Pulmonary Infections

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]

Recurrent invasive pneumococcal disease in children could be a signal of underlying primary immunodeficiency, according to a systematic review published in JAMA Pediatrics.

Coen Butters, BMed, DCH, of the Royal Children’s Hospital in Melbourne, and coauthors wrote that, even with optimal vaccine coverage, there is still a group of children with increased susceptibility to invasive pneumococcal disease (IPD), and this could be a potential marker of primary immunodeficiency.

They conducted a systematic review of 17 studies of 6,002 children to examine the evidence on the incidence of primary immunodeficiency in children who presented with IPD but without any other risk factors or predisposing conditions.

Overall, the frequency of primary immunodeficiency in children presenting with IPD who did not have any other predisposing condition ranged from 1% to 26%.

One study of 162 children with IPD, which had an overall frequency of primary immunodeficiency of 10%, found that children older than 2 years were significantly more likely to have primary immunodeficiency than those aged under 2 years (26% vs. 3%; P less than .001).

Primary antibody deficiency was the most commonly diagnosed immunodeficiency in these children with IPD, accounting for 71% of cases. These deficiencies presented as hypogammaglobulinemia, specific pneumococcal antibody deficiency, X-linked agammaglobulinemia, and IgG2 deficiency.

The review also included four studies that looked at the frequency of mannose-binding lectin deficiency in 1,493 children with primary IPD. Two of these studies reported a prevalence of mannose-binding lectin deficiency ranging from 31% in children aged younger than 2 years to 41% in children younger than 1 year.

Five studies looked at the rate of primary immunodeficiency in children presenting with recurrent IPD. In addition to other predisposing conditions such as sickle cell disease, cancer, and anatomical breach in the blood-brain barrier, the three studies that screened for primary immunodeficiency found rates ranging from 10% to 67%. The most common conditions were complement deficiency, pneumococcal antibody deficiency, and a single case of TLR-signaling defect.

In a study of 162 children with primary IPD, screening for asplenia identified a single case of congenital asplenia. In another study of 2,498 cases of IPD, 22 patients had asplenia at presentation, half of whom died at presentation.

Dr. Butters and associates concluded that “this review’s findings suggests that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of Streptococcus pneumoniae meningitis, pneumonia, or recurrent IPD. Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia.”

In an accompanying editorial, Stephen I. Pelton, MD, of the Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center, and coauthors wrote that in children with recurrent episodes of IPD caused by nonvaccine serotypes – particularly those aged over 5 years – evaluation for primary immunodeficiencies could uncover immune defects.

“Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with [primary immunodeficiency],” they wrote.

No funding or conflicts of interest were declared for the study. Two of the editorialists declared research funding or honoraria from the pharmaceutical sector.

SOURCES: Butters C et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3203; Pelton SI et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3185.

Recurrent invasive pneumococcal disease in children could be a signal of underlying primary immunodeficiency, according to a systematic review published in JAMA Pediatrics.

Coen Butters, BMed, DCH, of the Royal Children’s Hospital in Melbourne, and coauthors wrote that, even with optimal vaccine coverage, there is still a group of children with increased susceptibility to invasive pneumococcal disease (IPD), and this could be a potential marker of primary immunodeficiency.

They conducted a systematic review of 17 studies of 6,002 children to examine the evidence on the incidence of primary immunodeficiency in children who presented with IPD but without any other risk factors or predisposing conditions.

Overall, the frequency of primary immunodeficiency in children presenting with IPD who did not have any other predisposing condition ranged from 1% to 26%.

One study of 162 children with IPD, which had an overall frequency of primary immunodeficiency of 10%, found that children older than 2 years were significantly more likely to have primary immunodeficiency than those aged under 2 years (26% vs. 3%; P less than .001).

Primary antibody deficiency was the most commonly diagnosed immunodeficiency in these children with IPD, accounting for 71% of cases. These deficiencies presented as hypogammaglobulinemia, specific pneumococcal antibody deficiency, X-linked agammaglobulinemia, and IgG2 deficiency.

The review also included four studies that looked at the frequency of mannose-binding lectin deficiency in 1,493 children with primary IPD. Two of these studies reported a prevalence of mannose-binding lectin deficiency ranging from 31% in children aged younger than 2 years to 41% in children younger than 1 year.

Five studies looked at the rate of primary immunodeficiency in children presenting with recurrent IPD. In addition to other predisposing conditions such as sickle cell disease, cancer, and anatomical breach in the blood-brain barrier, the three studies that screened for primary immunodeficiency found rates ranging from 10% to 67%. The most common conditions were complement deficiency, pneumococcal antibody deficiency, and a single case of TLR-signaling defect.

In a study of 162 children with primary IPD, screening for asplenia identified a single case of congenital asplenia. In another study of 2,498 cases of IPD, 22 patients had asplenia at presentation, half of whom died at presentation.

Dr. Butters and associates concluded that “this review’s findings suggests that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of Streptococcus pneumoniae meningitis, pneumonia, or recurrent IPD. Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia.”

In an accompanying editorial, Stephen I. Pelton, MD, of the Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center, and coauthors wrote that in children with recurrent episodes of IPD caused by nonvaccine serotypes – particularly those aged over 5 years – evaluation for primary immunodeficiencies could uncover immune defects.

“Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with [primary immunodeficiency],” they wrote.

No funding or conflicts of interest were declared for the study. Two of the editorialists declared research funding or honoraria from the pharmaceutical sector.

SOURCES: Butters C et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3203; Pelton SI et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3185.

Recurrent invasive pneumococcal disease in children could be a signal of underlying primary immunodeficiency, according to a systematic review published in JAMA Pediatrics.

Coen Butters, BMed, DCH, of the Royal Children’s Hospital in Melbourne, and coauthors wrote that, even with optimal vaccine coverage, there is still a group of children with increased susceptibility to invasive pneumococcal disease (IPD), and this could be a potential marker of primary immunodeficiency.

They conducted a systematic review of 17 studies of 6,002 children to examine the evidence on the incidence of primary immunodeficiency in children who presented with IPD but without any other risk factors or predisposing conditions.

Overall, the frequency of primary immunodeficiency in children presenting with IPD who did not have any other predisposing condition ranged from 1% to 26%.

One study of 162 children with IPD, which had an overall frequency of primary immunodeficiency of 10%, found that children older than 2 years were significantly more likely to have primary immunodeficiency than those aged under 2 years (26% vs. 3%; P less than .001).

Primary antibody deficiency was the most commonly diagnosed immunodeficiency in these children with IPD, accounting for 71% of cases. These deficiencies presented as hypogammaglobulinemia, specific pneumococcal antibody deficiency, X-linked agammaglobulinemia, and IgG2 deficiency.

The review also included four studies that looked at the frequency of mannose-binding lectin deficiency in 1,493 children with primary IPD. Two of these studies reported a prevalence of mannose-binding lectin deficiency ranging from 31% in children aged younger than 2 years to 41% in children younger than 1 year.

Five studies looked at the rate of primary immunodeficiency in children presenting with recurrent IPD. In addition to other predisposing conditions such as sickle cell disease, cancer, and anatomical breach in the blood-brain barrier, the three studies that screened for primary immunodeficiency found rates ranging from 10% to 67%. The most common conditions were complement deficiency, pneumococcal antibody deficiency, and a single case of TLR-signaling defect.

In a study of 162 children with primary IPD, screening for asplenia identified a single case of congenital asplenia. In another study of 2,498 cases of IPD, 22 patients had asplenia at presentation, half of whom died at presentation.

Dr. Butters and associates concluded that “this review’s findings suggests that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of Streptococcus pneumoniae meningitis, pneumonia, or recurrent IPD. Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia.”

In an accompanying editorial, Stephen I. Pelton, MD, of the Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center, and coauthors wrote that in children with recurrent episodes of IPD caused by nonvaccine serotypes – particularly those aged over 5 years – evaluation for primary immunodeficiencies could uncover immune defects.

“Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with [primary immunodeficiency],” they wrote.

No funding or conflicts of interest were declared for the study. Two of the editorialists declared research funding or honoraria from the pharmaceutical sector.

SOURCES: Butters C et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3203; Pelton SI et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3185.

Vitamin C infusion did not improve outcomes related to organ failure, inflammation, or vascular injury for patients with sepsis and acute respiratory distress syndrome, based on data from 167 adults.

Dr_Microbe/Getty Images

“Previous research found that vitamin C attenuates systemic inflammation, corrects sepsis-induced coagulopathy, and attenuates vascular injury,” wrote Alpha A. Fowler III, MD, of Virginia Commonwealth University, Richmond, and colleagues.

To examine the impact of vitamin C infusion on patients with sepsis and acute respiratory distress syndrome (ARDS), the researchers designed the CITRIS-ALI trial, a randomized, double-blind, placebo-controlled study conducted at 7 medical intensive care units in the United States.

In the study, published in JAMA, the researchers randomized 167 adults with sepsis and ARDS to receive high-dose intravenous vitamin C (50 mg/kg in 5% dextrose in water) or placebo (5% dextrose in water only) every 6 hours for 96 hours. The primary outcomes were measures of organ failure based on changes in the modified Sequential Organ Failure Assessment score (mSOFA), inflammation (based on changes in C-reactive protein), and vascular injury based on thrombomodulin.

Overall, no significant differences appeared between the vitamin C and placebo groups, respectively in the three primary outcome measures: change in average SOFA score (3-point change vs. a 3.5-point change) at 96 hours; change in C-reactive protein levels (change of 54.1 mcg/mL vs. 46.1 mcg/mL) at 168 hours; and change in thrombomodulin levels (14.5 ng/mL vs. 13.8 ng/mL) at 168 hours.

The average age of the patients was 55 years, and 54% were men.

The researchers also assessed 46 secondary outcomes. Most of these showed no significant differences between the groups, but 28-day all-cause mortality was significantly lower in the vitamin C group, compared with the placebo group (46.3% vs. 29.8%), the researchers said. Vitamin C also was significantly associated with increased ICU-free days to day 28 and hospital-free days to day 60, compared with placebo.

No significant differences were seen between the groups on 43 other secondary outcomes including ventilator-free days and vasopressor use. However, “these findings were based on analyses that did not account for multiple comparisons and therefore must be considered exploratory,” they said.

“The inability of vitamin C to affect C-reactive protein and thrombomodulin levels in this trial possibly resulted from the advanced stages of sepsis that were present before the development of ARDS,” the researchers noted.

The findings were limited by several factors including the variability in the timing of vitamin C administration and the use of a single high dose of vitamin C, they emphasized. However, the results suggest that further research may be needed to determine the potential of vitamin C for improving outcomes in patients with sepsis and ARDS, they said.

The study was supported by the National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, VCU Wright Center for Translational Science Award, VCU Investigational Drug Services, and McGuff Pharmaceuticals, who supplied the vitamin C free of charge. Dr. Fowler disclosed funding from Virginia Polytechnic Institute and State University, Richmond; the NHLBI; and study materials from McGuff Pharmaceuticals.

SOURCE: Fowler AA et al. JAMA. 2019 Oct 1;322:1261-70. doi:10.1001/jama.2019.11825.

Vitamin C infusion did not improve outcomes related to organ failure, inflammation, or vascular injury for patients with sepsis and acute respiratory distress syndrome, based on data from 167 adults.

Dr_Microbe/Getty Images

“Previous research found that vitamin C attenuates systemic inflammation, corrects sepsis-induced coagulopathy, and attenuates vascular injury,” wrote Alpha A. Fowler III, MD, of Virginia Commonwealth University, Richmond, and colleagues.

To examine the impact of vitamin C infusion on patients with sepsis and acute respiratory distress syndrome (ARDS), the researchers designed the CITRIS-ALI trial, a randomized, double-blind, placebo-controlled study conducted at 7 medical intensive care units in the United States.

In the study, published in JAMA, the researchers randomized 167 adults with sepsis and ARDS to receive high-dose intravenous vitamin C (50 mg/kg in 5% dextrose in water) or placebo (5% dextrose in water only) every 6 hours for 96 hours. The primary outcomes were measures of organ failure based on changes in the modified Sequential Organ Failure Assessment score (mSOFA), inflammation (based on changes in C-reactive protein), and vascular injury based on thrombomodulin.

Overall, no significant differences appeared between the vitamin C and placebo groups, respectively in the three primary outcome measures: change in average SOFA score (3-point change vs. a 3.5-point change) at 96 hours; change in C-reactive protein levels (change of 54.1 mcg/mL vs. 46.1 mcg/mL) at 168 hours; and change in thrombomodulin levels (14.5 ng/mL vs. 13.8 ng/mL) at 168 hours.

The average age of the patients was 55 years, and 54% were men.

The researchers also assessed 46 secondary outcomes. Most of these showed no significant differences between the groups, but 28-day all-cause mortality was significantly lower in the vitamin C group, compared with the placebo group (46.3% vs. 29.8%), the researchers said. Vitamin C also was significantly associated with increased ICU-free days to day 28 and hospital-free days to day 60, compared with placebo.

No significant differences were seen between the groups on 43 other secondary outcomes including ventilator-free days and vasopressor use. However, “these findings were based on analyses that did not account for multiple comparisons and therefore must be considered exploratory,” they said.

“The inability of vitamin C to affect C-reactive protein and thrombomodulin levels in this trial possibly resulted from the advanced stages of sepsis that were present before the development of ARDS,” the researchers noted.

The findings were limited by several factors including the variability in the timing of vitamin C administration and the use of a single high dose of vitamin C, they emphasized. However, the results suggest that further research may be needed to determine the potential of vitamin C for improving outcomes in patients with sepsis and ARDS, they said.

The study was supported by the National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, VCU Wright Center for Translational Science Award, VCU Investigational Drug Services, and McGuff Pharmaceuticals, who supplied the vitamin C free of charge. Dr. Fowler disclosed funding from Virginia Polytechnic Institute and State University, Richmond; the NHLBI; and study materials from McGuff Pharmaceuticals.

SOURCE: Fowler AA et al. JAMA. 2019 Oct 1;322:1261-70. doi:10.1001/jama.2019.11825.

Vitamin C infusion did not improve outcomes related to organ failure, inflammation, or vascular injury for patients with sepsis and acute respiratory distress syndrome, based on data from 167 adults.

Dr_Microbe/Getty Images

“Previous research found that vitamin C attenuates systemic inflammation, corrects sepsis-induced coagulopathy, and attenuates vascular injury,” wrote Alpha A. Fowler III, MD, of Virginia Commonwealth University, Richmond, and colleagues.

To examine the impact of vitamin C infusion on patients with sepsis and acute respiratory distress syndrome (ARDS), the researchers designed the CITRIS-ALI trial, a randomized, double-blind, placebo-controlled study conducted at 7 medical intensive care units in the United States.

In the study, published in JAMA, the researchers randomized 167 adults with sepsis and ARDS to receive high-dose intravenous vitamin C (50 mg/kg in 5% dextrose in water) or placebo (5% dextrose in water only) every 6 hours for 96 hours. The primary outcomes were measures of organ failure based on changes in the modified Sequential Organ Failure Assessment score (mSOFA), inflammation (based on changes in C-reactive protein), and vascular injury based on thrombomodulin.

Overall, no significant differences appeared between the vitamin C and placebo groups, respectively in the three primary outcome measures: change in average SOFA score (3-point change vs. a 3.5-point change) at 96 hours; change in C-reactive protein levels (change of 54.1 mcg/mL vs. 46.1 mcg/mL) at 168 hours; and change in thrombomodulin levels (14.5 ng/mL vs. 13.8 ng/mL) at 168 hours.

The average age of the patients was 55 years, and 54% were men.

The researchers also assessed 46 secondary outcomes. Most of these showed no significant differences between the groups, but 28-day all-cause mortality was significantly lower in the vitamin C group, compared with the placebo group (46.3% vs. 29.8%), the researchers said. Vitamin C also was significantly associated with increased ICU-free days to day 28 and hospital-free days to day 60, compared with placebo.

No significant differences were seen between the groups on 43 other secondary outcomes including ventilator-free days and vasopressor use. However, “these findings were based on analyses that did not account for multiple comparisons and therefore must be considered exploratory,” they said.

“The inability of vitamin C to affect C-reactive protein and thrombomodulin levels in this trial possibly resulted from the advanced stages of sepsis that were present before the development of ARDS,” the researchers noted.

The findings were limited by several factors including the variability in the timing of vitamin C administration and the use of a single high dose of vitamin C, they emphasized. However, the results suggest that further research may be needed to determine the potential of vitamin C for improving outcomes in patients with sepsis and ARDS, they said.

The study was supported by the National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, VCU Wright Center for Translational Science Award, VCU Investigational Drug Services, and McGuff Pharmaceuticals, who supplied the vitamin C free of charge. Dr. Fowler disclosed funding from Virginia Polytechnic Institute and State University, Richmond; the NHLBI; and study materials from McGuff Pharmaceuticals.

SOURCE: Fowler AA et al. JAMA. 2019 Oct 1;322:1261-70. doi:10.1001/jama.2019.11825.

LJUBLJANA, SLOVENIA – Fever of unknown origin and pneumonia are two clinical features useful in distinguishing between influenza and respiratory syncytial virus infection as the cause of hospitalization in infants and young children, Cihan Papan, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

Dr. Papan, a pediatrician at University Children’s Hospital Mannheim (Germany) and Heidelberg (Germany) University, presented a retrospective single-center study of all 573 children aged under 2 years hospitalized over the course of several seasons for respiratory syncytial virus (RSV) or influenza as confirmed by rapid antigen testing. Even though these are two of the leading causes of hospitalization among young children, there is surprisingly sparse data comparing the two in terms of disease severity and hospital resource utilization, including antibiotic consumption. That information gap provided the basis for this study.

There were 476 children with confirmed RSV, 96 with influenza, and 1 RSV/influenza coinfection. Notably, even though the RSV group had lower temperatures and C-reactive protein levels, they were nevertheless more likely to be treated with antibiotics, by a margin of 29% to 23%.

“These findings open new possibilities for antimicrobial stewardship in these groups of virally infected children,” observed Dr. Papan.

Fever of unknown origin was present in 68.8% of the influenza-positive patients, compared with just 0.2% of the RSV-positive children. In contrast, 50.2% of the RSV group had pneumonia and 49.6% had bronchitis or bronchiolitis, versus just 22.9% and 6.3% of the influenza patients, respectively. A larger proportion of the young children with RSV infection presented in a severely ill–looking condition. Children with RSV infection also were significantly younger.

Dr. Papan reported having no financial conflicts regarding his study.

[email protected]

LJUBLJANA, SLOVENIA – Fever of unknown origin and pneumonia are two clinical features useful in distinguishing between influenza and respiratory syncytial virus infection as the cause of hospitalization in infants and young children, Cihan Papan, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

Dr. Papan, a pediatrician at University Children’s Hospital Mannheim (Germany) and Heidelberg (Germany) University, presented a retrospective single-center study of all 573 children aged under 2 years hospitalized over the course of several seasons for respiratory syncytial virus (RSV) or influenza as confirmed by rapid antigen testing. Even though these are two of the leading causes of hospitalization among young children, there is surprisingly sparse data comparing the two in terms of disease severity and hospital resource utilization, including antibiotic consumption. That information gap provided the basis for this study.

There were 476 children with confirmed RSV, 96 with influenza, and 1 RSV/influenza coinfection. Notably, even though the RSV group had lower temperatures and C-reactive protein levels, they were nevertheless more likely to be treated with antibiotics, by a margin of 29% to 23%.

“These findings open new possibilities for antimicrobial stewardship in these groups of virally infected children,” observed Dr. Papan.

Fever of unknown origin was present in 68.8% of the influenza-positive patients, compared with just 0.2% of the RSV-positive children. In contrast, 50.2% of the RSV group had pneumonia and 49.6% had bronchitis or bronchiolitis, versus just 22.9% and 6.3% of the influenza patients, respectively. A larger proportion of the young children with RSV infection presented in a severely ill–looking condition. Children with RSV infection also were significantly younger.

Dr. Papan reported having no financial conflicts regarding his study.

[email protected]

LJUBLJANA, SLOVENIA – Fever of unknown origin and pneumonia are two clinical features useful in distinguishing between influenza and respiratory syncytial virus infection as the cause of hospitalization in infants and young children, Cihan Papan, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

Dr. Papan, a pediatrician at University Children’s Hospital Mannheim (Germany) and Heidelberg (Germany) University, presented a retrospective single-center study of all 573 children aged under 2 years hospitalized over the course of several seasons for respiratory syncytial virus (RSV) or influenza as confirmed by rapid antigen testing. Even though these are two of the leading causes of hospitalization among young children, there is surprisingly sparse data comparing the two in terms of disease severity and hospital resource utilization, including antibiotic consumption. That information gap provided the basis for this study.

There were 476 children with confirmed RSV, 96 with influenza, and 1 RSV/influenza coinfection. Notably, even though the RSV group had lower temperatures and C-reactive protein levels, they were nevertheless more likely to be treated with antibiotics, by a margin of 29% to 23%.

“These findings open new possibilities for antimicrobial stewardship in these groups of virally infected children,” observed Dr. Papan.

Fever of unknown origin was present in 68.8% of the influenza-positive patients, compared with just 0.2% of the RSV-positive children. In contrast, 50.2% of the RSV group had pneumonia and 49.6% had bronchitis or bronchiolitis, versus just 22.9% and 6.3% of the influenza patients, respectively. A larger proportion of the young children with RSV infection presented in a severely ill–looking condition. Children with RSV infection also were significantly younger.

Dr. Papan reported having no financial conflicts regarding his study.

[email protected]

Cardiac biomarkers were used to predict the likelihood of cardiovascular events at day 1 and day 30 in patients with community-acquired pneumonia, in a recently conducted study.

Thomas Northcut/Thinkstock

These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.

“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”

Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.

Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.

With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.

After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO₂/FiO₂) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.

Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.

This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
 

SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.

Cardiac biomarkers were used to predict the likelihood of cardiovascular events at day 1 and day 30 in patients with community-acquired pneumonia, in a recently conducted study.

Thomas Northcut/Thinkstock

These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.

“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”

Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.

Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.

With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.

After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO₂/FiO₂) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.

Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.

This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
 

SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.

Cardiac biomarkers were used to predict the likelihood of cardiovascular events at day 1 and day 30 in patients with community-acquired pneumonia, in a recently conducted study.

Thomas Northcut/Thinkstock

These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.

“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”

Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.

Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.

With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.

After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO₂/FiO₂) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.

Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.

This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
 

SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.

Fluad (aIIV3), an adjuvanted flu vaccine that’s recommended for people aged 65 and older, does a better job than do conventional flu vaccines in young children, according to an industry-funded synthesis of six studies.

KatarzynaBialasiewicz/Thinkstock

The vaccine “offers significant advances over conventional inactivated influenza vaccines and presents an acceptable safety profile in children 6 months through 5 years of age,” Sanjay S. Patel, PhD, of Novartis Vaccines and Diagnostics, Cambridge, Mass., and associates wrote in the analysis, published in the International Journal of Infectious Diseases. “The noteworthy increases in antibody responses and decreases in influenza cases following vaccination suggest an alternative for use in a population that is heavily impacted by influenza disease.”

Children are, of course, vulnerable to flu. The Centers for Disease Control and Prevention reported that 186 children died of flu during the landmark 2017-2018 flu season. That’s the highest number of pediatric flu deaths since they became a notifiable condition in 2004 (exclusive of the 2009 pandemic, when 358 pediatric deaths were reported from April 15, 2009, to October 2, 2010).The CDC said the vaccine during that flu season had an overall effectiveness level of 40%. According to research of others, however, flu vaccines are less effective in younger children than in adolescents and adults (Vaccine. 2014;32[31]:3886-94; Cochrane Database Syst Rev. 2008. doi: 10.1002/14651858.CD004879.pub3).

Fluad – a MF59-adjuvanted inactivated trivalent seasonal influenza vaccine – is used in adults over 65 in the United States and 29 other countries, and it is approved for children aged 6 months through 23 months in Canada.

Dr. Patel and associates examined the results of six studies – one phase 1b, three phase 2, and two phase 3 – that tested Fluad with or without other vaccines in 11,942 children aged 6 months to 5 years. The studies, mostly multicenter, were conducted in various countries, mainly in Europe and South and Central America, from 2006 to 2012.

In general, children in the intervention groups in the studies received two doses of the Fluad vaccine 4 weeks apart: two 0.25-mL doses for children aged 6-35 months and two 0.5-mL doses for those aged 3 years or older. In most of the studies, parallel control groups received nonadjuvanted trivalent or quadrivalent influenza vaccines.

Most participants (93%-94%) completed the studies. Solicited adverse effects were common in all groups (72% in the Fluad group vs. 67% who received IIV3 vaccines), and generally mild to moderate and resolved in 1-3 days. Unsolicited adverse effects were similar (55% and 62%, respectively) in the two flu vaccine groups. The authors wrote that “these data reflect a safety profile consistent with other licensed inactivated influenza vaccines administered to children.”

As for results, Dr. Patel and colleagues said, “HI [hemagglutination inhibition] antibody responses to both homologous and heterologous influenza strains are higher following vaccination with aIIV3, and this increase in immunogenicity is observed across all age subgroups in children aged 6 months through 5 years, and most profound in the children 6 to 36 months.”

For example, in one of the phase 3 studies when the influenza viruses were antigenically matched (homologous) for A/H1N1 among the children aged 6-35 months seroconversion was 100% for allV3 (Fluad) and 38% for IIV3-1/IIV3-4 (trivalent/quadrivalent flu vaccines); among children aged 3-5 years seroconversion was 100% for allV3 and 82% for IIV3-1/IIV3-4. For AH3N2 homologous among children aged 6-35 months, seroconversion was 98% for allV3 and 44% for IIV3-1/IIV3-4. For the B strain homologous among children aged 6-35 months, seroconversion was 88% for allV3 and 19% for IIV3-1/IIV3-4; among children aged 3-5 years seroconversion for B was 99% for allV3 and 59% for IIV3-1/IIV3-4.

In the same study when the influenza viruses were antigenically mismatched (heterologous) for A/H1N1 among children of all ages 6 months to greater than 72 months, seroconversion was 96% for allV3 (Fluad) and 44% for IIV3-1/IIV3-4; for A/H3N2 it was 98% for allV3 and 49% for IIV3-1/IIV3-4, and for the B strain it was 10% for allV3 and 3% for IIV3-1/IIV3-4.

They added that “in addition, aIIV3 had the fastest onset of immunogenicity and longest persistence of immune response, which has implications for the real-world clinical setting, where the influenza season might start earlier than expected or last longer, and second (follow-up) vaccinations may be missed.”

Dr. Patel and associates said the MF59 adjuvant in Fluad “recruits immune cells (primarily monocytes, macrophages, neutrophils, and dendritic cells) at the site of injection and differentiates them into antigen-presenting cells. With an MF59-adjuvanted vaccine, more antigen is transported from the injection site to the draining lymph node, wherein MF59 leads to T-cell activation and an increased B-cell expansion and a greater number and diversity of antibodies.”

According to goodrx.com, one syringe of Fluad 0.5 mL costs $45-$74 with coupon. The same dose of Fluzone Quadrivalent, a flu vaccine recently approved by the Food and Drug Administration for use in young children aged 6-35 months, costs $31 with coupon.

The study was funded by Novartis Vaccines and Diagnostics and Seqirus (formerly part of Novartis Vaccines and Diagnostics). The study authors disclosed employment by Novartis and Seqirus.

SOURCE: Patel SS et al. Int J Infect Dis. 2019. doi: 10.1016/j.ijid.2019.05.009.

Fluad (aIIV3), an adjuvanted flu vaccine that’s recommended for people aged 65 and older, does a better job than do conventional flu vaccines in young children, according to an industry-funded synthesis of six studies.

KatarzynaBialasiewicz/Thinkstock

The vaccine “offers significant advances over conventional inactivated influenza vaccines and presents an acceptable safety profile in children 6 months through 5 years of age,” Sanjay S. Patel, PhD, of Novartis Vaccines and Diagnostics, Cambridge, Mass., and associates wrote in the analysis, published in the International Journal of Infectious Diseases. “The noteworthy increases in antibody responses and decreases in influenza cases following vaccination suggest an alternative for use in a population that is heavily impacted by influenza disease.”

Children are, of course, vulnerable to flu. The Centers for Disease Control and Prevention reported that 186 children died of flu during the landmark 2017-2018 flu season. That’s the highest number of pediatric flu deaths since they became a notifiable condition in 2004 (exclusive of the 2009 pandemic, when 358 pediatric deaths were reported from April 15, 2009, to October 2, 2010).The CDC said the vaccine during that flu season had an overall effectiveness level of 40%. According to research of others, however, flu vaccines are less effective in younger children than in adolescents and adults (Vaccine. 2014;32[31]:3886-94; Cochrane Database Syst Rev. 2008. doi: 10.1002/14651858.CD004879.pub3).

Fluad – a MF59-adjuvanted inactivated trivalent seasonal influenza vaccine – is used in adults over 65 in the United States and 29 other countries, and it is approved for children aged 6 months through 23 months in Canada.

Dr. Patel and associates examined the results of six studies – one phase 1b, three phase 2, and two phase 3 – that tested Fluad with or without other vaccines in 11,942 children aged 6 months to 5 years. The studies, mostly multicenter, were conducted in various countries, mainly in Europe and South and Central America, from 2006 to 2012.

In general, children in the intervention groups in the studies received two doses of the Fluad vaccine 4 weeks apart: two 0.25-mL doses for children aged 6-35 months and two 0.5-mL doses for those aged 3 years or older. In most of the studies, parallel control groups received nonadjuvanted trivalent or quadrivalent influenza vaccines.

Most participants (93%-94%) completed the studies. Solicited adverse effects were common in all groups (72% in the Fluad group vs. 67% who received IIV3 vaccines), and generally mild to moderate and resolved in 1-3 days. Unsolicited adverse effects were similar (55% and 62%, respectively) in the two flu vaccine groups. The authors wrote that “these data reflect a safety profile consistent with other licensed inactivated influenza vaccines administered to children.”

As for results, Dr. Patel and colleagues said, “HI [hemagglutination inhibition] antibody responses to both homologous and heterologous influenza strains are higher following vaccination with aIIV3, and this increase in immunogenicity is observed across all age subgroups in children aged 6 months through 5 years, and most profound in the children 6 to 36 months.”

For example, in one of the phase 3 studies when the influenza viruses were antigenically matched (homologous) for A/H1N1 among the children aged 6-35 months seroconversion was 100% for allV3 (Fluad) and 38% for IIV3-1/IIV3-4 (trivalent/quadrivalent flu vaccines); among children aged 3-5 years seroconversion was 100% for allV3 and 82% for IIV3-1/IIV3-4. For AH3N2 homologous among children aged 6-35 months, seroconversion was 98% for allV3 and 44% for IIV3-1/IIV3-4. For the B strain homologous among children aged 6-35 months, seroconversion was 88% for allV3 and 19% for IIV3-1/IIV3-4; among children aged 3-5 years seroconversion for B was 99% for allV3 and 59% for IIV3-1/IIV3-4.

In the same study when the influenza viruses were antigenically mismatched (heterologous) for A/H1N1 among children of all ages 6 months to greater than 72 months, seroconversion was 96% for allV3 (Fluad) and 44% for IIV3-1/IIV3-4; for A/H3N2 it was 98% for allV3 and 49% for IIV3-1/IIV3-4, and for the B strain it was 10% for allV3 and 3% for IIV3-1/IIV3-4.

They added that “in addition, aIIV3 had the fastest onset of immunogenicity and longest persistence of immune response, which has implications for the real-world clinical setting, where the influenza season might start earlier than expected or last longer, and second (follow-up) vaccinations may be missed.”

Dr. Patel and associates said the MF59 adjuvant in Fluad “recruits immune cells (primarily monocytes, macrophages, neutrophils, and dendritic cells) at the site of injection and differentiates them into antigen-presenting cells. With an MF59-adjuvanted vaccine, more antigen is transported from the injection site to the draining lymph node, wherein MF59 leads to T-cell activation and an increased B-cell expansion and a greater number and diversity of antibodies.”

According to goodrx.com, one syringe of Fluad 0.5 mL costs $45-$74 with coupon. The same dose of Fluzone Quadrivalent, a flu vaccine recently approved by the Food and Drug Administration for use in young children aged 6-35 months, costs $31 with coupon.

The study was funded by Novartis Vaccines and Diagnostics and Seqirus (formerly part of Novartis Vaccines and Diagnostics). The study authors disclosed employment by Novartis and Seqirus.

SOURCE: Patel SS et al. Int J Infect Dis. 2019. doi: 10.1016/j.ijid.2019.05.009.

Fluad (aIIV3), an adjuvanted flu vaccine that’s recommended for people aged 65 and older, does a better job than do conventional flu vaccines in young children, according to an industry-funded synthesis of six studies.

KatarzynaBialasiewicz/Thinkstock

The vaccine “offers significant advances over conventional inactivated influenza vaccines and presents an acceptable safety profile in children 6 months through 5 years of age,” Sanjay S. Patel, PhD, of Novartis Vaccines and Diagnostics, Cambridge, Mass., and associates wrote in the analysis, published in the International Journal of Infectious Diseases. “The noteworthy increases in antibody responses and decreases in influenza cases following vaccination suggest an alternative for use in a population that is heavily impacted by influenza disease.”

Children are, of course, vulnerable to flu. The Centers for Disease Control and Prevention reported that 186 children died of flu during the landmark 2017-2018 flu season. That’s the highest number of pediatric flu deaths since they became a notifiable condition in 2004 (exclusive of the 2009 pandemic, when 358 pediatric deaths were reported from April 15, 2009, to October 2, 2010).The CDC said the vaccine during that flu season had an overall effectiveness level of 40%. According to research of others, however, flu vaccines are less effective in younger children than in adolescents and adults (Vaccine. 2014;32[31]:3886-94; Cochrane Database Syst Rev. 2008. doi: 10.1002/14651858.CD004879.pub3).

Fluad – a MF59-adjuvanted inactivated trivalent seasonal influenza vaccine – is used in adults over 65 in the United States and 29 other countries, and it is approved for children aged 6 months through 23 months in Canada.

Dr. Patel and associates examined the results of six studies – one phase 1b, three phase 2, and two phase 3 – that tested Fluad with or without other vaccines in 11,942 children aged 6 months to 5 years. The studies, mostly multicenter, were conducted in various countries, mainly in Europe and South and Central America, from 2006 to 2012.

In general, children in the intervention groups in the studies received two doses of the Fluad vaccine 4 weeks apart: two 0.25-mL doses for children aged 6-35 months and two 0.5-mL doses for those aged 3 years or older. In most of the studies, parallel control groups received nonadjuvanted trivalent or quadrivalent influenza vaccines.

Most participants (93%-94%) completed the studies. Solicited adverse effects were common in all groups (72% in the Fluad group vs. 67% who received IIV3 vaccines), and generally mild to moderate and resolved in 1-3 days. Unsolicited adverse effects were similar (55% and 62%, respectively) in the two flu vaccine groups. The authors wrote that “these data reflect a safety profile consistent with other licensed inactivated influenza vaccines administered to children.”

As for results, Dr. Patel and colleagues said, “HI [hemagglutination inhibition] antibody responses to both homologous and heterologous influenza strains are higher following vaccination with aIIV3, and this increase in immunogenicity is observed across all age subgroups in children aged 6 months through 5 years, and most profound in the children 6 to 36 months.”

For example, in one of the phase 3 studies when the influenza viruses were antigenically matched (homologous) for A/H1N1 among the children aged 6-35 months seroconversion was 100% for allV3 (Fluad) and 38% for IIV3-1/IIV3-4 (trivalent/quadrivalent flu vaccines); among children aged 3-5 years seroconversion was 100% for allV3 and 82% for IIV3-1/IIV3-4. For AH3N2 homologous among children aged 6-35 months, seroconversion was 98% for allV3 and 44% for IIV3-1/IIV3-4. For the B strain homologous among children aged 6-35 months, seroconversion was 88% for allV3 and 19% for IIV3-1/IIV3-4; among children aged 3-5 years seroconversion for B was 99% for allV3 and 59% for IIV3-1/IIV3-4.

In the same study when the influenza viruses were antigenically mismatched (heterologous) for A/H1N1 among children of all ages 6 months to greater than 72 months, seroconversion was 96% for allV3 (Fluad) and 44% for IIV3-1/IIV3-4; for A/H3N2 it was 98% for allV3 and 49% for IIV3-1/IIV3-4, and for the B strain it was 10% for allV3 and 3% for IIV3-1/IIV3-4.

They added that “in addition, aIIV3 had the fastest onset of immunogenicity and longest persistence of immune response, which has implications for the real-world clinical setting, where the influenza season might start earlier than expected or last longer, and second (follow-up) vaccinations may be missed.”

Dr. Patel and associates said the MF59 adjuvant in Fluad “recruits immune cells (primarily monocytes, macrophages, neutrophils, and dendritic cells) at the site of injection and differentiates them into antigen-presenting cells. With an MF59-adjuvanted vaccine, more antigen is transported from the injection site to the draining lymph node, wherein MF59 leads to T-cell activation and an increased B-cell expansion and a greater number and diversity of antibodies.”

According to goodrx.com, one syringe of Fluad 0.5 mL costs $45-$74 with coupon. The same dose of Fluzone Quadrivalent, a flu vaccine recently approved by the Food and Drug Administration for use in young children aged 6-35 months, costs $31 with coupon.

The study was funded by Novartis Vaccines and Diagnostics and Seqirus (formerly part of Novartis Vaccines and Diagnostics). The study authors disclosed employment by Novartis and Seqirus.

SOURCE: Patel SS et al. Int J Infect Dis. 2019. doi: 10.1016/j.ijid.2019.05.009.

Patients with chronic obstructive pulmonary disease are at a significantly increased risk for hospitalization for community-acquired pneumonia (CAP), compared with patients without COPD, a large prospective study has found.

copyright stockdevil/Thinkstock

Jose Bordon, MD, and colleagues aimed to define incidence and outcomes of COPD patients hospitalized with pneumonia in the city of Louisville, Ky., and to extrapolate the burden of disease in the U.S. population. They conducted a secondary analysis of data from the University of Louisville Pneumonia Study, a prospective population-based cohort study of all hospitalized adults with CAP who were residents in the city of Louisville, Ky., from June 1, 2014, to May 31, 2016.

COPD prevalence in the city of Louisville was derived via data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS) as well as from the 2014 National Health Interview Survey (NHIS). In addition, the researchers analyzed clinical outcomes including time to clinical stability (TCS), length of hospital stay (LOS), and mortality, according to Dr. Bordon, an infectious disease specialist at Providence Health Center, Washington, and colleagues on behalf of the University of Louisville Pneumonia Study Group.

The researchers found an 18-fold greater incidence of community-acquired pneumonia in patients with COPD, compared with non-COPD patients.

A total of 18,246 individuals aged 40 and older with COPD were estimated to live in Louisville, Ky. The researchers found that 3,419 COPD patients were hospitalized due to CAP in Louisville during the 2-year study period. COPD patients, compared with non-COPD patients, were more likely to have a history of heart failure, more ICU admissions, and use of mechanical ventilation, compared with patients without COPD. The two groups had similar pneumonia severity index scores, and 17% received oral steroids prior to admission. COPD patients had more pneumococcal pneumonia, despite receiving pneumococcal vaccine significantly more often than non-COPD patients.

The annual incidence of hospitalized CAP was 9,369 cases per 100,000 COPD patients in the city of Louisville. In the same period, the incidence of CAP in patients without COPD was 509 per 100,000, a more than 18-fold difference.

Although the incidence of CAP in COPD patients was much higher than in those without, the difference didn’t appear to have an impact on clinical outcomes. There were no clinical differences among patients with vs. without COPD in regard to time to reach clinical improvement and time of hospital discharge, and in-hospital mortality was not statistically significantly different between the groups, the authors reported. The mortality of COPD patients during hospitalization, at 30 days, at 6 months, and at 1 year was 5.6% of patients, 11.9%, 24.3%, and 33.0%, respectively vs. 6.6%, 14.2%, 24.2%, and 30.1% in non-COPD patients. However, 1-year all-cause mortality was a significant 25% greater among COPD patients, as might be expected by the progression and effects of the underlying disease.

“[Our] observations mean that nearly 1 in 10 persons with COPD will be hospitalized annually due to CAP. This translates into approximately 500,000 COPD patients hospitalized with CAP every year in the U.S., resulting in a substantial burden of approximately 5 billion U.S. dollars in hospitalization costs,” the researchers stated.

“Modifiable factors associated with CAP such as tobacco smoking and immunizations should be health interventions to prevent the burden of CAP in COPD patients,” even though “pneumococcal vaccination was used more often in the COPD population than in other CAP patients, but pneumococcal pneumonia still occurred at a numerically higher rate,” they noted.

The study was supported by the University of Louisville, Ky., with partial support from Pfizer. The authors reported having no conflicts.

[email protected]

SOURCE: Bordon JM et al. Clin Microbiol Infect. 2019 Jun 26; doi: 10.1016/j.cmi.2019.06.025.

Patients with chronic obstructive pulmonary disease are at a significantly increased risk for hospitalization for community-acquired pneumonia (CAP), compared with patients without COPD, a large prospective study has found.

copyright stockdevil/Thinkstock

Jose Bordon, MD, and colleagues aimed to define incidence and outcomes of COPD patients hospitalized with pneumonia in the city of Louisville, Ky., and to extrapolate the burden of disease in the U.S. population. They conducted a secondary analysis of data from the University of Louisville Pneumonia Study, a prospective population-based cohort study of all hospitalized adults with CAP who were residents in the city of Louisville, Ky., from June 1, 2014, to May 31, 2016.

COPD prevalence in the city of Louisville was derived via data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS) as well as from the 2014 National Health Interview Survey (NHIS). In addition, the researchers analyzed clinical outcomes including time to clinical stability (TCS), length of hospital stay (LOS), and mortality, according to Dr. Bordon, an infectious disease specialist at Providence Health Center, Washington, and colleagues on behalf of the University of Louisville Pneumonia Study Group.

The researchers found an 18-fold greater incidence of community-acquired pneumonia in patients with COPD, compared with non-COPD patients.

A total of 18,246 individuals aged 40 and older with COPD were estimated to live in Louisville, Ky. The researchers found that 3,419 COPD patients were hospitalized due to CAP in Louisville during the 2-year study period. COPD patients, compared with non-COPD patients, were more likely to have a history of heart failure, more ICU admissions, and use of mechanical ventilation, compared with patients without COPD. The two groups had similar pneumonia severity index scores, and 17% received oral steroids prior to admission. COPD patients had more pneumococcal pneumonia, despite receiving pneumococcal vaccine significantly more often than non-COPD patients.

The annual incidence of hospitalized CAP was 9,369 cases per 100,000 COPD patients in the city of Louisville. In the same period, the incidence of CAP in patients without COPD was 509 per 100,000, a more than 18-fold difference.

Although the incidence of CAP in COPD patients was much higher than in those without, the difference didn’t appear to have an impact on clinical outcomes. There were no clinical differences among patients with vs. without COPD in regard to time to reach clinical improvement and time of hospital discharge, and in-hospital mortality was not statistically significantly different between the groups, the authors reported. The mortality of COPD patients during hospitalization, at 30 days, at 6 months, and at 1 year was 5.6% of patients, 11.9%, 24.3%, and 33.0%, respectively vs. 6.6%, 14.2%, 24.2%, and 30.1% in non-COPD patients. However, 1-year all-cause mortality was a significant 25% greater among COPD patients, as might be expected by the progression and effects of the underlying disease.

“[Our] observations mean that nearly 1 in 10 persons with COPD will be hospitalized annually due to CAP. This translates into approximately 500,000 COPD patients hospitalized with CAP every year in the U.S., resulting in a substantial burden of approximately 5 billion U.S. dollars in hospitalization costs,” the researchers stated.

“Modifiable factors associated with CAP such as tobacco smoking and immunizations should be health interventions to prevent the burden of CAP in COPD patients,” even though “pneumococcal vaccination was used more often in the COPD population than in other CAP patients, but pneumococcal pneumonia still occurred at a numerically higher rate,” they noted.

The study was supported by the University of Louisville, Ky., with partial support from Pfizer. The authors reported having no conflicts.

[email protected]

SOURCE: Bordon JM et al. Clin Microbiol Infect. 2019 Jun 26; doi: 10.1016/j.cmi.2019.06.025.

Patients with chronic obstructive pulmonary disease are at a significantly increased risk for hospitalization for community-acquired pneumonia (CAP), compared with patients without COPD, a large prospective study has found.

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Jose Bordon, MD, and colleagues aimed to define incidence and outcomes of COPD patients hospitalized with pneumonia in the city of Louisville, Ky., and to extrapolate the burden of disease in the U.S. population. They conducted a secondary analysis of data from the University of Louisville Pneumonia Study, a prospective population-based cohort study of all hospitalized adults with CAP who were residents in the city of Louisville, Ky., from June 1, 2014, to May 31, 2016.

COPD prevalence in the city of Louisville was derived via data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS) as well as from the 2014 National Health Interview Survey (NHIS). In addition, the researchers analyzed clinical outcomes including time to clinical stability (TCS), length of hospital stay (LOS), and mortality, according to Dr. Bordon, an infectious disease specialist at Providence Health Center, Washington, and colleagues on behalf of the University of Louisville Pneumonia Study Group.

The researchers found an 18-fold greater incidence of community-acquired pneumonia in patients with COPD, compared with non-COPD patients.

A total of 18,246 individuals aged 40 and older with COPD were estimated to live in Louisville, Ky. The researchers found that 3,419 COPD patients were hospitalized due to CAP in Louisville during the 2-year study period. COPD patients, compared with non-COPD patients, were more likely to have a history of heart failure, more ICU admissions, and use of mechanical ventilation, compared with patients without COPD. The two groups had similar pneumonia severity index scores, and 17% received oral steroids prior to admission. COPD patients had more pneumococcal pneumonia, despite receiving pneumococcal vaccine significantly more often than non-COPD patients.

The annual incidence of hospitalized CAP was 9,369 cases per 100,000 COPD patients in the city of Louisville. In the same period, the incidence of CAP in patients without COPD was 509 per 100,000, a more than 18-fold difference.

Although the incidence of CAP in COPD patients was much higher than in those without, the difference didn’t appear to have an impact on clinical outcomes. There were no clinical differences among patients with vs. without COPD in regard to time to reach clinical improvement and time of hospital discharge, and in-hospital mortality was not statistically significantly different between the groups, the authors reported. The mortality of COPD patients during hospitalization, at 30 days, at 6 months, and at 1 year was 5.6% of patients, 11.9%, 24.3%, and 33.0%, respectively vs. 6.6%, 14.2%, 24.2%, and 30.1% in non-COPD patients. However, 1-year all-cause mortality was a significant 25% greater among COPD patients, as might be expected by the progression and effects of the underlying disease.

“[Our] observations mean that nearly 1 in 10 persons with COPD will be hospitalized annually due to CAP. This translates into approximately 500,000 COPD patients hospitalized with CAP every year in the U.S., resulting in a substantial burden of approximately 5 billion U.S. dollars in hospitalization costs,” the researchers stated.

“Modifiable factors associated with CAP such as tobacco smoking and immunizations should be health interventions to prevent the burden of CAP in COPD patients,” even though “pneumococcal vaccination was used more often in the COPD population than in other CAP patients, but pneumococcal pneumonia still occurred at a numerically higher rate,” they noted.

The study was supported by the University of Louisville, Ky., with partial support from Pfizer. The authors reported having no conflicts.

[email protected]

SOURCE: Bordon JM et al. Clin Microbiol Infect. 2019 Jun 26; doi: 10.1016/j.cmi.2019.06.025.

The pediatric hexavalent vaccine (DTaP-[inactivated poliovirus] IPV-[hepatitis B] HepB-[Haemophilis influenzae type b] Hib) should be included as an option in the Vaccines for Children (VFC) program for the infant series at ages 2, 4, and 6 months, according to unanimous votes at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

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The addition of the vaccine to the VFC program required no motions on the part of the committee, but involved separate votes on each component of the vaccine.

Combination vaccination has been associated with increased coverage and more likely completion of the full infant vaccine series, said Sara Oliver, MD, of the CDC’s National Center for Immunization and Respiratory Diseases.

The new vaccine is being developed jointly by Sanofi and Merck, and has been approved by the Food and Drug Administration for use in children through age 4 years.

Dr. Oliver presented evidence that the safety profile of the combination vaccine is consistent with that of the component vaccines. In addition, “use of combination vaccines can reduce the number of injections patient receive and alleviate concern associated with the number of injections,” she said. However, “considerations should include provider assessment, patient preference, and the potential for adverse events.”

The vote does not make any changes to the current vaccination schedule, but adds the combination vaccine as an option in the VFC program, although it will not be available until 2021 in order to ensure sufficient supply, Dr. Oliver noted.

The combination vaccination work group considered whether the new vaccine should be preferentially recommended for American Indian and Alaskan Native populations, but they concluded that post–dose one immunogenicity data are needed before such a preferential recommendation can be made.

The ACIP members had no financial conflicts to disclose.

The pediatric hexavalent vaccine (DTaP-[inactivated poliovirus] IPV-[hepatitis B] HepB-[Haemophilis influenzae type b] Hib) should be included as an option in the Vaccines for Children (VFC) program for the infant series at ages 2, 4, and 6 months, according to unanimous votes at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

copyright itsmejust/Thinkstock

The addition of the vaccine to the VFC program required no motions on the part of the committee, but involved separate votes on each component of the vaccine.

Combination vaccination has been associated with increased coverage and more likely completion of the full infant vaccine series, said Sara Oliver, MD, of the CDC’s National Center for Immunization and Respiratory Diseases.

The new vaccine is being developed jointly by Sanofi and Merck, and has been approved by the Food and Drug Administration for use in children through age 4 years.

Dr. Oliver presented evidence that the safety profile of the combination vaccine is consistent with that of the component vaccines. In addition, “use of combination vaccines can reduce the number of injections patient receive and alleviate concern associated with the number of injections,” she said. However, “considerations should include provider assessment, patient preference, and the potential for adverse events.”

The vote does not make any changes to the current vaccination schedule, but adds the combination vaccine as an option in the VFC program, although it will not be available until 2021 in order to ensure sufficient supply, Dr. Oliver noted.

The combination vaccination work group considered whether the new vaccine should be preferentially recommended for American Indian and Alaskan Native populations, but they concluded that post–dose one immunogenicity data are needed before such a preferential recommendation can be made.

The ACIP members had no financial conflicts to disclose.

The pediatric hexavalent vaccine (DTaP-[inactivated poliovirus] IPV-[hepatitis B] HepB-[Haemophilis influenzae type b] Hib) should be included as an option in the Vaccines for Children (VFC) program for the infant series at ages 2, 4, and 6 months, according to unanimous votes at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

copyright itsmejust/Thinkstock

The addition of the vaccine to the VFC program required no motions on the part of the committee, but involved separate votes on each component of the vaccine.

Combination vaccination has been associated with increased coverage and more likely completion of the full infant vaccine series, said Sara Oliver, MD, of the CDC’s National Center for Immunization and Respiratory Diseases.

The new vaccine is being developed jointly by Sanofi and Merck, and has been approved by the Food and Drug Administration for use in children through age 4 years.

Dr. Oliver presented evidence that the safety profile of the combination vaccine is consistent with that of the component vaccines. In addition, “use of combination vaccines can reduce the number of injections patient receive and alleviate concern associated with the number of injections,” she said. However, “considerations should include provider assessment, patient preference, and the potential for adverse events.”

The vote does not make any changes to the current vaccination schedule, but adds the combination vaccine as an option in the VFC program, although it will not be available until 2021 in order to ensure sufficient supply, Dr. Oliver noted.

The combination vaccination work group considered whether the new vaccine should be preferentially recommended for American Indian and Alaskan Native populations, but they concluded that post–dose one immunogenicity data are needed before such a preferential recommendation can be made.

The ACIP members had no financial conflicts to disclose.

Pneumococcal vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) based on shared clinical decision making is recommended for immunocompetent adults aged 65 years and older who have not previously received PCV13, and all adults aged 65 years and older should continue to receive the pneumococcal polysaccharide vaccine (PPSV23), according to a vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

bowdenimages/iStock/Getty Images

The motion passed with an 11-1 vote after members voted down two other options to either discontinue or continue the current recommendation of PCV13 for all immunocompetent adults aged 65 years and older. The current recommendation for PCV13 for adults aged 65 years and older has been in place since 2014.

The pneumococcal work group assessed indirect effects of the pediatric PCV vaccination on older adults prior to 2014 and since 2014, and what additional benefits might be expected if routine vaccination of older adults continued.

“Indirect effects have been observed in all age groups” said Almea Matanock, MD, of the CDC’s National Center for Immunization and Respiratory Diseases. Although there were no safety concerns, the public health impact of continued vaccination of adults was minimal.

Although PCV13 resulted in a 75% reduction in vaccine-type invasive pneumococcal disease and a 45% reduction in vaccine-type nonbacteremic pneumonia in 2014, the annual number needed to vaccinate to prevent a single case of outpatient pneumonia was 2,600, said Dr. Matanock.

Dr. Matanock presented key issues from the Evidence to Recommendations Framework for and against the recommendation for PCV13 in older adults. Work group comments in favor of continuing the recommendation for PCV13 in older adults included effective disease prevention and the potential negative impact on the importance of adult vaccines if the vaccine was no longer recommended. However, some work group members and committee members expressed concern about resource allocation and steering vaccines away from younger age groups in whom they have been more consistently effective.

Paul Hunter, MD, of the City of Milwaukee Health Department, voted against the shared clinical decision making, and instead favored discontinuing the recommendation for PCV13 for older adults. “I think clinicians need a clear message,” he said, adding that “the public health bang for the buck is with the kids.”

“I think there was a recognition that the population level benefit is minimal,” said work group chair Grace Lee, MD.

Although the work group recognized some benefit for older adults, the burden of disease for PCV-specific disease is low, compared with all-cause pneumonia, said Dr. Lee of Lucile Packard Children’s Hospital at Stanford, Calif. However, the recommendation for shared clinical decision making allows for potential insurance coverage of the vaccine for adults who decide after discussion with their health care provider that they would benefit.

“We are still unpacking this construct” of shared clinical decision making, which in this case applies to adults without immunocompromising conditions, and is more of a provider assessment than a risk assessment, she said.

The ACIP members had no financial conflicts to disclose.

Pneumococcal vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) based on shared clinical decision making is recommended for immunocompetent adults aged 65 years and older who have not previously received PCV13, and all adults aged 65 years and older should continue to receive the pneumococcal polysaccharide vaccine (PPSV23), according to a vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

bowdenimages/iStock/Getty Images

The motion passed with an 11-1 vote after members voted down two other options to either discontinue or continue the current recommendation of PCV13 for all immunocompetent adults aged 65 years and older. The current recommendation for PCV13 for adults aged 65 years and older has been in place since 2014.

The pneumococcal work group assessed indirect effects of the pediatric PCV vaccination on older adults prior to 2014 and since 2014, and what additional benefits might be expected if routine vaccination of older adults continued.

“Indirect effects have been observed in all age groups” said Almea Matanock, MD, of the CDC’s National Center for Immunization and Respiratory Diseases. Although there were no safety concerns, the public health impact of continued vaccination of adults was minimal.

Although PCV13 resulted in a 75% reduction in vaccine-type invasive pneumococcal disease and a 45% reduction in vaccine-type nonbacteremic pneumonia in 2014, the annual number needed to vaccinate to prevent a single case of outpatient pneumonia was 2,600, said Dr. Matanock.

Dr. Matanock presented key issues from the Evidence to Recommendations Framework for and against the recommendation for PCV13 in older adults. Work group comments in favor of continuing the recommendation for PCV13 in older adults included effective disease prevention and the potential negative impact on the importance of adult vaccines if the vaccine was no longer recommended. However, some work group members and committee members expressed concern about resource allocation and steering vaccines away from younger age groups in whom they have been more consistently effective.

Paul Hunter, MD, of the City of Milwaukee Health Department, voted against the shared clinical decision making, and instead favored discontinuing the recommendation for PCV13 for older adults. “I think clinicians need a clear message,” he said, adding that “the public health bang for the buck is with the kids.”

“I think there was a recognition that the population level benefit is minimal,” said work group chair Grace Lee, MD.

Although the work group recognized some benefit for older adults, the burden of disease for PCV-specific disease is low, compared with all-cause pneumonia, said Dr. Lee of Lucile Packard Children’s Hospital at Stanford, Calif. However, the recommendation for shared clinical decision making allows for potential insurance coverage of the vaccine for adults who decide after discussion with their health care provider that they would benefit.

“We are still unpacking this construct” of shared clinical decision making, which in this case applies to adults without immunocompromising conditions, and is more of a provider assessment than a risk assessment, she said.

The ACIP members had no financial conflicts to disclose.

Pneumococcal vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) based on shared clinical decision making is recommended for immunocompetent adults aged 65 years and older who have not previously received PCV13, and all adults aged 65 years and older should continue to receive the pneumococcal polysaccharide vaccine (PPSV23), according to a vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

bowdenimages/iStock/Getty Images

The motion passed with an 11-1 vote after members voted down two other options to either discontinue or continue the current recommendation of PCV13 for all immunocompetent adults aged 65 years and older. The current recommendation for PCV13 for adults aged 65 years and older has been in place since 2014.

The pneumococcal work group assessed indirect effects of the pediatric PCV vaccination on older adults prior to 2014 and since 2014, and what additional benefits might be expected if routine vaccination of older adults continued.

“Indirect effects have been observed in all age groups” said Almea Matanock, MD, of the CDC’s National Center for Immunization and Respiratory Diseases. Although there were no safety concerns, the public health impact of continued vaccination of adults was minimal.

Although PCV13 resulted in a 75% reduction in vaccine-type invasive pneumococcal disease and a 45% reduction in vaccine-type nonbacteremic pneumonia in 2014, the annual number needed to vaccinate to prevent a single case of outpatient pneumonia was 2,600, said Dr. Matanock.

Dr. Matanock presented key issues from the Evidence to Recommendations Framework for and against the recommendation for PCV13 in older adults. Work group comments in favor of continuing the recommendation for PCV13 in older adults included effective disease prevention and the potential negative impact on the importance of adult vaccines if the vaccine was no longer recommended. However, some work group members and committee members expressed concern about resource allocation and steering vaccines away from younger age groups in whom they have been more consistently effective.

Paul Hunter, MD, of the City of Milwaukee Health Department, voted against the shared clinical decision making, and instead favored discontinuing the recommendation for PCV13 for older adults. “I think clinicians need a clear message,” he said, adding that “the public health bang for the buck is with the kids.”

“I think there was a recognition that the population level benefit is minimal,” said work group chair Grace Lee, MD.

Although the work group recognized some benefit for older adults, the burden of disease for PCV-specific disease is low, compared with all-cause pneumonia, said Dr. Lee of Lucile Packard Children’s Hospital at Stanford, Calif. However, the recommendation for shared clinical decision making allows for potential insurance coverage of the vaccine for adults who decide after discussion with their health care provider that they would benefit.

“We are still unpacking this construct” of shared clinical decision making, which in this case applies to adults without immunocompromising conditions, and is more of a provider assessment than a risk assessment, she said.

The ACIP members had no financial conflicts to disclose.

With record-high cases of measles throughout Europe, U.S. travelers to the region should be up to date on measles immunization and other recommended vaccines, researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.

CDC/Molly Kurnit, M.P.H.

More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.

France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.

“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.

But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.

Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.

“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”

“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.

In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.

“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.

“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”

Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.

Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.

The statement was funded by the CDC. The authors reported no relevant financial disclosures.

SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.

With record-high cases of measles throughout Europe, U.S. travelers to the region should be up to date on measles immunization and other recommended vaccines, researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.

CDC/Molly Kurnit, M.P.H.

More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.

France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.

“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.

But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.

Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.

“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”

“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.

In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.

“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.

“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”

Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.

Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.

The statement was funded by the CDC. The authors reported no relevant financial disclosures.

SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.

With record-high cases of measles throughout Europe, U.S. travelers to the region should be up to date on measles immunization and other recommended vaccines, researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.

CDC/Molly Kurnit, M.P.H.

More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.

France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.

“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.

But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.

Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.

“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”

“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.

In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.

“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.

“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”

Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.

Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.

The statement was funded by the CDC. The authors reported no relevant financial disclosures.

SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.