 10 was reported last week as 7.5%, but it has been revised downward.
State reports of ILI activity support the decreases seen in the national outpatient rate. There were 33 states at level 10 on the CDC’s 1-10 scale for the week ending Feb. 17 – down from 39 the week before – and a total of 41 states in the “high” range from levels 8-10, compared with 45 the previous week, CDC’s FluView website shows.
Reports of flu-related pediatric deaths continued: 13 deaths were reported during the week, although 9 occurred in previous weeks. The total for the 2017-2018 season is now 97. There were 110 pediatric deaths in the entire 2016-2017 season, 93 during the 2015-2016 season, and 149 in 2014-2015, the CDC said.
Flu increase may be slowing
A bit of revisionist history has outpatient influenza activity at a lower level than was reported last week, even though it hasn’t dropped.
The proportion of outpatient visits for influenza-like illness (ILI) for the week ending Feb. 10 was 7.5%, according to the Centers for Disease Control. That is lower than the 7.7% previously reported for the week ending Feb. 3, which would seem to be a drop, but the CDC also has revised that earlier number to 7.5%, so there is no change. (This is not the first time an earlier ILI level has been retroactively lowered: The figure reported for the week ending Jan. 13 was revised in the following report from 6.3% down to 6.0%.)
Hospital visits, however, continue to rise at record levels. The cumulative rate for the week ending Feb. 10 was 67.9 visits per 100,000 population, which is higher than the same week for the 2014-2015 (52.9 per 100,000) when flu hospitalizations for the season hit a high of 710,000. Flu-related pediatric deaths also went up, with 22 new reports; this brings the total to 84 for the 2017-2018 season.
A bit of revisionist history has outpatient influenza activity at a lower level than was reported last week, even though it hasn’t dropped.
The proportion of outpatient visits for influenza-like illness (ILI) for the week ending Feb. 10 was 7.5%, according to the Centers for Disease Control. That is lower than the 7.7% previously reported for the week ending Feb. 3, which would seem to be a drop, but the CDC also has revised that earlier number to 7.5%, so there is no change. (This is not the first time an earlier ILI level has been retroactively lowered: The figure reported for the week ending Jan. 13 was revised in the following report from 6.3% down to 6.0%.)
Hospital visits, however, continue to rise at record levels. The cumulative rate for the week ending Feb. 10 was 67.9 visits per 100,000 population, which is higher than the same week for the 2014-2015 (52.9 per 100,000) when flu hospitalizations for the season hit a high of 710,000. Flu-related pediatric deaths also went up, with 22 new reports; this brings the total to 84 for the 2017-2018 season.
A bit of revisionist history has outpatient influenza activity at a lower level than was reported last week, even though it hasn’t dropped.
The proportion of outpatient visits for influenza-like illness (ILI) for the week ending Feb. 10 was 7.5%, according to the Centers for Disease Control. That is lower than the 7.7% previously reported for the week ending Feb. 3, which would seem to be a drop, but the CDC also has revised that earlier number to 7.5%, so there is no change. (This is not the first time an earlier ILI level has been retroactively lowered: The figure reported for the week ending Jan. 13 was revised in the following report from 6.3% down to 6.0%.)
Hospital visits, however, continue to rise at record levels. The cumulative rate for the week ending Feb. 10 was 67.9 visits per 100,000 population, which is higher than the same week for the 2014-2015 (52.9 per 100,000) when flu hospitalizations for the season hit a high of 710,000. Flu-related pediatric deaths also went up, with 22 new reports; this brings the total to 84 for the 2017-2018 season.
FROM THE CDC WEEKLY U.S. INFLUENZA SURVEILLANCE REPORT
MMWR: Current flu vaccine does not protect elderly
, according to the Feb. 16 issue of Morbidity and Mortality Weekly Report.
The elderly are not among them. Although the vaccine was somewhat protective in children and adults up to 49 years old, “no statistically significant protection was observed in other age groups,” including people 65 years and older, reported investigators led by Brendan Flannery, PhD, of the Centers for Disease Control and Prevention influenza division.
They also reported that the cumulative hospitalization rate attributed to laboratory-confirmed influenza for the week ending Feb. 3, 2018 (59.9/100,000), exceeded the rate for the same week in 2014-2015 (50.9/100,000), an A(H3N2) virus–predominant season, and is the highest rate observed for this week since the system expanded to include adults during the 2005-2006 season.
This year’s overall effectiveness rating was in contrast to the 2016-2017 seasonal effectiveness of 48% (MMWR. 2017 Feb 17;66[6];167-71).
The CDC noted that influenza is going to be active for several more weeks, so “vaccination is still recommended,” but “treatment with influenza antiviral medications, where appropriate, is especially important this season.” Meanwhile, “influenza vaccines with improved effectiveness are needed,” the CDC said.
The estimates are based on 4,562 patients 6 months to over 65 years old presenting with acute respiratory illness in 2018 from Nov. 2 to Feb. 3 at five outpatient medical clinics scattered across the United States. Nasal and oropharyngeal swabs were tested with reverse transcription polymerase chain reaction for the presence of influenza viruses; 413 subjects were 65 years or older.
Vaccine effectiveness against the less common virus A(H1N1)pdm09 was 67%, and 42% against the even rarer influenza B viruses. Estimates were adjusted for a range of confounders, including study site, age, general health, and week of illness. Vaccination rates ranged from 45% to 59% across the study sites; 38% of the subjects tested positive for influenza, most for type A viruses. The shot didn’t work too well: 43% of the influenza cases had gotten it.
The 25% effectiveness against A(H3N2) is a bit higher than recent reports of 17% from Canada and 10% from Australia, but similar to the 32% efficacy reported in the United States for the 2016-2017 season.
“These interim estimates reflect ongoing challenges with the A(H3N2) vaccine component since the 2011-12 season,” the investigators wrote. “Multiple factors might be contributing to the reported [vaccine effectiveness] against A(H3N2) viruses this season. … Genetic changes in the vaccine virus hemagglutinin protein that arise during passage in eggs might result in a vaccine immune response that is less effective against circulating viruses.”
On a related note, on Feb. 18, Senators Edward J. Markey (D-Mass.), Richard Blumenthal (D-Conn.), and Amy Klobuchar (D-Minn.) held a press conference to announce they were introducing the Flu Vaccine Bill to dedicate $1 billion over a 5-year period in order to develop a flu vaccine that could provide lifetime protection.
The investigators had no conflicts of interest.
SOURCE: Flannery B. et al. MMWR. 2018 Feb 16;67(6):180-5; Budd A. et al. MMWR. 2018 Feb 16;67(6):169-79.
, according to the Feb. 16 issue of Morbidity and Mortality Weekly Report.
The elderly are not among them. Although the vaccine was somewhat protective in children and adults up to 49 years old, “no statistically significant protection was observed in other age groups,” including people 65 years and older, reported investigators led by Brendan Flannery, PhD, of the Centers for Disease Control and Prevention influenza division.
They also reported that the cumulative hospitalization rate attributed to laboratory-confirmed influenza for the week ending Feb. 3, 2018 (59.9/100,000), exceeded the rate for the same week in 2014-2015 (50.9/100,000), an A(H3N2) virus–predominant season, and is the highest rate observed for this week since the system expanded to include adults during the 2005-2006 season.
This year’s overall effectiveness rating was in contrast to the 2016-2017 seasonal effectiveness of 48% (MMWR. 2017 Feb 17;66[6];167-71).
The CDC noted that influenza is going to be active for several more weeks, so “vaccination is still recommended,” but “treatment with influenza antiviral medications, where appropriate, is especially important this season.” Meanwhile, “influenza vaccines with improved effectiveness are needed,” the CDC said.
The estimates are based on 4,562 patients 6 months to over 65 years old presenting with acute respiratory illness in 2018 from Nov. 2 to Feb. 3 at five outpatient medical clinics scattered across the United States. Nasal and oropharyngeal swabs were tested with reverse transcription polymerase chain reaction for the presence of influenza viruses; 413 subjects were 65 years or older.
Vaccine effectiveness against the less common virus A(H1N1)pdm09 was 67%, and 42% against the even rarer influenza B viruses. Estimates were adjusted for a range of confounders, including study site, age, general health, and week of illness. Vaccination rates ranged from 45% to 59% across the study sites; 38% of the subjects tested positive for influenza, most for type A viruses. The shot didn’t work too well: 43% of the influenza cases had gotten it.
The 25% effectiveness against A(H3N2) is a bit higher than recent reports of 17% from Canada and 10% from Australia, but similar to the 32% efficacy reported in the United States for the 2016-2017 season.
“These interim estimates reflect ongoing challenges with the A(H3N2) vaccine component since the 2011-12 season,” the investigators wrote. “Multiple factors might be contributing to the reported [vaccine effectiveness] against A(H3N2) viruses this season. … Genetic changes in the vaccine virus hemagglutinin protein that arise during passage in eggs might result in a vaccine immune response that is less effective against circulating viruses.”
On a related note, on Feb. 18, Senators Edward J. Markey (D-Mass.), Richard Blumenthal (D-Conn.), and Amy Klobuchar (D-Minn.) held a press conference to announce they were introducing the Flu Vaccine Bill to dedicate $1 billion over a 5-year period in order to develop a flu vaccine that could provide lifetime protection.
The investigators had no conflicts of interest.
SOURCE: Flannery B. et al. MMWR. 2018 Feb 16;67(6):180-5; Budd A. et al. MMWR. 2018 Feb 16;67(6):169-79.
, according to the Feb. 16 issue of Morbidity and Mortality Weekly Report.
The elderly are not among them. Although the vaccine was somewhat protective in children and adults up to 49 years old, “no statistically significant protection was observed in other age groups,” including people 65 years and older, reported investigators led by Brendan Flannery, PhD, of the Centers for Disease Control and Prevention influenza division.
They also reported that the cumulative hospitalization rate attributed to laboratory-confirmed influenza for the week ending Feb. 3, 2018 (59.9/100,000), exceeded the rate for the same week in 2014-2015 (50.9/100,000), an A(H3N2) virus–predominant season, and is the highest rate observed for this week since the system expanded to include adults during the 2005-2006 season.
This year’s overall effectiveness rating was in contrast to the 2016-2017 seasonal effectiveness of 48% (MMWR. 2017 Feb 17;66[6];167-71).
The CDC noted that influenza is going to be active for several more weeks, so “vaccination is still recommended,” but “treatment with influenza antiviral medications, where appropriate, is especially important this season.” Meanwhile, “influenza vaccines with improved effectiveness are needed,” the CDC said.
The estimates are based on 4,562 patients 6 months to over 65 years old presenting with acute respiratory illness in 2018 from Nov. 2 to Feb. 3 at five outpatient medical clinics scattered across the United States. Nasal and oropharyngeal swabs were tested with reverse transcription polymerase chain reaction for the presence of influenza viruses; 413 subjects were 65 years or older.
Vaccine effectiveness against the less common virus A(H1N1)pdm09 was 67%, and 42% against the even rarer influenza B viruses. Estimates were adjusted for a range of confounders, including study site, age, general health, and week of illness. Vaccination rates ranged from 45% to 59% across the study sites; 38% of the subjects tested positive for influenza, most for type A viruses. The shot didn’t work too well: 43% of the influenza cases had gotten it.
The 25% effectiveness against A(H3N2) is a bit higher than recent reports of 17% from Canada and 10% from Australia, but similar to the 32% efficacy reported in the United States for the 2016-2017 season.
“These interim estimates reflect ongoing challenges with the A(H3N2) vaccine component since the 2011-12 season,” the investigators wrote. “Multiple factors might be contributing to the reported [vaccine effectiveness] against A(H3N2) viruses this season. … Genetic changes in the vaccine virus hemagglutinin protein that arise during passage in eggs might result in a vaccine immune response that is less effective against circulating viruses.”
On a related note, on Feb. 18, Senators Edward J. Markey (D-Mass.), Richard Blumenthal (D-Conn.), and Amy Klobuchar (D-Minn.) held a press conference to announce they were introducing the Flu Vaccine Bill to dedicate $1 billion over a 5-year period in order to develop a flu vaccine that could provide lifetime protection.
The investigators had no conflicts of interest.
SOURCE: Flannery B. et al. MMWR. 2018 Feb 16;67(6):180-5; Budd A. et al. MMWR. 2018 Feb 16;67(6):169-79.
FROM MORBIDITY AND MORTALITY WEEKLY REPORT
This is what a flu pandemic looks like
For the week ending Feb. 3, 2018, the proportion of outpatient visits for influenza-like illness (ILI) was 7.7%, which would appear to equal the mark of 7.7% set in October of 2009. The earlier 7.7%, however, is rounded down from 7.715%, while the current mark is rounded up from 7.653%, data from the CDC’s Fluview website show.
Deaths attributed to pneumonia and influenza were above the epidemic threshold set by the National Center for Health Statistics Mortality Surveillance system, acting CDC director Anne Schuchat, MD, said in a teleconference sponsored by the agency.
ILI activity was at level 10 on the CDC’s 1-10 scale in 41 states, compared with 34 the week before, and was categorized in the “high” range (levels 8-10) in another 3 states and Puerto Rico, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network. In California, which was noted as a possible bright spot last week by Dr. Schuchat because activity there had been decreasing, the ILI level went back up to level 9 after being at 7 the week before.
Flu-related hospitalizations are continuing to rise at a record clip, with the cumulative rate for the week of Feb. 3 at 59.9 per 100,000 population, the CDC reported. A total of 1 in 10 hospital-based deaths last week were related to influenza. At this point in the 2014-2015 flu season – which has the highest number of hospitalizations at 710,000 – the hospitalization rate was only 50.9 per 100,000 population.
There were 10 pediatric deaths reported for the week ending Feb. 3, although 9 occurred in previous weeks. There have been 63 flu-related deaths among children so far during the 2017-2018 season.
Dr. Schuchat continued to recommend members of the public to get a flu shot and to stay home if they are feeling sick.
“What could be mild symptoms for you could be deadly for someone else,” Dr. Schuchat said, adding that antiviral medications remain important. “Physicians do not have to wait for confirmatory flu testing. They should begin treatment with antiviral drugs immediately in they suspect they have a severely ill or a high risk patient.”
“Flu vaccines often have lower effectiveness against H3N1 viruses. However, some protection is better than none. The vaccine’s effectiveness against other flu viruses, like B and H1N1, is better. Because of the ongoing intensity of the flu season and the increasing circulation of influenza B and h1n1, we do continue to recommend vaccination even this late in the season.”
Dr. Schuchat stressed the importance of the pneumococcal pneumonia vaccine. “Flu can make people more vulnerable to secondary infections like bacterial pneumonia. We recommend people aged 65 and over get a pneumococcal pneumonia vaccine,” she said.
For the week ending Feb. 3, 2018, the proportion of outpatient visits for influenza-like illness (ILI) was 7.7%, which would appear to equal the mark of 7.7% set in October of 2009. The earlier 7.7%, however, is rounded down from 7.715%, while the current mark is rounded up from 7.653%, data from the CDC’s Fluview website show.
Deaths attributed to pneumonia and influenza were above the epidemic threshold set by the National Center for Health Statistics Mortality Surveillance system, acting CDC director Anne Schuchat, MD, said in a teleconference sponsored by the agency.
ILI activity was at level 10 on the CDC’s 1-10 scale in 41 states, compared with 34 the week before, and was categorized in the “high” range (levels 8-10) in another 3 states and Puerto Rico, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network. In California, which was noted as a possible bright spot last week by Dr. Schuchat because activity there had been decreasing, the ILI level went back up to level 9 after being at 7 the week before.
Flu-related hospitalizations are continuing to rise at a record clip, with the cumulative rate for the week of Feb. 3 at 59.9 per 100,000 population, the CDC reported. A total of 1 in 10 hospital-based deaths last week were related to influenza. At this point in the 2014-2015 flu season – which has the highest number of hospitalizations at 710,000 – the hospitalization rate was only 50.9 per 100,000 population.
There were 10 pediatric deaths reported for the week ending Feb. 3, although 9 occurred in previous weeks. There have been 63 flu-related deaths among children so far during the 2017-2018 season.
Dr. Schuchat continued to recommend members of the public to get a flu shot and to stay home if they are feeling sick.
“What could be mild symptoms for you could be deadly for someone else,” Dr. Schuchat said, adding that antiviral medications remain important. “Physicians do not have to wait for confirmatory flu testing. They should begin treatment with antiviral drugs immediately in they suspect they have a severely ill or a high risk patient.”
“Flu vaccines often have lower effectiveness against H3N1 viruses. However, some protection is better than none. The vaccine’s effectiveness against other flu viruses, like B and H1N1, is better. Because of the ongoing intensity of the flu season and the increasing circulation of influenza B and h1n1, we do continue to recommend vaccination even this late in the season.”
Dr. Schuchat stressed the importance of the pneumococcal pneumonia vaccine. “Flu can make people more vulnerable to secondary infections like bacterial pneumonia. We recommend people aged 65 and over get a pneumococcal pneumonia vaccine,” she said.
For the week ending Feb. 3, 2018, the proportion of outpatient visits for influenza-like illness (ILI) was 7.7%, which would appear to equal the mark of 7.7% set in October of 2009. The earlier 7.7%, however, is rounded down from 7.715%, while the current mark is rounded up from 7.653%, data from the CDC’s Fluview website show.
Deaths attributed to pneumonia and influenza were above the epidemic threshold set by the National Center for Health Statistics Mortality Surveillance system, acting CDC director Anne Schuchat, MD, said in a teleconference sponsored by the agency.
ILI activity was at level 10 on the CDC’s 1-10 scale in 41 states, compared with 34 the week before, and was categorized in the “high” range (levels 8-10) in another 3 states and Puerto Rico, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network. In California, which was noted as a possible bright spot last week by Dr. Schuchat because activity there had been decreasing, the ILI level went back up to level 9 after being at 7 the week before.
Flu-related hospitalizations are continuing to rise at a record clip, with the cumulative rate for the week of Feb. 3 at 59.9 per 100,000 population, the CDC reported. A total of 1 in 10 hospital-based deaths last week were related to influenza. At this point in the 2014-2015 flu season – which has the highest number of hospitalizations at 710,000 – the hospitalization rate was only 50.9 per 100,000 population.
There were 10 pediatric deaths reported for the week ending Feb. 3, although 9 occurred in previous weeks. There have been 63 flu-related deaths among children so far during the 2017-2018 season.
Dr. Schuchat continued to recommend members of the public to get a flu shot and to stay home if they are feeling sick.
“What could be mild symptoms for you could be deadly for someone else,” Dr. Schuchat said, adding that antiviral medications remain important. “Physicians do not have to wait for confirmatory flu testing. They should begin treatment with antiviral drugs immediately in they suspect they have a severely ill or a high risk patient.”
“Flu vaccines often have lower effectiveness against H3N1 viruses. However, some protection is better than none. The vaccine’s effectiveness against other flu viruses, like B and H1N1, is better. Because of the ongoing intensity of the flu season and the increasing circulation of influenza B and h1n1, we do continue to recommend vaccination even this late in the season.”
Dr. Schuchat stressed the importance of the pneumococcal pneumonia vaccine. “Flu can make people more vulnerable to secondary infections like bacterial pneumonia. We recommend people aged 65 and over get a pneumococcal pneumonia vaccine,” she said.
FROM A CDC TELECONFERENCE
Hospitals filling as flu season worsens
Through the last full week of January, the cumulative “hospitalization rate is the highest we’ve seen,” acting Centers for Disease Control and Prevention director Anne Schuchat, MD, said. For the current season so far, the hospitalization rate stands at 51.4 per 100,000 population, putting it on pace to top the total of 710,000 flu-related admissions that occurred during the 2014-2015 season, she said in a weekly briefing Feb. 2.
Flu-related pediatric deaths also took a big jump for the week as another 16 were reported, which brings the total for the season to 53. Of the children who have died so far, only 20% were vaccinated, said Dan Jernigan, MD, MPH, director of the influenza division at the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta. He also noted that half of the children who have been hospitalized did not had an underlying condition.
The one bit of good news for the week was that activity in the West seems to be easing up, Dr. Schuchat said. The geographic spread of ILI was reported as widespread in 48 states, which is down from 49 the previous week because Oregon dropped off the list. To go along with that, the ILI activity level in California has dropped 2 weeks in a row and now stands at level 7, the CDC data show.
Through the last full week of January, the cumulative “hospitalization rate is the highest we’ve seen,” acting Centers for Disease Control and Prevention director Anne Schuchat, MD, said. For the current season so far, the hospitalization rate stands at 51.4 per 100,000 population, putting it on pace to top the total of 710,000 flu-related admissions that occurred during the 2014-2015 season, she said in a weekly briefing Feb. 2.
Flu-related pediatric deaths also took a big jump for the week as another 16 were reported, which brings the total for the season to 53. Of the children who have died so far, only 20% were vaccinated, said Dan Jernigan, MD, MPH, director of the influenza division at the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta. He also noted that half of the children who have been hospitalized did not had an underlying condition.
The one bit of good news for the week was that activity in the West seems to be easing up, Dr. Schuchat said. The geographic spread of ILI was reported as widespread in 48 states, which is down from 49 the previous week because Oregon dropped off the list. To go along with that, the ILI activity level in California has dropped 2 weeks in a row and now stands at level 7, the CDC data show.
Through the last full week of January, the cumulative “hospitalization rate is the highest we’ve seen,” acting Centers for Disease Control and Prevention director Anne Schuchat, MD, said. For the current season so far, the hospitalization rate stands at 51.4 per 100,000 population, putting it on pace to top the total of 710,000 flu-related admissions that occurred during the 2014-2015 season, she said in a weekly briefing Feb. 2.
Flu-related pediatric deaths also took a big jump for the week as another 16 were reported, which brings the total for the season to 53. Of the children who have died so far, only 20% were vaccinated, said Dan Jernigan, MD, MPH, director of the influenza division at the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta. He also noted that half of the children who have been hospitalized did not had an underlying condition.
The one bit of good news for the week was that activity in the West seems to be easing up, Dr. Schuchat said. The geographic spread of ILI was reported as widespread in 48 states, which is down from 49 the previous week because Oregon dropped off the list. To go along with that, the ILI activity level in California has dropped 2 weeks in a row and now stands at level 7, the CDC data show.
Birth cohort affected 2015-2016 flu vaccine effectiveness
The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.
Using the Influenza Vaccine Effectiveness Network, researchers analyzed data from 2,115 patients with medically attended acute respiratory illness who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 patients who tested negative for the influenza virus, from 2010-2011 to 2015-2016 (excluding the 2014-2015 influenza season).
Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.
However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.
When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.
When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.
While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.
“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.
They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.
If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.
“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.
The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.
SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.
This study proposes that influenza virus strains encountered early in life focus the immune response to later infection or vaccination on shared epitopes between the early and later strains. Supporting this hypothesis is evidence from other studies showing that 60% of the serological response to inactivated influenza vaccines is the result of boosting pre-existing antibodies, rather than the creation of new, vaccine-induced antibodies.
However there are also some flaws to this argument, and we should be careful to avoid confirmation bias. For example, the reduction in effectiveness of vaccines against A(H1N1) has been observed in North America, where this study is located, but to a lesser extent in studies conducted in other regions. Reductions in vaccine effectiveness have also been observed in other birth cohorts and during other influenza seasons.
That aside, accumulating evidence suggests that the vaccine strain be updated from A/California/7/2009 to A/Michigan/45/2015 (a clade 6B.1 strain) for the 2016-2017 influenza seasons.
Allen C. Cheng, PhD, is from the School of Public Health and Preventive Medicine at Monash University, Melbourne, and Kanta Subbarao, MBBS, is from the World Health Organization Collaborating Centre for Reference and Research on Influenza and the Peter Doherty Institute for Infection and Immunity, Australia. These comments are taken from an accompanying editorial (J Infect Dis. 2018, Jan 18. doi: 10.1093/infdis/jix635). The authors declared support from the Australian Department of Health and the Australian National Health and Medical Research Council. No conflicts of interest were declared.
This study proposes that influenza virus strains encountered early in life focus the immune response to later infection or vaccination on shared epitopes between the early and later strains. Supporting this hypothesis is evidence from other studies showing that 60% of the serological response to inactivated influenza vaccines is the result of boosting pre-existing antibodies, rather than the creation of new, vaccine-induced antibodies.
However there are also some flaws to this argument, and we should be careful to avoid confirmation bias. For example, the reduction in effectiveness of vaccines against A(H1N1) has been observed in North America, where this study is located, but to a lesser extent in studies conducted in other regions. Reductions in vaccine effectiveness have also been observed in other birth cohorts and during other influenza seasons.
That aside, accumulating evidence suggests that the vaccine strain be updated from A/California/7/2009 to A/Michigan/45/2015 (a clade 6B.1 strain) for the 2016-2017 influenza seasons.
Allen C. Cheng, PhD, is from the School of Public Health and Preventive Medicine at Monash University, Melbourne, and Kanta Subbarao, MBBS, is from the World Health Organization Collaborating Centre for Reference and Research on Influenza and the Peter Doherty Institute for Infection and Immunity, Australia. These comments are taken from an accompanying editorial (J Infect Dis. 2018, Jan 18. doi: 10.1093/infdis/jix635). The authors declared support from the Australian Department of Health and the Australian National Health and Medical Research Council. No conflicts of interest were declared.
This study proposes that influenza virus strains encountered early in life focus the immune response to later infection or vaccination on shared epitopes between the early and later strains. Supporting this hypothesis is evidence from other studies showing that 60% of the serological response to inactivated influenza vaccines is the result of boosting pre-existing antibodies, rather than the creation of new, vaccine-induced antibodies.
However there are also some flaws to this argument, and we should be careful to avoid confirmation bias. For example, the reduction in effectiveness of vaccines against A(H1N1) has been observed in North America, where this study is located, but to a lesser extent in studies conducted in other regions. Reductions in vaccine effectiveness have also been observed in other birth cohorts and during other influenza seasons.
That aside, accumulating evidence suggests that the vaccine strain be updated from A/California/7/2009 to A/Michigan/45/2015 (a clade 6B.1 strain) for the 2016-2017 influenza seasons.
Allen C. Cheng, PhD, is from the School of Public Health and Preventive Medicine at Monash University, Melbourne, and Kanta Subbarao, MBBS, is from the World Health Organization Collaborating Centre for Reference and Research on Influenza and the Peter Doherty Institute for Infection and Immunity, Australia. These comments are taken from an accompanying editorial (J Infect Dis. 2018, Jan 18. doi: 10.1093/infdis/jix635). The authors declared support from the Australian Department of Health and the Australian National Health and Medical Research Council. No conflicts of interest were declared.
The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.
Using the Influenza Vaccine Effectiveness Network, researchers analyzed data from 2,115 patients with medically attended acute respiratory illness who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 patients who tested negative for the influenza virus, from 2010-2011 to 2015-2016 (excluding the 2014-2015 influenza season).
Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.
However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.
When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.
When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.
While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.
“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.
They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.
If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.
“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.
The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.
SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.
The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.
Using the Influenza Vaccine Effectiveness Network, researchers analyzed data from 2,115 patients with medically attended acute respiratory illness who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 patients who tested negative for the influenza virus, from 2010-2011 to 2015-2016 (excluding the 2014-2015 influenza season).
Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.
However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.
When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.
When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.
While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.
“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.
They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.
If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.
“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.
The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.
SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.
FROM THE JOURNAL OF INFECTIOUS DISEASES
Key clinical point:
Major finding: The influenza vaccine effectiveness during the 2015-2016 season was just 22% in individuals born between 1958 and 1979.
Data source: A retrospective case-control study of 2,115 patients who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 negative controls.
Disclosures: The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.
Source: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.