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Measles complications in the U.S. unchanged in posteradication era
CHICAGO – An evaluation of the measles threat in the modern era gives no indication that the risk of complications or death is any different than it was before a vaccine became available, according to an analysis of inpatient complications between 2002 and 2013.
In 2000, measles was declared eliminated in the United States, but for those who have been infected since that time, the risk of serious complications and death has not diminished, noted Raj Chovatiya, MD, PhD, in a session at the annual meeting of the Society for Investigative Dermatology.
By eliminated, the Centers of Disease Control and Prevention – which reported 86 confirmed cases of measles in 2000 – was referring to a technical definition of no new endemic or continuous transmissions in the previous 12 months. It was expected that a modest number of cases of this reportable disease would continue to accrue for an infection that remains common elsewhere in the world.
“Worldwide there are about 20 million cases of measles annually with an estimated 100,000 deaths attributed to this cause,” said Dr. Chovatiya, who is a dermatology resident at Northwestern University, Chicago.
In the United States, posteradication infection rates remained at low levels for several years but were already rising from 2002 to 2013, when Dr. Chovatiya and his coinvestigators sought to describe the incidence, associations, comorbidities, and outcomes of hospitalizations for measles. Toward the end of the period the researchers were examining the incidence rates climbed more steeply.
“So far this year, 764 CDC cases of measles [were] reported. That is the most we have seen in the U.S. since 1994,” Dr. Chovatiya said.
Based on his analysis of hospitalizations from 2002 to 2013, the threat of these outbreaks is no different then that before the disease was declared eliminated or before a vaccine became available.
The cross-sectional study was conducted with data from the Nationwide Inpatient Sample, an all-payer database that is considered to be a representative of national trends.
Characteristic of measles, the majority of the 582 hospitalizations evaluated over this period occurred in children aged between 1 and 9 years. The proportion of patients with preexisting chronic comorbid conditions was low. Rather, “most were pretty healthy” prior to admission, according to Dr. Chovatiya, who said that the majority of admissions were from an emergency department.
Measles, which targets epithelial cells and depresses the immune system, is a potentially serious disease because of its ability to produce complications in essentially every organ of the body, including the lungs, kidneys, blood, and central nervous system. Consistent with past studies, the most common complication in this series was pneumonia, observed in 20% of patients. The list of other serious complications identified in this study period, including encephalitis and acute renal failure, was long.
“We observed death in 4.3% of our 582 cases, or about 25 cases,” reported Dr. Chovatiya. He indicated that this is a high percentage among a population composed largely of children who were well before hospitalization.
The mortality rate from measles was numerically but not statistically higher than that of overall hospital admissions during this period, but an admission for measles was associated with significantly longer average length of stay (3.7 vs. 3.5 days) and slightly but significantly higher direct costs ($18,907 vs. $18,474).
“I want to point out that these are just direct inpatient costs,” Dr. Chovatiya said. Extrapolating from published data about indirect expenses, he said that the total health cost burden “is absolutely staggering.”
Previous studies have suggested that about 25% of patients with measles require hospitalization and 1 in every 1,000 patients will die. The data collected by Dr. Chovatiya support these often-cited figures, indicating that they remain unchanged in the modern era.
particularly insufficient penetration of vaccination in many communities.
The vaccine “is inexpensive, extremely effective, and lifesaving,” said Dr. Chovatiya, making the point that all of the morbidity, mortality, and costs he described are largely avoidable.
Attempting to provide perspective of the measles threat and the impact of the vaccine, Dr. Chovatiya cited a hypothetical calculation that 732,000 deaths from measles would have been expected in the United States among the pool of children born between 1994 and 2013 had no vaccine been offered. Again, most of these deaths would have occurred in otherwise healthy children.
Dr. Chovatiya reported no potential conflicts of interest.
CHICAGO – An evaluation of the measles threat in the modern era gives no indication that the risk of complications or death is any different than it was before a vaccine became available, according to an analysis of inpatient complications between 2002 and 2013.
In 2000, measles was declared eliminated in the United States, but for those who have been infected since that time, the risk of serious complications and death has not diminished, noted Raj Chovatiya, MD, PhD, in a session at the annual meeting of the Society for Investigative Dermatology.
By eliminated, the Centers of Disease Control and Prevention – which reported 86 confirmed cases of measles in 2000 – was referring to a technical definition of no new endemic or continuous transmissions in the previous 12 months. It was expected that a modest number of cases of this reportable disease would continue to accrue for an infection that remains common elsewhere in the world.
“Worldwide there are about 20 million cases of measles annually with an estimated 100,000 deaths attributed to this cause,” said Dr. Chovatiya, who is a dermatology resident at Northwestern University, Chicago.
In the United States, posteradication infection rates remained at low levels for several years but were already rising from 2002 to 2013, when Dr. Chovatiya and his coinvestigators sought to describe the incidence, associations, comorbidities, and outcomes of hospitalizations for measles. Toward the end of the period the researchers were examining the incidence rates climbed more steeply.
“So far this year, 764 CDC cases of measles [were] reported. That is the most we have seen in the U.S. since 1994,” Dr. Chovatiya said.
Based on his analysis of hospitalizations from 2002 to 2013, the threat of these outbreaks is no different then that before the disease was declared eliminated or before a vaccine became available.
The cross-sectional study was conducted with data from the Nationwide Inpatient Sample, an all-payer database that is considered to be a representative of national trends.
Characteristic of measles, the majority of the 582 hospitalizations evaluated over this period occurred in children aged between 1 and 9 years. The proportion of patients with preexisting chronic comorbid conditions was low. Rather, “most were pretty healthy” prior to admission, according to Dr. Chovatiya, who said that the majority of admissions were from an emergency department.
Measles, which targets epithelial cells and depresses the immune system, is a potentially serious disease because of its ability to produce complications in essentially every organ of the body, including the lungs, kidneys, blood, and central nervous system. Consistent with past studies, the most common complication in this series was pneumonia, observed in 20% of patients. The list of other serious complications identified in this study period, including encephalitis and acute renal failure, was long.
“We observed death in 4.3% of our 582 cases, or about 25 cases,” reported Dr. Chovatiya. He indicated that this is a high percentage among a population composed largely of children who were well before hospitalization.
The mortality rate from measles was numerically but not statistically higher than that of overall hospital admissions during this period, but an admission for measles was associated with significantly longer average length of stay (3.7 vs. 3.5 days) and slightly but significantly higher direct costs ($18,907 vs. $18,474).
“I want to point out that these are just direct inpatient costs,” Dr. Chovatiya said. Extrapolating from published data about indirect expenses, he said that the total health cost burden “is absolutely staggering.”
Previous studies have suggested that about 25% of patients with measles require hospitalization and 1 in every 1,000 patients will die. The data collected by Dr. Chovatiya support these often-cited figures, indicating that they remain unchanged in the modern era.
particularly insufficient penetration of vaccination in many communities.
The vaccine “is inexpensive, extremely effective, and lifesaving,” said Dr. Chovatiya, making the point that all of the morbidity, mortality, and costs he described are largely avoidable.
Attempting to provide perspective of the measles threat and the impact of the vaccine, Dr. Chovatiya cited a hypothetical calculation that 732,000 deaths from measles would have been expected in the United States among the pool of children born between 1994 and 2013 had no vaccine been offered. Again, most of these deaths would have occurred in otherwise healthy children.
Dr. Chovatiya reported no potential conflicts of interest.
CHICAGO – An evaluation of the measles threat in the modern era gives no indication that the risk of complications or death is any different than it was before a vaccine became available, according to an analysis of inpatient complications between 2002 and 2013.
In 2000, measles was declared eliminated in the United States, but for those who have been infected since that time, the risk of serious complications and death has not diminished, noted Raj Chovatiya, MD, PhD, in a session at the annual meeting of the Society for Investigative Dermatology.
By eliminated, the Centers of Disease Control and Prevention – which reported 86 confirmed cases of measles in 2000 – was referring to a technical definition of no new endemic or continuous transmissions in the previous 12 months. It was expected that a modest number of cases of this reportable disease would continue to accrue for an infection that remains common elsewhere in the world.
“Worldwide there are about 20 million cases of measles annually with an estimated 100,000 deaths attributed to this cause,” said Dr. Chovatiya, who is a dermatology resident at Northwestern University, Chicago.
In the United States, posteradication infection rates remained at low levels for several years but were already rising from 2002 to 2013, when Dr. Chovatiya and his coinvestigators sought to describe the incidence, associations, comorbidities, and outcomes of hospitalizations for measles. Toward the end of the period the researchers were examining the incidence rates climbed more steeply.
“So far this year, 764 CDC cases of measles [were] reported. That is the most we have seen in the U.S. since 1994,” Dr. Chovatiya said.
Based on his analysis of hospitalizations from 2002 to 2013, the threat of these outbreaks is no different then that before the disease was declared eliminated or before a vaccine became available.
The cross-sectional study was conducted with data from the Nationwide Inpatient Sample, an all-payer database that is considered to be a representative of national trends.
Characteristic of measles, the majority of the 582 hospitalizations evaluated over this period occurred in children aged between 1 and 9 years. The proportion of patients with preexisting chronic comorbid conditions was low. Rather, “most were pretty healthy” prior to admission, according to Dr. Chovatiya, who said that the majority of admissions were from an emergency department.
Measles, which targets epithelial cells and depresses the immune system, is a potentially serious disease because of its ability to produce complications in essentially every organ of the body, including the lungs, kidneys, blood, and central nervous system. Consistent with past studies, the most common complication in this series was pneumonia, observed in 20% of patients. The list of other serious complications identified in this study period, including encephalitis and acute renal failure, was long.
“We observed death in 4.3% of our 582 cases, or about 25 cases,” reported Dr. Chovatiya. He indicated that this is a high percentage among a population composed largely of children who were well before hospitalization.
The mortality rate from measles was numerically but not statistically higher than that of overall hospital admissions during this period, but an admission for measles was associated with significantly longer average length of stay (3.7 vs. 3.5 days) and slightly but significantly higher direct costs ($18,907 vs. $18,474).
“I want to point out that these are just direct inpatient costs,” Dr. Chovatiya said. Extrapolating from published data about indirect expenses, he said that the total health cost burden “is absolutely staggering.”
Previous studies have suggested that about 25% of patients with measles require hospitalization and 1 in every 1,000 patients will die. The data collected by Dr. Chovatiya support these often-cited figures, indicating that they remain unchanged in the modern era.
particularly insufficient penetration of vaccination in many communities.
The vaccine “is inexpensive, extremely effective, and lifesaving,” said Dr. Chovatiya, making the point that all of the morbidity, mortality, and costs he described are largely avoidable.
Attempting to provide perspective of the measles threat and the impact of the vaccine, Dr. Chovatiya cited a hypothetical calculation that 732,000 deaths from measles would have been expected in the United States among the pool of children born between 1994 and 2013 had no vaccine been offered. Again, most of these deaths would have occurred in otherwise healthy children.
Dr. Chovatiya reported no potential conflicts of interest.
REPORTING FROM SID 2019
Maternal immunization protects against serious RSV infection in infancy
LJUBLJANA, SLOVENIA – Passive protection of infants from severe respiratory syncytial virus lower respiratory tract infection during the first 6 months of life has convincingly been achieved through maternal immunization using a novel nanoparticle vaccine in the landmark PREPARE trial.
“I think it’s important for everyone, especially people like myself who’ve been working on maternal immunization for about 20 years, to realize that this is a historic study,” Flor M. Munoz, MD, declared in reporting the study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
“We have here for the first time a phase-3, global, randomized, placebo-controlled, observer-blinded clinical trial looking at an experimental vaccine in pregnant women for the protection of infants from a disease for which we really don’t have other potential solutions quite yet, and in a period of high vulnerability,” said Dr. Munoz, a pediatric infectious disease specialist at Baylor College of Medicine, Houston.
Indeed, respiratory syncytial virus (RSV) is the No. 2 cause of mortality worldwide during the first year of life. Moreover, most cases of severe RSV lower respiratory tract infection occur in otherwise healthy infants aged less than 5 months, when active immunization presents daunting challenges.
“While certainly mortality is uncommon in high-income countries, we do see significant hospitalization there due to severe RSV lower respiratory tract infection in the first year of life, sometimes more than other common diseases, like influenza,” she noted.
PREPARE included 4,636 women with low-risk pregnancies who were randomized 2:1 to a single intramuscular injection of the investigational RSV vaccine or placebo during gestational weeks 28-36, with efficacy assessed through the first 180 days of life. The study took place at 87 sites in 11 countries during 4 years worth of RSV seasons. Roughly half of participants were South African, one-quarter were in the United States, and the rest were drawn from nine other low-, middle-, or high-income countries in the Northern and Southern Hemispheres. The median gestational age at vaccination was 32 weeks.
The primary efficacy endpoint specified by the Food and Drug Administration – but not other regulatory agencies – was the placebo-subtracted rate of RSV lower respiratory tract infection as defined by RSV detected by reverse transcription polymerase chain reaction, along with at least one clinical manifestation of lower respiratory tract infection, oxygen saturation below 95%, and/or tachypnea. The risk of this outcome was reduced by 39% during the first 90 days of life and by 27% through 180 days in infants in the maternal immunization group, a difference which didn’t achieve statistical significance.
However, prespecified major secondary endpoints arguably of greater clinical relevance were consistently positive. Notably, when levels of transplacentally transferred neutralizing antibodies against RSV A and B were highest, with events occurring in 57 of 2,765 evaluable infants in the active treatment arm and in 53 of 1,430 controls. Similarly, there was a 40% reduction through day 180. Moreover, rates of another key secondary endpoint – RSV lower respiratory tract infection plus severe hypoxemia with an oxygen saturation below 92% – were reduced by 48% and 42% through days 90 and 180, respectively. Thus, the vaccine’s protective effect was greatest against the most severe outcomes of RSV infection in infancy, according to Dr. Munoz.
No safety signals related to this immunization strategy were seen during 1 year of follow-up of infants and 6 months for the mothers. Side effects were essentially limited to mild, self-limited injection site reactions, with zero impact on pregnancy and delivery.
An intriguing finding in an exploratory analysis was that the vaccine appeared to have ancillary benefits beyond prevention of medically significant RSV disease in the young infants. For example, the rate of all lower respiratory tract infections with severe hypoxemia – with no requirement for demonstration of RSV infection – was reduced by 46% during the first 90 days of life in the immunized group. Similarly, the rate of all-cause lower respiratory tract infection resulting in hospitalization was reduced by 28%.
“This is actually quite interesting, because these are unexpected benefits in terms of all-cause effects,” the pediatrician commented, adding that she and her coinvestigators are delving into this phenomenon in order to gain better understanding.
Additional analyses of the recently completed PREPARE study are ongoing but already have yielded some important findings. For example, women immunized before 33 weeks’ gestation had significantly greater transplacental antibody transfer than those immunized later in pregnancy, with resultant markedly greater vaccine efficacy in their offspring as well: A placebo-subtracted 70% reduction in RSV lower respiratory tract infection with severe hypoxemia through 90 days, compared with a 44% reduction associated with immunization at gestational week 33 or later. And when the interval between immunization and delivery was at least 30 days, the risk of this endpoint was reduced by 65%; in contrast, there was no significant difference between vaccine and placebo groups when time from immunization to delivery was less than 30 days.
Also noteworthy was that maternal immunization afforded no infant protection in the United States. This unanticipated finding is still under investigation, although suspicion centers around the fact that RSV seasons were generally milder there, and American women were vaccinated at a later gestational age, with a corresponding shorter interval to delivery.
The novel recombinant nanoparticle vaccine tested in PREPARE contains a nearly full-length RSV fusion protein produced in insect cells. The nanoparticles express both prefusion epitopes and epitopes common to pre- and postfusion conformations. Aluminum phosphate is employed as the adjuvant.
Novavax’s stock price has been kicked to the curb since the company earlier reported that a large phase 3 trial of the vaccine failed to meet its primary endpoint for prevention of RSV lower respiratory tract infection in older adults. Now the vaccine’s failure to meet its prespecified FDA-mandated primary endpoint in the maternal immunization study will doubtless spawn further financially dismissive headlines in the business press as well.
But pediatricians are famously advocates for children, and PREPARE received a warm welcome from the pediatric infectious disease community, regardless of investor response. Indeed, PREPARE was the only clinical trial deemed of sufficient import to be featured in the opening plenary session of ESPID 2019.
Ulrich Heininger, MD, professor of pediatrics at the University of Basel (Switzerland), who cochaired the session, jointly sponsored by ESPID and the Pediatric Infectious Diseases Society, declared, “These findings, I think, are a great step forward.”
Dr. Munoz reported receiving research grants from Janssen, the National Institutes of Health, the Centers for Disease Control and Prevention, and Novavax, which sponsored the PREPARE trial, assisted by an $89 million grant from the Bill and Melinda Gates Foundation.
LJUBLJANA, SLOVENIA – Passive protection of infants from severe respiratory syncytial virus lower respiratory tract infection during the first 6 months of life has convincingly been achieved through maternal immunization using a novel nanoparticle vaccine in the landmark PREPARE trial.
“I think it’s important for everyone, especially people like myself who’ve been working on maternal immunization for about 20 years, to realize that this is a historic study,” Flor M. Munoz, MD, declared in reporting the study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
“We have here for the first time a phase-3, global, randomized, placebo-controlled, observer-blinded clinical trial looking at an experimental vaccine in pregnant women for the protection of infants from a disease for which we really don’t have other potential solutions quite yet, and in a period of high vulnerability,” said Dr. Munoz, a pediatric infectious disease specialist at Baylor College of Medicine, Houston.
Indeed, respiratory syncytial virus (RSV) is the No. 2 cause of mortality worldwide during the first year of life. Moreover, most cases of severe RSV lower respiratory tract infection occur in otherwise healthy infants aged less than 5 months, when active immunization presents daunting challenges.
“While certainly mortality is uncommon in high-income countries, we do see significant hospitalization there due to severe RSV lower respiratory tract infection in the first year of life, sometimes more than other common diseases, like influenza,” she noted.
PREPARE included 4,636 women with low-risk pregnancies who were randomized 2:1 to a single intramuscular injection of the investigational RSV vaccine or placebo during gestational weeks 28-36, with efficacy assessed through the first 180 days of life. The study took place at 87 sites in 11 countries during 4 years worth of RSV seasons. Roughly half of participants were South African, one-quarter were in the United States, and the rest were drawn from nine other low-, middle-, or high-income countries in the Northern and Southern Hemispheres. The median gestational age at vaccination was 32 weeks.
The primary efficacy endpoint specified by the Food and Drug Administration – but not other regulatory agencies – was the placebo-subtracted rate of RSV lower respiratory tract infection as defined by RSV detected by reverse transcription polymerase chain reaction, along with at least one clinical manifestation of lower respiratory tract infection, oxygen saturation below 95%, and/or tachypnea. The risk of this outcome was reduced by 39% during the first 90 days of life and by 27% through 180 days in infants in the maternal immunization group, a difference which didn’t achieve statistical significance.
However, prespecified major secondary endpoints arguably of greater clinical relevance were consistently positive. Notably, when levels of transplacentally transferred neutralizing antibodies against RSV A and B were highest, with events occurring in 57 of 2,765 evaluable infants in the active treatment arm and in 53 of 1,430 controls. Similarly, there was a 40% reduction through day 180. Moreover, rates of another key secondary endpoint – RSV lower respiratory tract infection plus severe hypoxemia with an oxygen saturation below 92% – were reduced by 48% and 42% through days 90 and 180, respectively. Thus, the vaccine’s protective effect was greatest against the most severe outcomes of RSV infection in infancy, according to Dr. Munoz.
No safety signals related to this immunization strategy were seen during 1 year of follow-up of infants and 6 months for the mothers. Side effects were essentially limited to mild, self-limited injection site reactions, with zero impact on pregnancy and delivery.
An intriguing finding in an exploratory analysis was that the vaccine appeared to have ancillary benefits beyond prevention of medically significant RSV disease in the young infants. For example, the rate of all lower respiratory tract infections with severe hypoxemia – with no requirement for demonstration of RSV infection – was reduced by 46% during the first 90 days of life in the immunized group. Similarly, the rate of all-cause lower respiratory tract infection resulting in hospitalization was reduced by 28%.
“This is actually quite interesting, because these are unexpected benefits in terms of all-cause effects,” the pediatrician commented, adding that she and her coinvestigators are delving into this phenomenon in order to gain better understanding.
Additional analyses of the recently completed PREPARE study are ongoing but already have yielded some important findings. For example, women immunized before 33 weeks’ gestation had significantly greater transplacental antibody transfer than those immunized later in pregnancy, with resultant markedly greater vaccine efficacy in their offspring as well: A placebo-subtracted 70% reduction in RSV lower respiratory tract infection with severe hypoxemia through 90 days, compared with a 44% reduction associated with immunization at gestational week 33 or later. And when the interval between immunization and delivery was at least 30 days, the risk of this endpoint was reduced by 65%; in contrast, there was no significant difference between vaccine and placebo groups when time from immunization to delivery was less than 30 days.
Also noteworthy was that maternal immunization afforded no infant protection in the United States. This unanticipated finding is still under investigation, although suspicion centers around the fact that RSV seasons were generally milder there, and American women were vaccinated at a later gestational age, with a corresponding shorter interval to delivery.
The novel recombinant nanoparticle vaccine tested in PREPARE contains a nearly full-length RSV fusion protein produced in insect cells. The nanoparticles express both prefusion epitopes and epitopes common to pre- and postfusion conformations. Aluminum phosphate is employed as the adjuvant.
Novavax’s stock price has been kicked to the curb since the company earlier reported that a large phase 3 trial of the vaccine failed to meet its primary endpoint for prevention of RSV lower respiratory tract infection in older adults. Now the vaccine’s failure to meet its prespecified FDA-mandated primary endpoint in the maternal immunization study will doubtless spawn further financially dismissive headlines in the business press as well.
But pediatricians are famously advocates for children, and PREPARE received a warm welcome from the pediatric infectious disease community, regardless of investor response. Indeed, PREPARE was the only clinical trial deemed of sufficient import to be featured in the opening plenary session of ESPID 2019.
Ulrich Heininger, MD, professor of pediatrics at the University of Basel (Switzerland), who cochaired the session, jointly sponsored by ESPID and the Pediatric Infectious Diseases Society, declared, “These findings, I think, are a great step forward.”
Dr. Munoz reported receiving research grants from Janssen, the National Institutes of Health, the Centers for Disease Control and Prevention, and Novavax, which sponsored the PREPARE trial, assisted by an $89 million grant from the Bill and Melinda Gates Foundation.
LJUBLJANA, SLOVENIA – Passive protection of infants from severe respiratory syncytial virus lower respiratory tract infection during the first 6 months of life has convincingly been achieved through maternal immunization using a novel nanoparticle vaccine in the landmark PREPARE trial.
“I think it’s important for everyone, especially people like myself who’ve been working on maternal immunization for about 20 years, to realize that this is a historic study,” Flor M. Munoz, MD, declared in reporting the study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
“We have here for the first time a phase-3, global, randomized, placebo-controlled, observer-blinded clinical trial looking at an experimental vaccine in pregnant women for the protection of infants from a disease for which we really don’t have other potential solutions quite yet, and in a period of high vulnerability,” said Dr. Munoz, a pediatric infectious disease specialist at Baylor College of Medicine, Houston.
Indeed, respiratory syncytial virus (RSV) is the No. 2 cause of mortality worldwide during the first year of life. Moreover, most cases of severe RSV lower respiratory tract infection occur in otherwise healthy infants aged less than 5 months, when active immunization presents daunting challenges.
“While certainly mortality is uncommon in high-income countries, we do see significant hospitalization there due to severe RSV lower respiratory tract infection in the first year of life, sometimes more than other common diseases, like influenza,” she noted.
PREPARE included 4,636 women with low-risk pregnancies who were randomized 2:1 to a single intramuscular injection of the investigational RSV vaccine or placebo during gestational weeks 28-36, with efficacy assessed through the first 180 days of life. The study took place at 87 sites in 11 countries during 4 years worth of RSV seasons. Roughly half of participants were South African, one-quarter were in the United States, and the rest were drawn from nine other low-, middle-, or high-income countries in the Northern and Southern Hemispheres. The median gestational age at vaccination was 32 weeks.
The primary efficacy endpoint specified by the Food and Drug Administration – but not other regulatory agencies – was the placebo-subtracted rate of RSV lower respiratory tract infection as defined by RSV detected by reverse transcription polymerase chain reaction, along with at least one clinical manifestation of lower respiratory tract infection, oxygen saturation below 95%, and/or tachypnea. The risk of this outcome was reduced by 39% during the first 90 days of life and by 27% through 180 days in infants in the maternal immunization group, a difference which didn’t achieve statistical significance.
However, prespecified major secondary endpoints arguably of greater clinical relevance were consistently positive. Notably, when levels of transplacentally transferred neutralizing antibodies against RSV A and B were highest, with events occurring in 57 of 2,765 evaluable infants in the active treatment arm and in 53 of 1,430 controls. Similarly, there was a 40% reduction through day 180. Moreover, rates of another key secondary endpoint – RSV lower respiratory tract infection plus severe hypoxemia with an oxygen saturation below 92% – were reduced by 48% and 42% through days 90 and 180, respectively. Thus, the vaccine’s protective effect was greatest against the most severe outcomes of RSV infection in infancy, according to Dr. Munoz.
No safety signals related to this immunization strategy were seen during 1 year of follow-up of infants and 6 months for the mothers. Side effects were essentially limited to mild, self-limited injection site reactions, with zero impact on pregnancy and delivery.
An intriguing finding in an exploratory analysis was that the vaccine appeared to have ancillary benefits beyond prevention of medically significant RSV disease in the young infants. For example, the rate of all lower respiratory tract infections with severe hypoxemia – with no requirement for demonstration of RSV infection – was reduced by 46% during the first 90 days of life in the immunized group. Similarly, the rate of all-cause lower respiratory tract infection resulting in hospitalization was reduced by 28%.
“This is actually quite interesting, because these are unexpected benefits in terms of all-cause effects,” the pediatrician commented, adding that she and her coinvestigators are delving into this phenomenon in order to gain better understanding.
Additional analyses of the recently completed PREPARE study are ongoing but already have yielded some important findings. For example, women immunized before 33 weeks’ gestation had significantly greater transplacental antibody transfer than those immunized later in pregnancy, with resultant markedly greater vaccine efficacy in their offspring as well: A placebo-subtracted 70% reduction in RSV lower respiratory tract infection with severe hypoxemia through 90 days, compared with a 44% reduction associated with immunization at gestational week 33 or later. And when the interval between immunization and delivery was at least 30 days, the risk of this endpoint was reduced by 65%; in contrast, there was no significant difference between vaccine and placebo groups when time from immunization to delivery was less than 30 days.
Also noteworthy was that maternal immunization afforded no infant protection in the United States. This unanticipated finding is still under investigation, although suspicion centers around the fact that RSV seasons were generally milder there, and American women were vaccinated at a later gestational age, with a corresponding shorter interval to delivery.
The novel recombinant nanoparticle vaccine tested in PREPARE contains a nearly full-length RSV fusion protein produced in insect cells. The nanoparticles express both prefusion epitopes and epitopes common to pre- and postfusion conformations. Aluminum phosphate is employed as the adjuvant.
Novavax’s stock price has been kicked to the curb since the company earlier reported that a large phase 3 trial of the vaccine failed to meet its primary endpoint for prevention of RSV lower respiratory tract infection in older adults. Now the vaccine’s failure to meet its prespecified FDA-mandated primary endpoint in the maternal immunization study will doubtless spawn further financially dismissive headlines in the business press as well.
But pediatricians are famously advocates for children, and PREPARE received a warm welcome from the pediatric infectious disease community, regardless of investor response. Indeed, PREPARE was the only clinical trial deemed of sufficient import to be featured in the opening plenary session of ESPID 2019.
Ulrich Heininger, MD, professor of pediatrics at the University of Basel (Switzerland), who cochaired the session, jointly sponsored by ESPID and the Pediatric Infectious Diseases Society, declared, “These findings, I think, are a great step forward.”
Dr. Munoz reported receiving research grants from Janssen, the National Institutes of Health, the Centers for Disease Control and Prevention, and Novavax, which sponsored the PREPARE trial, assisted by an $89 million grant from the Bill and Melinda Gates Foundation.
REPORTING FROM ESPID 2019
Is it measles? – Diagnosis and management for the pediatric provider
The mother of an 8-month-old calls your office and is hysterical. Her daughter has had cough for a few days with high fevers and now has developed a full body rash. She is worried about measles and is on her way to your office.
We are in the middle of a measles epidemic, there’s no denying it. Measles was declared eliminated in 2000, but reported cases in the United States have been on the rise, and are now at the highest number since 2014. Five months into 2019, there have been 839 reported cases as of May 13). Measles outbreaks (defined by the Centers for Disease Control and Prevention as three or more cases) have been reported in California, Georgia, Maryland, Michigan, New Jersey, New York, and Pennsylvania. When vaccination rates fall, it is easy for measles to spread. The virus is highly contagious in nonimmune people, because of its airborne spread and its persistence in the environment for hours.
First – is it really measles?
It can be difficult to distinguish the maculopapular rash of measles from similar rashes that occur with more benign viral illnesses. Adding to the challenge, the last major measles outbreak in the United States was over 2 decades ago, and many practicing pediatricians have never seen a single case. So, what clinical features can help distinguish measles from other febrile illnesses?
The prodromal phase of measles lasts approximately 2-4 days and children have high fevers (103°-105° F), anorexia, and malaise. Conjunctivitis, coryza, and cough develop during this phase, and precede any rash. Koplik spots appear during the prodromal phase, but are not seen in all cases. These spots are 1- to 3-mm blue-white lesions on an erythematous base on the buccal mucosa, classically opposite the first molar. The spots often slough once the rash appears. The rash appears 2-4 days after the onset of fever, and is initially maculopapular and blanching. The first lesions appear on the face and neck, and the rash spreads cranial to caudal, typically sparing palms and soles. After days 3-4, the rash will no longer blanch. High fevers persist for 2-4 more days with rash, ongoing respiratory symptoms, conjunctivitis, and pharyngitis. Note that the fever will persist even with development of the rash, unlike in roseola.
It is not only important to diagnosis measles from a public health standpoint, but also because measles can have severe complications, especially in infants and children under 5 years. During the 1989-1991 outbreak, the mortality rate was 2.2 deaths per 1,000 cases (J Infect Dis. 2004 May 1. doi: 10.1086/377694).
Six percent of patients develop pneumonia, which in infants and toddlers can lead to respiratory distress or failure requiring hospitalization. Pneumonia is responsible for 60% of measles deaths, according to the CDC “Pink Book,” Epidemiology and Prevention of Vaccine-Preventable Diseases, chapter 13 on measles, 13th Ed., 2015. Ocular complications include keratitis and corneal ulceration. Measles also can cause serious neurologic complications. Encephalitis, seen in 1 per 1,000 cases, usually arises several days after the rash and may present with seizure or encephalopathy. Acute disseminated encephalomyelitis (ADEM), an inflammatory demyelinating disease of the central nervous system, occurs in approximately 1 per 1,000 cases, typically presents during the recovery phase (1-2 weeks after rash), and can have long-term sequelae. Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal neurodegenerative disorder, and presents 7-10 years after measles infection.
Should you transfer the patient to a hospital?
Unless there is a medical need for the child to be admitted, sending a patient with potential measles to the hospital is not necessary, and can cause exposure to a large group of medical personnel, and patients who cannot be vaccinated (such as infants, immunocompromised patients, and pregnant women). However, if there is concern for complications such as seizures, encephalitis, or pneumonia, then transfer is indicated. Call the accepting hospital in advance so the staff can prepare for the patient. During transfer, place a standard face mask on the patient and instruct the patient not to remove it.
For hospitals accepting a suspected measles case, meet the patient outside of the facility and ensure that the patient is wearing a standard face mask. All staff interacting with the patient should practice contact and airborne precautions (N95 respirator mask). Take the patient directly to an isolation room with negative airflow. Caution pregnant staff that they should not have contact with the patient.
Which diagnostic tests should you use?
Diagnosis can be made based on serum antibody tests (measles IgM and IgG), throat or urine viral cultures, and nasopharyngeal and throat specimen polymerase chain reaction (PCR) testing. The CDC recommends obtaining a serum sample for measles IgM testing and a throat swab for PCR in all suspected cases, but local health departments vary in their specific testing recommendations. Familiarize yourself with the tests recommended by your local department of health, and where they prefer testing on outpatients to be done. Confirmed measles should be reported to your department of health.
What are considerations for community pediatric offices?
Update families in emails to call ahead if they suspect measles. This way the office can prepare a room for the family, and have the family immediately brought back without exposing staff and other families in the waiting area. It may be more prudent to examine these children at the end of the clinic day as the virus can persist for up to 2 hours on fomites and in the air. Therefore, all waiting areas and shared air spaces (including those with shared air ducts) should be cleared for 2 hours after the patient leaves.
When should you provide prophylaxis after exposure?
A patient with suspected measles does not require immediate vaccination. If it is measles, it is already too late to vaccinate. If measles is ruled out, the child should follow the standard measles vaccination guidelines.
Individuals are contagious from 4 days before to 4 days after the rash appears.
If measles is confirmed, all people who are unvaccinated or undervaccinated and were exposed to the confirmed case during the contagious period should be vaccinated within 72 hours of exposure. Infants 6 months or older may safely receive the MMR vaccine. However, infants vaccinated with MMR before their first birthday must be vaccinated again at age 12-15 months (greater than 28 days after prior vaccine) and at 4-6 years. Immunoglobulin prophylaxis should be given intramuscularly in exposed infants ages birth to less than 6 months, and in those ages 6-12 months who present beyond the 72-hour window. Unvaccinated or undervaccinated, exposed individuals at high risk for complications from measles (immunocompromised, pregnant) also should receive immunoglobulin.
What should you tell traveling families?
Several countries have large, ongoing measles outbreaks, including Israel, Ukraine, and the Philippines. Before international travel, infants 6-11 months should receive one dose of MMR vaccine, and children 12 months and older need two doses separated by at least 28 days. For unvaccinated or undervaccinated children, consider advising families to hold off travel to high-risk countries, or understand the indications to vaccinate a child upon return.
Dr. Angelica DesPain is a pediatric emergency medicine fellow at Children’s National Medical Center in Washington. She said she has no relevant financial disclosures. Dr. Emily Willner is a pediatric emergency medicine attending at Children’s National Medical Center, and an assistant professor of pediatrics and emergency medicine at George Washington University, Washington. She has no relevant financial disclosures.
The mother of an 8-month-old calls your office and is hysterical. Her daughter has had cough for a few days with high fevers and now has developed a full body rash. She is worried about measles and is on her way to your office.
We are in the middle of a measles epidemic, there’s no denying it. Measles was declared eliminated in 2000, but reported cases in the United States have been on the rise, and are now at the highest number since 2014. Five months into 2019, there have been 839 reported cases as of May 13). Measles outbreaks (defined by the Centers for Disease Control and Prevention as three or more cases) have been reported in California, Georgia, Maryland, Michigan, New Jersey, New York, and Pennsylvania. When vaccination rates fall, it is easy for measles to spread. The virus is highly contagious in nonimmune people, because of its airborne spread and its persistence in the environment for hours.
First – is it really measles?
It can be difficult to distinguish the maculopapular rash of measles from similar rashes that occur with more benign viral illnesses. Adding to the challenge, the last major measles outbreak in the United States was over 2 decades ago, and many practicing pediatricians have never seen a single case. So, what clinical features can help distinguish measles from other febrile illnesses?
The prodromal phase of measles lasts approximately 2-4 days and children have high fevers (103°-105° F), anorexia, and malaise. Conjunctivitis, coryza, and cough develop during this phase, and precede any rash. Koplik spots appear during the prodromal phase, but are not seen in all cases. These spots are 1- to 3-mm blue-white lesions on an erythematous base on the buccal mucosa, classically opposite the first molar. The spots often slough once the rash appears. The rash appears 2-4 days after the onset of fever, and is initially maculopapular and blanching. The first lesions appear on the face and neck, and the rash spreads cranial to caudal, typically sparing palms and soles. After days 3-4, the rash will no longer blanch. High fevers persist for 2-4 more days with rash, ongoing respiratory symptoms, conjunctivitis, and pharyngitis. Note that the fever will persist even with development of the rash, unlike in roseola.
It is not only important to diagnosis measles from a public health standpoint, but also because measles can have severe complications, especially in infants and children under 5 years. During the 1989-1991 outbreak, the mortality rate was 2.2 deaths per 1,000 cases (J Infect Dis. 2004 May 1. doi: 10.1086/377694).
Six percent of patients develop pneumonia, which in infants and toddlers can lead to respiratory distress or failure requiring hospitalization. Pneumonia is responsible for 60% of measles deaths, according to the CDC “Pink Book,” Epidemiology and Prevention of Vaccine-Preventable Diseases, chapter 13 on measles, 13th Ed., 2015. Ocular complications include keratitis and corneal ulceration. Measles also can cause serious neurologic complications. Encephalitis, seen in 1 per 1,000 cases, usually arises several days after the rash and may present with seizure or encephalopathy. Acute disseminated encephalomyelitis (ADEM), an inflammatory demyelinating disease of the central nervous system, occurs in approximately 1 per 1,000 cases, typically presents during the recovery phase (1-2 weeks after rash), and can have long-term sequelae. Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal neurodegenerative disorder, and presents 7-10 years after measles infection.
Should you transfer the patient to a hospital?
Unless there is a medical need for the child to be admitted, sending a patient with potential measles to the hospital is not necessary, and can cause exposure to a large group of medical personnel, and patients who cannot be vaccinated (such as infants, immunocompromised patients, and pregnant women). However, if there is concern for complications such as seizures, encephalitis, or pneumonia, then transfer is indicated. Call the accepting hospital in advance so the staff can prepare for the patient. During transfer, place a standard face mask on the patient and instruct the patient not to remove it.
For hospitals accepting a suspected measles case, meet the patient outside of the facility and ensure that the patient is wearing a standard face mask. All staff interacting with the patient should practice contact and airborne precautions (N95 respirator mask). Take the patient directly to an isolation room with negative airflow. Caution pregnant staff that they should not have contact with the patient.
Which diagnostic tests should you use?
Diagnosis can be made based on serum antibody tests (measles IgM and IgG), throat or urine viral cultures, and nasopharyngeal and throat specimen polymerase chain reaction (PCR) testing. The CDC recommends obtaining a serum sample for measles IgM testing and a throat swab for PCR in all suspected cases, but local health departments vary in their specific testing recommendations. Familiarize yourself with the tests recommended by your local department of health, and where they prefer testing on outpatients to be done. Confirmed measles should be reported to your department of health.
What are considerations for community pediatric offices?
Update families in emails to call ahead if they suspect measles. This way the office can prepare a room for the family, and have the family immediately brought back without exposing staff and other families in the waiting area. It may be more prudent to examine these children at the end of the clinic day as the virus can persist for up to 2 hours on fomites and in the air. Therefore, all waiting areas and shared air spaces (including those with shared air ducts) should be cleared for 2 hours after the patient leaves.
When should you provide prophylaxis after exposure?
A patient with suspected measles does not require immediate vaccination. If it is measles, it is already too late to vaccinate. If measles is ruled out, the child should follow the standard measles vaccination guidelines.
Individuals are contagious from 4 days before to 4 days after the rash appears.
If measles is confirmed, all people who are unvaccinated or undervaccinated and were exposed to the confirmed case during the contagious period should be vaccinated within 72 hours of exposure. Infants 6 months or older may safely receive the MMR vaccine. However, infants vaccinated with MMR before their first birthday must be vaccinated again at age 12-15 months (greater than 28 days after prior vaccine) and at 4-6 years. Immunoglobulin prophylaxis should be given intramuscularly in exposed infants ages birth to less than 6 months, and in those ages 6-12 months who present beyond the 72-hour window. Unvaccinated or undervaccinated, exposed individuals at high risk for complications from measles (immunocompromised, pregnant) also should receive immunoglobulin.
What should you tell traveling families?
Several countries have large, ongoing measles outbreaks, including Israel, Ukraine, and the Philippines. Before international travel, infants 6-11 months should receive one dose of MMR vaccine, and children 12 months and older need two doses separated by at least 28 days. For unvaccinated or undervaccinated children, consider advising families to hold off travel to high-risk countries, or understand the indications to vaccinate a child upon return.
Dr. Angelica DesPain is a pediatric emergency medicine fellow at Children’s National Medical Center in Washington. She said she has no relevant financial disclosures. Dr. Emily Willner is a pediatric emergency medicine attending at Children’s National Medical Center, and an assistant professor of pediatrics and emergency medicine at George Washington University, Washington. She has no relevant financial disclosures.
The mother of an 8-month-old calls your office and is hysterical. Her daughter has had cough for a few days with high fevers and now has developed a full body rash. She is worried about measles and is on her way to your office.
We are in the middle of a measles epidemic, there’s no denying it. Measles was declared eliminated in 2000, but reported cases in the United States have been on the rise, and are now at the highest number since 2014. Five months into 2019, there have been 839 reported cases as of May 13). Measles outbreaks (defined by the Centers for Disease Control and Prevention as three or more cases) have been reported in California, Georgia, Maryland, Michigan, New Jersey, New York, and Pennsylvania. When vaccination rates fall, it is easy for measles to spread. The virus is highly contagious in nonimmune people, because of its airborne spread and its persistence in the environment for hours.
First – is it really measles?
It can be difficult to distinguish the maculopapular rash of measles from similar rashes that occur with more benign viral illnesses. Adding to the challenge, the last major measles outbreak in the United States was over 2 decades ago, and many practicing pediatricians have never seen a single case. So, what clinical features can help distinguish measles from other febrile illnesses?
The prodromal phase of measles lasts approximately 2-4 days and children have high fevers (103°-105° F), anorexia, and malaise. Conjunctivitis, coryza, and cough develop during this phase, and precede any rash. Koplik spots appear during the prodromal phase, but are not seen in all cases. These spots are 1- to 3-mm blue-white lesions on an erythematous base on the buccal mucosa, classically opposite the first molar. The spots often slough once the rash appears. The rash appears 2-4 days after the onset of fever, and is initially maculopapular and blanching. The first lesions appear on the face and neck, and the rash spreads cranial to caudal, typically sparing palms and soles. After days 3-4, the rash will no longer blanch. High fevers persist for 2-4 more days with rash, ongoing respiratory symptoms, conjunctivitis, and pharyngitis. Note that the fever will persist even with development of the rash, unlike in roseola.
It is not only important to diagnosis measles from a public health standpoint, but also because measles can have severe complications, especially in infants and children under 5 years. During the 1989-1991 outbreak, the mortality rate was 2.2 deaths per 1,000 cases (J Infect Dis. 2004 May 1. doi: 10.1086/377694).
Six percent of patients develop pneumonia, which in infants and toddlers can lead to respiratory distress or failure requiring hospitalization. Pneumonia is responsible for 60% of measles deaths, according to the CDC “Pink Book,” Epidemiology and Prevention of Vaccine-Preventable Diseases, chapter 13 on measles, 13th Ed., 2015. Ocular complications include keratitis and corneal ulceration. Measles also can cause serious neurologic complications. Encephalitis, seen in 1 per 1,000 cases, usually arises several days after the rash and may present with seizure or encephalopathy. Acute disseminated encephalomyelitis (ADEM), an inflammatory demyelinating disease of the central nervous system, occurs in approximately 1 per 1,000 cases, typically presents during the recovery phase (1-2 weeks after rash), and can have long-term sequelae. Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal neurodegenerative disorder, and presents 7-10 years after measles infection.
Should you transfer the patient to a hospital?
Unless there is a medical need for the child to be admitted, sending a patient with potential measles to the hospital is not necessary, and can cause exposure to a large group of medical personnel, and patients who cannot be vaccinated (such as infants, immunocompromised patients, and pregnant women). However, if there is concern for complications such as seizures, encephalitis, or pneumonia, then transfer is indicated. Call the accepting hospital in advance so the staff can prepare for the patient. During transfer, place a standard face mask on the patient and instruct the patient not to remove it.
For hospitals accepting a suspected measles case, meet the patient outside of the facility and ensure that the patient is wearing a standard face mask. All staff interacting with the patient should practice contact and airborne precautions (N95 respirator mask). Take the patient directly to an isolation room with negative airflow. Caution pregnant staff that they should not have contact with the patient.
Which diagnostic tests should you use?
Diagnosis can be made based on serum antibody tests (measles IgM and IgG), throat or urine viral cultures, and nasopharyngeal and throat specimen polymerase chain reaction (PCR) testing. The CDC recommends obtaining a serum sample for measles IgM testing and a throat swab for PCR in all suspected cases, but local health departments vary in their specific testing recommendations. Familiarize yourself with the tests recommended by your local department of health, and where they prefer testing on outpatients to be done. Confirmed measles should be reported to your department of health.
What are considerations for community pediatric offices?
Update families in emails to call ahead if they suspect measles. This way the office can prepare a room for the family, and have the family immediately brought back without exposing staff and other families in the waiting area. It may be more prudent to examine these children at the end of the clinic day as the virus can persist for up to 2 hours on fomites and in the air. Therefore, all waiting areas and shared air spaces (including those with shared air ducts) should be cleared for 2 hours after the patient leaves.
When should you provide prophylaxis after exposure?
A patient with suspected measles does not require immediate vaccination. If it is measles, it is already too late to vaccinate. If measles is ruled out, the child should follow the standard measles vaccination guidelines.
Individuals are contagious from 4 days before to 4 days after the rash appears.
If measles is confirmed, all people who are unvaccinated or undervaccinated and were exposed to the confirmed case during the contagious period should be vaccinated within 72 hours of exposure. Infants 6 months or older may safely receive the MMR vaccine. However, infants vaccinated with MMR before their first birthday must be vaccinated again at age 12-15 months (greater than 28 days after prior vaccine) and at 4-6 years. Immunoglobulin prophylaxis should be given intramuscularly in exposed infants ages birth to less than 6 months, and in those ages 6-12 months who present beyond the 72-hour window. Unvaccinated or undervaccinated, exposed individuals at high risk for complications from measles (immunocompromised, pregnant) also should receive immunoglobulin.
What should you tell traveling families?
Several countries have large, ongoing measles outbreaks, including Israel, Ukraine, and the Philippines. Before international travel, infants 6-11 months should receive one dose of MMR vaccine, and children 12 months and older need two doses separated by at least 28 days. For unvaccinated or undervaccinated children, consider advising families to hold off travel to high-risk countries, or understand the indications to vaccinate a child upon return.
Dr. Angelica DesPain is a pediatric emergency medicine fellow at Children’s National Medical Center in Washington. She said she has no relevant financial disclosures. Dr. Emily Willner is a pediatric emergency medicine attending at Children’s National Medical Center, and an assistant professor of pediatrics and emergency medicine at George Washington University, Washington. She has no relevant financial disclosures.
Infections within first year of life predicted IBD
according to the findings of a large population-based study.
It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.
IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.
Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.
Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.
Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.
“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.
The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.
SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.
Understanding and exploring factors that could impact inflammatory bowel disease (IBD) development is imperative. This study by Bernstein et al. evaluated whether environmental factors in the first year of life may impact subsequent diagnosis of IBD using population-based cohort data with robust and detailed health information. Maternal history of IBD was the most predictive factor in development of IBD, further evidence of a genetic component to disease pathogenesis. However, environmental factors such as high socioeconomic status within the first year of life were predictive of diagnosis of IBD later in life, possibly lending further support to the “hygiene hypothesis.”
Also, significant infections identified in the clinical setting or requiring hospitalization were predictive of subsequent IBD diagnosis. This is particularly interesting as gut microbiome perturbations increasingly take the stage as a possible pathway of significance in IBD. Could infection within the first year of life or the subsequent antibiotic use required affect the gut microbiome so significantly and perhaps permanently to affect development of later childhood or adult IBD?
Sara Horst, MD, MPH, is an associate professor of medicine in the department of gastroenterology, hepatology, and medicine at Vanderbilt University, Nashville, Tenn. She has consulted for Janssen, UCB, and Boehringer Ingelheim.
Understanding and exploring factors that could impact inflammatory bowel disease (IBD) development is imperative. This study by Bernstein et al. evaluated whether environmental factors in the first year of life may impact subsequent diagnosis of IBD using population-based cohort data with robust and detailed health information. Maternal history of IBD was the most predictive factor in development of IBD, further evidence of a genetic component to disease pathogenesis. However, environmental factors such as high socioeconomic status within the first year of life were predictive of diagnosis of IBD later in life, possibly lending further support to the “hygiene hypothesis.”
Also, significant infections identified in the clinical setting or requiring hospitalization were predictive of subsequent IBD diagnosis. This is particularly interesting as gut microbiome perturbations increasingly take the stage as a possible pathway of significance in IBD. Could infection within the first year of life or the subsequent antibiotic use required affect the gut microbiome so significantly and perhaps permanently to affect development of later childhood or adult IBD?
Sara Horst, MD, MPH, is an associate professor of medicine in the department of gastroenterology, hepatology, and medicine at Vanderbilt University, Nashville, Tenn. She has consulted for Janssen, UCB, and Boehringer Ingelheim.
Understanding and exploring factors that could impact inflammatory bowel disease (IBD) development is imperative. This study by Bernstein et al. evaluated whether environmental factors in the first year of life may impact subsequent diagnosis of IBD using population-based cohort data with robust and detailed health information. Maternal history of IBD was the most predictive factor in development of IBD, further evidence of a genetic component to disease pathogenesis. However, environmental factors such as high socioeconomic status within the first year of life were predictive of diagnosis of IBD later in life, possibly lending further support to the “hygiene hypothesis.”
Also, significant infections identified in the clinical setting or requiring hospitalization were predictive of subsequent IBD diagnosis. This is particularly interesting as gut microbiome perturbations increasingly take the stage as a possible pathway of significance in IBD. Could infection within the first year of life or the subsequent antibiotic use required affect the gut microbiome so significantly and perhaps permanently to affect development of later childhood or adult IBD?
Sara Horst, MD, MPH, is an associate professor of medicine in the department of gastroenterology, hepatology, and medicine at Vanderbilt University, Nashville, Tenn. She has consulted for Janssen, UCB, and Boehringer Ingelheim.
according to the findings of a large population-based study.
It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.
IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.
Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.
Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.
Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.
“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.
The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.
SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.
according to the findings of a large population-based study.
It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.
IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.
Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.
Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.
Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.
“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.
The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.
SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.
FROM GASTROENTEROLOGY
Part 2: Why the Increase?
As established last week, there has been a startling increase in sexually transmitted infections (STIs) among older adults in the United States. The burning question on everyone’s mind (certainly mine!) is: Why? Engaging in some “educated speculation” yields many factors possibly driving this trend. For example:
1. Provider Reluctance. Older Americans may not get regular screenings for STIs because their health care providers are often reluctant to raise the issue. That may be fueled by lack of awareness on the clinician’s part: More than 60% of individuals older than 60 have sex at least once a month, yet this population is rarely considered to be “at risk” for STIs.1
2. Patient Embarrassment/awkwardness. For many older Americans, admitting that they are having sex makes them feel awkward or embarrassed. Reluctance to share intimate details means they may not seek evaluation and treatment for symptoms that seem related to their sexual health or activity.
3. Effects of Aging. There are 2 sides to this coin: actual physiologic changes that occur with age and assumptions that all changes are just part of aging. As people get older, their immune systems tend to deteriorate, making them more vulnerable to contracting any disease—including STIs. After menopause, women's vaginal tissues thin and natural lubrication declines, increasing their risk for microtears that can leave them susceptible to infectious organisms. And let’s be honest: Some STI symptoms, such as fatigue, weakness, and changes in memory, are nonspecific and may be mistaken by clinicians for the regular progression of age.2
4. Social Changes. The world has changed since most older adults last dove into the dating pool. We now have online dating services, some of which cater to a mature audience; as a result, people may be less familiar with their partner’s sexual history. Compounding that, many older adults just aren’t accustomed to thinking of themselves or a partner as being at high risk for STIs—and if you don’t even think about it, you definitely won’t ask. Widowed or divorced adults may date more than one person at a time, raising their risk for infection after a long period of monogamy. Seniors also may not be accustomed to using a condom or do not use one because they think the risk for STIs is minimal or nonexistent. Seniors may not consider oral or anal sex as a way of contracting or transmitting STIs.3
5. Medical Advances. Compared with previous generations, today’s seniors have an easier time having sex at an older age, thanks to the availability of medications such as sildenafil (Viagra) and tadalafil (Cialis) for men with erectile dysfunction. There has also been an increase in postmenopausal women requesting and receiving bioidentical hormone replacement. With increased libido and ability to perform come more sexual encounters among the older population—and as a result, more opportunities for STIs to spread. Are there other reasons for the increase in STIs in this population? Next week we’ll consider the unique societal influences of the Baby Boom generation. In the meantime, please share your insights with me at [email protected].
1. Boskey E. STDs in the elderly community. Verywell Health. February 14, 2018. www.verywellhealth.com/stds-the-elderly-3133189. Accessed May 8, 2019.
2. East A. (2017). Seniors and STDs: common sexually transmitted diseases. CaringPeople. June 23, 2017. https://caringpeopleinc.com/blog/seniors-common-sexually-transmitted-diseases. Accessed May 8, 2019.
3. Harvard Medical School. Sexually transmitted disease? At my age? Harvard Health Letter. February 2018. www.health.harvard.edu/diseases-and-conditions/sexually-transmitted-disease-at-my-age. Accessed May 8, 2019.
As established last week, there has been a startling increase in sexually transmitted infections (STIs) among older adults in the United States. The burning question on everyone’s mind (certainly mine!) is: Why? Engaging in some “educated speculation” yields many factors possibly driving this trend. For example:
1. Provider Reluctance. Older Americans may not get regular screenings for STIs because their health care providers are often reluctant to raise the issue. That may be fueled by lack of awareness on the clinician’s part: More than 60% of individuals older than 60 have sex at least once a month, yet this population is rarely considered to be “at risk” for STIs.1
2. Patient Embarrassment/awkwardness. For many older Americans, admitting that they are having sex makes them feel awkward or embarrassed. Reluctance to share intimate details means they may not seek evaluation and treatment for symptoms that seem related to their sexual health or activity.
3. Effects of Aging. There are 2 sides to this coin: actual physiologic changes that occur with age and assumptions that all changes are just part of aging. As people get older, their immune systems tend to deteriorate, making them more vulnerable to contracting any disease—including STIs. After menopause, women's vaginal tissues thin and natural lubrication declines, increasing their risk for microtears that can leave them susceptible to infectious organisms. And let’s be honest: Some STI symptoms, such as fatigue, weakness, and changes in memory, are nonspecific and may be mistaken by clinicians for the regular progression of age.2
4. Social Changes. The world has changed since most older adults last dove into the dating pool. We now have online dating services, some of which cater to a mature audience; as a result, people may be less familiar with their partner’s sexual history. Compounding that, many older adults just aren’t accustomed to thinking of themselves or a partner as being at high risk for STIs—and if you don’t even think about it, you definitely won’t ask. Widowed or divorced adults may date more than one person at a time, raising their risk for infection after a long period of monogamy. Seniors also may not be accustomed to using a condom or do not use one because they think the risk for STIs is minimal or nonexistent. Seniors may not consider oral or anal sex as a way of contracting or transmitting STIs.3
5. Medical Advances. Compared with previous generations, today’s seniors have an easier time having sex at an older age, thanks to the availability of medications such as sildenafil (Viagra) and tadalafil (Cialis) for men with erectile dysfunction. There has also been an increase in postmenopausal women requesting and receiving bioidentical hormone replacement. With increased libido and ability to perform come more sexual encounters among the older population—and as a result, more opportunities for STIs to spread. Are there other reasons for the increase in STIs in this population? Next week we’ll consider the unique societal influences of the Baby Boom generation. In the meantime, please share your insights with me at [email protected].
As established last week, there has been a startling increase in sexually transmitted infections (STIs) among older adults in the United States. The burning question on everyone’s mind (certainly mine!) is: Why? Engaging in some “educated speculation” yields many factors possibly driving this trend. For example:
1. Provider Reluctance. Older Americans may not get regular screenings for STIs because their health care providers are often reluctant to raise the issue. That may be fueled by lack of awareness on the clinician’s part: More than 60% of individuals older than 60 have sex at least once a month, yet this population is rarely considered to be “at risk” for STIs.1
2. Patient Embarrassment/awkwardness. For many older Americans, admitting that they are having sex makes them feel awkward or embarrassed. Reluctance to share intimate details means they may not seek evaluation and treatment for symptoms that seem related to their sexual health or activity.
3. Effects of Aging. There are 2 sides to this coin: actual physiologic changes that occur with age and assumptions that all changes are just part of aging. As people get older, their immune systems tend to deteriorate, making them more vulnerable to contracting any disease—including STIs. After menopause, women's vaginal tissues thin and natural lubrication declines, increasing their risk for microtears that can leave them susceptible to infectious organisms. And let’s be honest: Some STI symptoms, such as fatigue, weakness, and changes in memory, are nonspecific and may be mistaken by clinicians for the regular progression of age.2
4. Social Changes. The world has changed since most older adults last dove into the dating pool. We now have online dating services, some of which cater to a mature audience; as a result, people may be less familiar with their partner’s sexual history. Compounding that, many older adults just aren’t accustomed to thinking of themselves or a partner as being at high risk for STIs—and if you don’t even think about it, you definitely won’t ask. Widowed or divorced adults may date more than one person at a time, raising their risk for infection after a long period of monogamy. Seniors also may not be accustomed to using a condom or do not use one because they think the risk for STIs is minimal or nonexistent. Seniors may not consider oral or anal sex as a way of contracting or transmitting STIs.3
5. Medical Advances. Compared with previous generations, today’s seniors have an easier time having sex at an older age, thanks to the availability of medications such as sildenafil (Viagra) and tadalafil (Cialis) for men with erectile dysfunction. There has also been an increase in postmenopausal women requesting and receiving bioidentical hormone replacement. With increased libido and ability to perform come more sexual encounters among the older population—and as a result, more opportunities for STIs to spread. Are there other reasons for the increase in STIs in this population? Next week we’ll consider the unique societal influences of the Baby Boom generation. In the meantime, please share your insights with me at [email protected].
1. Boskey E. STDs in the elderly community. Verywell Health. February 14, 2018. www.verywellhealth.com/stds-the-elderly-3133189. Accessed May 8, 2019.
2. East A. (2017). Seniors and STDs: common sexually transmitted diseases. CaringPeople. June 23, 2017. https://caringpeopleinc.com/blog/seniors-common-sexually-transmitted-diseases. Accessed May 8, 2019.
3. Harvard Medical School. Sexually transmitted disease? At my age? Harvard Health Letter. February 2018. www.health.harvard.edu/diseases-and-conditions/sexually-transmitted-disease-at-my-age. Accessed May 8, 2019.
1. Boskey E. STDs in the elderly community. Verywell Health. February 14, 2018. www.verywellhealth.com/stds-the-elderly-3133189. Accessed May 8, 2019.
2. East A. (2017). Seniors and STDs: common sexually transmitted diseases. CaringPeople. June 23, 2017. https://caringpeopleinc.com/blog/seniors-common-sexually-transmitted-diseases. Accessed May 8, 2019.
3. Harvard Medical School. Sexually transmitted disease? At my age? Harvard Health Letter. February 2018. www.health.harvard.edu/diseases-and-conditions/sexually-transmitted-disease-at-my-age. Accessed May 8, 2019.
Flu vaccine visits reveal missed opportunities for HPV vaccination
BALTIMORE – according to a study.
“Overall in preventive visits, missed opportunities were much higher for HPV, compared to the other two vaccines” recommended for adolescents, MenACWY (meningococcal conjugate vaccine) and Tdap, Mary Kate Kelly, MPH, of Children’s Hospital of Philadelphia, told attendees at the Pediatric Academic Societies annual meeting. “In order to increase vaccination rates, it’s essential to implement efforts to reduce missed opportunities.”
According to 2018 Centers for Disease Control and Prevention data, Ms. Kelly said, vaccine coverage for the HPV vaccine is approximately 66%, compared with 85% for the MenACWY vaccine and 89% for the Tdap vaccine.
Ms. Kelly and her colleagues investigated how often children or adolescents missed an opportunity to get an HPV vaccine when they received an influenza vaccine during an office visit. This study was part of the larger STOP HPV trial funded by the National Institutes of Health and aimed at implementing evidence-based interventions to reduce missed opportunities for HPV vaccination in primary care.
The researchers retrospectively reviewed EHRs from 2015 to 2018 for 48 pediatric practices across 19 states. All practices were part of the American Academy of Pediatrics’ Pediatric Research in Office Settings (PROS) national pediatric primary care network. The researchers isolated all visits for patients aged 11-17 years who received their flu vaccine and were eligible to receive the HPV vaccine.
The investigators defined a missed opportunity as one in which a patient was due for the HPV vaccine but did not receive one at the visit when they received their flu vaccine.
The study involved 40,129 patients who received the flu vaccine at 52,818 visits when they also were eligible to receive the HPV vaccine. The median age of patients was 12 years old, and 47% were female.
In 68% of visits, the patient could have received an HPV vaccine but did not – even though they were due and eligible for one. The rate was the same for boys and for girls. By contrast, only 38% of visits involved a missed opportunity for the MenACWY vaccines and 39% for the Tdap vaccine.
Rates of missed opportunities for HPV vaccination ranged among individual practices from 22% to 81% of overall visits. Patients were more than twice as likely to miss the opportunity for an HPV vaccine dose if it would have been their first dose – 70% of missed opportunities – versus being a second or third dose, which comprised 30% of missed opportunities (adjusted relative risk, 2.48; P less than .001)).
“However, missed opportunities were also common for subsequent HPV doses when vaccine hesitancy is less likely to be an issue,” Ms. Kelly added.
It also was much more likely that missed opportunities occurred during nurse visits or visits for an acute or chronic condition rather than preventive visits, which made up about half (51%) of all visits analyzed. While 48% of preventive visits involved a missed opportunity, 93% of nurse visits (aRR compared with preventive, 2.18; P less than.001) and 89% of acute or chronic visits (aRR, 2.11; P less than .001) did.
Percentages of missed opportunities were similarly high for the MenACWY and Tdap vaccines at nurse visits and acute/chronic visits, but much lower at preventive visits for the MenACWY (12%) and Tdap (15%) vaccines.
“Increasing simultaneous administration of HPV and other adolescent vaccines with the influenza vaccine may help to improve coverage,” Ms. Kelly concluded.
The study was limited by its use of a convenience sample from practices that were interested in participating and willing to stock the HPV vaccine. Additionally, the researchers could not detect or adjust for EHR errors or inaccurate or incomplete vaccine histories, and they were unable to look at vaccine hesitancy or refusal with the EHRs.
The research was funded by the National Institutes of Health, the U.S. Department of Health & Human Services, and the National Research Network to Improve Children’s Health. The authors reported no relevant financial disclosures.
BALTIMORE – according to a study.
“Overall in preventive visits, missed opportunities were much higher for HPV, compared to the other two vaccines” recommended for adolescents, MenACWY (meningococcal conjugate vaccine) and Tdap, Mary Kate Kelly, MPH, of Children’s Hospital of Philadelphia, told attendees at the Pediatric Academic Societies annual meeting. “In order to increase vaccination rates, it’s essential to implement efforts to reduce missed opportunities.”
According to 2018 Centers for Disease Control and Prevention data, Ms. Kelly said, vaccine coverage for the HPV vaccine is approximately 66%, compared with 85% for the MenACWY vaccine and 89% for the Tdap vaccine.
Ms. Kelly and her colleagues investigated how often children or adolescents missed an opportunity to get an HPV vaccine when they received an influenza vaccine during an office visit. This study was part of the larger STOP HPV trial funded by the National Institutes of Health and aimed at implementing evidence-based interventions to reduce missed opportunities for HPV vaccination in primary care.
The researchers retrospectively reviewed EHRs from 2015 to 2018 for 48 pediatric practices across 19 states. All practices were part of the American Academy of Pediatrics’ Pediatric Research in Office Settings (PROS) national pediatric primary care network. The researchers isolated all visits for patients aged 11-17 years who received their flu vaccine and were eligible to receive the HPV vaccine.
The investigators defined a missed opportunity as one in which a patient was due for the HPV vaccine but did not receive one at the visit when they received their flu vaccine.
The study involved 40,129 patients who received the flu vaccine at 52,818 visits when they also were eligible to receive the HPV vaccine. The median age of patients was 12 years old, and 47% were female.
In 68% of visits, the patient could have received an HPV vaccine but did not – even though they were due and eligible for one. The rate was the same for boys and for girls. By contrast, only 38% of visits involved a missed opportunity for the MenACWY vaccines and 39% for the Tdap vaccine.
Rates of missed opportunities for HPV vaccination ranged among individual practices from 22% to 81% of overall visits. Patients were more than twice as likely to miss the opportunity for an HPV vaccine dose if it would have been their first dose – 70% of missed opportunities – versus being a second or third dose, which comprised 30% of missed opportunities (adjusted relative risk, 2.48; P less than .001)).
“However, missed opportunities were also common for subsequent HPV doses when vaccine hesitancy is less likely to be an issue,” Ms. Kelly added.
It also was much more likely that missed opportunities occurred during nurse visits or visits for an acute or chronic condition rather than preventive visits, which made up about half (51%) of all visits analyzed. While 48% of preventive visits involved a missed opportunity, 93% of nurse visits (aRR compared with preventive, 2.18; P less than.001) and 89% of acute or chronic visits (aRR, 2.11; P less than .001) did.
Percentages of missed opportunities were similarly high for the MenACWY and Tdap vaccines at nurse visits and acute/chronic visits, but much lower at preventive visits for the MenACWY (12%) and Tdap (15%) vaccines.
“Increasing simultaneous administration of HPV and other adolescent vaccines with the influenza vaccine may help to improve coverage,” Ms. Kelly concluded.
The study was limited by its use of a convenience sample from practices that were interested in participating and willing to stock the HPV vaccine. Additionally, the researchers could not detect or adjust for EHR errors or inaccurate or incomplete vaccine histories, and they were unable to look at vaccine hesitancy or refusal with the EHRs.
The research was funded by the National Institutes of Health, the U.S. Department of Health & Human Services, and the National Research Network to Improve Children’s Health. The authors reported no relevant financial disclosures.
BALTIMORE – according to a study.
“Overall in preventive visits, missed opportunities were much higher for HPV, compared to the other two vaccines” recommended for adolescents, MenACWY (meningococcal conjugate vaccine) and Tdap, Mary Kate Kelly, MPH, of Children’s Hospital of Philadelphia, told attendees at the Pediatric Academic Societies annual meeting. “In order to increase vaccination rates, it’s essential to implement efforts to reduce missed opportunities.”
According to 2018 Centers for Disease Control and Prevention data, Ms. Kelly said, vaccine coverage for the HPV vaccine is approximately 66%, compared with 85% for the MenACWY vaccine and 89% for the Tdap vaccine.
Ms. Kelly and her colleagues investigated how often children or adolescents missed an opportunity to get an HPV vaccine when they received an influenza vaccine during an office visit. This study was part of the larger STOP HPV trial funded by the National Institutes of Health and aimed at implementing evidence-based interventions to reduce missed opportunities for HPV vaccination in primary care.
The researchers retrospectively reviewed EHRs from 2015 to 2018 for 48 pediatric practices across 19 states. All practices were part of the American Academy of Pediatrics’ Pediatric Research in Office Settings (PROS) national pediatric primary care network. The researchers isolated all visits for patients aged 11-17 years who received their flu vaccine and were eligible to receive the HPV vaccine.
The investigators defined a missed opportunity as one in which a patient was due for the HPV vaccine but did not receive one at the visit when they received their flu vaccine.
The study involved 40,129 patients who received the flu vaccine at 52,818 visits when they also were eligible to receive the HPV vaccine. The median age of patients was 12 years old, and 47% were female.
In 68% of visits, the patient could have received an HPV vaccine but did not – even though they were due and eligible for one. The rate was the same for boys and for girls. By contrast, only 38% of visits involved a missed opportunity for the MenACWY vaccines and 39% for the Tdap vaccine.
Rates of missed opportunities for HPV vaccination ranged among individual practices from 22% to 81% of overall visits. Patients were more than twice as likely to miss the opportunity for an HPV vaccine dose if it would have been their first dose – 70% of missed opportunities – versus being a second or third dose, which comprised 30% of missed opportunities (adjusted relative risk, 2.48; P less than .001)).
“However, missed opportunities were also common for subsequent HPV doses when vaccine hesitancy is less likely to be an issue,” Ms. Kelly added.
It also was much more likely that missed opportunities occurred during nurse visits or visits for an acute or chronic condition rather than preventive visits, which made up about half (51%) of all visits analyzed. While 48% of preventive visits involved a missed opportunity, 93% of nurse visits (aRR compared with preventive, 2.18; P less than.001) and 89% of acute or chronic visits (aRR, 2.11; P less than .001) did.
Percentages of missed opportunities were similarly high for the MenACWY and Tdap vaccines at nurse visits and acute/chronic visits, but much lower at preventive visits for the MenACWY (12%) and Tdap (15%) vaccines.
“Increasing simultaneous administration of HPV and other adolescent vaccines with the influenza vaccine may help to improve coverage,” Ms. Kelly concluded.
The study was limited by its use of a convenience sample from practices that were interested in participating and willing to stock the HPV vaccine. Additionally, the researchers could not detect or adjust for EHR errors or inaccurate or incomplete vaccine histories, and they were unable to look at vaccine hesitancy or refusal with the EHRs.
The research was funded by the National Institutes of Health, the U.S. Department of Health & Human Services, and the National Research Network to Improve Children’s Health. The authors reported no relevant financial disclosures.
REPORTING FROM PAS 2019
U.S. measles cases climb to over 800 for the year
according to the Centers for Disease Control and Prevention.
There are 10 states dealing with ongoing outbreaks now that Pennsylvania has been added to the list, the CDC reported May 13. The state has had five cases so far, all in Allegheny County. New York City continued to have the most active outbreak, adding 43 more cases in Brooklyn last week for a total of 410 in the city since the beginning of 2019, NYC Health said.
Several of this year’s outbreaks were predicted in an analysis published in the Lancet Infectious Diseases (2019 May 9. doi: 10.1016/S1473-3099(19)30231-2). Investigators identified the 25 counties most likely to experience a measles outbreak in 2019 – a list that includes Queens, N.Y. (adjacent to Brooklyn), Multnomah, Ore. (adjacent to Clark County, Wash., where 71 people were infected earlier this year), and San Mateo, Calif., where 4 cases have been reported.
“We recommend that public health officials and policymakers prioritize monitoring the counties we identify to be at high risk that have not yet reported cases, especially those that lie adjacent to counties with ongoing outbreaks and those that house large international airports,” senior author Lauren Gardner of Johns Hopkins University, Baltimore, said in a written statement.
The outbreak in Clark County was declared over in late April, but Gov. Jay Inslee signed a bill on May 10 that removes the personal/philosophical exemption for the MMR vaccine from the state’s school and child care immunization requirements. “We must step up our leadership to educate the public about the critical role vaccines have in keeping us healthy and safe, and continue working with communities to improve vaccination rates,” Washington State Secretary of Health John Wiesman said in a written statement.
In Oregon, a bill that would eliminate religious and philosophical exemptions to child vaccination requirements passed the state house of representatives by a 35-25 vote and is moving to the senate. Gov. Kate Brown has said that she plans to sign the bill, according to OregonLive.com.
according to the Centers for Disease Control and Prevention.
There are 10 states dealing with ongoing outbreaks now that Pennsylvania has been added to the list, the CDC reported May 13. The state has had five cases so far, all in Allegheny County. New York City continued to have the most active outbreak, adding 43 more cases in Brooklyn last week for a total of 410 in the city since the beginning of 2019, NYC Health said.
Several of this year’s outbreaks were predicted in an analysis published in the Lancet Infectious Diseases (2019 May 9. doi: 10.1016/S1473-3099(19)30231-2). Investigators identified the 25 counties most likely to experience a measles outbreak in 2019 – a list that includes Queens, N.Y. (adjacent to Brooklyn), Multnomah, Ore. (adjacent to Clark County, Wash., where 71 people were infected earlier this year), and San Mateo, Calif., where 4 cases have been reported.
“We recommend that public health officials and policymakers prioritize monitoring the counties we identify to be at high risk that have not yet reported cases, especially those that lie adjacent to counties with ongoing outbreaks and those that house large international airports,” senior author Lauren Gardner of Johns Hopkins University, Baltimore, said in a written statement.
The outbreak in Clark County was declared over in late April, but Gov. Jay Inslee signed a bill on May 10 that removes the personal/philosophical exemption for the MMR vaccine from the state’s school and child care immunization requirements. “We must step up our leadership to educate the public about the critical role vaccines have in keeping us healthy and safe, and continue working with communities to improve vaccination rates,” Washington State Secretary of Health John Wiesman said in a written statement.
In Oregon, a bill that would eliminate religious and philosophical exemptions to child vaccination requirements passed the state house of representatives by a 35-25 vote and is moving to the senate. Gov. Kate Brown has said that she plans to sign the bill, according to OregonLive.com.
according to the Centers for Disease Control and Prevention.
There are 10 states dealing with ongoing outbreaks now that Pennsylvania has been added to the list, the CDC reported May 13. The state has had five cases so far, all in Allegheny County. New York City continued to have the most active outbreak, adding 43 more cases in Brooklyn last week for a total of 410 in the city since the beginning of 2019, NYC Health said.
Several of this year’s outbreaks were predicted in an analysis published in the Lancet Infectious Diseases (2019 May 9. doi: 10.1016/S1473-3099(19)30231-2). Investigators identified the 25 counties most likely to experience a measles outbreak in 2019 – a list that includes Queens, N.Y. (adjacent to Brooklyn), Multnomah, Ore. (adjacent to Clark County, Wash., where 71 people were infected earlier this year), and San Mateo, Calif., where 4 cases have been reported.
“We recommend that public health officials and policymakers prioritize monitoring the counties we identify to be at high risk that have not yet reported cases, especially those that lie adjacent to counties with ongoing outbreaks and those that house large international airports,” senior author Lauren Gardner of Johns Hopkins University, Baltimore, said in a written statement.
The outbreak in Clark County was declared over in late April, but Gov. Jay Inslee signed a bill on May 10 that removes the personal/philosophical exemption for the MMR vaccine from the state’s school and child care immunization requirements. “We must step up our leadership to educate the public about the critical role vaccines have in keeping us healthy and safe, and continue working with communities to improve vaccination rates,” Washington State Secretary of Health John Wiesman said in a written statement.
In Oregon, a bill that would eliminate religious and philosophical exemptions to child vaccination requirements passed the state house of representatives by a 35-25 vote and is moving to the senate. Gov. Kate Brown has said that she plans to sign the bill, according to OregonLive.com.
N.Y. hospitals report near-universal CMV screening when newborns fail hearing tests
BALTIMORE – Over the past 2 years, Northwell Health, a large medical system in the metropolitan New York area, increased cytomegalovirus screening for infants who fail hearing tests from 6.6% to 95% at five of its birth hospitals, according to a presentation at the Pediatric Academic Societies annual meeting.
Three cases of congenital cytomegalovirus (CMV) have been picked up so far. The plan is to roll the program out to all 10 of the system’s birth hospitals, where over 40,000 children are born each year.
“We feel very satisfied and proud” of the progress that’s been made at Northwell in such a short time, said Alia Chauhan, MD, a Northwell pediatrician who presented the findings.
Northwell launched its “Hearing Plus” program in 2017 to catch the infection before infants leave the hospital. Several other health systems around the country have launched similar programs, and a handful of states – including New York – now require CMV screening for infants who fail mandated hearing tests.
The issue is gaining traction because hearing loss is often the only sign of congenital CMV, so it’s a bellwether for infection. Screening children with hearing loss is an easy way to pick it up early, so steps can be taken to prevent problems down the road. As it is, congenital CMV is the leading nongenetic cause of hearing loss in infants, accounting for at least 10% of cases.
The Northwell program kicked off with an education campaign to build consensus among pediatricians, hospitalists, and nurses. A flyer was made about CMV screening for moms whose infants fail hearing tests, printed in both English and Spanish.
Initially, the program used urine PCR [polymerase chain reaction] to screen for CMV, but waiting for infants to produce a sample often delayed discharge, so a switch was soon made to saliva swab PCRs, which take seconds, with urine PCR held in reserve to confirm positive swabs.
To streamline the process, a standing order was added to the electronic records system so nurses could order saliva PCRs without having to get physician approval. “I think [that] was one of the biggest things that’s helped us,” Dr. Chauhan said.
Children who test positive must have urine confirmation within 21 days of birth; most are long gone from the hospital by then and have to be called back in. “We haven’t lost anyone to follow-up, but it can be stressful trying to get someone to come back,” she said.
Six of 449 infants have screened positive on saliva – three were false positives with negative urine screens. Of the three confirmed cases, two infants later turned out to have normal hearing on repeat testing and were otherwise asymptomatic.
These days, Dr. Chauhan said, if children have a positive saliva PCR but later turn out to have normal hearing, and are otherwise free of symptoms with no CMV risk factors, “we are not confirming with urine.”
Dr. Chauhan did not have any disclosures. No funding source was mentioned.
SOURCE: Chauhan A et al. PAS 2019. Abstract 306
BALTIMORE – Over the past 2 years, Northwell Health, a large medical system in the metropolitan New York area, increased cytomegalovirus screening for infants who fail hearing tests from 6.6% to 95% at five of its birth hospitals, according to a presentation at the Pediatric Academic Societies annual meeting.
Three cases of congenital cytomegalovirus (CMV) have been picked up so far. The plan is to roll the program out to all 10 of the system’s birth hospitals, where over 40,000 children are born each year.
“We feel very satisfied and proud” of the progress that’s been made at Northwell in such a short time, said Alia Chauhan, MD, a Northwell pediatrician who presented the findings.
Northwell launched its “Hearing Plus” program in 2017 to catch the infection before infants leave the hospital. Several other health systems around the country have launched similar programs, and a handful of states – including New York – now require CMV screening for infants who fail mandated hearing tests.
The issue is gaining traction because hearing loss is often the only sign of congenital CMV, so it’s a bellwether for infection. Screening children with hearing loss is an easy way to pick it up early, so steps can be taken to prevent problems down the road. As it is, congenital CMV is the leading nongenetic cause of hearing loss in infants, accounting for at least 10% of cases.
The Northwell program kicked off with an education campaign to build consensus among pediatricians, hospitalists, and nurses. A flyer was made about CMV screening for moms whose infants fail hearing tests, printed in both English and Spanish.
Initially, the program used urine PCR [polymerase chain reaction] to screen for CMV, but waiting for infants to produce a sample often delayed discharge, so a switch was soon made to saliva swab PCRs, which take seconds, with urine PCR held in reserve to confirm positive swabs.
To streamline the process, a standing order was added to the electronic records system so nurses could order saliva PCRs without having to get physician approval. “I think [that] was one of the biggest things that’s helped us,” Dr. Chauhan said.
Children who test positive must have urine confirmation within 21 days of birth; most are long gone from the hospital by then and have to be called back in. “We haven’t lost anyone to follow-up, but it can be stressful trying to get someone to come back,” she said.
Six of 449 infants have screened positive on saliva – three were false positives with negative urine screens. Of the three confirmed cases, two infants later turned out to have normal hearing on repeat testing and were otherwise asymptomatic.
These days, Dr. Chauhan said, if children have a positive saliva PCR but later turn out to have normal hearing, and are otherwise free of symptoms with no CMV risk factors, “we are not confirming with urine.”
Dr. Chauhan did not have any disclosures. No funding source was mentioned.
SOURCE: Chauhan A et al. PAS 2019. Abstract 306
BALTIMORE – Over the past 2 years, Northwell Health, a large medical system in the metropolitan New York area, increased cytomegalovirus screening for infants who fail hearing tests from 6.6% to 95% at five of its birth hospitals, according to a presentation at the Pediatric Academic Societies annual meeting.
Three cases of congenital cytomegalovirus (CMV) have been picked up so far. The plan is to roll the program out to all 10 of the system’s birth hospitals, where over 40,000 children are born each year.
“We feel very satisfied and proud” of the progress that’s been made at Northwell in such a short time, said Alia Chauhan, MD, a Northwell pediatrician who presented the findings.
Northwell launched its “Hearing Plus” program in 2017 to catch the infection before infants leave the hospital. Several other health systems around the country have launched similar programs, and a handful of states – including New York – now require CMV screening for infants who fail mandated hearing tests.
The issue is gaining traction because hearing loss is often the only sign of congenital CMV, so it’s a bellwether for infection. Screening children with hearing loss is an easy way to pick it up early, so steps can be taken to prevent problems down the road. As it is, congenital CMV is the leading nongenetic cause of hearing loss in infants, accounting for at least 10% of cases.
The Northwell program kicked off with an education campaign to build consensus among pediatricians, hospitalists, and nurses. A flyer was made about CMV screening for moms whose infants fail hearing tests, printed in both English and Spanish.
Initially, the program used urine PCR [polymerase chain reaction] to screen for CMV, but waiting for infants to produce a sample often delayed discharge, so a switch was soon made to saliva swab PCRs, which take seconds, with urine PCR held in reserve to confirm positive swabs.
To streamline the process, a standing order was added to the electronic records system so nurses could order saliva PCRs without having to get physician approval. “I think [that] was one of the biggest things that’s helped us,” Dr. Chauhan said.
Children who test positive must have urine confirmation within 21 days of birth; most are long gone from the hospital by then and have to be called back in. “We haven’t lost anyone to follow-up, but it can be stressful trying to get someone to come back,” she said.
Six of 449 infants have screened positive on saliva – three were false positives with negative urine screens. Of the three confirmed cases, two infants later turned out to have normal hearing on repeat testing and were otherwise asymptomatic.
These days, Dr. Chauhan said, if children have a positive saliva PCR but later turn out to have normal hearing, and are otherwise free of symptoms with no CMV risk factors, “we are not confirming with urine.”
Dr. Chauhan did not have any disclosures. No funding source was mentioned.
SOURCE: Chauhan A et al. PAS 2019. Abstract 306
REPORTING FROM PAS 2019
Key clinical point: A metropolitan N.Y. health system provides a model for how to implement cytomegalovirus screening for infants who fail hearing tests.
Major finding: .
Study details: Pre-post quality improvement project.
Disclosures: The lead investigator had no disclosures. No funding source was mentioned.
Source: Chauhan A et al. PAS 2019. Abstract 306.
HM19: Pediatric clinical conundrums
Atypical symptoms and diagnoses
Presenters
Yemisi Jones, MD; Mirna Giordano, MD
Session title
Pediatric Clinical Conundrums
Session summary
Dr. Mirna Giordano of Columbia University Irving Medical Center, New York, and Dr. Yemisi Jones of Cincinnati Children’s Hospital Medical Center, moderated the Pediatric Clinical Conundrums session at HM19. After reviewing multiple submissions, they invited four trainees to present their interesting cases.
Malignancy or infection? Dr. Jeremy Brown, a resident at the University of Louisville, presented a case of a 15-year-old male with right upper quadrant abdominal pain with associated weight loss and intermittent fevers, over the course of several weeks. CT revealed multiple liver lesions, providing concern for possible malignancy, although liver biopsy proved otherwise, with mostly liquefactive tissue and benign liver parenchyma. After a large infectious work-up ensued, the patient was diagnosed with disseminated Bartonella. He was treated with a 10-day course of azithromycin, and his symptoms resolved.
Leg blisters as an uncommon manifestation of a common childhood disease. Dr. Stefan Mammele, a resident at Kapi’olani Medical Center in Honolulu, and the University of Hawaii, presented a case of an 11-year-old boy with a painful and pruritic rash associated with multiple 5- to 10-mm tense bullae located on the patient’s bilateral lower extremities with extension to the trunk. The patient was also found to have hematuria and proteinuria. The bullae drained both serosanguinous and purulent material. Fluid culture grew group A Streptococcus and skin biopsy confirmed IgA vasculitis. Bullae are a rare characteristic of Henoch Schönlein pupura in children, but are more commonly seen as a disease manifestation in adults. The patient was treated with cefazolin, and his lesions improved over the course of several weeks with resolution of his hematuria by 6 months.
Is she crying blood? Dr. Joshua Price, a resident at Baystate Children’s Hospital in Springfield, Mass., described a 12-year-old female who presented with 7 days of left-sided hemolacria with acute vision loss and unilateral eye pain. This patient did not respond to outpatient topical steroids and antibiotics, as prescribed by ophthalmology. For this reason, she underwent further work-up and imaging. MRI of the head and orbits revealed left maxillary sinus disease. She was treated with antibiotics for acute left maxillary sinusitis and her hemolacria resolved within 24 hours. While the differential diagnosis for hemolacria is broad, rarely acute sinusitis has been reported as a cause in medical literature.
Recurrent bronchiolitis or something more? Dr. Moira Black, a resident at Children’s Memorial Hermann in Houston, presented a case of a 7-month-old female with a history of recurrent admissions for increased work of breathing believed to be secondary to viral bronchiolitis. Her first hospitalization occurred at 7 weeks of age and was complicated by spontaneous pneumothorax requiring chest tube placement. She was again hospitalized at 5 months of age with resolution of her increased work of breathing with high-flow nasal cannula. She presented again at 7 months of age with presumed bronchiolitis, however, she decompensated and required intubation on the 5th day of hospitalization. A bronchoscopy was performed and revealed a significantly narrowed left bronchus at the carina and a blind pouch on the right with notable pulsation of the walls. She underwent further imaging and was ultimately diagnosed with a left pulmonary artery sling. Left pulmonary artery slings are a rare, but potentially fatal anomaly that can present with wheezing, stridor, and recurrent respiratory infections. Patient underwent correction by cardiovascular surgery and has since been doing well.
Key takeaways for HM
• Bartonella is a common cause of fever of unknown origin, and should be considered in unusual presentations of febrile illnesses.
• Bullae in IgA vasculitis are rare in children and do not have prognostic value, but streptococcal infection may be a trigger for IgA vasculitis.
• Hemolacria is an atypical presentation of rare and common diagnoses that should prompt further work-up.
• Acute respiratory distress can be caused by underlying cardiac or vascular anomalies and can be mistaken for common viral illnesses.
Dr. Marsicek is a pediatric hospital medicine fellow at Johns Hopkins All Children’s Hospital, St. Petersburg, Fla. Dr. Wysocka is a pediatric resident at Johns Hopkins All Children’s Hospital.
Atypical symptoms and diagnoses
Atypical symptoms and diagnoses
Presenters
Yemisi Jones, MD; Mirna Giordano, MD
Session title
Pediatric Clinical Conundrums
Session summary
Dr. Mirna Giordano of Columbia University Irving Medical Center, New York, and Dr. Yemisi Jones of Cincinnati Children’s Hospital Medical Center, moderated the Pediatric Clinical Conundrums session at HM19. After reviewing multiple submissions, they invited four trainees to present their interesting cases.
Malignancy or infection? Dr. Jeremy Brown, a resident at the University of Louisville, presented a case of a 15-year-old male with right upper quadrant abdominal pain with associated weight loss and intermittent fevers, over the course of several weeks. CT revealed multiple liver lesions, providing concern for possible malignancy, although liver biopsy proved otherwise, with mostly liquefactive tissue and benign liver parenchyma. After a large infectious work-up ensued, the patient was diagnosed with disseminated Bartonella. He was treated with a 10-day course of azithromycin, and his symptoms resolved.
Leg blisters as an uncommon manifestation of a common childhood disease. Dr. Stefan Mammele, a resident at Kapi’olani Medical Center in Honolulu, and the University of Hawaii, presented a case of an 11-year-old boy with a painful and pruritic rash associated with multiple 5- to 10-mm tense bullae located on the patient’s bilateral lower extremities with extension to the trunk. The patient was also found to have hematuria and proteinuria. The bullae drained both serosanguinous and purulent material. Fluid culture grew group A Streptococcus and skin biopsy confirmed IgA vasculitis. Bullae are a rare characteristic of Henoch Schönlein pupura in children, but are more commonly seen as a disease manifestation in adults. The patient was treated with cefazolin, and his lesions improved over the course of several weeks with resolution of his hematuria by 6 months.
Is she crying blood? Dr. Joshua Price, a resident at Baystate Children’s Hospital in Springfield, Mass., described a 12-year-old female who presented with 7 days of left-sided hemolacria with acute vision loss and unilateral eye pain. This patient did not respond to outpatient topical steroids and antibiotics, as prescribed by ophthalmology. For this reason, she underwent further work-up and imaging. MRI of the head and orbits revealed left maxillary sinus disease. She was treated with antibiotics for acute left maxillary sinusitis and her hemolacria resolved within 24 hours. While the differential diagnosis for hemolacria is broad, rarely acute sinusitis has been reported as a cause in medical literature.
Recurrent bronchiolitis or something more? Dr. Moira Black, a resident at Children’s Memorial Hermann in Houston, presented a case of a 7-month-old female with a history of recurrent admissions for increased work of breathing believed to be secondary to viral bronchiolitis. Her first hospitalization occurred at 7 weeks of age and was complicated by spontaneous pneumothorax requiring chest tube placement. She was again hospitalized at 5 months of age with resolution of her increased work of breathing with high-flow nasal cannula. She presented again at 7 months of age with presumed bronchiolitis, however, she decompensated and required intubation on the 5th day of hospitalization. A bronchoscopy was performed and revealed a significantly narrowed left bronchus at the carina and a blind pouch on the right with notable pulsation of the walls. She underwent further imaging and was ultimately diagnosed with a left pulmonary artery sling. Left pulmonary artery slings are a rare, but potentially fatal anomaly that can present with wheezing, stridor, and recurrent respiratory infections. Patient underwent correction by cardiovascular surgery and has since been doing well.
Key takeaways for HM
• Bartonella is a common cause of fever of unknown origin, and should be considered in unusual presentations of febrile illnesses.
• Bullae in IgA vasculitis are rare in children and do not have prognostic value, but streptococcal infection may be a trigger for IgA vasculitis.
• Hemolacria is an atypical presentation of rare and common diagnoses that should prompt further work-up.
• Acute respiratory distress can be caused by underlying cardiac or vascular anomalies and can be mistaken for common viral illnesses.
Dr. Marsicek is a pediatric hospital medicine fellow at Johns Hopkins All Children’s Hospital, St. Petersburg, Fla. Dr. Wysocka is a pediatric resident at Johns Hopkins All Children’s Hospital.
Presenters
Yemisi Jones, MD; Mirna Giordano, MD
Session title
Pediatric Clinical Conundrums
Session summary
Dr. Mirna Giordano of Columbia University Irving Medical Center, New York, and Dr. Yemisi Jones of Cincinnati Children’s Hospital Medical Center, moderated the Pediatric Clinical Conundrums session at HM19. After reviewing multiple submissions, they invited four trainees to present their interesting cases.
Malignancy or infection? Dr. Jeremy Brown, a resident at the University of Louisville, presented a case of a 15-year-old male with right upper quadrant abdominal pain with associated weight loss and intermittent fevers, over the course of several weeks. CT revealed multiple liver lesions, providing concern for possible malignancy, although liver biopsy proved otherwise, with mostly liquefactive tissue and benign liver parenchyma. After a large infectious work-up ensued, the patient was diagnosed with disseminated Bartonella. He was treated with a 10-day course of azithromycin, and his symptoms resolved.
Leg blisters as an uncommon manifestation of a common childhood disease. Dr. Stefan Mammele, a resident at Kapi’olani Medical Center in Honolulu, and the University of Hawaii, presented a case of an 11-year-old boy with a painful and pruritic rash associated with multiple 5- to 10-mm tense bullae located on the patient’s bilateral lower extremities with extension to the trunk. The patient was also found to have hematuria and proteinuria. The bullae drained both serosanguinous and purulent material. Fluid culture grew group A Streptococcus and skin biopsy confirmed IgA vasculitis. Bullae are a rare characteristic of Henoch Schönlein pupura in children, but are more commonly seen as a disease manifestation in adults. The patient was treated with cefazolin, and his lesions improved over the course of several weeks with resolution of his hematuria by 6 months.
Is she crying blood? Dr. Joshua Price, a resident at Baystate Children’s Hospital in Springfield, Mass., described a 12-year-old female who presented with 7 days of left-sided hemolacria with acute vision loss and unilateral eye pain. This patient did not respond to outpatient topical steroids and antibiotics, as prescribed by ophthalmology. For this reason, she underwent further work-up and imaging. MRI of the head and orbits revealed left maxillary sinus disease. She was treated with antibiotics for acute left maxillary sinusitis and her hemolacria resolved within 24 hours. While the differential diagnosis for hemolacria is broad, rarely acute sinusitis has been reported as a cause in medical literature.
Recurrent bronchiolitis or something more? Dr. Moira Black, a resident at Children’s Memorial Hermann in Houston, presented a case of a 7-month-old female with a history of recurrent admissions for increased work of breathing believed to be secondary to viral bronchiolitis. Her first hospitalization occurred at 7 weeks of age and was complicated by spontaneous pneumothorax requiring chest tube placement. She was again hospitalized at 5 months of age with resolution of her increased work of breathing with high-flow nasal cannula. She presented again at 7 months of age with presumed bronchiolitis, however, she decompensated and required intubation on the 5th day of hospitalization. A bronchoscopy was performed and revealed a significantly narrowed left bronchus at the carina and a blind pouch on the right with notable pulsation of the walls. She underwent further imaging and was ultimately diagnosed with a left pulmonary artery sling. Left pulmonary artery slings are a rare, but potentially fatal anomaly that can present with wheezing, stridor, and recurrent respiratory infections. Patient underwent correction by cardiovascular surgery and has since been doing well.
Key takeaways for HM
• Bartonella is a common cause of fever of unknown origin, and should be considered in unusual presentations of febrile illnesses.
• Bullae in IgA vasculitis are rare in children and do not have prognostic value, but streptococcal infection may be a trigger for IgA vasculitis.
• Hemolacria is an atypical presentation of rare and common diagnoses that should prompt further work-up.
• Acute respiratory distress can be caused by underlying cardiac or vascular anomalies and can be mistaken for common viral illnesses.
Dr. Marsicek is a pediatric hospital medicine fellow at Johns Hopkins All Children’s Hospital, St. Petersburg, Fla. Dr. Wysocka is a pediatric resident at Johns Hopkins All Children’s Hospital.
No exudates or fever? Age over 11? Skip strep test
BALTIMORE – In children with pharyngitis, it’s safe to skip group A Streptococcus testing if there are no exudates, children are 11 years or older, and there is either no cervical adenopathy or adenopathy without fever, according to a Boston Children’s Hospital investigation.
The prevalence of group A Streptococcus among children who meet those criteria is 13%, less than the estimated asymptomatic carriage rate of about 15%. Among 67,127 children tested for strep and treated for sore throats in a network of retail health clinics across the United States, 35% fit the profile.
Investigators led by Daniel Shapiro, MD, a pediatrics fellow at Boston Children’s, concluded that “laboratory testing for GAS [group A Streptococcus] might be safely avoided in a large proportion of patients with sore throats. In doing so, we may avoid some of the downstream effects of unnecessary antibiotic use.” Incorporating the rules into EHRs “might help physicians identify patients who are at low risk of GAS pharyngitis.”
The study team tackled a long-standing and vexing problem in general pediatrics: how to distinguish viral from GAS pharyngitis. They often present the same way, so it’s difficult to tell them apart, but important to do so to prevent misuse of antibiotics. Health care providers generally rely on rapid strep tests and other assays to make the call, but they have to be used cautiously, because asymptomatic carriers also will test positive and be at risk for unnecessary treatment, Dr. Shapiro said at the Pediatric Academic Societies annual meeting.
To try to prevent that, the Infectious Disease Society of America (IDSA) recommends against strep testing in children who present with overt viral signs, including cough, rhinorrhea, oral ulcers, and hoarseness (Clin Infect Dis. 2012 Nov 15;55[10]:1279-82).
In a previous study at Boston Children’s ED, however, Dr. Shapiro and his colleagues found that 29% of children with overt viral features were positive for GAS, suggesting that the IDSA guidelines probably go too far (Pediatrics. 2017 May;139[5]. pii: e20163403).
“One might conclude that while it’s a good rule of thumb to avoid testing patients with viral features, some of the patients with viral features really do have GAS pharyngitis, so the recommendation to forgo testing in all these kids needs a little bit of refinement,” he said.
That was the goal of the new study; the team sought to identify viral features that signaled a low risk of GAS pharyngitis and, therefore, no need for testing. Low risk was defined as less than 15%, in keeping with the asymptomatic carriage rate.
The 67,127 patients were aged 3-21 years. Their signs and symptoms were collected at the retail clinics in a standardized form. The subjects had rapid strep tests, with negative results confirmed by DNA probe or culture.
Fifty-four percent had viral features, defined in the study as cough, runny nose, or hoarseness (oral ulcers weren’t collected on the form). The overall prevalence of GAS was 35%, similar to previous studies; 39% of children with no viral features tested positive for GAS versus 26% of children with all three. Exudates and age below 11 years were strongly associated with GAS among patients with viral features.
It turned out that just 23% of children without exudates were GAS positive; the number fell to 15% when limited to children 11 years or older, and to 13% when either no cervical adenopathy or adenopathy without fever were added to the mix.
There was no industry funding, and Dr. Shapiro didn’t have any disclosures.
BALTIMORE – In children with pharyngitis, it’s safe to skip group A Streptococcus testing if there are no exudates, children are 11 years or older, and there is either no cervical adenopathy or adenopathy without fever, according to a Boston Children’s Hospital investigation.
The prevalence of group A Streptococcus among children who meet those criteria is 13%, less than the estimated asymptomatic carriage rate of about 15%. Among 67,127 children tested for strep and treated for sore throats in a network of retail health clinics across the United States, 35% fit the profile.
Investigators led by Daniel Shapiro, MD, a pediatrics fellow at Boston Children’s, concluded that “laboratory testing for GAS [group A Streptococcus] might be safely avoided in a large proportion of patients with sore throats. In doing so, we may avoid some of the downstream effects of unnecessary antibiotic use.” Incorporating the rules into EHRs “might help physicians identify patients who are at low risk of GAS pharyngitis.”
The study team tackled a long-standing and vexing problem in general pediatrics: how to distinguish viral from GAS pharyngitis. They often present the same way, so it’s difficult to tell them apart, but important to do so to prevent misuse of antibiotics. Health care providers generally rely on rapid strep tests and other assays to make the call, but they have to be used cautiously, because asymptomatic carriers also will test positive and be at risk for unnecessary treatment, Dr. Shapiro said at the Pediatric Academic Societies annual meeting.
To try to prevent that, the Infectious Disease Society of America (IDSA) recommends against strep testing in children who present with overt viral signs, including cough, rhinorrhea, oral ulcers, and hoarseness (Clin Infect Dis. 2012 Nov 15;55[10]:1279-82).
In a previous study at Boston Children’s ED, however, Dr. Shapiro and his colleagues found that 29% of children with overt viral features were positive for GAS, suggesting that the IDSA guidelines probably go too far (Pediatrics. 2017 May;139[5]. pii: e20163403).
“One might conclude that while it’s a good rule of thumb to avoid testing patients with viral features, some of the patients with viral features really do have GAS pharyngitis, so the recommendation to forgo testing in all these kids needs a little bit of refinement,” he said.
That was the goal of the new study; the team sought to identify viral features that signaled a low risk of GAS pharyngitis and, therefore, no need for testing. Low risk was defined as less than 15%, in keeping with the asymptomatic carriage rate.
The 67,127 patients were aged 3-21 years. Their signs and symptoms were collected at the retail clinics in a standardized form. The subjects had rapid strep tests, with negative results confirmed by DNA probe or culture.
Fifty-four percent had viral features, defined in the study as cough, runny nose, or hoarseness (oral ulcers weren’t collected on the form). The overall prevalence of GAS was 35%, similar to previous studies; 39% of children with no viral features tested positive for GAS versus 26% of children with all three. Exudates and age below 11 years were strongly associated with GAS among patients with viral features.
It turned out that just 23% of children without exudates were GAS positive; the number fell to 15% when limited to children 11 years or older, and to 13% when either no cervical adenopathy or adenopathy without fever were added to the mix.
There was no industry funding, and Dr. Shapiro didn’t have any disclosures.
BALTIMORE – In children with pharyngitis, it’s safe to skip group A Streptococcus testing if there are no exudates, children are 11 years or older, and there is either no cervical adenopathy or adenopathy without fever, according to a Boston Children’s Hospital investigation.
The prevalence of group A Streptococcus among children who meet those criteria is 13%, less than the estimated asymptomatic carriage rate of about 15%. Among 67,127 children tested for strep and treated for sore throats in a network of retail health clinics across the United States, 35% fit the profile.
Investigators led by Daniel Shapiro, MD, a pediatrics fellow at Boston Children’s, concluded that “laboratory testing for GAS [group A Streptococcus] might be safely avoided in a large proportion of patients with sore throats. In doing so, we may avoid some of the downstream effects of unnecessary antibiotic use.” Incorporating the rules into EHRs “might help physicians identify patients who are at low risk of GAS pharyngitis.”
The study team tackled a long-standing and vexing problem in general pediatrics: how to distinguish viral from GAS pharyngitis. They often present the same way, so it’s difficult to tell them apart, but important to do so to prevent misuse of antibiotics. Health care providers generally rely on rapid strep tests and other assays to make the call, but they have to be used cautiously, because asymptomatic carriers also will test positive and be at risk for unnecessary treatment, Dr. Shapiro said at the Pediatric Academic Societies annual meeting.
To try to prevent that, the Infectious Disease Society of America (IDSA) recommends against strep testing in children who present with overt viral signs, including cough, rhinorrhea, oral ulcers, and hoarseness (Clin Infect Dis. 2012 Nov 15;55[10]:1279-82).
In a previous study at Boston Children’s ED, however, Dr. Shapiro and his colleagues found that 29% of children with overt viral features were positive for GAS, suggesting that the IDSA guidelines probably go too far (Pediatrics. 2017 May;139[5]. pii: e20163403).
“One might conclude that while it’s a good rule of thumb to avoid testing patients with viral features, some of the patients with viral features really do have GAS pharyngitis, so the recommendation to forgo testing in all these kids needs a little bit of refinement,” he said.
That was the goal of the new study; the team sought to identify viral features that signaled a low risk of GAS pharyngitis and, therefore, no need for testing. Low risk was defined as less than 15%, in keeping with the asymptomatic carriage rate.
The 67,127 patients were aged 3-21 years. Their signs and symptoms were collected at the retail clinics in a standardized form. The subjects had rapid strep tests, with negative results confirmed by DNA probe or culture.
Fifty-four percent had viral features, defined in the study as cough, runny nose, or hoarseness (oral ulcers weren’t collected on the form). The overall prevalence of GAS was 35%, similar to previous studies; 39% of children with no viral features tested positive for GAS versus 26% of children with all three. Exudates and age below 11 years were strongly associated with GAS among patients with viral features.
It turned out that just 23% of children without exudates were GAS positive; the number fell to 15% when limited to children 11 years or older, and to 13% when either no cervical adenopathy or adenopathy without fever were added to the mix.
There was no industry funding, and Dr. Shapiro didn’t have any disclosures.
REPORTING FROM PAS 2019