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Oral flu vaccine protects, evokes mucosal immunity
SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*
The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.
In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.
It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.
*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.
SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.
SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*
The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.
In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.
It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.
*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.
SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.
SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*
The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.
In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.
It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.
*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.
SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.
REPORTING FROM IDWEEK 2018
Flu outbreaks may be more intense in small cities
Influenza outbreaks in the United States tend to be concentrated and intense in small cities and more evenly spread throughout the season in large cities, results of a recent study show.
Swings in humidity further intensified the influenza spikes in small cities, but didn’t seem to have as much of an effect in large cities, the results suggest.
These findings help explain differences in influenza transmission patterns between cities that have similar climates and virus epidemiology, according to researcher Benjamin D. Dalziel, PhD, of the departments of integrative biology and mathematics at Oregon State University in Corvallis.
“City size and structure can play a role in determining how other factors such as climate affect and influence transmission,” Dr. Dalziel said in a press conference.
“Our results show how metropolises play a disproportionately important role in this process, as epidemic foci, and as potential sentinel hubs, where epidemiological observatories could integrate local strain dynamics to predict larger-scale patterns. As the growth and form of cities affect their function as climate-driven incubators of infectious disease, it may be possible to design smarter cities that better control epidemics in the face of accelerating global change,” the researchers wrote in their study.
Dr. Dalziel and his coauthors analyzed the weekly incidence of influenza-like illness across 603 U.S. ZIP codes using data obtained from medical claims from 2002 to 2008. They used epidemic intensity as a summary statistic to compare cities. By this variable, low epidemic intensity indicated a diffuse spread evenly across weeks of the flu season, whereas high epidemic intensity indicated intensively focused outbreaks on particular weeks.
In small cities, epidemics were more intensely focused on shorter periods at the peak of flu season, they found. In large cities, incidence was more diffuse, according to results published in Science.
Patterns of where people live and work in a city may account for the more diffuse and prolonged outbreaks seen in large cities, the authors wrote. Large cities have organized population movement patterns and crowding. In more highly established work locations, for example, the population density is pronounced during the day.
“We found the structure makes a difference for how the flu spreads at different times of year,” Dr. Dalziel said of the study, which used U.S. Census data to evaluate spatial population distributions. “In large cities with more highly organized patterns, conditions play a relatively smaller role in flu transmission.”
Humidity’s lower impact on outbreaks in large cities might also be explained by population effects: “If an infected person is sitting beside you, it matters less what the specific humidity is,” Dr. Dalziel said, adding that the proximity helps the virus find hosts even when climatic conditions are not at their most favorable.
The study findings may have implications for health care resources in small cities, which could be strained by intense outbreaks, said coinvestigator Cecile Viboud, PhD, of the Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Md.
Intense outbreaks could overload the health care system, making it challenging to respond, especially around the peak of the epidemic. Pressure on the health care system may be less intense in cities such as Miami or New York, where flu epidemics are more diffuse and spread out during the year, she said.
Variations in vaccination coverage were not associated with variations in epidemic intensity at the state level. However, the data period that was analyzed ended in 2008, a time when flu vaccination rates were much lower than they are today, according to Dr. Viboud.
“It would be important to revisit the effect of city structure and humidity on flu transmission in a high vaccination regime in more recent years, especially if there is a lot of interest in developing broadly cross-protective flu vaccines, which might become available in the market in the future,” she said.
The researchers declared no competing interests related to their research, which was supported by a grant from the Bill & Melinda Gates Foundation, the RAPIDD program of the Science and Technology Directorate Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.
SOURCE: Dalziel BD et al. Science. 2018 Oct 5;362(6410):75-9.
Public health policy makers may need to switch up their thinking about infection control during influenza outbreaks. Instead of targeting the population at large, it may make sense to focus on specific small towns or metropolitan areas for control.
Summary statistics, such as epidemic intensity, help to identify which places require more surge capacity to deal with peak health care demand. They also help to guide locations for active influenza surveillance where long transmission chains of influenza occur, and where new genetic variants of the influenza virus can be detected.
The findings of this study could foster the development of more accurate short-term, small-scale forecasts of the expected health care demand in a season. Most important, they could guide long-term projections that reveal how the shifting demography, growth of cities, and the changing climate alter infection dynamics and required control efforts.
Prof. Jacco Wallinga is with the Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands, and the Department of Biomedical Data Sciences, Leiden (the Netherlands) University Medical Center. These comments appeared in his editorial in Science (2018 Oct 5;362[6410]:29-30).
Public health policy makers may need to switch up their thinking about infection control during influenza outbreaks. Instead of targeting the population at large, it may make sense to focus on specific small towns or metropolitan areas for control.
Summary statistics, such as epidemic intensity, help to identify which places require more surge capacity to deal with peak health care demand. They also help to guide locations for active influenza surveillance where long transmission chains of influenza occur, and where new genetic variants of the influenza virus can be detected.
The findings of this study could foster the development of more accurate short-term, small-scale forecasts of the expected health care demand in a season. Most important, they could guide long-term projections that reveal how the shifting demography, growth of cities, and the changing climate alter infection dynamics and required control efforts.
Prof. Jacco Wallinga is with the Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands, and the Department of Biomedical Data Sciences, Leiden (the Netherlands) University Medical Center. These comments appeared in his editorial in Science (2018 Oct 5;362[6410]:29-30).
Public health policy makers may need to switch up their thinking about infection control during influenza outbreaks. Instead of targeting the population at large, it may make sense to focus on specific small towns or metropolitan areas for control.
Summary statistics, such as epidemic intensity, help to identify which places require more surge capacity to deal with peak health care demand. They also help to guide locations for active influenza surveillance where long transmission chains of influenza occur, and where new genetic variants of the influenza virus can be detected.
The findings of this study could foster the development of more accurate short-term, small-scale forecasts of the expected health care demand in a season. Most important, they could guide long-term projections that reveal how the shifting demography, growth of cities, and the changing climate alter infection dynamics and required control efforts.
Prof. Jacco Wallinga is with the Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands, and the Department of Biomedical Data Sciences, Leiden (the Netherlands) University Medical Center. These comments appeared in his editorial in Science (2018 Oct 5;362[6410]:29-30).
Influenza outbreaks in the United States tend to be concentrated and intense in small cities and more evenly spread throughout the season in large cities, results of a recent study show.
Swings in humidity further intensified the influenza spikes in small cities, but didn’t seem to have as much of an effect in large cities, the results suggest.
These findings help explain differences in influenza transmission patterns between cities that have similar climates and virus epidemiology, according to researcher Benjamin D. Dalziel, PhD, of the departments of integrative biology and mathematics at Oregon State University in Corvallis.
“City size and structure can play a role in determining how other factors such as climate affect and influence transmission,” Dr. Dalziel said in a press conference.
“Our results show how metropolises play a disproportionately important role in this process, as epidemic foci, and as potential sentinel hubs, where epidemiological observatories could integrate local strain dynamics to predict larger-scale patterns. As the growth and form of cities affect their function as climate-driven incubators of infectious disease, it may be possible to design smarter cities that better control epidemics in the face of accelerating global change,” the researchers wrote in their study.
Dr. Dalziel and his coauthors analyzed the weekly incidence of influenza-like illness across 603 U.S. ZIP codes using data obtained from medical claims from 2002 to 2008. They used epidemic intensity as a summary statistic to compare cities. By this variable, low epidemic intensity indicated a diffuse spread evenly across weeks of the flu season, whereas high epidemic intensity indicated intensively focused outbreaks on particular weeks.
In small cities, epidemics were more intensely focused on shorter periods at the peak of flu season, they found. In large cities, incidence was more diffuse, according to results published in Science.
Patterns of where people live and work in a city may account for the more diffuse and prolonged outbreaks seen in large cities, the authors wrote. Large cities have organized population movement patterns and crowding. In more highly established work locations, for example, the population density is pronounced during the day.
“We found the structure makes a difference for how the flu spreads at different times of year,” Dr. Dalziel said of the study, which used U.S. Census data to evaluate spatial population distributions. “In large cities with more highly organized patterns, conditions play a relatively smaller role in flu transmission.”
Humidity’s lower impact on outbreaks in large cities might also be explained by population effects: “If an infected person is sitting beside you, it matters less what the specific humidity is,” Dr. Dalziel said, adding that the proximity helps the virus find hosts even when climatic conditions are not at their most favorable.
The study findings may have implications for health care resources in small cities, which could be strained by intense outbreaks, said coinvestigator Cecile Viboud, PhD, of the Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Md.
Intense outbreaks could overload the health care system, making it challenging to respond, especially around the peak of the epidemic. Pressure on the health care system may be less intense in cities such as Miami or New York, where flu epidemics are more diffuse and spread out during the year, she said.
Variations in vaccination coverage were not associated with variations in epidemic intensity at the state level. However, the data period that was analyzed ended in 2008, a time when flu vaccination rates were much lower than they are today, according to Dr. Viboud.
“It would be important to revisit the effect of city structure and humidity on flu transmission in a high vaccination regime in more recent years, especially if there is a lot of interest in developing broadly cross-protective flu vaccines, which might become available in the market in the future,” she said.
The researchers declared no competing interests related to their research, which was supported by a grant from the Bill & Melinda Gates Foundation, the RAPIDD program of the Science and Technology Directorate Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.
SOURCE: Dalziel BD et al. Science. 2018 Oct 5;362(6410):75-9.
Influenza outbreaks in the United States tend to be concentrated and intense in small cities and more evenly spread throughout the season in large cities, results of a recent study show.
Swings in humidity further intensified the influenza spikes in small cities, but didn’t seem to have as much of an effect in large cities, the results suggest.
These findings help explain differences in influenza transmission patterns between cities that have similar climates and virus epidemiology, according to researcher Benjamin D. Dalziel, PhD, of the departments of integrative biology and mathematics at Oregon State University in Corvallis.
“City size and structure can play a role in determining how other factors such as climate affect and influence transmission,” Dr. Dalziel said in a press conference.
“Our results show how metropolises play a disproportionately important role in this process, as epidemic foci, and as potential sentinel hubs, where epidemiological observatories could integrate local strain dynamics to predict larger-scale patterns. As the growth and form of cities affect their function as climate-driven incubators of infectious disease, it may be possible to design smarter cities that better control epidemics in the face of accelerating global change,” the researchers wrote in their study.
Dr. Dalziel and his coauthors analyzed the weekly incidence of influenza-like illness across 603 U.S. ZIP codes using data obtained from medical claims from 2002 to 2008. They used epidemic intensity as a summary statistic to compare cities. By this variable, low epidemic intensity indicated a diffuse spread evenly across weeks of the flu season, whereas high epidemic intensity indicated intensively focused outbreaks on particular weeks.
In small cities, epidemics were more intensely focused on shorter periods at the peak of flu season, they found. In large cities, incidence was more diffuse, according to results published in Science.
Patterns of where people live and work in a city may account for the more diffuse and prolonged outbreaks seen in large cities, the authors wrote. Large cities have organized population movement patterns and crowding. In more highly established work locations, for example, the population density is pronounced during the day.
“We found the structure makes a difference for how the flu spreads at different times of year,” Dr. Dalziel said of the study, which used U.S. Census data to evaluate spatial population distributions. “In large cities with more highly organized patterns, conditions play a relatively smaller role in flu transmission.”
Humidity’s lower impact on outbreaks in large cities might also be explained by population effects: “If an infected person is sitting beside you, it matters less what the specific humidity is,” Dr. Dalziel said, adding that the proximity helps the virus find hosts even when climatic conditions are not at their most favorable.
The study findings may have implications for health care resources in small cities, which could be strained by intense outbreaks, said coinvestigator Cecile Viboud, PhD, of the Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Md.
Intense outbreaks could overload the health care system, making it challenging to respond, especially around the peak of the epidemic. Pressure on the health care system may be less intense in cities such as Miami or New York, where flu epidemics are more diffuse and spread out during the year, she said.
Variations in vaccination coverage were not associated with variations in epidemic intensity at the state level. However, the data period that was analyzed ended in 2008, a time when flu vaccination rates were much lower than they are today, according to Dr. Viboud.
“It would be important to revisit the effect of city structure and humidity on flu transmission in a high vaccination regime in more recent years, especially if there is a lot of interest in developing broadly cross-protective flu vaccines, which might become available in the market in the future,” she said.
The researchers declared no competing interests related to their research, which was supported by a grant from the Bill & Melinda Gates Foundation, the RAPIDD program of the Science and Technology Directorate Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.
SOURCE: Dalziel BD et al. Science. 2018 Oct 5;362(6410):75-9.
FROM SCIENCE
Key clinical point: The intensity of influenza epidemics in U.S. cities varies according to population.
Major finding: Smaller cities had more intense outbreaks concentrated around the peak of flu season, while larger cities had cases spread throughout the season.
Study details: Analysis of weekly influenza-like illness incidence for 603 U.S. ZIP codes in medical claims data from 2002 to 2008.
Disclosures: The authors declared no competing interests. Funding came from the Bill & Melinda Gates Foundation, the Science and Technology Directorate Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.
Source: Dalziel BD et al. Science. 2018 Oct 5;362(6410):75-9.
CDC: Trivalent adjuvanted influenza vaccine aIIV3 safe in elderly adults
ATLANTA – according to an analysis of reports to the Vaccine Adverse Event Reporting System (VAERS) during July 2016 through March 2018.
VAERS received 630 reports related to the vaccine (aIIV3; FLUAD) during the study period, of which 521 involved adults aged 65 years and older.
“Eighteen (3%) were serious reports, including two death reports (0.4%), all in adults aged [at least] 65 years,” Penina Haber and her colleagues at the Immunization Safety Office at the Centers for Disease Control and Prevention reported in a poster at the International Conference on Emerging Infectious Diseases.
The deaths included a 75-year-old man who died from Sjögren’s syndrome and a 65-year-old man who died from a myocardial infarction. The other serious events included five neurologic disorders (two cases of Guillain-Barré syndrome and one each of Bell’s palsy, Bickerstaff encephalitis, and lower-extremity weakness), five musculoskeletal and connective tissue disorders (three with shoulder pain and two with arm pain), three general disorders and administration site conditions (two cases of fever/chills and one case of cellulitis/bursitis), and one case each of a gastrointestinal disorder (acute diarrhea/gastroenteritis), an injury (a fall), and a skin/subcutaneous tissue disorder (keratosis pilaris rubra), according to the investigators.
There were no reports of anaphylaxis.
For the sake of comparison, the investigators also looked at reports associated with IIV3-HD and IIV3/IIV4 vaccines in adults aged 65 years and older during the same time period; they found that patient characteristics and reported events were similar for all the vaccines. For example, the percentages of reports involving patients aged 65 years and older were 65% or 66% for each, and those involving patients aged 75-84 years were 27%-29%. Further, 0.2%-0.6% of reports for each vaccine involved death.
The most frequently reported events for aIIV3, IIV3-HD, and IIV3/IIV4, respectively, were extremity pain (21%, 17%, and 15%, respectively), injection site erythema (18%, 19%, and 15%), and injection site pain (15%, 16%, and 16%), they said.
The aIIV3 vaccine – the first seasonal inactivated trivalent influenza vaccine produced from three influenza virus strains (two subtype A strains and one type B strain) – was approved by the Food and Drug Administration in 2015 for adults aged 65 years and older. It was the first influenza vaccine containing the adjuvant MF59 – a purified oil-in-water emulsion of squalene oil added to boost immune response in that population. Its safety was assessed in 15 randomized, controlled clinical studies, and several trials in older adults supported its efficacy and safety over nonadjuvanted influenza vaccines, the investigators reported. They noted that the Advisory Committee on Immunization Practices (ACIP) recommended the vaccine as an option for routine use in adults aged 65 years and older during the 2016-2017 flu seasons.
For the 2018-2019 flu season, ACIP determined that “For persons aged ≥65 years, any age-appropriate IIV formulation (standard-dose or high-dose, trivalent or quadrivalent, unadjuvanted or adjuvanted) or RIV4 are acceptable options.”
The findings of the analysis of the 2017-2018 flu season data are consistent with prelicensure studies, Ms. Haber and her colleagues concluded, noting that data mining did not detect disproportional reporting of any unexpected adverse event.
“[There were] no safety concerns following aIIV3 when compared to the nonadjuvanted influenza vaccines (IIV3-HD or IIV3/IIV4),” they wrote, adding that the “CDC and FDA will continue to monitor and ensure the safety of aIIV3.”
Ms. Haber reported having no disclosures
SOURCE: Haber P et al. ICEID 2018, Board 320.
ATLANTA – according to an analysis of reports to the Vaccine Adverse Event Reporting System (VAERS) during July 2016 through March 2018.
VAERS received 630 reports related to the vaccine (aIIV3; FLUAD) during the study period, of which 521 involved adults aged 65 years and older.
“Eighteen (3%) were serious reports, including two death reports (0.4%), all in adults aged [at least] 65 years,” Penina Haber and her colleagues at the Immunization Safety Office at the Centers for Disease Control and Prevention reported in a poster at the International Conference on Emerging Infectious Diseases.
The deaths included a 75-year-old man who died from Sjögren’s syndrome and a 65-year-old man who died from a myocardial infarction. The other serious events included five neurologic disorders (two cases of Guillain-Barré syndrome and one each of Bell’s palsy, Bickerstaff encephalitis, and lower-extremity weakness), five musculoskeletal and connective tissue disorders (three with shoulder pain and two with arm pain), three general disorders and administration site conditions (two cases of fever/chills and one case of cellulitis/bursitis), and one case each of a gastrointestinal disorder (acute diarrhea/gastroenteritis), an injury (a fall), and a skin/subcutaneous tissue disorder (keratosis pilaris rubra), according to the investigators.
There were no reports of anaphylaxis.
For the sake of comparison, the investigators also looked at reports associated with IIV3-HD and IIV3/IIV4 vaccines in adults aged 65 years and older during the same time period; they found that patient characteristics and reported events were similar for all the vaccines. For example, the percentages of reports involving patients aged 65 years and older were 65% or 66% for each, and those involving patients aged 75-84 years were 27%-29%. Further, 0.2%-0.6% of reports for each vaccine involved death.
The most frequently reported events for aIIV3, IIV3-HD, and IIV3/IIV4, respectively, were extremity pain (21%, 17%, and 15%, respectively), injection site erythema (18%, 19%, and 15%), and injection site pain (15%, 16%, and 16%), they said.
The aIIV3 vaccine – the first seasonal inactivated trivalent influenza vaccine produced from three influenza virus strains (two subtype A strains and one type B strain) – was approved by the Food and Drug Administration in 2015 for adults aged 65 years and older. It was the first influenza vaccine containing the adjuvant MF59 – a purified oil-in-water emulsion of squalene oil added to boost immune response in that population. Its safety was assessed in 15 randomized, controlled clinical studies, and several trials in older adults supported its efficacy and safety over nonadjuvanted influenza vaccines, the investigators reported. They noted that the Advisory Committee on Immunization Practices (ACIP) recommended the vaccine as an option for routine use in adults aged 65 years and older during the 2016-2017 flu seasons.
For the 2018-2019 flu season, ACIP determined that “For persons aged ≥65 years, any age-appropriate IIV formulation (standard-dose or high-dose, trivalent or quadrivalent, unadjuvanted or adjuvanted) or RIV4 are acceptable options.”
The findings of the analysis of the 2017-2018 flu season data are consistent with prelicensure studies, Ms. Haber and her colleagues concluded, noting that data mining did not detect disproportional reporting of any unexpected adverse event.
“[There were] no safety concerns following aIIV3 when compared to the nonadjuvanted influenza vaccines (IIV3-HD or IIV3/IIV4),” they wrote, adding that the “CDC and FDA will continue to monitor and ensure the safety of aIIV3.”
Ms. Haber reported having no disclosures
SOURCE: Haber P et al. ICEID 2018, Board 320.
ATLANTA – according to an analysis of reports to the Vaccine Adverse Event Reporting System (VAERS) during July 2016 through March 2018.
VAERS received 630 reports related to the vaccine (aIIV3; FLUAD) during the study period, of which 521 involved adults aged 65 years and older.
“Eighteen (3%) were serious reports, including two death reports (0.4%), all in adults aged [at least] 65 years,” Penina Haber and her colleagues at the Immunization Safety Office at the Centers for Disease Control and Prevention reported in a poster at the International Conference on Emerging Infectious Diseases.
The deaths included a 75-year-old man who died from Sjögren’s syndrome and a 65-year-old man who died from a myocardial infarction. The other serious events included five neurologic disorders (two cases of Guillain-Barré syndrome and one each of Bell’s palsy, Bickerstaff encephalitis, and lower-extremity weakness), five musculoskeletal and connective tissue disorders (three with shoulder pain and two with arm pain), three general disorders and administration site conditions (two cases of fever/chills and one case of cellulitis/bursitis), and one case each of a gastrointestinal disorder (acute diarrhea/gastroenteritis), an injury (a fall), and a skin/subcutaneous tissue disorder (keratosis pilaris rubra), according to the investigators.
There were no reports of anaphylaxis.
For the sake of comparison, the investigators also looked at reports associated with IIV3-HD and IIV3/IIV4 vaccines in adults aged 65 years and older during the same time period; they found that patient characteristics and reported events were similar for all the vaccines. For example, the percentages of reports involving patients aged 65 years and older were 65% or 66% for each, and those involving patients aged 75-84 years were 27%-29%. Further, 0.2%-0.6% of reports for each vaccine involved death.
The most frequently reported events for aIIV3, IIV3-HD, and IIV3/IIV4, respectively, were extremity pain (21%, 17%, and 15%, respectively), injection site erythema (18%, 19%, and 15%), and injection site pain (15%, 16%, and 16%), they said.
The aIIV3 vaccine – the first seasonal inactivated trivalent influenza vaccine produced from three influenza virus strains (two subtype A strains and one type B strain) – was approved by the Food and Drug Administration in 2015 for adults aged 65 years and older. It was the first influenza vaccine containing the adjuvant MF59 – a purified oil-in-water emulsion of squalene oil added to boost immune response in that population. Its safety was assessed in 15 randomized, controlled clinical studies, and several trials in older adults supported its efficacy and safety over nonadjuvanted influenza vaccines, the investigators reported. They noted that the Advisory Committee on Immunization Practices (ACIP) recommended the vaccine as an option for routine use in adults aged 65 years and older during the 2016-2017 flu seasons.
For the 2018-2019 flu season, ACIP determined that “For persons aged ≥65 years, any age-appropriate IIV formulation (standard-dose or high-dose, trivalent or quadrivalent, unadjuvanted or adjuvanted) or RIV4 are acceptable options.”
The findings of the analysis of the 2017-2018 flu season data are consistent with prelicensure studies, Ms. Haber and her colleagues concluded, noting that data mining did not detect disproportional reporting of any unexpected adverse event.
“[There were] no safety concerns following aIIV3 when compared to the nonadjuvanted influenza vaccines (IIV3-HD or IIV3/IIV4),” they wrote, adding that the “CDC and FDA will continue to monitor and ensure the safety of aIIV3.”
Ms. Haber reported having no disclosures
SOURCE: Haber P et al. ICEID 2018, Board 320.
REPORTING FROM ICEID 2018
Key clinical point: No new or unexpected adverse events were reported among the 630 reports related to the vaccine during the study period, of which 521 involved adults aged 65 years and older.
Major finding: Of 521 reports, 18 were serious, and there were two deaths.
Study details: A review of 521 reports to the Vaccine Adverse Event Reporting System in 2017-2018.
Disclosures: Ms. Haber reported having no disclosures.
Source: Haber P et al. ICEID 2018, Board 320.
Single-dose influenza drug baloxavir similar to oseltamivir in efficacy
A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.
Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.
The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.
In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.
The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.
Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.
The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.
Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.
Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.
“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.
“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.
Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.
CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.
The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
These two studies of baloxavir show that the drug has a clinical benefit similar to that of oseltamivir in individuals with uncomplicated influenza infection. As a single-dose treatment, baloxavir has the advantage in reducing concerns about adherence compared to the treatment regimen for oseltamivir, which requires 5 days of twice-daily dosing.
However, these studies should be viewed as the first step. While baloxavir showed significantly greater reductions in viral load at 24 hours and a shorter duration of infectious virus detection than did oseltamivir or placebo, it also induced the emergence of viral escape mutants with reduced susceptibility.
It’s not yet known whether these influenza viruses with reduced susceptibility are transmissible, and whether surveillance for I38T and other markers will be needed. We also need trials to identify which patients are most likely to benefit from baloxavir, and the timing for treatment.
Timothy M. Uyeki, MD, is with the Influenza Division at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. These comments are taken from an editorial (N Engl J Med. 2018;397:975-7. doi: 10.1056/NEJMe1810815. No conflicts of interest were declared.
These two studies of baloxavir show that the drug has a clinical benefit similar to that of oseltamivir in individuals with uncomplicated influenza infection. As a single-dose treatment, baloxavir has the advantage in reducing concerns about adherence compared to the treatment regimen for oseltamivir, which requires 5 days of twice-daily dosing.
However, these studies should be viewed as the first step. While baloxavir showed significantly greater reductions in viral load at 24 hours and a shorter duration of infectious virus detection than did oseltamivir or placebo, it also induced the emergence of viral escape mutants with reduced susceptibility.
It’s not yet known whether these influenza viruses with reduced susceptibility are transmissible, and whether surveillance for I38T and other markers will be needed. We also need trials to identify which patients are most likely to benefit from baloxavir, and the timing for treatment.
Timothy M. Uyeki, MD, is with the Influenza Division at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. These comments are taken from an editorial (N Engl J Med. 2018;397:975-7. doi: 10.1056/NEJMe1810815. No conflicts of interest were declared.
These two studies of baloxavir show that the drug has a clinical benefit similar to that of oseltamivir in individuals with uncomplicated influenza infection. As a single-dose treatment, baloxavir has the advantage in reducing concerns about adherence compared to the treatment regimen for oseltamivir, which requires 5 days of twice-daily dosing.
However, these studies should be viewed as the first step. While baloxavir showed significantly greater reductions in viral load at 24 hours and a shorter duration of infectious virus detection than did oseltamivir or placebo, it also induced the emergence of viral escape mutants with reduced susceptibility.
It’s not yet known whether these influenza viruses with reduced susceptibility are transmissible, and whether surveillance for I38T and other markers will be needed. We also need trials to identify which patients are most likely to benefit from baloxavir, and the timing for treatment.
Timothy M. Uyeki, MD, is with the Influenza Division at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. These comments are taken from an editorial (N Engl J Med. 2018;397:975-7. doi: 10.1056/NEJMe1810815. No conflicts of interest were declared.
A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.
Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.
The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.
In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.
The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.
Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.
The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.
Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.
Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.
“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.
“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.
Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.
CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.
The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.
Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.
The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.
In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.
The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.
Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.
The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.
Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.
Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.
“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.
“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.
Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.
CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.
The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Single-dose influenza antiviral baloxavir shows efficacy similar to that of oseltamivir.
Major finding: Baloxavir shows similar time to alleviation of influenza symptoms compared with oseltamivir, but greater reductions in viral load.
Study details: Phase 2 and phase 3 randomized controlled trials in 389 and 1,366 otherwise healthy patients with influenza.
Disclosures: The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.
Source: Hayden F et al. N Engl J Med 2018;379:913-23. doi: 10.1056/NEJMoa1716197.
Live attenuated flu vaccine gets ACIP nod for 2018-2019 season
The latest seasonal influenza vaccine recommendations from the Advisory Committee on Immunization Practices provide several key updates that will impact clinical practice in the 2018-2019 influenza season.
Of note, , following two seasons in which the committee recommended it not be used.
ACIP also updated its recommendations for individuals with a history of egg allergy, described the vaccine strains chosen for 2018-2019 season, and detailed the changes in age indications for Afluria Quadrivalent and Fluarix Quadrivalent that have been made since publication of its previous guidelines.
Published in MMWR Recommendations and Reports, the updated ACIP recommendations reflect discussions and decisions from the three public meetings of ACIP that have taken place since the last annual update.
All individuals 6 months of age and older who have no contraindications to influenza vaccine should receive routine annual influenza vaccine, ACIP also said in its report, reinforcing a key recommendation that has been in place since 2010.
“To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations,” wrote authors of the report, including lead author Lisa A. Grohskopf, MD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.
Dr. Grohskopf and coauthors made no specific recommendations on which vaccine to use. They said providers should choose licensed, age-appropriate recommended vaccines expected to be available for the 2018-2019 season, including inactivated influenza vaccines (IIV), a recombinant influenza vaccine (RIV4), and the LAIV option.
FluMist Quadrivalent, the one LAIV product expected to be available for the 2018-2019 season, is licensed for individuals aged 2-49 years.
In its deliberations over the updated LAIV recommendation, ACIP reviewed observational data from previous seasons suggesting that the vaccine was poorly effective, and significantly less effective than IIV, against influenza A(H1N1) pdm09 viruses.
The current formulation of FluMist includes a new H1N1pdm09-like vaccine virus. While no effectiveness estimates were available at the time of review, ACIP said it did consider manufacturer data on shedding and immunogenicity for the current vaccine in children between the ages of 24 months through less than 4 years.
“These data suggest that this new H1N1pdm09-like virus has improved replicative fitness over previous H1N1pdm09-like viruses included in LAIV,” Dr. Grohskopf and colleagues wrote.
Individuals with an egg allergy history also can receive any licensed, recommended, age-appropriate IIV, RIV, or LAIV vaccine, said ACIP. This updated recommendation was based in part on the committee’s review and discussion of three studies that showed no cases of anaphylaxis in egg-allergic children receiving LAIV.
The ACIP recommendation update also outlines the strains selected earlier this year for the 2018-2019 season. Trivalent influenza vaccines in the United States will include an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent vaccines will include those strains plus a B/Phuket/3073/2013–like virus (Yamagata lineage).
The report also acknowledges the recent expansion of age indication for two vaccines that have occurred since the last ACIP recommendations.
Afluria Quadrivalent was previously licensed for individuals 18 years of age and older. In August 2017, the Food and Drug Administration approved expansion of the indication to individuals 5 years of age or older. In January 2018, FDA approved expansion of the Fluarix Quadrivalent indication, previously licensed for age 3 and older, to individuals 6 months and older.
Report coauthor Emmanuel B. Walter disclosed grants from Novavax and Merck. The remaining report authors reported no relevant financial disclosures.
SOURCE: Grohskopf LA et al. MMWR Recomm Rep. 2018 Aug 24;67(3):1-20.
The latest seasonal influenza vaccine recommendations from the Advisory Committee on Immunization Practices provide several key updates that will impact clinical practice in the 2018-2019 influenza season.
Of note, , following two seasons in which the committee recommended it not be used.
ACIP also updated its recommendations for individuals with a history of egg allergy, described the vaccine strains chosen for 2018-2019 season, and detailed the changes in age indications for Afluria Quadrivalent and Fluarix Quadrivalent that have been made since publication of its previous guidelines.
Published in MMWR Recommendations and Reports, the updated ACIP recommendations reflect discussions and decisions from the three public meetings of ACIP that have taken place since the last annual update.
All individuals 6 months of age and older who have no contraindications to influenza vaccine should receive routine annual influenza vaccine, ACIP also said in its report, reinforcing a key recommendation that has been in place since 2010.
“To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations,” wrote authors of the report, including lead author Lisa A. Grohskopf, MD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.
Dr. Grohskopf and coauthors made no specific recommendations on which vaccine to use. They said providers should choose licensed, age-appropriate recommended vaccines expected to be available for the 2018-2019 season, including inactivated influenza vaccines (IIV), a recombinant influenza vaccine (RIV4), and the LAIV option.
FluMist Quadrivalent, the one LAIV product expected to be available for the 2018-2019 season, is licensed for individuals aged 2-49 years.
In its deliberations over the updated LAIV recommendation, ACIP reviewed observational data from previous seasons suggesting that the vaccine was poorly effective, and significantly less effective than IIV, against influenza A(H1N1) pdm09 viruses.
The current formulation of FluMist includes a new H1N1pdm09-like vaccine virus. While no effectiveness estimates were available at the time of review, ACIP said it did consider manufacturer data on shedding and immunogenicity for the current vaccine in children between the ages of 24 months through less than 4 years.
“These data suggest that this new H1N1pdm09-like virus has improved replicative fitness over previous H1N1pdm09-like viruses included in LAIV,” Dr. Grohskopf and colleagues wrote.
Individuals with an egg allergy history also can receive any licensed, recommended, age-appropriate IIV, RIV, or LAIV vaccine, said ACIP. This updated recommendation was based in part on the committee’s review and discussion of three studies that showed no cases of anaphylaxis in egg-allergic children receiving LAIV.
The ACIP recommendation update also outlines the strains selected earlier this year for the 2018-2019 season. Trivalent influenza vaccines in the United States will include an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent vaccines will include those strains plus a B/Phuket/3073/2013–like virus (Yamagata lineage).
The report also acknowledges the recent expansion of age indication for two vaccines that have occurred since the last ACIP recommendations.
Afluria Quadrivalent was previously licensed for individuals 18 years of age and older. In August 2017, the Food and Drug Administration approved expansion of the indication to individuals 5 years of age or older. In January 2018, FDA approved expansion of the Fluarix Quadrivalent indication, previously licensed for age 3 and older, to individuals 6 months and older.
Report coauthor Emmanuel B. Walter disclosed grants from Novavax and Merck. The remaining report authors reported no relevant financial disclosures.
SOURCE: Grohskopf LA et al. MMWR Recomm Rep. 2018 Aug 24;67(3):1-20.
The latest seasonal influenza vaccine recommendations from the Advisory Committee on Immunization Practices provide several key updates that will impact clinical practice in the 2018-2019 influenza season.
Of note, , following two seasons in which the committee recommended it not be used.
ACIP also updated its recommendations for individuals with a history of egg allergy, described the vaccine strains chosen for 2018-2019 season, and detailed the changes in age indications for Afluria Quadrivalent and Fluarix Quadrivalent that have been made since publication of its previous guidelines.
Published in MMWR Recommendations and Reports, the updated ACIP recommendations reflect discussions and decisions from the three public meetings of ACIP that have taken place since the last annual update.
All individuals 6 months of age and older who have no contraindications to influenza vaccine should receive routine annual influenza vaccine, ACIP also said in its report, reinforcing a key recommendation that has been in place since 2010.
“To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations,” wrote authors of the report, including lead author Lisa A. Grohskopf, MD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.
Dr. Grohskopf and coauthors made no specific recommendations on which vaccine to use. They said providers should choose licensed, age-appropriate recommended vaccines expected to be available for the 2018-2019 season, including inactivated influenza vaccines (IIV), a recombinant influenza vaccine (RIV4), and the LAIV option.
FluMist Quadrivalent, the one LAIV product expected to be available for the 2018-2019 season, is licensed for individuals aged 2-49 years.
In its deliberations over the updated LAIV recommendation, ACIP reviewed observational data from previous seasons suggesting that the vaccine was poorly effective, and significantly less effective than IIV, against influenza A(H1N1) pdm09 viruses.
The current formulation of FluMist includes a new H1N1pdm09-like vaccine virus. While no effectiveness estimates were available at the time of review, ACIP said it did consider manufacturer data on shedding and immunogenicity for the current vaccine in children between the ages of 24 months through less than 4 years.
“These data suggest that this new H1N1pdm09-like virus has improved replicative fitness over previous H1N1pdm09-like viruses included in LAIV,” Dr. Grohskopf and colleagues wrote.
Individuals with an egg allergy history also can receive any licensed, recommended, age-appropriate IIV, RIV, or LAIV vaccine, said ACIP. This updated recommendation was based in part on the committee’s review and discussion of three studies that showed no cases of anaphylaxis in egg-allergic children receiving LAIV.
The ACIP recommendation update also outlines the strains selected earlier this year for the 2018-2019 season. Trivalent influenza vaccines in the United States will include an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent vaccines will include those strains plus a B/Phuket/3073/2013–like virus (Yamagata lineage).
The report also acknowledges the recent expansion of age indication for two vaccines that have occurred since the last ACIP recommendations.
Afluria Quadrivalent was previously licensed for individuals 18 years of age and older. In August 2017, the Food and Drug Administration approved expansion of the indication to individuals 5 years of age or older. In January 2018, FDA approved expansion of the Fluarix Quadrivalent indication, previously licensed for age 3 and older, to individuals 6 months and older.
Report coauthor Emmanuel B. Walter disclosed grants from Novavax and Merck. The remaining report authors reported no relevant financial disclosures.
SOURCE: Grohskopf LA et al. MMWR Recomm Rep. 2018 Aug 24;67(3):1-20.
FROM MMWR
Simple tool improves inpatient influenza vaccination rates
TORONTO –
“When we looked at the immunization status of children in New York City, we found that one of the vaccines most commonly missed was influenza vaccine, especially from 2011 through 2014,” one of the study authors, Anmol Goyal, MD, of SUNY Downstate Medical Center, Brooklyn, N.Y., said in an interview at the Pediatric Academic Societies meeting.
“Given this year’s epidemic of influenza and the increasing deaths, we decided to look back on interventions we had done in the past to see if any can be reimplemented to help improve the vaccination status for these children,” he said. “The national goal is 80%, but if we look at the recent trend, even though we have been able to improve vaccination status, it is still below the national goal.” For example, he said, according to New York Department of Health data, the 2012-2013 influenza vaccination rates in New York City were 65% among children 6 months to 5 years old, 47% among those 5-8 years old, and 31% among those 9-18 years old, which were well below the national goal.
In an effort to improve influenza vaccine access, lead author Stephan Kohlhoff, MD, a pediatric infectious disease specialist at the medical center, and his associates, implemented a simple vaccine screening tool to use in the inpatient setting as an opportunity to improve vaccination rates among children in New York City. It consisted of nursing staff assessing the patient’s influenza immunization status on admission and conducting source verification using the citywide immunization registry, or with vaccine cards brought by parents or guardians during admission. Influenza vaccine was administered as a standing order before discharge, unless refused by the parents or guardians. The study population comprised 602 patients between the ages of 6 months and 21 years who were admitted to the inpatient unit during 2 months of the influenza season (November and December) from 2011 to 2013.
Dr. Goyal, a second-year pediatric resident at the medical center, reported that the influenza vaccination status on admission was positive in only 31% of children in 2011, 30% in 2012, and 34% in 2013. The vaccine screening tool was implemented in 64% of admitted children in 2012 and 70% in 2013. Following implementation, the researchers observed a 5% increase in immunization rates in 2012 and an 11% increase in 2013, with an overall increase of 8% over 2 years (P less than .001). He was quick to point out that the influenza rate could have been improved by an additional 22% had 77% of patients not refused vaccination.
“Unfortunately, as our primary objective was to assess the utility of our screening tool in improving inpatient immunization status, we had very limited data points toward refusal of vaccine,” Dr. Goyal said. “Some of the reasons for refusal that were gathered during screening included preferred vaccination by their primary care provider after discharge. Or, maybe they don’t want the vaccine because they feel that the vaccine will make their kids sick. We don’t have enough data to point to any particular reason. This study provides information on acceptance rate of inpatient immunization, which may be useful for implementing additional educational initiatives to overcome potential barriers and help us reach our national goal.”
The researchers reported having no financial disclosures.
TORONTO –
“When we looked at the immunization status of children in New York City, we found that one of the vaccines most commonly missed was influenza vaccine, especially from 2011 through 2014,” one of the study authors, Anmol Goyal, MD, of SUNY Downstate Medical Center, Brooklyn, N.Y., said in an interview at the Pediatric Academic Societies meeting.
“Given this year’s epidemic of influenza and the increasing deaths, we decided to look back on interventions we had done in the past to see if any can be reimplemented to help improve the vaccination status for these children,” he said. “The national goal is 80%, but if we look at the recent trend, even though we have been able to improve vaccination status, it is still below the national goal.” For example, he said, according to New York Department of Health data, the 2012-2013 influenza vaccination rates in New York City were 65% among children 6 months to 5 years old, 47% among those 5-8 years old, and 31% among those 9-18 years old, which were well below the national goal.
In an effort to improve influenza vaccine access, lead author Stephan Kohlhoff, MD, a pediatric infectious disease specialist at the medical center, and his associates, implemented a simple vaccine screening tool to use in the inpatient setting as an opportunity to improve vaccination rates among children in New York City. It consisted of nursing staff assessing the patient’s influenza immunization status on admission and conducting source verification using the citywide immunization registry, or with vaccine cards brought by parents or guardians during admission. Influenza vaccine was administered as a standing order before discharge, unless refused by the parents or guardians. The study population comprised 602 patients between the ages of 6 months and 21 years who were admitted to the inpatient unit during 2 months of the influenza season (November and December) from 2011 to 2013.
Dr. Goyal, a second-year pediatric resident at the medical center, reported that the influenza vaccination status on admission was positive in only 31% of children in 2011, 30% in 2012, and 34% in 2013. The vaccine screening tool was implemented in 64% of admitted children in 2012 and 70% in 2013. Following implementation, the researchers observed a 5% increase in immunization rates in 2012 and an 11% increase in 2013, with an overall increase of 8% over 2 years (P less than .001). He was quick to point out that the influenza rate could have been improved by an additional 22% had 77% of patients not refused vaccination.
“Unfortunately, as our primary objective was to assess the utility of our screening tool in improving inpatient immunization status, we had very limited data points toward refusal of vaccine,” Dr. Goyal said. “Some of the reasons for refusal that were gathered during screening included preferred vaccination by their primary care provider after discharge. Or, maybe they don’t want the vaccine because they feel that the vaccine will make their kids sick. We don’t have enough data to point to any particular reason. This study provides information on acceptance rate of inpatient immunization, which may be useful for implementing additional educational initiatives to overcome potential barriers and help us reach our national goal.”
The researchers reported having no financial disclosures.
TORONTO –
“When we looked at the immunization status of children in New York City, we found that one of the vaccines most commonly missed was influenza vaccine, especially from 2011 through 2014,” one of the study authors, Anmol Goyal, MD, of SUNY Downstate Medical Center, Brooklyn, N.Y., said in an interview at the Pediatric Academic Societies meeting.
“Given this year’s epidemic of influenza and the increasing deaths, we decided to look back on interventions we had done in the past to see if any can be reimplemented to help improve the vaccination status for these children,” he said. “The national goal is 80%, but if we look at the recent trend, even though we have been able to improve vaccination status, it is still below the national goal.” For example, he said, according to New York Department of Health data, the 2012-2013 influenza vaccination rates in New York City were 65% among children 6 months to 5 years old, 47% among those 5-8 years old, and 31% among those 9-18 years old, which were well below the national goal.
In an effort to improve influenza vaccine access, lead author Stephan Kohlhoff, MD, a pediatric infectious disease specialist at the medical center, and his associates, implemented a simple vaccine screening tool to use in the inpatient setting as an opportunity to improve vaccination rates among children in New York City. It consisted of nursing staff assessing the patient’s influenza immunization status on admission and conducting source verification using the citywide immunization registry, or with vaccine cards brought by parents or guardians during admission. Influenza vaccine was administered as a standing order before discharge, unless refused by the parents or guardians. The study population comprised 602 patients between the ages of 6 months and 21 years who were admitted to the inpatient unit during 2 months of the influenza season (November and December) from 2011 to 2013.
Dr. Goyal, a second-year pediatric resident at the medical center, reported that the influenza vaccination status on admission was positive in only 31% of children in 2011, 30% in 2012, and 34% in 2013. The vaccine screening tool was implemented in 64% of admitted children in 2012 and 70% in 2013. Following implementation, the researchers observed a 5% increase in immunization rates in 2012 and an 11% increase in 2013, with an overall increase of 8% over 2 years (P less than .001). He was quick to point out that the influenza rate could have been improved by an additional 22% had 77% of patients not refused vaccination.
“Unfortunately, as our primary objective was to assess the utility of our screening tool in improving inpatient immunization status, we had very limited data points toward refusal of vaccine,” Dr. Goyal said. “Some of the reasons for refusal that were gathered during screening included preferred vaccination by their primary care provider after discharge. Or, maybe they don’t want the vaccine because they feel that the vaccine will make their kids sick. We don’t have enough data to point to any particular reason. This study provides information on acceptance rate of inpatient immunization, which may be useful for implementing additional educational initiatives to overcome potential barriers and help us reach our national goal.”
The researchers reported having no financial disclosures.
AT PAS 18
Key clinical point: The inpatient setting can be used to successfully improve influenza vaccine rates.
Major finding: Following implementation of a simple inpatient vaccine screening tool, a 5% increase in immunization rates occurred in 2012 and an 11% increase occurred in 2013.
Study details: A review of 602 patients between the ages of 6 months and 21 years who were admitted to the inpatient unit during 2 months of the influenza season (November and December) from 2011 to 2013.
Disclosures: The researchers reported having no financial disclosures.
ESBL-B before colorectal surgery ups risk of surgical site infection
MADRID – Patients who are carriers of , despite a standard prophylactic antibiotic regimen.
Surgical site infections (SSIs) occurred in 23% of those who tested positive for the pathogens preoperatively, compared with 10.5% of ESBL-B–negative patients – a significant increased risk of 2.25, Yehuda Carmeli, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual congress.
ESBL-B was not the infective pathogen in most infection cases, but being a carrier increased the likelihood of an ESBL-B SSI. ESBL-B was the pathogen in 7.2% of the carriers and 1.6% of the noncarriers. However, investigators are still working to determine if the species present in the wound infection are the same as the ones present at baseline, said Dr. Carmeli of Tel Aviv Medical Center.
All of these results are emerging from the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in Gram-Negative Organisms: Studying Intervention Strategies” is a 12-million-euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multi-drug resistant Gram-negative bacteria. From 2012 to 2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures).
Several of the studies were reported at ECCMID 2018.
This portion of R-GNOSIS was intended to investigate the relationship between ESBL-B carriage and postoperative surgical site infections among colorectal surgery patients.
The study comprised 3,626 patients who were preoperatively screened for ESBL-B within 2 weeks of colorectal surgery. The ESBL-B carriage rate was 15.3% overall, but ranged from 12% to 20% by site. Of the carriers, 222 were included in this study sample. They were randomly matched with 444 noncarriers.
Anywhere from 2 weeks to 2 days before surgery, all of the patients received a standard prophylactic antibiotic. This was most often an infusion of 1.5 g cefuroxime plus 500 mg metronidazole. Other cephalosporins were allowed at the clinician’s discretion.
Patients were a mean of 62 years old. Nearly half (48%) had cardiovascular disease and about a third had undergone a prior colorectal surgical procedure. Cancer was the surgical indication in about 70%. Other indications were inflammatory bowel disease and diverticular disease.
A multivariate analysis controlled for age, cardiovascular disease, indication for surgery, and whether the procedure included a rectal resection, retention of drain at the surgical site, or stoma. The model also controlled for National Nosocomial Infection Surveillance score, a three-point scale that estimates surgical infection risk. Among this cohort, 48% were at low risk, 43% at moderate risk, and 10% at high risk.
Dr. Carmeli made no financial disclosures.
SOURCE: Carmeli et al, ECCMID 2018, Oral Abstract O1133.
MADRID – Patients who are carriers of , despite a standard prophylactic antibiotic regimen.
Surgical site infections (SSIs) occurred in 23% of those who tested positive for the pathogens preoperatively, compared with 10.5% of ESBL-B–negative patients – a significant increased risk of 2.25, Yehuda Carmeli, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual congress.
ESBL-B was not the infective pathogen in most infection cases, but being a carrier increased the likelihood of an ESBL-B SSI. ESBL-B was the pathogen in 7.2% of the carriers and 1.6% of the noncarriers. However, investigators are still working to determine if the species present in the wound infection are the same as the ones present at baseline, said Dr. Carmeli of Tel Aviv Medical Center.
All of these results are emerging from the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in Gram-Negative Organisms: Studying Intervention Strategies” is a 12-million-euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multi-drug resistant Gram-negative bacteria. From 2012 to 2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures).
Several of the studies were reported at ECCMID 2018.
This portion of R-GNOSIS was intended to investigate the relationship between ESBL-B carriage and postoperative surgical site infections among colorectal surgery patients.
The study comprised 3,626 patients who were preoperatively screened for ESBL-B within 2 weeks of colorectal surgery. The ESBL-B carriage rate was 15.3% overall, but ranged from 12% to 20% by site. Of the carriers, 222 were included in this study sample. They were randomly matched with 444 noncarriers.
Anywhere from 2 weeks to 2 days before surgery, all of the patients received a standard prophylactic antibiotic. This was most often an infusion of 1.5 g cefuroxime plus 500 mg metronidazole. Other cephalosporins were allowed at the clinician’s discretion.
Patients were a mean of 62 years old. Nearly half (48%) had cardiovascular disease and about a third had undergone a prior colorectal surgical procedure. Cancer was the surgical indication in about 70%. Other indications were inflammatory bowel disease and diverticular disease.
A multivariate analysis controlled for age, cardiovascular disease, indication for surgery, and whether the procedure included a rectal resection, retention of drain at the surgical site, or stoma. The model also controlled for National Nosocomial Infection Surveillance score, a three-point scale that estimates surgical infection risk. Among this cohort, 48% were at low risk, 43% at moderate risk, and 10% at high risk.
Dr. Carmeli made no financial disclosures.
SOURCE: Carmeli et al, ECCMID 2018, Oral Abstract O1133.
MADRID – Patients who are carriers of , despite a standard prophylactic antibiotic regimen.
Surgical site infections (SSIs) occurred in 23% of those who tested positive for the pathogens preoperatively, compared with 10.5% of ESBL-B–negative patients – a significant increased risk of 2.25, Yehuda Carmeli, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual congress.
ESBL-B was not the infective pathogen in most infection cases, but being a carrier increased the likelihood of an ESBL-B SSI. ESBL-B was the pathogen in 7.2% of the carriers and 1.6% of the noncarriers. However, investigators are still working to determine if the species present in the wound infection are the same as the ones present at baseline, said Dr. Carmeli of Tel Aviv Medical Center.
All of these results are emerging from the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in Gram-Negative Organisms: Studying Intervention Strategies” is a 12-million-euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multi-drug resistant Gram-negative bacteria. From 2012 to 2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures).
Several of the studies were reported at ECCMID 2018.
This portion of R-GNOSIS was intended to investigate the relationship between ESBL-B carriage and postoperative surgical site infections among colorectal surgery patients.
The study comprised 3,626 patients who were preoperatively screened for ESBL-B within 2 weeks of colorectal surgery. The ESBL-B carriage rate was 15.3% overall, but ranged from 12% to 20% by site. Of the carriers, 222 were included in this study sample. They were randomly matched with 444 noncarriers.
Anywhere from 2 weeks to 2 days before surgery, all of the patients received a standard prophylactic antibiotic. This was most often an infusion of 1.5 g cefuroxime plus 500 mg metronidazole. Other cephalosporins were allowed at the clinician’s discretion.
Patients were a mean of 62 years old. Nearly half (48%) had cardiovascular disease and about a third had undergone a prior colorectal surgical procedure. Cancer was the surgical indication in about 70%. Other indications were inflammatory bowel disease and diverticular disease.
A multivariate analysis controlled for age, cardiovascular disease, indication for surgery, and whether the procedure included a rectal resection, retention of drain at the surgical site, or stoma. The model also controlled for National Nosocomial Infection Surveillance score, a three-point scale that estimates surgical infection risk. Among this cohort, 48% were at low risk, 43% at moderate risk, and 10% at high risk.
Dr. Carmeli made no financial disclosures.
SOURCE: Carmeli et al, ECCMID 2018, Oral Abstract O1133.
REPORTING FROM ECCMID 2018
Key clinical point: ESBL-B colonization increased the risk of surgical site infections after colorectal surgery, despite use of standard preoperative antibiotics.
Major finding: ESBL-B carriage more than doubled the risk of a colorectal surgical site infection by (OR 2.25).
Study details: The prospective study comprised 222 carriers and 444 noncarriers.
Disclosures: The study is part of the R-GNOSIS project, a 12-million-euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multi-drug resistant Gram-negative bacteria.
Source: Carmeli Y et al. ECCMID 2018, Oral Abstract O1130.
Phase 2 ‘universal flu vaccine’ trial announced
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, announced on May 4 that is sponsoring a phase 2 trial of a universal flu vaccine, M-001. The trial will test the experimental vaccine for safety and its ability to produce potentially broad protective immune responses, both on its own and when followed by a standard seasonal influenza vaccine. It is being conducted at four U.S. sites that are part of the Vaccine and Treatment Evaluation Units, funded by NIAID.
“An effective universal influenza vaccine would lessen the public health burden of influenza, alleviate suffering, and save lives,” said NIAID Director Anthony S. Fauci, MD. Such a vaccine would help eliminate the problem of unanticipated seasonal variation in the flu virus mix, which can make the chosen vaccine combination for that season less effective.
The study is a randomized, double-blind, placebo-controlled trial that will enroll 120 men and nonpregnant women, aged 18-49 years, inclusive, and is designed to assess the safety, reactogenicity, and immunogenicity of two priming doses of M-001 followed by a seasonal quadrivalent inactivated influenza vaccine.
The primary objectives are to assess the safety as measured by vaccine-related adverse events, reactogenicity, and laboratory adverse events; and to assess the T-cell responses to M-001 component peptides.
More information about the study can be found at ClinicalTrials.gov, using the identifier NCT03058692.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, announced on May 4 that is sponsoring a phase 2 trial of a universal flu vaccine, M-001. The trial will test the experimental vaccine for safety and its ability to produce potentially broad protective immune responses, both on its own and when followed by a standard seasonal influenza vaccine. It is being conducted at four U.S. sites that are part of the Vaccine and Treatment Evaluation Units, funded by NIAID.
“An effective universal influenza vaccine would lessen the public health burden of influenza, alleviate suffering, and save lives,” said NIAID Director Anthony S. Fauci, MD. Such a vaccine would help eliminate the problem of unanticipated seasonal variation in the flu virus mix, which can make the chosen vaccine combination for that season less effective.
The study is a randomized, double-blind, placebo-controlled trial that will enroll 120 men and nonpregnant women, aged 18-49 years, inclusive, and is designed to assess the safety, reactogenicity, and immunogenicity of two priming doses of M-001 followed by a seasonal quadrivalent inactivated influenza vaccine.
The primary objectives are to assess the safety as measured by vaccine-related adverse events, reactogenicity, and laboratory adverse events; and to assess the T-cell responses to M-001 component peptides.
More information about the study can be found at ClinicalTrials.gov, using the identifier NCT03058692.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, announced on May 4 that is sponsoring a phase 2 trial of a universal flu vaccine, M-001. The trial will test the experimental vaccine for safety and its ability to produce potentially broad protective immune responses, both on its own and when followed by a standard seasonal influenza vaccine. It is being conducted at four U.S. sites that are part of the Vaccine and Treatment Evaluation Units, funded by NIAID.
“An effective universal influenza vaccine would lessen the public health burden of influenza, alleviate suffering, and save lives,” said NIAID Director Anthony S. Fauci, MD. Such a vaccine would help eliminate the problem of unanticipated seasonal variation in the flu virus mix, which can make the chosen vaccine combination for that season less effective.
The study is a randomized, double-blind, placebo-controlled trial that will enroll 120 men and nonpregnant women, aged 18-49 years, inclusive, and is designed to assess the safety, reactogenicity, and immunogenicity of two priming doses of M-001 followed by a seasonal quadrivalent inactivated influenza vaccine.
The primary objectives are to assess the safety as measured by vaccine-related adverse events, reactogenicity, and laboratory adverse events; and to assess the T-cell responses to M-001 component peptides.
More information about the study can be found at ClinicalTrials.gov, using the identifier NCT03058692.
Common infections are potent risk factor for MI, stroke
ORLANDO – , according to a “big data” registry study from the United Kingdom.
“Our data show infection was just as much a risk factor or more compared with the traditional atherosclerotic cardiovascular disease risk factors,” Paul Carter, MD, said at the annual meeting of the American College of Cardiology.
Dr. Carter of Aston Medical School in Birmingham, England, presented a retrospective analysis from the ACALM (Algorithm for Comorbidities Associated with Length of stay and Mortality) study of administrative data on all of the more than 1.22 million patients admitted to seven U.K. hospitals in 2000-2013. His analysis included all 34,027 adults aged 40 years or older admitted with a urinary tract or respiratory infection on their index hospitalization who had no history of ischemic heart disease or ischemic stroke.
These patients, with a mean age of 73 years, 59% of whom were women, were compared with an equal number of age- and gender-matched adults whose index hospitalization was for reasons other than ischemic heart disease, stroke, urinary tract infection (UTI), or respiratory infection – the two most common infections resulting in hospitalization in the United Kingdom.
Patients with a respiratory infection or UTI had a 9.9% incidence of new-onset ischemic heart disease and a 4.1% rate of ischemic stroke during follow-up starting upon discharge from their index hospitalization, significantly higher than the 5.9% and 1.5% rates in controls. In a multivariate logistic regression analysis adjusted for demographics, standard cardiovascular risk factors, and the top 10 causes of mortality in the United Kingdom, patients with respiratory infection or UTI as their admitting diagnosis had a 1.36-fold increased likelihood of developing ischemic heart disease post discharge and a 2.5-fold greater risk of ischemic stroke than matched controls.
Moreover, mortality following diagnosis of ischemic heart disease was 75.2% in patients whose index hospitalization was for infection, compared with 51.1% in controls who developed ischemic heart disease without a history of hospitalization for infection, for an adjusted 2.98-fold increased likelihood of death. Similarly, mortality after an ischemic stroke was 59.8% in patients with a prior severe infection, compared with 30.8% in controls, which translated to an adjusted 3.1-fold increased risk of death post stroke in patients with a prior hospitalization for infection.
In the multivariate analysis, hospitalization for infection was a stronger risk factor for subsequent ischemic stroke than was atrial fibrillation, heart failure, type 1 or type 2 diabetes, hypertension, or hyperlipidemia. The risk of ischemic heart disease in patients with an infectious disease hospitalization was similar to the risks associated with most of those recognized risk factors.
Two possible mechanisms by which infection might predispose to subsequent ischemic heart disease and stroke are via a direct effect whereby pathogens such as Chlamydia pneumoniae are taken up into arterial plaques, where they cause a local inflammatory response, or an indirect effect in which systemic inflammation primes the atherosclerotic plaque through distribution of inflammatory cytokines, according to Dr. Carter.
He said the ACALM findings are particularly intriguing when considered in the context of the 2017 results of the landmark CANTOS trial, in which canakinumab (Ilaris), a targeted anti-inflammatory agent that inhibits the interleukin-1 beta innate immunity pathway, reduced recurrent ischemic events in post-MI patients who had high systemic inflammation as evidenced by their elevated C-reactive protein level but a normal-range LDL cholesterol (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
“If atherosclerosis is an inflammatory condition, this begs the question of whether other inflammatory conditions, like infection, which induces a large systemic inflammatory response, might drive atherosclerosis,” Dr. Carter commented.
“It’s now very well understood that inflammatory mediators, cells, and processes are involved in every step from the initial endothelial dysfunction that leads to uptake of LDL, inflammatory cells, and monocytes all the way through to plaque progression and rupture, where Th1 cytokines have been implicated in causing that rupture, and ultimately in patient presentation at the hospital,” he added.
He sees the ACALM findings as hypothesis generating, serving to help lay the groundwork for future clinical trials of vaccine or anti-inflammatory antibiotic therapies.
Dr. Carter reported having no financial conflicts related to his presentation.
SOURCE: Carter P. ACC 2018, Abstract 1325M-0.
ORLANDO – , according to a “big data” registry study from the United Kingdom.
“Our data show infection was just as much a risk factor or more compared with the traditional atherosclerotic cardiovascular disease risk factors,” Paul Carter, MD, said at the annual meeting of the American College of Cardiology.
Dr. Carter of Aston Medical School in Birmingham, England, presented a retrospective analysis from the ACALM (Algorithm for Comorbidities Associated with Length of stay and Mortality) study of administrative data on all of the more than 1.22 million patients admitted to seven U.K. hospitals in 2000-2013. His analysis included all 34,027 adults aged 40 years or older admitted with a urinary tract or respiratory infection on their index hospitalization who had no history of ischemic heart disease or ischemic stroke.
These patients, with a mean age of 73 years, 59% of whom were women, were compared with an equal number of age- and gender-matched adults whose index hospitalization was for reasons other than ischemic heart disease, stroke, urinary tract infection (UTI), or respiratory infection – the two most common infections resulting in hospitalization in the United Kingdom.
Patients with a respiratory infection or UTI had a 9.9% incidence of new-onset ischemic heart disease and a 4.1% rate of ischemic stroke during follow-up starting upon discharge from their index hospitalization, significantly higher than the 5.9% and 1.5% rates in controls. In a multivariate logistic regression analysis adjusted for demographics, standard cardiovascular risk factors, and the top 10 causes of mortality in the United Kingdom, patients with respiratory infection or UTI as their admitting diagnosis had a 1.36-fold increased likelihood of developing ischemic heart disease post discharge and a 2.5-fold greater risk of ischemic stroke than matched controls.
Moreover, mortality following diagnosis of ischemic heart disease was 75.2% in patients whose index hospitalization was for infection, compared with 51.1% in controls who developed ischemic heart disease without a history of hospitalization for infection, for an adjusted 2.98-fold increased likelihood of death. Similarly, mortality after an ischemic stroke was 59.8% in patients with a prior severe infection, compared with 30.8% in controls, which translated to an adjusted 3.1-fold increased risk of death post stroke in patients with a prior hospitalization for infection.
In the multivariate analysis, hospitalization for infection was a stronger risk factor for subsequent ischemic stroke than was atrial fibrillation, heart failure, type 1 or type 2 diabetes, hypertension, or hyperlipidemia. The risk of ischemic heart disease in patients with an infectious disease hospitalization was similar to the risks associated with most of those recognized risk factors.
Two possible mechanisms by which infection might predispose to subsequent ischemic heart disease and stroke are via a direct effect whereby pathogens such as Chlamydia pneumoniae are taken up into arterial plaques, where they cause a local inflammatory response, or an indirect effect in which systemic inflammation primes the atherosclerotic plaque through distribution of inflammatory cytokines, according to Dr. Carter.
He said the ACALM findings are particularly intriguing when considered in the context of the 2017 results of the landmark CANTOS trial, in which canakinumab (Ilaris), a targeted anti-inflammatory agent that inhibits the interleukin-1 beta innate immunity pathway, reduced recurrent ischemic events in post-MI patients who had high systemic inflammation as evidenced by their elevated C-reactive protein level but a normal-range LDL cholesterol (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
“If atherosclerosis is an inflammatory condition, this begs the question of whether other inflammatory conditions, like infection, which induces a large systemic inflammatory response, might drive atherosclerosis,” Dr. Carter commented.
“It’s now very well understood that inflammatory mediators, cells, and processes are involved in every step from the initial endothelial dysfunction that leads to uptake of LDL, inflammatory cells, and monocytes all the way through to plaque progression and rupture, where Th1 cytokines have been implicated in causing that rupture, and ultimately in patient presentation at the hospital,” he added.
He sees the ACALM findings as hypothesis generating, serving to help lay the groundwork for future clinical trials of vaccine or anti-inflammatory antibiotic therapies.
Dr. Carter reported having no financial conflicts related to his presentation.
SOURCE: Carter P. ACC 2018, Abstract 1325M-0.
ORLANDO – , according to a “big data” registry study from the United Kingdom.
“Our data show infection was just as much a risk factor or more compared with the traditional atherosclerotic cardiovascular disease risk factors,” Paul Carter, MD, said at the annual meeting of the American College of Cardiology.
Dr. Carter of Aston Medical School in Birmingham, England, presented a retrospective analysis from the ACALM (Algorithm for Comorbidities Associated with Length of stay and Mortality) study of administrative data on all of the more than 1.22 million patients admitted to seven U.K. hospitals in 2000-2013. His analysis included all 34,027 adults aged 40 years or older admitted with a urinary tract or respiratory infection on their index hospitalization who had no history of ischemic heart disease or ischemic stroke.
These patients, with a mean age of 73 years, 59% of whom were women, were compared with an equal number of age- and gender-matched adults whose index hospitalization was for reasons other than ischemic heart disease, stroke, urinary tract infection (UTI), or respiratory infection – the two most common infections resulting in hospitalization in the United Kingdom.
Patients with a respiratory infection or UTI had a 9.9% incidence of new-onset ischemic heart disease and a 4.1% rate of ischemic stroke during follow-up starting upon discharge from their index hospitalization, significantly higher than the 5.9% and 1.5% rates in controls. In a multivariate logistic regression analysis adjusted for demographics, standard cardiovascular risk factors, and the top 10 causes of mortality in the United Kingdom, patients with respiratory infection or UTI as their admitting diagnosis had a 1.36-fold increased likelihood of developing ischemic heart disease post discharge and a 2.5-fold greater risk of ischemic stroke than matched controls.
Moreover, mortality following diagnosis of ischemic heart disease was 75.2% in patients whose index hospitalization was for infection, compared with 51.1% in controls who developed ischemic heart disease without a history of hospitalization for infection, for an adjusted 2.98-fold increased likelihood of death. Similarly, mortality after an ischemic stroke was 59.8% in patients with a prior severe infection, compared with 30.8% in controls, which translated to an adjusted 3.1-fold increased risk of death post stroke in patients with a prior hospitalization for infection.
In the multivariate analysis, hospitalization for infection was a stronger risk factor for subsequent ischemic stroke than was atrial fibrillation, heart failure, type 1 or type 2 diabetes, hypertension, or hyperlipidemia. The risk of ischemic heart disease in patients with an infectious disease hospitalization was similar to the risks associated with most of those recognized risk factors.
Two possible mechanisms by which infection might predispose to subsequent ischemic heart disease and stroke are via a direct effect whereby pathogens such as Chlamydia pneumoniae are taken up into arterial plaques, where they cause a local inflammatory response, or an indirect effect in which systemic inflammation primes the atherosclerotic plaque through distribution of inflammatory cytokines, according to Dr. Carter.
He said the ACALM findings are particularly intriguing when considered in the context of the 2017 results of the landmark CANTOS trial, in which canakinumab (Ilaris), a targeted anti-inflammatory agent that inhibits the interleukin-1 beta innate immunity pathway, reduced recurrent ischemic events in post-MI patients who had high systemic inflammation as evidenced by their elevated C-reactive protein level but a normal-range LDL cholesterol (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
“If atherosclerosis is an inflammatory condition, this begs the question of whether other inflammatory conditions, like infection, which induces a large systemic inflammatory response, might drive atherosclerosis,” Dr. Carter commented.
“It’s now very well understood that inflammatory mediators, cells, and processes are involved in every step from the initial endothelial dysfunction that leads to uptake of LDL, inflammatory cells, and monocytes all the way through to plaque progression and rupture, where Th1 cytokines have been implicated in causing that rupture, and ultimately in patient presentation at the hospital,” he added.
He sees the ACALM findings as hypothesis generating, serving to help lay the groundwork for future clinical trials of vaccine or anti-inflammatory antibiotic therapies.
Dr. Carter reported having no financial conflicts related to his presentation.
SOURCE: Carter P. ACC 2018, Abstract 1325M-0.
REPORTING FROM ACC 2018
Key clinical point: Once patients have been hospitalized for a respiratory infection or UTI, their postdischarge risk of ischemic stroke is 2.5-fold greater than in those without such a history.
Major finding: Patients with a history of hospitalization for UTI or a respiratory infection who later develop ischemic heart disease or stroke have a threefold higher mortality risk than those without such a hospitalization.
Study details: This was a retrospective study of more than 68,000 subjects in the U.K. ACALM registry study.
Disclosures: The study presenter reported having no financial conflicts of interest.
Source: Carter P. ACC 2018, Abstract 1325M-0.
Flu activity continues to decline
The 2017-2018 flu season continued to loosen its grip on the country as both outpatient activity and pediatric deaths dropped during the week ending March 3, according to the Centers for Disease Control and Prevention.
After five consecutive weeks of double-digit pediatric deaths related to influenza-like illness (ILI), five deaths were reported for the week ending March 3, four of which occurred in previous weeks. The total for the 2017-2018 season is now 119, the CDC said in its weekly surveillance report.
The proportion of outpatient visits for ILI was 3.7% for the week, which is down from 4.9% the week before and less than half of the seasonal high of 7.5% that was recorded for the week of Feb. 3, CDC data show. The national baseline level of outpatient activity is 2.2%.
The cumulative hospitalization rate for the 2017-2018 flu season climbed from 84.2 the previous week to 86.3 per 100,000 population – well above the rate of 57.2 per 100,000 that was recorded for the corresponding week of the hospitalization-record-setting 2014-2015 season, FluView data show.
The 2017-2018 flu season continued to loosen its grip on the country as both outpatient activity and pediatric deaths dropped during the week ending March 3, according to the Centers for Disease Control and Prevention.
After five consecutive weeks of double-digit pediatric deaths related to influenza-like illness (ILI), five deaths were reported for the week ending March 3, four of which occurred in previous weeks. The total for the 2017-2018 season is now 119, the CDC said in its weekly surveillance report.
The proportion of outpatient visits for ILI was 3.7% for the week, which is down from 4.9% the week before and less than half of the seasonal high of 7.5% that was recorded for the week of Feb. 3, CDC data show. The national baseline level of outpatient activity is 2.2%.
The cumulative hospitalization rate for the 2017-2018 flu season climbed from 84.2 the previous week to 86.3 per 100,000 population – well above the rate of 57.2 per 100,000 that was recorded for the corresponding week of the hospitalization-record-setting 2014-2015 season, FluView data show.
The 2017-2018 flu season continued to loosen its grip on the country as both outpatient activity and pediatric deaths dropped during the week ending March 3, according to the Centers for Disease Control and Prevention.
After five consecutive weeks of double-digit pediatric deaths related to influenza-like illness (ILI), five deaths were reported for the week ending March 3, four of which occurred in previous weeks. The total for the 2017-2018 season is now 119, the CDC said in its weekly surveillance report.
The proportion of outpatient visits for ILI was 3.7% for the week, which is down from 4.9% the week before and less than half of the seasonal high of 7.5% that was recorded for the week of Feb. 3, CDC data show. The national baseline level of outpatient activity is 2.2%.
The cumulative hospitalization rate for the 2017-2018 flu season climbed from 84.2 the previous week to 86.3 per 100,000 population – well above the rate of 57.2 per 100,000 that was recorded for the corresponding week of the hospitalization-record-setting 2014-2015 season, FluView data show.