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A Late and Light Flu Season
The 2011-2012 influenza season is late and likely to be light.
The season only officially began at the end of February, marked by the point at which the third consecutive weekly percent of respiratory specimens testing positive for influenza surpassed 10%. This is the latest start to the U.S. flu season in 24 years. According to the Centers for Disease Control and Prevention, the percentage of respiratory samples testing positive for flu has remained below the 10% mark until February only once before, during the 1987-1988 season.
Clinicians around the country have been seeing essentially no flu among our pediatric patients. But at the same time, we are seeing a prolonged respiratory syncytial virus (RSV) season. Usually we see RSV in the northeast from about December through January, when it’s replaced by flu. This year, RSV has continued through all of February and into March. Because RSV is predominantly a more severe and symptomatic illness in younger children, our population of respiratory illness patients mostly involved visits by children less than 3 years old. Flu, in contrast, results in significant symptomatic illness in all ages of pediatric practice.
The CDC is still recommending that people get vaccinated, but many primary care providers have administered all of the influenza vaccine they ordered months ago. Unless there’s a serious resurgence, it would be unlikely many would order more at this late point in the winter season with spring just around the corner.
We don’t really know why the 1987-1988 season was late, but this time around we have several possible explanations. There was no change in vaccine strains circulating in the 2011-2012 winter season compared to the 2010-2011 season. Since there was no change in influenza strains, patients who were vaccinated last year are still protected this year. In fact, the H1N1 component from the 2009 pandemic has remained the same for three consecutive seasons now, so I think we’re seeing much wider persisting immunity throughout the population.
Add to that patients who missed their vaccine last year but got their flu vaccine this year are protected too, as are patients who were vaccinated last year and this year. The vaccine given this year really boosted their immunity to sky-high levels. Together, it seems we have achieved very high herd immunity. Recall that herd immunity occurs with many vaccines. Herd immunity occurs because vaccinated persons are unable to contract and transmit an infectious disease, so even those who are not vaccinated get protection because there is less circulation of the infectious agent and thereby less transmission (contagion).
There has long been a mistaken belief that immunity to the flu vaccine wanes toward the end of the season. This is not true. The reason that flu vaccines are recommended for annual administration is because the flu strains "drift," resulting in a loss of protection afforded by the vaccine strains included in the previous year’s vaccine. I have been asked by parents whether they should postpone flu vaccination until early winter rather than receive the vaccine in the fall when it becomes available. They think the protection from flu vaccine is short-lived and may not last through the flu season. I explain that there is no need to delay vaccination. Immunity induced by vaccination lasts for years, not months.
A second factor that may be contributing to the late and light flu season could well be the uptake of the influenza vaccine among all pediatric age groups. Since the CDC and American Academy of Pediatrics recommended universal vaccination for all children down to 6 months of age, the number of vaccinated patients has been steadily rising. This too adds to the herd immunity effect. We don’t have national data yet, but our pediatric practice has been purchasing more vaccine each year since 2009. I suspect this is a national trend of increasing use among all pediatric age groups.
A third factor that influences the flu season is the weather – colder weather. We had a mild winter. Influenza is transmitted through respiratory droplets, mainly by sneezes and coughing. When people remain indoors due to colder weather there is more opportunity for sneezing and coughing to result in respiratory virus transmission. With less indoor crowding, we would expect to see less transmission.
The benefits of a light flu season are many. Fewer flu cases result in fewer cases of otitis media. Part of this could be due to the impact of the new 13-valent pneumococcal conjugate vaccine. However, there is ample evidence that kids get ear infections with flu. I think the decline this year in ear infections is due to both factors.
Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. He said he had no relevant financial disclosures.
The 2011-2012 influenza season is late and likely to be light.
The season only officially began at the end of February, marked by the point at which the third consecutive weekly percent of respiratory specimens testing positive for influenza surpassed 10%. This is the latest start to the U.S. flu season in 24 years. According to the Centers for Disease Control and Prevention, the percentage of respiratory samples testing positive for flu has remained below the 10% mark until February only once before, during the 1987-1988 season.
Clinicians around the country have been seeing essentially no flu among our pediatric patients. But at the same time, we are seeing a prolonged respiratory syncytial virus (RSV) season. Usually we see RSV in the northeast from about December through January, when it’s replaced by flu. This year, RSV has continued through all of February and into March. Because RSV is predominantly a more severe and symptomatic illness in younger children, our population of respiratory illness patients mostly involved visits by children less than 3 years old. Flu, in contrast, results in significant symptomatic illness in all ages of pediatric practice.
The CDC is still recommending that people get vaccinated, but many primary care providers have administered all of the influenza vaccine they ordered months ago. Unless there’s a serious resurgence, it would be unlikely many would order more at this late point in the winter season with spring just around the corner.
We don’t really know why the 1987-1988 season was late, but this time around we have several possible explanations. There was no change in vaccine strains circulating in the 2011-2012 winter season compared to the 2010-2011 season. Since there was no change in influenza strains, patients who were vaccinated last year are still protected this year. In fact, the H1N1 component from the 2009 pandemic has remained the same for three consecutive seasons now, so I think we’re seeing much wider persisting immunity throughout the population.
Add to that patients who missed their vaccine last year but got their flu vaccine this year are protected too, as are patients who were vaccinated last year and this year. The vaccine given this year really boosted their immunity to sky-high levels. Together, it seems we have achieved very high herd immunity. Recall that herd immunity occurs with many vaccines. Herd immunity occurs because vaccinated persons are unable to contract and transmit an infectious disease, so even those who are not vaccinated get protection because there is less circulation of the infectious agent and thereby less transmission (contagion).
There has long been a mistaken belief that immunity to the flu vaccine wanes toward the end of the season. This is not true. The reason that flu vaccines are recommended for annual administration is because the flu strains "drift," resulting in a loss of protection afforded by the vaccine strains included in the previous year’s vaccine. I have been asked by parents whether they should postpone flu vaccination until early winter rather than receive the vaccine in the fall when it becomes available. They think the protection from flu vaccine is short-lived and may not last through the flu season. I explain that there is no need to delay vaccination. Immunity induced by vaccination lasts for years, not months.
A second factor that may be contributing to the late and light flu season could well be the uptake of the influenza vaccine among all pediatric age groups. Since the CDC and American Academy of Pediatrics recommended universal vaccination for all children down to 6 months of age, the number of vaccinated patients has been steadily rising. This too adds to the herd immunity effect. We don’t have national data yet, but our pediatric practice has been purchasing more vaccine each year since 2009. I suspect this is a national trend of increasing use among all pediatric age groups.
A third factor that influences the flu season is the weather – colder weather. We had a mild winter. Influenza is transmitted through respiratory droplets, mainly by sneezes and coughing. When people remain indoors due to colder weather there is more opportunity for sneezing and coughing to result in respiratory virus transmission. With less indoor crowding, we would expect to see less transmission.
The benefits of a light flu season are many. Fewer flu cases result in fewer cases of otitis media. Part of this could be due to the impact of the new 13-valent pneumococcal conjugate vaccine. However, there is ample evidence that kids get ear infections with flu. I think the decline this year in ear infections is due to both factors.
Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. He said he had no relevant financial disclosures.
The 2011-2012 influenza season is late and likely to be light.
The season only officially began at the end of February, marked by the point at which the third consecutive weekly percent of respiratory specimens testing positive for influenza surpassed 10%. This is the latest start to the U.S. flu season in 24 years. According to the Centers for Disease Control and Prevention, the percentage of respiratory samples testing positive for flu has remained below the 10% mark until February only once before, during the 1987-1988 season.
Clinicians around the country have been seeing essentially no flu among our pediatric patients. But at the same time, we are seeing a prolonged respiratory syncytial virus (RSV) season. Usually we see RSV in the northeast from about December through January, when it’s replaced by flu. This year, RSV has continued through all of February and into March. Because RSV is predominantly a more severe and symptomatic illness in younger children, our population of respiratory illness patients mostly involved visits by children less than 3 years old. Flu, in contrast, results in significant symptomatic illness in all ages of pediatric practice.
The CDC is still recommending that people get vaccinated, but many primary care providers have administered all of the influenza vaccine they ordered months ago. Unless there’s a serious resurgence, it would be unlikely many would order more at this late point in the winter season with spring just around the corner.
We don’t really know why the 1987-1988 season was late, but this time around we have several possible explanations. There was no change in vaccine strains circulating in the 2011-2012 winter season compared to the 2010-2011 season. Since there was no change in influenza strains, patients who were vaccinated last year are still protected this year. In fact, the H1N1 component from the 2009 pandemic has remained the same for three consecutive seasons now, so I think we’re seeing much wider persisting immunity throughout the population.
Add to that patients who missed their vaccine last year but got their flu vaccine this year are protected too, as are patients who were vaccinated last year and this year. The vaccine given this year really boosted their immunity to sky-high levels. Together, it seems we have achieved very high herd immunity. Recall that herd immunity occurs with many vaccines. Herd immunity occurs because vaccinated persons are unable to contract and transmit an infectious disease, so even those who are not vaccinated get protection because there is less circulation of the infectious agent and thereby less transmission (contagion).
There has long been a mistaken belief that immunity to the flu vaccine wanes toward the end of the season. This is not true. The reason that flu vaccines are recommended for annual administration is because the flu strains "drift," resulting in a loss of protection afforded by the vaccine strains included in the previous year’s vaccine. I have been asked by parents whether they should postpone flu vaccination until early winter rather than receive the vaccine in the fall when it becomes available. They think the protection from flu vaccine is short-lived and may not last through the flu season. I explain that there is no need to delay vaccination. Immunity induced by vaccination lasts for years, not months.
A second factor that may be contributing to the late and light flu season could well be the uptake of the influenza vaccine among all pediatric age groups. Since the CDC and American Academy of Pediatrics recommended universal vaccination for all children down to 6 months of age, the number of vaccinated patients has been steadily rising. This too adds to the herd immunity effect. We don’t have national data yet, but our pediatric practice has been purchasing more vaccine each year since 2009. I suspect this is a national trend of increasing use among all pediatric age groups.
A third factor that influences the flu season is the weather – colder weather. We had a mild winter. Influenza is transmitted through respiratory droplets, mainly by sneezes and coughing. When people remain indoors due to colder weather there is more opportunity for sneezing and coughing to result in respiratory virus transmission. With less indoor crowding, we would expect to see less transmission.
The benefits of a light flu season are many. Fewer flu cases result in fewer cases of otitis media. Part of this could be due to the impact of the new 13-valent pneumococcal conjugate vaccine. However, there is ample evidence that kids get ear infections with flu. I think the decline this year in ear infections is due to both factors.
Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. He said he had no relevant financial disclosures.
Her Chief Complaint Is ... And by the Way She’s Also Pregnant
We emergency physicians are generally a confident bunch. But in the time it takes to slip on a peel and hit the pavement (a bananosecond), some of us ratchet up adrenaline output when we pick up a chart and notice a history like 22 yo F, minor MVC, c/o headache and back pain, 32 weeks pregnant.
From whence comes this anxiety? A bit may stem from reading about those seven-figure lawsuit verdicts for pregnancy-related malpractice cases. However, tied to this are those questions and comments I often hear from residents seeking assurance, even when they know the answers.
Can I get this x-ray?
Is it OK to give her morphine IV? Should I start with 1 mg? (Sure, if it’s in the right acupuncture point.)
Wow, I’m so used to not treating asymptomatic elevated BP that I almost forgot to address it for this pregnant patient.
Getting answers from specialists can often be frustrating. The OB doc may be uncomfortable with the non-OB aspects of the case, while the other consulting specialists may be uncomfortable applying their expertise in the context of pregnancy.
I recall asking a surgeon to look at a third-trimester patient with likely appendicitis and an equivocal ultrasound. His plan related to me was, "We’ll sit on it overnight." After making some remark about his own application of procto-tocin, I suggested an MRI. He was a bit leery, but with some education and pressure on our radiologist to do our hospital’s first MRI to rule out appendicitis (accomplished without procedural sedation on that radiologist), we identified an acute appy.
As with many aspects of EM, it may be up to the EP to coordinate optimal care in these situations. In 1981, Dr. Arnold Greensher and I developed a system called Prenatal Care – A Systems Approach to help OBs and primary care physicians integrate prenatal care within a comprehensive risk management system. It includes frequently updated information on managing nonobstetric illness and injury in this population. The system’s development was coordinated with a panel of well-regarded academic specialists, including a group of perinatologists.
The track record for the system has been quite surprising to us, as well as to the medical malpractice insurers who purchased the system for their docs: There were more than 1.5 million deliveries during this time period with only 8 malpractice claims. The expected number of claims would be 400-700. For a large number of users, premium rates went down dramatically during a time when national rates were going in the opposite direction.
Over the past year, I’ve contributed two well-received articles for the Focus On series in ACEP News: Trauma in the Obstetric Patient in July 2010 and Perinatal Disaster Management in September 2011 (both can be found at www.acep.org/focuson). I was honored to be invited by the publication’s editorial panel to provide a quarterly column that focuses on unique aspects of emergency care of the pregnant patient. The goal of this column will be to provide practical recommendations for the EP on common presenting problems in this population. I will often have coauthors, including specialists in that topic, as well as perinatologist input. One of our residents will be an integral part of this group. Our column is not intended to be a standard of care, but rather a sound, easy-to-use package of recommendations that would be considered one avenue for providing optimal care.
Each article will have a clinical tool – a summary that can stand alone for easy reference. In fact, our Trauma Table is posted in a number of EDs that I have visited. As ACEP News technology progresses, we hope to have these as a library with the tables hyperlinked to the specific didactic parts of the articles.
In this issue, we debut our first article, Stroke in Pregnancy (pp. XX-XX). This will provide a nice supplement to any stroke protocols at your hospital. Later in 2012, we plan to have one on sepsis and another on cardiac emergencies, including acute coronary syndromes.
I look forward to sharing this column with you.
Dr. Roemer is an Associate Professor in the Department of Emergency Medicine, Oklahoma University School of Community Medicine, Tulsa.
We emergency physicians are generally a confident bunch. But in the time it takes to slip on a peel and hit the pavement (a bananosecond), some of us ratchet up adrenaline output when we pick up a chart and notice a history like 22 yo F, minor MVC, c/o headache and back pain, 32 weeks pregnant.
From whence comes this anxiety? A bit may stem from reading about those seven-figure lawsuit verdicts for pregnancy-related malpractice cases. However, tied to this are those questions and comments I often hear from residents seeking assurance, even when they know the answers.
Can I get this x-ray?
Is it OK to give her morphine IV? Should I start with 1 mg? (Sure, if it’s in the right acupuncture point.)
Wow, I’m so used to not treating asymptomatic elevated BP that I almost forgot to address it for this pregnant patient.
Getting answers from specialists can often be frustrating. The OB doc may be uncomfortable with the non-OB aspects of the case, while the other consulting specialists may be uncomfortable applying their expertise in the context of pregnancy.
I recall asking a surgeon to look at a third-trimester patient with likely appendicitis and an equivocal ultrasound. His plan related to me was, "We’ll sit on it overnight." After making some remark about his own application of procto-tocin, I suggested an MRI. He was a bit leery, but with some education and pressure on our radiologist to do our hospital’s first MRI to rule out appendicitis (accomplished without procedural sedation on that radiologist), we identified an acute appy.
As with many aspects of EM, it may be up to the EP to coordinate optimal care in these situations. In 1981, Dr. Arnold Greensher and I developed a system called Prenatal Care – A Systems Approach to help OBs and primary care physicians integrate prenatal care within a comprehensive risk management system. It includes frequently updated information on managing nonobstetric illness and injury in this population. The system’s development was coordinated with a panel of well-regarded academic specialists, including a group of perinatologists.
The track record for the system has been quite surprising to us, as well as to the medical malpractice insurers who purchased the system for their docs: There were more than 1.5 million deliveries during this time period with only 8 malpractice claims. The expected number of claims would be 400-700. For a large number of users, premium rates went down dramatically during a time when national rates were going in the opposite direction.
Over the past year, I’ve contributed two well-received articles for the Focus On series in ACEP News: Trauma in the Obstetric Patient in July 2010 and Perinatal Disaster Management in September 2011 (both can be found at www.acep.org/focuson). I was honored to be invited by the publication’s editorial panel to provide a quarterly column that focuses on unique aspects of emergency care of the pregnant patient. The goal of this column will be to provide practical recommendations for the EP on common presenting problems in this population. I will often have coauthors, including specialists in that topic, as well as perinatologist input. One of our residents will be an integral part of this group. Our column is not intended to be a standard of care, but rather a sound, easy-to-use package of recommendations that would be considered one avenue for providing optimal care.
Each article will have a clinical tool – a summary that can stand alone for easy reference. In fact, our Trauma Table is posted in a number of EDs that I have visited. As ACEP News technology progresses, we hope to have these as a library with the tables hyperlinked to the specific didactic parts of the articles.
In this issue, we debut our first article, Stroke in Pregnancy (pp. XX-XX). This will provide a nice supplement to any stroke protocols at your hospital. Later in 2012, we plan to have one on sepsis and another on cardiac emergencies, including acute coronary syndromes.
I look forward to sharing this column with you.
Dr. Roemer is an Associate Professor in the Department of Emergency Medicine, Oklahoma University School of Community Medicine, Tulsa.
We emergency physicians are generally a confident bunch. But in the time it takes to slip on a peel and hit the pavement (a bananosecond), some of us ratchet up adrenaline output when we pick up a chart and notice a history like 22 yo F, minor MVC, c/o headache and back pain, 32 weeks pregnant.
From whence comes this anxiety? A bit may stem from reading about those seven-figure lawsuit verdicts for pregnancy-related malpractice cases. However, tied to this are those questions and comments I often hear from residents seeking assurance, even when they know the answers.
Can I get this x-ray?
Is it OK to give her morphine IV? Should I start with 1 mg? (Sure, if it’s in the right acupuncture point.)
Wow, I’m so used to not treating asymptomatic elevated BP that I almost forgot to address it for this pregnant patient.
Getting answers from specialists can often be frustrating. The OB doc may be uncomfortable with the non-OB aspects of the case, while the other consulting specialists may be uncomfortable applying their expertise in the context of pregnancy.
I recall asking a surgeon to look at a third-trimester patient with likely appendicitis and an equivocal ultrasound. His plan related to me was, "We’ll sit on it overnight." After making some remark about his own application of procto-tocin, I suggested an MRI. He was a bit leery, but with some education and pressure on our radiologist to do our hospital’s first MRI to rule out appendicitis (accomplished without procedural sedation on that radiologist), we identified an acute appy.
As with many aspects of EM, it may be up to the EP to coordinate optimal care in these situations. In 1981, Dr. Arnold Greensher and I developed a system called Prenatal Care – A Systems Approach to help OBs and primary care physicians integrate prenatal care within a comprehensive risk management system. It includes frequently updated information on managing nonobstetric illness and injury in this population. The system’s development was coordinated with a panel of well-regarded academic specialists, including a group of perinatologists.
The track record for the system has been quite surprising to us, as well as to the medical malpractice insurers who purchased the system for their docs: There were more than 1.5 million deliveries during this time period with only 8 malpractice claims. The expected number of claims would be 400-700. For a large number of users, premium rates went down dramatically during a time when national rates were going in the opposite direction.
Over the past year, I’ve contributed two well-received articles for the Focus On series in ACEP News: Trauma in the Obstetric Patient in July 2010 and Perinatal Disaster Management in September 2011 (both can be found at www.acep.org/focuson). I was honored to be invited by the publication’s editorial panel to provide a quarterly column that focuses on unique aspects of emergency care of the pregnant patient. The goal of this column will be to provide practical recommendations for the EP on common presenting problems in this population. I will often have coauthors, including specialists in that topic, as well as perinatologist input. One of our residents will be an integral part of this group. Our column is not intended to be a standard of care, but rather a sound, easy-to-use package of recommendations that would be considered one avenue for providing optimal care.
Each article will have a clinical tool – a summary that can stand alone for easy reference. In fact, our Trauma Table is posted in a number of EDs that I have visited. As ACEP News technology progresses, we hope to have these as a library with the tables hyperlinked to the specific didactic parts of the articles.
In this issue, we debut our first article, Stroke in Pregnancy (pp. XX-XX). This will provide a nice supplement to any stroke protocols at your hospital. Later in 2012, we plan to have one on sepsis and another on cardiac emergencies, including acute coronary syndromes.
I look forward to sharing this column with you.
Dr. Roemer is an Associate Professor in the Department of Emergency Medicine, Oklahoma University School of Community Medicine, Tulsa.
Ensuring That Newborns Receive the Hepatitis B Vaccine
Amidst the many changes surrounding the birth of a child, the family must make an important decision before leaving the hospital regarding the birth dose of hepatitis B vaccine. Many infants still aren’t receiving it, and new data shed some light on why that may be.
The birth dose of hepatitis B vaccine (HBV) is recommended by both the American Academy of Pediatrics and the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices as a way of making sure that all infants of potentially infected mothers are covered.
This is important because approximately 90% of neonatal infections result in chronic hepatitis B infection. In contrast, only 10% of adult-acquired hepatitis B infections become chronic. Also, at the time of delivery in the real world, we don’t always have results for maternal hepatitis B testing from prenatal visits, and even when early prenatal results are available, results could have changed by the time of delivery.
In 2005, ACIP recommended the implementation of policies as well as procedures, laws, and regulations for birthing hospitals to ensure that all medically stable infants of HBsAg-negative mothers weighing more than 2,000 g at birth receive a birth dose of HBV before discharge from the newborn nursery (MMWR Recomm. Rep. 2005;54[RR-16]:1-23).
(Separate recommendations are given for premature infants weighing less than 2,000 g at birth. There is some confusing language in the AAP’s Red Book, and I’ll address that later in this column.)
In a retrospective cohort study of 64,425 infants born in Colorado in 2008, more than a third (38%) did not receive a birth dose of HBV (Pediatr. Infect. Dis. J. 2012;31:1-4). Of note, the proportion of infants who did not receive the birth dose increased as household income increased, with 46% of babies in households with annual incomes greater than $75,000 not receiving it, compared with just 27% of infants whose mothers reported incomes less than $15,000 per year.
The investigators also found that newborns of mothers with more education were less likely to receive the birth dose. Compared with those whose mothers had an eighth-grade education or less, those whose mothers had a bachelor’s degree, master’s degree, or doctorate/professional degree were 38%, 66%, and 51% less likely, respectively, to receive a birth dose.
Although the study could not evaluate the reasons for nonreceipt of HBV, the pattern is essentially the same as in mothers whose children have purposeful delays or who don’t receive other recommended vaccines. This surprised me a bit, although I guess it shouldn’t have. I expected to see more evenly distributed proportions across all socioeconomic groups for nonreceipt of HBV.
Hospital policy made a difference, too, the researchers found. Not surprisingly, infants born at facilities that did not offer HBV to all newborns before discharge were the least likely to receive it. Compared with infants born in hospitals that had a birth dose policy, those born in hospitals that had no policy were 39% less likely to receive it. Infants born in hospitals that had a policy to review maternal hepatitis B status but not to offer HBV to all newborns were more than twice as likely not to receive the birth dose.
To me, these data suggest two things: First, we need to be advocates for a birth dose policy in our local hospitals. Second, we need to start educating parents as early as possible about vaccines in general and the birth HBV dose in particular, ideally before the infant is born. It is important to assess the parents’ attitudes toward vaccines, and the reasons for any hesitation at any available prenatal visits, and to tailor your educational message accordingly.
Considering your approach during an initial family contact before or near birth brings up another touchy subject: whether your practice has a policy that does not permit vaccine-refusing families. What do you do if parents are insistent on vaccine refusal? If you plan to follow the prescribed method of discharging or not accepting such a family, consider also offering them a list of trustworthy colleagues in the community who are willing to accommodate the family’s approach. Leaving children unvaccinated is far from optimal, but I believe that providing information on trustworthy alternative practices is in the child’s best interest. Otherwise, parents may end up choosing a practice in which overall care is substandard.
Finally, I recently was made aware of potentially confusing wording in the ACIP and 2009 Red Book recommendations regarding infants born weighing less than 2,000 grams. The wording states that preterm infants of HBsAg-negative mothers with a birth weight less than 2,000 g can receive HBV starting at 1 month of chronological age, or at hospital discharge prior to 1 month of chronological age. This implies that a dose given when the weight is less than 2,000 g could count as one of the three required doses, if it is given at hospital discharge. However, in reality, that dose cannot be considered the first in the series if the infant still weighs less than 2,000 g at that time. The child will still need three more doses after its weight surpasses 2,000 g. This potentially confusing wording is likely to change in the upcoming 2012 Red Book edition.
Dr. Harrison is a professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison said he has no relevant financial disclosures. E-mail him at [email protected].
Amidst the many changes surrounding the birth of a child, the family must make an important decision before leaving the hospital regarding the birth dose of hepatitis B vaccine. Many infants still aren’t receiving it, and new data shed some light on why that may be.
The birth dose of hepatitis B vaccine (HBV) is recommended by both the American Academy of Pediatrics and the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices as a way of making sure that all infants of potentially infected mothers are covered.
This is important because approximately 90% of neonatal infections result in chronic hepatitis B infection. In contrast, only 10% of adult-acquired hepatitis B infections become chronic. Also, at the time of delivery in the real world, we don’t always have results for maternal hepatitis B testing from prenatal visits, and even when early prenatal results are available, results could have changed by the time of delivery.
In 2005, ACIP recommended the implementation of policies as well as procedures, laws, and regulations for birthing hospitals to ensure that all medically stable infants of HBsAg-negative mothers weighing more than 2,000 g at birth receive a birth dose of HBV before discharge from the newborn nursery (MMWR Recomm. Rep. 2005;54[RR-16]:1-23).
(Separate recommendations are given for premature infants weighing less than 2,000 g at birth. There is some confusing language in the AAP’s Red Book, and I’ll address that later in this column.)
In a retrospective cohort study of 64,425 infants born in Colorado in 2008, more than a third (38%) did not receive a birth dose of HBV (Pediatr. Infect. Dis. J. 2012;31:1-4). Of note, the proportion of infants who did not receive the birth dose increased as household income increased, with 46% of babies in households with annual incomes greater than $75,000 not receiving it, compared with just 27% of infants whose mothers reported incomes less than $15,000 per year.
The investigators also found that newborns of mothers with more education were less likely to receive the birth dose. Compared with those whose mothers had an eighth-grade education or less, those whose mothers had a bachelor’s degree, master’s degree, or doctorate/professional degree were 38%, 66%, and 51% less likely, respectively, to receive a birth dose.
Although the study could not evaluate the reasons for nonreceipt of HBV, the pattern is essentially the same as in mothers whose children have purposeful delays or who don’t receive other recommended vaccines. This surprised me a bit, although I guess it shouldn’t have. I expected to see more evenly distributed proportions across all socioeconomic groups for nonreceipt of HBV.
Hospital policy made a difference, too, the researchers found. Not surprisingly, infants born at facilities that did not offer HBV to all newborns before discharge were the least likely to receive it. Compared with infants born in hospitals that had a birth dose policy, those born in hospitals that had no policy were 39% less likely to receive it. Infants born in hospitals that had a policy to review maternal hepatitis B status but not to offer HBV to all newborns were more than twice as likely not to receive the birth dose.
To me, these data suggest two things: First, we need to be advocates for a birth dose policy in our local hospitals. Second, we need to start educating parents as early as possible about vaccines in general and the birth HBV dose in particular, ideally before the infant is born. It is important to assess the parents’ attitudes toward vaccines, and the reasons for any hesitation at any available prenatal visits, and to tailor your educational message accordingly.
Considering your approach during an initial family contact before or near birth brings up another touchy subject: whether your practice has a policy that does not permit vaccine-refusing families. What do you do if parents are insistent on vaccine refusal? If you plan to follow the prescribed method of discharging or not accepting such a family, consider also offering them a list of trustworthy colleagues in the community who are willing to accommodate the family’s approach. Leaving children unvaccinated is far from optimal, but I believe that providing information on trustworthy alternative practices is in the child’s best interest. Otherwise, parents may end up choosing a practice in which overall care is substandard.
Finally, I recently was made aware of potentially confusing wording in the ACIP and 2009 Red Book recommendations regarding infants born weighing less than 2,000 grams. The wording states that preterm infants of HBsAg-negative mothers with a birth weight less than 2,000 g can receive HBV starting at 1 month of chronological age, or at hospital discharge prior to 1 month of chronological age. This implies that a dose given when the weight is less than 2,000 g could count as one of the three required doses, if it is given at hospital discharge. However, in reality, that dose cannot be considered the first in the series if the infant still weighs less than 2,000 g at that time. The child will still need three more doses after its weight surpasses 2,000 g. This potentially confusing wording is likely to change in the upcoming 2012 Red Book edition.
Dr. Harrison is a professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison said he has no relevant financial disclosures. E-mail him at [email protected].
Amidst the many changes surrounding the birth of a child, the family must make an important decision before leaving the hospital regarding the birth dose of hepatitis B vaccine. Many infants still aren’t receiving it, and new data shed some light on why that may be.
The birth dose of hepatitis B vaccine (HBV) is recommended by both the American Academy of Pediatrics and the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices as a way of making sure that all infants of potentially infected mothers are covered.
This is important because approximately 90% of neonatal infections result in chronic hepatitis B infection. In contrast, only 10% of adult-acquired hepatitis B infections become chronic. Also, at the time of delivery in the real world, we don’t always have results for maternal hepatitis B testing from prenatal visits, and even when early prenatal results are available, results could have changed by the time of delivery.
In 2005, ACIP recommended the implementation of policies as well as procedures, laws, and regulations for birthing hospitals to ensure that all medically stable infants of HBsAg-negative mothers weighing more than 2,000 g at birth receive a birth dose of HBV before discharge from the newborn nursery (MMWR Recomm. Rep. 2005;54[RR-16]:1-23).
(Separate recommendations are given for premature infants weighing less than 2,000 g at birth. There is some confusing language in the AAP’s Red Book, and I’ll address that later in this column.)
In a retrospective cohort study of 64,425 infants born in Colorado in 2008, more than a third (38%) did not receive a birth dose of HBV (Pediatr. Infect. Dis. J. 2012;31:1-4). Of note, the proportion of infants who did not receive the birth dose increased as household income increased, with 46% of babies in households with annual incomes greater than $75,000 not receiving it, compared with just 27% of infants whose mothers reported incomes less than $15,000 per year.
The investigators also found that newborns of mothers with more education were less likely to receive the birth dose. Compared with those whose mothers had an eighth-grade education or less, those whose mothers had a bachelor’s degree, master’s degree, or doctorate/professional degree were 38%, 66%, and 51% less likely, respectively, to receive a birth dose.
Although the study could not evaluate the reasons for nonreceipt of HBV, the pattern is essentially the same as in mothers whose children have purposeful delays or who don’t receive other recommended vaccines. This surprised me a bit, although I guess it shouldn’t have. I expected to see more evenly distributed proportions across all socioeconomic groups for nonreceipt of HBV.
Hospital policy made a difference, too, the researchers found. Not surprisingly, infants born at facilities that did not offer HBV to all newborns before discharge were the least likely to receive it. Compared with infants born in hospitals that had a birth dose policy, those born in hospitals that had no policy were 39% less likely to receive it. Infants born in hospitals that had a policy to review maternal hepatitis B status but not to offer HBV to all newborns were more than twice as likely not to receive the birth dose.
To me, these data suggest two things: First, we need to be advocates for a birth dose policy in our local hospitals. Second, we need to start educating parents as early as possible about vaccines in general and the birth HBV dose in particular, ideally before the infant is born. It is important to assess the parents’ attitudes toward vaccines, and the reasons for any hesitation at any available prenatal visits, and to tailor your educational message accordingly.
Considering your approach during an initial family contact before or near birth brings up another touchy subject: whether your practice has a policy that does not permit vaccine-refusing families. What do you do if parents are insistent on vaccine refusal? If you plan to follow the prescribed method of discharging or not accepting such a family, consider also offering them a list of trustworthy colleagues in the community who are willing to accommodate the family’s approach. Leaving children unvaccinated is far from optimal, but I believe that providing information on trustworthy alternative practices is in the child’s best interest. Otherwise, parents may end up choosing a practice in which overall care is substandard.
Finally, I recently was made aware of potentially confusing wording in the ACIP and 2009 Red Book recommendations regarding infants born weighing less than 2,000 grams. The wording states that preterm infants of HBsAg-negative mothers with a birth weight less than 2,000 g can receive HBV starting at 1 month of chronological age, or at hospital discharge prior to 1 month of chronological age. This implies that a dose given when the weight is less than 2,000 g could count as one of the three required doses, if it is given at hospital discharge. However, in reality, that dose cannot be considered the first in the series if the infant still weighs less than 2,000 g at that time. The child will still need three more doses after its weight surpasses 2,000 g. This potentially confusing wording is likely to change in the upcoming 2012 Red Book edition.
Dr. Harrison is a professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison said he has no relevant financial disclosures. E-mail him at [email protected].
My Predictions for 2012
Nine trends and a wish for New Year blessings for your family and friends!
• Rethinking clindamycin. Many experts have recommended clindamycin as the go-to antibiotic for stable children hospitalized with skin, soft tissue, or musculoskeletal infections, and for complicated community-acquired pneumonia (in the latter, usually in combination with a third-generation cephalosporin). Over the last year, clindamycin resistance rates from our center have risen to 25%-30% for invasive isolates (higher for methicillin-sensitive Staphylococcus aureus than methicillin-resistant S. aureus). We are changing our recommendations for empiric treatment in cases where S. aureus is an etiologic consideration, and are depending on culture data to provide susceptibility information (using polymerase chain reaction in culture-negative cases) to guide our definitive therapy. Clinicians will need to carefully review their local clindamycin resistance rates for S aureus isolates, and to discuss the implications with their local pediatric infectious diseases specialists.
• Good news about MRSA. Thankfully, MRSA skin abscesses will be less commonly diagnosed. For several years now, a pediatric wound care clinic has been staffed by our emergency medicine faculty for the follow-up of children who had a skin abscess drained in the emergency department setting. At the peak of the MRSA epidemic in our community, this clinic cared for 350 children a month. The data for the last 6 months indicate that there has been a 60% decrease in the number of children seen, a welcome trend for both patient and doctor.
• New pneumococci. I suspect we will continue to see new serotypes of pneumococcus emerge, perhaps even after the 13-valent pneumococcal conjugate vaccine (PCV13) is fully implemented. In the last year, we confirmed an unexpected increase in infections from serotype 35, which is not a capsule serotype included in PCV13 vaccine, and almost one-quarter of these were penicillin nonsusceptible.
• Vaccinating adults, part 1. In 2012, pediatricians will be front and center in the process of building better systems for providing influenza immunization to children, but now will also be asked to address their parents. Look for American Academy of Pediatrics recommendations for providing parent vaccines at the pediatrician’s office; these will target the provision of tetanus-diphtheria-acellular pertussis (Tdap) and influenza vaccines.
• Vaccinating adults, part 2. New recommendations that followed the large 2010 California outbreak of pertussis emphasized the provision of a single dose of Tdap vaccine – not only for adolescents and adults, but also for the incompletely immunized child older than age 7 years and for adults older than 64 years. At least 5 years of pertussis protection is provided by the Tdap vaccine, but as additional data on the duration of protection are analyzed, we may be talking about a Tdap booster in the not-so-distant future.
• Measles won’t leave us. Measles outbreaks in 2012 will continue to be reported internationally and within the United States because of importation of cases and inadequate vaccination coverage in certain populations.
• Resisting resistances. Multidrug-resistant, gram-negative organisms will be an increasing problem for hospitalized children. This will fuel recommendations in 2012 that emphasize the judicious use of antibiotics both in hospitalized patients and for outpatient infections. Look for upcoming recommendations related to judicious use for antibiotic treatment of respiratory tract infections (that is, pharyngitis, otitis, and sinusitis) in children.
• Rising sulfa sensitivity. Long recognized but possibly forgotten, trimethoprim sulfamethoxazole (TMP-SMX) hypersensitivity reactions appear to be on the rise, and are correlated with the increase in the use of sulfa-based agents for treatment of MRSA skin infection. Parents should be instructed to contact you if their child develops a rash while taking TMP-SMX, because the hypersensitivity reactions related to this drug can be serious and potentially life threatening.
• Watching for flu. Pediatricians will be gearing up for the 2012 influenza season after the holidays, and are expecting the traditional potential mix of influenza A and influenza B viruses. Limited data from the Centers for Disease Control and Prevention confirm that all viruses circulating so far are included in this year’s seasonal influenza vaccine. There was a recent report describing infection caused by a reassortant swine-derived novel influenza virus in three children from separate counties in Iowa, prompting enhanced CDC surveillance for Iowa and the surrounding states. More swine flu for 2012? I think not, but keep an eye on trends at the CDC’s flu surveillance website.
This column, "ID Consult," regularly appears in Pediatric News, an Elsevier publication. Dr. Jackson is the chief of infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. She has no disclosures to declare.
Nine trends and a wish for New Year blessings for your family and friends!
• Rethinking clindamycin. Many experts have recommended clindamycin as the go-to antibiotic for stable children hospitalized with skin, soft tissue, or musculoskeletal infections, and for complicated community-acquired pneumonia (in the latter, usually in combination with a third-generation cephalosporin). Over the last year, clindamycin resistance rates from our center have risen to 25%-30% for invasive isolates (higher for methicillin-sensitive Staphylococcus aureus than methicillin-resistant S. aureus). We are changing our recommendations for empiric treatment in cases where S. aureus is an etiologic consideration, and are depending on culture data to provide susceptibility information (using polymerase chain reaction in culture-negative cases) to guide our definitive therapy. Clinicians will need to carefully review their local clindamycin resistance rates for S aureus isolates, and to discuss the implications with their local pediatric infectious diseases specialists.
• Good news about MRSA. Thankfully, MRSA skin abscesses will be less commonly diagnosed. For several years now, a pediatric wound care clinic has been staffed by our emergency medicine faculty for the follow-up of children who had a skin abscess drained in the emergency department setting. At the peak of the MRSA epidemic in our community, this clinic cared for 350 children a month. The data for the last 6 months indicate that there has been a 60% decrease in the number of children seen, a welcome trend for both patient and doctor.
• New pneumococci. I suspect we will continue to see new serotypes of pneumococcus emerge, perhaps even after the 13-valent pneumococcal conjugate vaccine (PCV13) is fully implemented. In the last year, we confirmed an unexpected increase in infections from serotype 35, which is not a capsule serotype included in PCV13 vaccine, and almost one-quarter of these were penicillin nonsusceptible.
• Vaccinating adults, part 1. In 2012, pediatricians will be front and center in the process of building better systems for providing influenza immunization to children, but now will also be asked to address their parents. Look for American Academy of Pediatrics recommendations for providing parent vaccines at the pediatrician’s office; these will target the provision of tetanus-diphtheria-acellular pertussis (Tdap) and influenza vaccines.
• Vaccinating adults, part 2. New recommendations that followed the large 2010 California outbreak of pertussis emphasized the provision of a single dose of Tdap vaccine – not only for adolescents and adults, but also for the incompletely immunized child older than age 7 years and for adults older than 64 years. At least 5 years of pertussis protection is provided by the Tdap vaccine, but as additional data on the duration of protection are analyzed, we may be talking about a Tdap booster in the not-so-distant future.
• Measles won’t leave us. Measles outbreaks in 2012 will continue to be reported internationally and within the United States because of importation of cases and inadequate vaccination coverage in certain populations.
• Resisting resistances. Multidrug-resistant, gram-negative organisms will be an increasing problem for hospitalized children. This will fuel recommendations in 2012 that emphasize the judicious use of antibiotics both in hospitalized patients and for outpatient infections. Look for upcoming recommendations related to judicious use for antibiotic treatment of respiratory tract infections (that is, pharyngitis, otitis, and sinusitis) in children.
• Rising sulfa sensitivity. Long recognized but possibly forgotten, trimethoprim sulfamethoxazole (TMP-SMX) hypersensitivity reactions appear to be on the rise, and are correlated with the increase in the use of sulfa-based agents for treatment of MRSA skin infection. Parents should be instructed to contact you if their child develops a rash while taking TMP-SMX, because the hypersensitivity reactions related to this drug can be serious and potentially life threatening.
• Watching for flu. Pediatricians will be gearing up for the 2012 influenza season after the holidays, and are expecting the traditional potential mix of influenza A and influenza B viruses. Limited data from the Centers for Disease Control and Prevention confirm that all viruses circulating so far are included in this year’s seasonal influenza vaccine. There was a recent report describing infection caused by a reassortant swine-derived novel influenza virus in three children from separate counties in Iowa, prompting enhanced CDC surveillance for Iowa and the surrounding states. More swine flu for 2012? I think not, but keep an eye on trends at the CDC’s flu surveillance website.
This column, "ID Consult," regularly appears in Pediatric News, an Elsevier publication. Dr. Jackson is the chief of infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. She has no disclosures to declare.
Nine trends and a wish for New Year blessings for your family and friends!
• Rethinking clindamycin. Many experts have recommended clindamycin as the go-to antibiotic for stable children hospitalized with skin, soft tissue, or musculoskeletal infections, and for complicated community-acquired pneumonia (in the latter, usually in combination with a third-generation cephalosporin). Over the last year, clindamycin resistance rates from our center have risen to 25%-30% for invasive isolates (higher for methicillin-sensitive Staphylococcus aureus than methicillin-resistant S. aureus). We are changing our recommendations for empiric treatment in cases where S. aureus is an etiologic consideration, and are depending on culture data to provide susceptibility information (using polymerase chain reaction in culture-negative cases) to guide our definitive therapy. Clinicians will need to carefully review their local clindamycin resistance rates for S aureus isolates, and to discuss the implications with their local pediatric infectious diseases specialists.
• Good news about MRSA. Thankfully, MRSA skin abscesses will be less commonly diagnosed. For several years now, a pediatric wound care clinic has been staffed by our emergency medicine faculty for the follow-up of children who had a skin abscess drained in the emergency department setting. At the peak of the MRSA epidemic in our community, this clinic cared for 350 children a month. The data for the last 6 months indicate that there has been a 60% decrease in the number of children seen, a welcome trend for both patient and doctor.
• New pneumococci. I suspect we will continue to see new serotypes of pneumococcus emerge, perhaps even after the 13-valent pneumococcal conjugate vaccine (PCV13) is fully implemented. In the last year, we confirmed an unexpected increase in infections from serotype 35, which is not a capsule serotype included in PCV13 vaccine, and almost one-quarter of these were penicillin nonsusceptible.
• Vaccinating adults, part 1. In 2012, pediatricians will be front and center in the process of building better systems for providing influenza immunization to children, but now will also be asked to address their parents. Look for American Academy of Pediatrics recommendations for providing parent vaccines at the pediatrician’s office; these will target the provision of tetanus-diphtheria-acellular pertussis (Tdap) and influenza vaccines.
• Vaccinating adults, part 2. New recommendations that followed the large 2010 California outbreak of pertussis emphasized the provision of a single dose of Tdap vaccine – not only for adolescents and adults, but also for the incompletely immunized child older than age 7 years and for adults older than 64 years. At least 5 years of pertussis protection is provided by the Tdap vaccine, but as additional data on the duration of protection are analyzed, we may be talking about a Tdap booster in the not-so-distant future.
• Measles won’t leave us. Measles outbreaks in 2012 will continue to be reported internationally and within the United States because of importation of cases and inadequate vaccination coverage in certain populations.
• Resisting resistances. Multidrug-resistant, gram-negative organisms will be an increasing problem for hospitalized children. This will fuel recommendations in 2012 that emphasize the judicious use of antibiotics both in hospitalized patients and for outpatient infections. Look for upcoming recommendations related to judicious use for antibiotic treatment of respiratory tract infections (that is, pharyngitis, otitis, and sinusitis) in children.
• Rising sulfa sensitivity. Long recognized but possibly forgotten, trimethoprim sulfamethoxazole (TMP-SMX) hypersensitivity reactions appear to be on the rise, and are correlated with the increase in the use of sulfa-based agents for treatment of MRSA skin infection. Parents should be instructed to contact you if their child develops a rash while taking TMP-SMX, because the hypersensitivity reactions related to this drug can be serious and potentially life threatening.
• Watching for flu. Pediatricians will be gearing up for the 2012 influenza season after the holidays, and are expecting the traditional potential mix of influenza A and influenza B viruses. Limited data from the Centers for Disease Control and Prevention confirm that all viruses circulating so far are included in this year’s seasonal influenza vaccine. There was a recent report describing infection caused by a reassortant swine-derived novel influenza virus in three children from separate counties in Iowa, prompting enhanced CDC surveillance for Iowa and the surrounding states. More swine flu for 2012? I think not, but keep an eye on trends at the CDC’s flu surveillance website.
This column, "ID Consult," regularly appears in Pediatric News, an Elsevier publication. Dr. Jackson is the chief of infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. She has no disclosures to declare.
Universal SCIDS Screening Gaining Ground
Universal newborn screening for severe combined immunodeficiency syndrome is being adopted increasingly around the country.
Severe combined immunodeficiency (SCIDS) is a syndrome caused by a spectrum of mutations in genes necessary for the normal development and function of T cells, and therefore B cells. Identification of newborns with these mutations allows for early hematopoietic stem cell transplantation and a vastly improved prognosis. The evidence for an improved outcome for those identified early comes from studies comparing the outcome in first cases in a family with those in subsequent siblings who are diagnosed and transplanted earlier in life (Blood 2011;117:3243-6).
In May 2010, U.S. Secretary of Health and Human Services Kathleen Sebelius announced the addition of SCIDS to the national Recommended Uniform Screening Panel. Thus far, pilot programs for universal newborn SCIDS screening have been implemented in five states: California, Louisiana, Massachusetts, New York, and Wisconsin, and also in Puerto Rico. Another eight states, Colorado, Delaware, Florida, Iowa, Michigan, Minnesota, North Carolina, and Rhode Island, are prepared to implement SCIDS Newborn Screening Programs in the near future.
There are several types of SCIDS. Deficiency of the common gamma chain of the T-cell receptor is the most common, affecting nearly 45% of all cases. This mutation of the "cg" (for common gamma chain) gene on the X chromosome results in very low T-lymphocyte and NK-lymphocyte counts but the B-lymphocyte count is high. Only males have this type of SCIDS, but females may carry the gene.
The second-most common type, adenosine deaminase (ADA) deficiency, is caused by mutations in a gene that encodes the ADA enzyme, which is essential for the metabolic function of a variety of body cells, but especially T cells. The absence of ADA leads to accumulation of toxic metabolic by-products within lymphocytes that cause the cells to die. Infants with this type of SCIDS have the lowest total lymphocyte counts of all, and the T, B and NK-lymphocyte counts are all very low.
Another, less common SCIDS type is deficiency of the alpha chain of the IL-7 receptor, in which the infant has B and NK cells, but no T cells. However, the B cells don’t work because of the lack of T cells.
Other less frequent types include deficiency of Janus kinase 3 (JAK3), in which the infants have lab values similar to X-linked SCIDS (T, B+, NK), and deficiencies in the CD3 or CD45 chains that play key roles in T-cell function.
The classic symptoms of SCIDS are recurrent severe infections, chronic diarrhea, and failure to thrive. Persistent mucocutaneous candidiasis is a common early finding, and opportunistic infections with normally nonpathogenic organisms, such as Pneumocystis jiroveci (formerly carinii) also occur. Attenuated vaccine organisms, rotavirus and varicella, may cause severe or fatal infection. About 10 cases SCIDS presenting with persistent diarrhea following rotavirus vaccine have been reported (Vaccine 2010;28:6609-12).
The strategy for newborn SCIDS screening is based upon polymerase chain reaction quantification of T-cell receptor excision circles (TRECs) – small circles of DNA created in T-cells during their passage through the thymus – from dried blood spots (DBS) on newborn screening cards. A normal number, based on an evaluation of 5,766 Wisconsin newborns, is 708 TRECs/3.2 mm DBS (Public Health Rep. 2010;125 [Suppl 2]:88-95).
A low TREC number implies abnormal thymic function. Children with SCIDS are expected to have near zero (the screening cutoff is 25 TREC/uL). Children with an abnormally low TREC count on screening should be followed by more formal testing of T-cell number, including naive cell markers and T-cell function (mitogen stimulation) if sufficient T cells are present.
When notified about a positive test, the physician should immediately refer the infant to a center for lymphocyte subset analysis to confirm or refute the diagnosis. These infants should be "isolated" within the home by avoiding young children and any potentially contagious contacts. Prophylaxis for Pneumocystis jiroveci pneumonia could be given if a delay in further testing is likely, as well as replacement therapy with immune globulin might be indicated if assessment of humoral immunity demonstrates hypogammaglobulinemia.
Live attenuated vaccines normally given by 2 months of age, including rotavirus, bacille Calmette-Guérin, and oral poliovirus vaccine should NOT be administered to the infant, and measles-mumps-rubella and varicella vaccines should not be administered to the infant’s caregivers or family.
In Wisconsin, the first state to offer universal newborn SCIDS screening, 0.05% (35) newborns out of a total 71,000 had positive tests and underwent confirmatory testing. Another 0.17% (119) had initial unsatisfactory test results that required repeat. Of 194,056 newborns screened in Massachusetts during 2008-2011, 4 were identified with SCIDS. This gives us a rate of approximately 1 in 50,000 live births. Importantly, two of those four were identified prior to exhibiting any symptoms. The oldest, who had the JAK3 defect but was never ill prior to receiving a stem cell transplant, is now more than 10 months post transplant and is doing well. The second, who has been transplanted and is at home, had been hospitalized and "very ill" at the time of the screening but had not received a diagnosis (of deficiency of common gamma chain).
The latter two have also been transplanted. One was sick by 10 days of age with classic SCIDS symptoms (thrush, febrile, failure to thrive) and was admitted. The fourth was reportedly healthy at the time of the report but had been seen for a weight check because the mother was worried. She had previously lost two children who had died at 4 months of age of pneumonia.
Although early in the adoption of SCIDS screening, the Massachusetts’ experience demonstrates that infants with SCIDS can be identified early, often before signs and symptoms are present. However, most abnormal tests are not caused by SCIDS or other immune deficits, which may also be identified early as a result of TREC screening.
Dr. Pelton is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures.
*This story was updated December 2, 2011.
Universal newborn screening for severe combined immunodeficiency syndrome is being adopted increasingly around the country.
Severe combined immunodeficiency (SCIDS) is a syndrome caused by a spectrum of mutations in genes necessary for the normal development and function of T cells, and therefore B cells. Identification of newborns with these mutations allows for early hematopoietic stem cell transplantation and a vastly improved prognosis. The evidence for an improved outcome for those identified early comes from studies comparing the outcome in first cases in a family with those in subsequent siblings who are diagnosed and transplanted earlier in life (Blood 2011;117:3243-6).
In May 2010, U.S. Secretary of Health and Human Services Kathleen Sebelius announced the addition of SCIDS to the national Recommended Uniform Screening Panel. Thus far, pilot programs for universal newborn SCIDS screening have been implemented in five states: California, Louisiana, Massachusetts, New York, and Wisconsin, and also in Puerto Rico. Another eight states, Colorado, Delaware, Florida, Iowa, Michigan, Minnesota, North Carolina, and Rhode Island, are prepared to implement SCIDS Newborn Screening Programs in the near future.
There are several types of SCIDS. Deficiency of the common gamma chain of the T-cell receptor is the most common, affecting nearly 45% of all cases. This mutation of the "cg" (for common gamma chain) gene on the X chromosome results in very low T-lymphocyte and NK-lymphocyte counts but the B-lymphocyte count is high. Only males have this type of SCIDS, but females may carry the gene.
The second-most common type, adenosine deaminase (ADA) deficiency, is caused by mutations in a gene that encodes the ADA enzyme, which is essential for the metabolic function of a variety of body cells, but especially T cells. The absence of ADA leads to accumulation of toxic metabolic by-products within lymphocytes that cause the cells to die. Infants with this type of SCIDS have the lowest total lymphocyte counts of all, and the T, B and NK-lymphocyte counts are all very low.
Another, less common SCIDS type is deficiency of the alpha chain of the IL-7 receptor, in which the infant has B and NK cells, but no T cells. However, the B cells don’t work because of the lack of T cells.
Other less frequent types include deficiency of Janus kinase 3 (JAK3), in which the infants have lab values similar to X-linked SCIDS (T, B+, NK), and deficiencies in the CD3 or CD45 chains that play key roles in T-cell function.
The classic symptoms of SCIDS are recurrent severe infections, chronic diarrhea, and failure to thrive. Persistent mucocutaneous candidiasis is a common early finding, and opportunistic infections with normally nonpathogenic organisms, such as Pneumocystis jiroveci (formerly carinii) also occur. Attenuated vaccine organisms, rotavirus and varicella, may cause severe or fatal infection. About 10 cases SCIDS presenting with persistent diarrhea following rotavirus vaccine have been reported (Vaccine 2010;28:6609-12).
The strategy for newborn SCIDS screening is based upon polymerase chain reaction quantification of T-cell receptor excision circles (TRECs) – small circles of DNA created in T-cells during their passage through the thymus – from dried blood spots (DBS) on newborn screening cards. A normal number, based on an evaluation of 5,766 Wisconsin newborns, is 708 TRECs/3.2 mm DBS (Public Health Rep. 2010;125 [Suppl 2]:88-95).
A low TREC number implies abnormal thymic function. Children with SCIDS are expected to have near zero (the screening cutoff is 25 TREC/uL). Children with an abnormally low TREC count on screening should be followed by more formal testing of T-cell number, including naive cell markers and T-cell function (mitogen stimulation) if sufficient T cells are present.
When notified about a positive test, the physician should immediately refer the infant to a center for lymphocyte subset analysis to confirm or refute the diagnosis. These infants should be "isolated" within the home by avoiding young children and any potentially contagious contacts. Prophylaxis for Pneumocystis jiroveci pneumonia could be given if a delay in further testing is likely, as well as replacement therapy with immune globulin might be indicated if assessment of humoral immunity demonstrates hypogammaglobulinemia.
Live attenuated vaccines normally given by 2 months of age, including rotavirus, bacille Calmette-Guérin, and oral poliovirus vaccine should NOT be administered to the infant, and measles-mumps-rubella and varicella vaccines should not be administered to the infant’s caregivers or family.
In Wisconsin, the first state to offer universal newborn SCIDS screening, 0.05% (35) newborns out of a total 71,000 had positive tests and underwent confirmatory testing. Another 0.17% (119) had initial unsatisfactory test results that required repeat. Of 194,056 newborns screened in Massachusetts during 2008-2011, 4 were identified with SCIDS. This gives us a rate of approximately 1 in 50,000 live births. Importantly, two of those four were identified prior to exhibiting any symptoms. The oldest, who had the JAK3 defect but was never ill prior to receiving a stem cell transplant, is now more than 10 months post transplant and is doing well. The second, who has been transplanted and is at home, had been hospitalized and "very ill" at the time of the screening but had not received a diagnosis (of deficiency of common gamma chain).
The latter two have also been transplanted. One was sick by 10 days of age with classic SCIDS symptoms (thrush, febrile, failure to thrive) and was admitted. The fourth was reportedly healthy at the time of the report but had been seen for a weight check because the mother was worried. She had previously lost two children who had died at 4 months of age of pneumonia.
Although early in the adoption of SCIDS screening, the Massachusetts’ experience demonstrates that infants with SCIDS can be identified early, often before signs and symptoms are present. However, most abnormal tests are not caused by SCIDS or other immune deficits, which may also be identified early as a result of TREC screening.
Dr. Pelton is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures.
*This story was updated December 2, 2011.
Universal newborn screening for severe combined immunodeficiency syndrome is being adopted increasingly around the country.
Severe combined immunodeficiency (SCIDS) is a syndrome caused by a spectrum of mutations in genes necessary for the normal development and function of T cells, and therefore B cells. Identification of newborns with these mutations allows for early hematopoietic stem cell transplantation and a vastly improved prognosis. The evidence for an improved outcome for those identified early comes from studies comparing the outcome in first cases in a family with those in subsequent siblings who are diagnosed and transplanted earlier in life (Blood 2011;117:3243-6).
In May 2010, U.S. Secretary of Health and Human Services Kathleen Sebelius announced the addition of SCIDS to the national Recommended Uniform Screening Panel. Thus far, pilot programs for universal newborn SCIDS screening have been implemented in five states: California, Louisiana, Massachusetts, New York, and Wisconsin, and also in Puerto Rico. Another eight states, Colorado, Delaware, Florida, Iowa, Michigan, Minnesota, North Carolina, and Rhode Island, are prepared to implement SCIDS Newborn Screening Programs in the near future.
There are several types of SCIDS. Deficiency of the common gamma chain of the T-cell receptor is the most common, affecting nearly 45% of all cases. This mutation of the "cg" (for common gamma chain) gene on the X chromosome results in very low T-lymphocyte and NK-lymphocyte counts but the B-lymphocyte count is high. Only males have this type of SCIDS, but females may carry the gene.
The second-most common type, adenosine deaminase (ADA) deficiency, is caused by mutations in a gene that encodes the ADA enzyme, which is essential for the metabolic function of a variety of body cells, but especially T cells. The absence of ADA leads to accumulation of toxic metabolic by-products within lymphocytes that cause the cells to die. Infants with this type of SCIDS have the lowest total lymphocyte counts of all, and the T, B and NK-lymphocyte counts are all very low.
Another, less common SCIDS type is deficiency of the alpha chain of the IL-7 receptor, in which the infant has B and NK cells, but no T cells. However, the B cells don’t work because of the lack of T cells.
Other less frequent types include deficiency of Janus kinase 3 (JAK3), in which the infants have lab values similar to X-linked SCIDS (T, B+, NK), and deficiencies in the CD3 or CD45 chains that play key roles in T-cell function.
The classic symptoms of SCIDS are recurrent severe infections, chronic diarrhea, and failure to thrive. Persistent mucocutaneous candidiasis is a common early finding, and opportunistic infections with normally nonpathogenic organisms, such as Pneumocystis jiroveci (formerly carinii) also occur. Attenuated vaccine organisms, rotavirus and varicella, may cause severe or fatal infection. About 10 cases SCIDS presenting with persistent diarrhea following rotavirus vaccine have been reported (Vaccine 2010;28:6609-12).
The strategy for newborn SCIDS screening is based upon polymerase chain reaction quantification of T-cell receptor excision circles (TRECs) – small circles of DNA created in T-cells during their passage through the thymus – from dried blood spots (DBS) on newborn screening cards. A normal number, based on an evaluation of 5,766 Wisconsin newborns, is 708 TRECs/3.2 mm DBS (Public Health Rep. 2010;125 [Suppl 2]:88-95).
A low TREC number implies abnormal thymic function. Children with SCIDS are expected to have near zero (the screening cutoff is 25 TREC/uL). Children with an abnormally low TREC count on screening should be followed by more formal testing of T-cell number, including naive cell markers and T-cell function (mitogen stimulation) if sufficient T cells are present.
When notified about a positive test, the physician should immediately refer the infant to a center for lymphocyte subset analysis to confirm or refute the diagnosis. These infants should be "isolated" within the home by avoiding young children and any potentially contagious contacts. Prophylaxis for Pneumocystis jiroveci pneumonia could be given if a delay in further testing is likely, as well as replacement therapy with immune globulin might be indicated if assessment of humoral immunity demonstrates hypogammaglobulinemia.
Live attenuated vaccines normally given by 2 months of age, including rotavirus, bacille Calmette-Guérin, and oral poliovirus vaccine should NOT be administered to the infant, and measles-mumps-rubella and varicella vaccines should not be administered to the infant’s caregivers or family.
In Wisconsin, the first state to offer universal newborn SCIDS screening, 0.05% (35) newborns out of a total 71,000 had positive tests and underwent confirmatory testing. Another 0.17% (119) had initial unsatisfactory test results that required repeat. Of 194,056 newborns screened in Massachusetts during 2008-2011, 4 were identified with SCIDS. This gives us a rate of approximately 1 in 50,000 live births. Importantly, two of those four were identified prior to exhibiting any symptoms. The oldest, who had the JAK3 defect but was never ill prior to receiving a stem cell transplant, is now more than 10 months post transplant and is doing well. The second, who has been transplanted and is at home, had been hospitalized and "very ill" at the time of the screening but had not received a diagnosis (of deficiency of common gamma chain).
The latter two have also been transplanted. One was sick by 10 days of age with classic SCIDS symptoms (thrush, febrile, failure to thrive) and was admitted. The fourth was reportedly healthy at the time of the report but had been seen for a weight check because the mother was worried. She had previously lost two children who had died at 4 months of age of pneumonia.
Although early in the adoption of SCIDS screening, the Massachusetts’ experience demonstrates that infants with SCIDS can be identified early, often before signs and symptoms are present. However, most abnormal tests are not caused by SCIDS or other immune deficits, which may also be identified early as a result of TREC screening.
Dr. Pelton is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures.
*This story was updated December 2, 2011.
Assess Risk/Benefits Before Using Fluoroquinolones
Fluoroquinolones continue to play a role in pediatrics, but providers should continue to restrict their use to specific clinical situations and after a careful risk/benefit discussion with parents.
As in the 2006 American Academy of Pediatrics Clinical Report on use of systemic and topical fluoroquinolones, the use of parenteral fluoroquinolones is still endorsed for treatment of infections caused by multidrug-resistant pathogens and/or in situations where there is no other safe and effective parenteral agent. Oral fluoroquinolones also are considered for treatment of infections when the only other option is intravenous treatment with other classes of antibiotic agents.
The 2011 update to the AAP’s 2006 policy statement (Pediatrics 2011;128:e1034-45) reiterated this overall advice to restrict fluoroquinolone use in children, but added recent data on safety as well as information for newer agents such as levofloxacin, that were not discussed in the 2006 statement (Pediatrics 2006;118:1287-92).
Most of the current use of fluoroquinolones in children remains off label. The only Food and Drug Administration pediatric approvals are for the first-generation agent nalidixic acid for urinary tract infections (UTIs), ciprofloxacin for inhalational anthrax and complicated UTI and pyelonephritis, and the respiratory fluoroquinolone, levofloxacin, for inhalational anthrax. Moreover, only ciprofloxacin and levofloxacin are available in a suspension formulation.
Since publication of the previous AAP policy, the clinical value of fluoroquinolones for the treatment of UTIs caused by antibiotic-resistant uropathogens has been further documented. Moreover, the use of topical fluoroquinolone drops for external otitis/tympanostomy tube otorrhea – for which we have far less concern about toxicity – is now recommended as well.
When to Use Fluoroquinolons
A situation beyond UTI where an oral fluoroquinolone such as ciprofloxacin might be considered is in the setting of Pseudomonas aeruginosa osteomyelitis. Only 1.5% of nail puncture wounds are associated with subsequent infection (early infection is usually due to Streptococcus aureus) but when an only modestly painful infectious process at the site occurs beyond days 3-4 after the puncture, suspect P. aeruginosa. Such infections are usually initially treated with parenteral third- or fourth-generation cephalosporins with good pseudomonal coverage, i.e. ceftazidime or cefepime. But following good surgical debridement and when identification of the pathogen is available, outpatient treatment with oral ciprofloxacin is considered reasonable (assuming you have confirmed susceptibility).
A respiratory fluoroquinolone such as levofloxacin might be considered for treatment of nonmeningeal multidrug-resistant pneumococcal infection. We recently cared for a 5-month-old who presented with classic signs of mastoiditis with a large subperiosteal mastoid abscess. Serotype 19A Streptococcus pneumoniae was isolated from middle ear, the subperiosteal abscess, and mastoid bone. She responded well to surgical drainage and mastoidectomy with myringotomy tube placement and initial parenteral therapy with vancomycin (plus ceftriaxone), and was transitioned to oral levofloxacin.
Fluoroquinolone Safety in Children
We have more safety data now than we did in 2006, although still not enough to say with complete certainty that fluoroquinolones are without osteoarticular risk in children. Despite signals of cartilage damage seen in animal studies using very high or prolonged dosing, no published reports exist of physician-diagnosed cartilage damage in children in the United States, either from controlled clinical trials of fluoroquinolones or from unsolicited reporting to the FDA or drug manufacturers.
Two prospective, randomized studies on fluoroquinolone safety in children have been published since 2006. One study, involving 684 children aged 1-17 years, was performed at the request of the FDA by Bayer for ciprofloxacin in the treatment of complicated UTI and pyelonephritis. The other study, a 5-year safety assessment of 2,233 children who received levofloxacin treatment, was performed by Johnson & Johnson as part of their FDA-coordinated program of pediatric drug development. Some evidence of increased musculoskeletal complaints with fluoroquinolones was found in both studies, although neither data set strongly supported the occurrence of sustained injury to developing bones or joints in children with the two fluoroquinolones, compared with agents of other classes.
More safety data will become available in the future and will inform our decision making further, but I still don’t foresee widespread pediatric use. Fluoroquinolones are considered among the most broad-spectrum agents. In this era of increasing antimicrobial resistance, as we exercise responsible antimicrobial stewardship, the use of any broad spectrum agent needs to be carefully considered before use in every case. Fortunately at this time, the need to "go to" parenteral or oral fluoroquinolone therapy remains an uncommon occurrence for most pediatricians.
Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. She and Dr. John Bradley were the cowriters of the statement, which comes from the Committee on Infectious Diseases of the AAP.
Fluoroquinolones continue to play a role in pediatrics, but providers should continue to restrict their use to specific clinical situations and after a careful risk/benefit discussion with parents.
As in the 2006 American Academy of Pediatrics Clinical Report on use of systemic and topical fluoroquinolones, the use of parenteral fluoroquinolones is still endorsed for treatment of infections caused by multidrug-resistant pathogens and/or in situations where there is no other safe and effective parenteral agent. Oral fluoroquinolones also are considered for treatment of infections when the only other option is intravenous treatment with other classes of antibiotic agents.
The 2011 update to the AAP’s 2006 policy statement (Pediatrics 2011;128:e1034-45) reiterated this overall advice to restrict fluoroquinolone use in children, but added recent data on safety as well as information for newer agents such as levofloxacin, that were not discussed in the 2006 statement (Pediatrics 2006;118:1287-92).
Most of the current use of fluoroquinolones in children remains off label. The only Food and Drug Administration pediatric approvals are for the first-generation agent nalidixic acid for urinary tract infections (UTIs), ciprofloxacin for inhalational anthrax and complicated UTI and pyelonephritis, and the respiratory fluoroquinolone, levofloxacin, for inhalational anthrax. Moreover, only ciprofloxacin and levofloxacin are available in a suspension formulation.
Since publication of the previous AAP policy, the clinical value of fluoroquinolones for the treatment of UTIs caused by antibiotic-resistant uropathogens has been further documented. Moreover, the use of topical fluoroquinolone drops for external otitis/tympanostomy tube otorrhea – for which we have far less concern about toxicity – is now recommended as well.
When to Use Fluoroquinolons
A situation beyond UTI where an oral fluoroquinolone such as ciprofloxacin might be considered is in the setting of Pseudomonas aeruginosa osteomyelitis. Only 1.5% of nail puncture wounds are associated with subsequent infection (early infection is usually due to Streptococcus aureus) but when an only modestly painful infectious process at the site occurs beyond days 3-4 after the puncture, suspect P. aeruginosa. Such infections are usually initially treated with parenteral third- or fourth-generation cephalosporins with good pseudomonal coverage, i.e. ceftazidime or cefepime. But following good surgical debridement and when identification of the pathogen is available, outpatient treatment with oral ciprofloxacin is considered reasonable (assuming you have confirmed susceptibility).
A respiratory fluoroquinolone such as levofloxacin might be considered for treatment of nonmeningeal multidrug-resistant pneumococcal infection. We recently cared for a 5-month-old who presented with classic signs of mastoiditis with a large subperiosteal mastoid abscess. Serotype 19A Streptococcus pneumoniae was isolated from middle ear, the subperiosteal abscess, and mastoid bone. She responded well to surgical drainage and mastoidectomy with myringotomy tube placement and initial parenteral therapy with vancomycin (plus ceftriaxone), and was transitioned to oral levofloxacin.
Fluoroquinolone Safety in Children
We have more safety data now than we did in 2006, although still not enough to say with complete certainty that fluoroquinolones are without osteoarticular risk in children. Despite signals of cartilage damage seen in animal studies using very high or prolonged dosing, no published reports exist of physician-diagnosed cartilage damage in children in the United States, either from controlled clinical trials of fluoroquinolones or from unsolicited reporting to the FDA or drug manufacturers.
Two prospective, randomized studies on fluoroquinolone safety in children have been published since 2006. One study, involving 684 children aged 1-17 years, was performed at the request of the FDA by Bayer for ciprofloxacin in the treatment of complicated UTI and pyelonephritis. The other study, a 5-year safety assessment of 2,233 children who received levofloxacin treatment, was performed by Johnson & Johnson as part of their FDA-coordinated program of pediatric drug development. Some evidence of increased musculoskeletal complaints with fluoroquinolones was found in both studies, although neither data set strongly supported the occurrence of sustained injury to developing bones or joints in children with the two fluoroquinolones, compared with agents of other classes.
More safety data will become available in the future and will inform our decision making further, but I still don’t foresee widespread pediatric use. Fluoroquinolones are considered among the most broad-spectrum agents. In this era of increasing antimicrobial resistance, as we exercise responsible antimicrobial stewardship, the use of any broad spectrum agent needs to be carefully considered before use in every case. Fortunately at this time, the need to "go to" parenteral or oral fluoroquinolone therapy remains an uncommon occurrence for most pediatricians.
Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. She and Dr. John Bradley were the cowriters of the statement, which comes from the Committee on Infectious Diseases of the AAP.
Fluoroquinolones continue to play a role in pediatrics, but providers should continue to restrict their use to specific clinical situations and after a careful risk/benefit discussion with parents.
As in the 2006 American Academy of Pediatrics Clinical Report on use of systemic and topical fluoroquinolones, the use of parenteral fluoroquinolones is still endorsed for treatment of infections caused by multidrug-resistant pathogens and/or in situations where there is no other safe and effective parenteral agent. Oral fluoroquinolones also are considered for treatment of infections when the only other option is intravenous treatment with other classes of antibiotic agents.
The 2011 update to the AAP’s 2006 policy statement (Pediatrics 2011;128:e1034-45) reiterated this overall advice to restrict fluoroquinolone use in children, but added recent data on safety as well as information for newer agents such as levofloxacin, that were not discussed in the 2006 statement (Pediatrics 2006;118:1287-92).
Most of the current use of fluoroquinolones in children remains off label. The only Food and Drug Administration pediatric approvals are for the first-generation agent nalidixic acid for urinary tract infections (UTIs), ciprofloxacin for inhalational anthrax and complicated UTI and pyelonephritis, and the respiratory fluoroquinolone, levofloxacin, for inhalational anthrax. Moreover, only ciprofloxacin and levofloxacin are available in a suspension formulation.
Since publication of the previous AAP policy, the clinical value of fluoroquinolones for the treatment of UTIs caused by antibiotic-resistant uropathogens has been further documented. Moreover, the use of topical fluoroquinolone drops for external otitis/tympanostomy tube otorrhea – for which we have far less concern about toxicity – is now recommended as well.
When to Use Fluoroquinolons
A situation beyond UTI where an oral fluoroquinolone such as ciprofloxacin might be considered is in the setting of Pseudomonas aeruginosa osteomyelitis. Only 1.5% of nail puncture wounds are associated with subsequent infection (early infection is usually due to Streptococcus aureus) but when an only modestly painful infectious process at the site occurs beyond days 3-4 after the puncture, suspect P. aeruginosa. Such infections are usually initially treated with parenteral third- or fourth-generation cephalosporins with good pseudomonal coverage, i.e. ceftazidime or cefepime. But following good surgical debridement and when identification of the pathogen is available, outpatient treatment with oral ciprofloxacin is considered reasonable (assuming you have confirmed susceptibility).
A respiratory fluoroquinolone such as levofloxacin might be considered for treatment of nonmeningeal multidrug-resistant pneumococcal infection. We recently cared for a 5-month-old who presented with classic signs of mastoiditis with a large subperiosteal mastoid abscess. Serotype 19A Streptococcus pneumoniae was isolated from middle ear, the subperiosteal abscess, and mastoid bone. She responded well to surgical drainage and mastoidectomy with myringotomy tube placement and initial parenteral therapy with vancomycin (plus ceftriaxone), and was transitioned to oral levofloxacin.
Fluoroquinolone Safety in Children
We have more safety data now than we did in 2006, although still not enough to say with complete certainty that fluoroquinolones are without osteoarticular risk in children. Despite signals of cartilage damage seen in animal studies using very high or prolonged dosing, no published reports exist of physician-diagnosed cartilage damage in children in the United States, either from controlled clinical trials of fluoroquinolones or from unsolicited reporting to the FDA or drug manufacturers.
Two prospective, randomized studies on fluoroquinolone safety in children have been published since 2006. One study, involving 684 children aged 1-17 years, was performed at the request of the FDA by Bayer for ciprofloxacin in the treatment of complicated UTI and pyelonephritis. The other study, a 5-year safety assessment of 2,233 children who received levofloxacin treatment, was performed by Johnson & Johnson as part of their FDA-coordinated program of pediatric drug development. Some evidence of increased musculoskeletal complaints with fluoroquinolones was found in both studies, although neither data set strongly supported the occurrence of sustained injury to developing bones or joints in children with the two fluoroquinolones, compared with agents of other classes.
More safety data will become available in the future and will inform our decision making further, but I still don’t foresee widespread pediatric use. Fluoroquinolones are considered among the most broad-spectrum agents. In this era of increasing antimicrobial resistance, as we exercise responsible antimicrobial stewardship, the use of any broad spectrum agent needs to be carefully considered before use in every case. Fortunately at this time, the need to "go to" parenteral or oral fluoroquinolone therapy remains an uncommon occurrence for most pediatricians.
Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. She and Dr. John Bradley were the cowriters of the statement, which comes from the Committee on Infectious Diseases of the AAP.
Diagnosing C. difficile in Children: No Simple Matter
Clostridium difficile was not given its name because it is easy to diagnose. Indeed, the name reflects the difficulty that the original discoverers of this bacterium had in isolating the germ and getting it to grow. In many respects, C. difficile continues to be a difficult pathogen for today’s practitioners.
As an important reemerging nosocomial and community-acquired pathogen, C. difficile (CD) can cause mild to severe diarrhea or no symptoms at all. In children especially, colonization with the anaerobic, gram-positive, spore-forming bacillus does not necessarily mean that CD is the cause of diarrhea nor that treatment is always necessary, even when toxin is present. Indeed, depending on the screening/diagnostic test used, false positives may occur and thus a combination of tests often is warranted.
Further complicating the process, CD can be a normal component of the bowel flora of infants. Therefore, routine testing is currently suggested for children over 1 year of age with symptoms consistent with C. difficile infection (CDI) and with a history of recent antibiotic use. We currently do not have good guidelines for what to do with infants less than 1 year of age.
Prior to the mid-1990s, if children older than 1 year of age with diarrhea needed CD testing, a direct cell cytotoxicity neutralization assay (CCNA) was used. While the advantages of using a CCNA included moderate to high sensitivity and high specificity, turnaround time was slow (3-7 days), the testing procedure was labor intensive, and interpretation of the results required special technical expertise. Clinicians were forced to consider empiric treatment until the results came back. Even then a positive toxin assay did not necessarily mean that the toxin was the cause of the child’s current diarrhea. Some children beyond infancy, especially those in group homes and institutionalized settings, can be asymptomatic carriers of toxin-producing strains.
More recently, enzyme immunoassays (EIAs) became available to detect C. difficile toxins A (TcdA) and B (TcdB), as well as the CD-specific antigen glutamate dehydrogenase (GDH). GDH is found in both toxin and nontoxin producing CD strains. Compared with CCNA or toxigenic culture, these assays have more rapid turnaround time, are less labor-intensive, and don’t require special laboratory expertise for interpretation. However, recently, it has become clear that the EIA toxin assays lack sufficient sensitivity for use as the sole diagnostic test for CDI. On the other hand, the GDH EIA’s better sensitivity, compared with the toxin EIAs, is counterbalanced by its inability to distinguish between toxigenic and nontoxigenic CD. So, the best EIA approach combines GDH, TcdA, and/or TcdB testing.
More recently, CD testing via nucleic acid amplification tests (NAATs), usually by polymerase chain reaction testing (PCR), has become available. Although developed more than 15 years ago, it has been improved. The potentially high sensitivity and specificity of PCR might make it the optimal CD test just when we need it because of recent changes in epidemiology and severity of CDI: The increase in community-acquired CD cases that are not associated with antibiotics, and the emergence of a fluoroquinolone-resistant epidemic strain (Anaerobe 2003;9:289-94).
In addition to PCR’s high sensitivity and specificity, other advantages include short turnaround time and ease of performance with minimal hands-on time. The main downside is cost, which can be 3-10 times more than EIA.
A nice paper summarizing the pros and cons of various CD tests and a treatment algorithm taking into account a multistep testing approach was recently published (Clin. Infect. Dis. 2011;52:1451-7).
At our institution, we use GDH EIA plus the toxin A&B EIA tests to screen symptomatic children older than 1 year of age. We reserve PCR as a "tiebreaker" for those with positive GDH but negative for both toxins. In this scenario, if the PCR is positive and ongoing symptoms are consistent with CDI, treatment is warranted. Keep in mind, however, that successfully treated CDI patients may have persistent but asymptomatic CD colonization (and detectable toxin by PCR) for several weeks after treatment. So PCR is not necessarily reliable in those patients. A study at our institution is currently actively assessing physician understanding and comfort with evolving CD diagnostic and treatment modalities, including our recent implementation of the two-step method.
While we now have more precise CD testing tools for older children, infants younger than 1 year of age should not routinely be tested or treated for CDI. They should be evaluated for other, more likely causes of diarrhea. And we likely will not have clearer guidelines in this area anytime soon.
Dr. Harrison is a professor of pediatrics and pediatric infectious diseases and Dr. Klatte is a second-year fellow in pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Neither Dr. Harrison nor Dr. Klatte has any relevant financial disclosures.
Clostridium difficile was not given its name because it is easy to diagnose. Indeed, the name reflects the difficulty that the original discoverers of this bacterium had in isolating the germ and getting it to grow. In many respects, C. difficile continues to be a difficult pathogen for today’s practitioners.
As an important reemerging nosocomial and community-acquired pathogen, C. difficile (CD) can cause mild to severe diarrhea or no symptoms at all. In children especially, colonization with the anaerobic, gram-positive, spore-forming bacillus does not necessarily mean that CD is the cause of diarrhea nor that treatment is always necessary, even when toxin is present. Indeed, depending on the screening/diagnostic test used, false positives may occur and thus a combination of tests often is warranted.
Further complicating the process, CD can be a normal component of the bowel flora of infants. Therefore, routine testing is currently suggested for children over 1 year of age with symptoms consistent with C. difficile infection (CDI) and with a history of recent antibiotic use. We currently do not have good guidelines for what to do with infants less than 1 year of age.
Prior to the mid-1990s, if children older than 1 year of age with diarrhea needed CD testing, a direct cell cytotoxicity neutralization assay (CCNA) was used. While the advantages of using a CCNA included moderate to high sensitivity and high specificity, turnaround time was slow (3-7 days), the testing procedure was labor intensive, and interpretation of the results required special technical expertise. Clinicians were forced to consider empiric treatment until the results came back. Even then a positive toxin assay did not necessarily mean that the toxin was the cause of the child’s current diarrhea. Some children beyond infancy, especially those in group homes and institutionalized settings, can be asymptomatic carriers of toxin-producing strains.
More recently, enzyme immunoassays (EIAs) became available to detect C. difficile toxins A (TcdA) and B (TcdB), as well as the CD-specific antigen glutamate dehydrogenase (GDH). GDH is found in both toxin and nontoxin producing CD strains. Compared with CCNA or toxigenic culture, these assays have more rapid turnaround time, are less labor-intensive, and don’t require special laboratory expertise for interpretation. However, recently, it has become clear that the EIA toxin assays lack sufficient sensitivity for use as the sole diagnostic test for CDI. On the other hand, the GDH EIA’s better sensitivity, compared with the toxin EIAs, is counterbalanced by its inability to distinguish between toxigenic and nontoxigenic CD. So, the best EIA approach combines GDH, TcdA, and/or TcdB testing.
More recently, CD testing via nucleic acid amplification tests (NAATs), usually by polymerase chain reaction testing (PCR), has become available. Although developed more than 15 years ago, it has been improved. The potentially high sensitivity and specificity of PCR might make it the optimal CD test just when we need it because of recent changes in epidemiology and severity of CDI: The increase in community-acquired CD cases that are not associated with antibiotics, and the emergence of a fluoroquinolone-resistant epidemic strain (Anaerobe 2003;9:289-94).
In addition to PCR’s high sensitivity and specificity, other advantages include short turnaround time and ease of performance with minimal hands-on time. The main downside is cost, which can be 3-10 times more than EIA.
A nice paper summarizing the pros and cons of various CD tests and a treatment algorithm taking into account a multistep testing approach was recently published (Clin. Infect. Dis. 2011;52:1451-7).
At our institution, we use GDH EIA plus the toxin A&B EIA tests to screen symptomatic children older than 1 year of age. We reserve PCR as a "tiebreaker" for those with positive GDH but negative for both toxins. In this scenario, if the PCR is positive and ongoing symptoms are consistent with CDI, treatment is warranted. Keep in mind, however, that successfully treated CDI patients may have persistent but asymptomatic CD colonization (and detectable toxin by PCR) for several weeks after treatment. So PCR is not necessarily reliable in those patients. A study at our institution is currently actively assessing physician understanding and comfort with evolving CD diagnostic and treatment modalities, including our recent implementation of the two-step method.
While we now have more precise CD testing tools for older children, infants younger than 1 year of age should not routinely be tested or treated for CDI. They should be evaluated for other, more likely causes of diarrhea. And we likely will not have clearer guidelines in this area anytime soon.
Dr. Harrison is a professor of pediatrics and pediatric infectious diseases and Dr. Klatte is a second-year fellow in pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Neither Dr. Harrison nor Dr. Klatte has any relevant financial disclosures.
Clostridium difficile was not given its name because it is easy to diagnose. Indeed, the name reflects the difficulty that the original discoverers of this bacterium had in isolating the germ and getting it to grow. In many respects, C. difficile continues to be a difficult pathogen for today’s practitioners.
As an important reemerging nosocomial and community-acquired pathogen, C. difficile (CD) can cause mild to severe diarrhea or no symptoms at all. In children especially, colonization with the anaerobic, gram-positive, spore-forming bacillus does not necessarily mean that CD is the cause of diarrhea nor that treatment is always necessary, even when toxin is present. Indeed, depending on the screening/diagnostic test used, false positives may occur and thus a combination of tests often is warranted.
Further complicating the process, CD can be a normal component of the bowel flora of infants. Therefore, routine testing is currently suggested for children over 1 year of age with symptoms consistent with C. difficile infection (CDI) and with a history of recent antibiotic use. We currently do not have good guidelines for what to do with infants less than 1 year of age.
Prior to the mid-1990s, if children older than 1 year of age with diarrhea needed CD testing, a direct cell cytotoxicity neutralization assay (CCNA) was used. While the advantages of using a CCNA included moderate to high sensitivity and high specificity, turnaround time was slow (3-7 days), the testing procedure was labor intensive, and interpretation of the results required special technical expertise. Clinicians were forced to consider empiric treatment until the results came back. Even then a positive toxin assay did not necessarily mean that the toxin was the cause of the child’s current diarrhea. Some children beyond infancy, especially those in group homes and institutionalized settings, can be asymptomatic carriers of toxin-producing strains.
More recently, enzyme immunoassays (EIAs) became available to detect C. difficile toxins A (TcdA) and B (TcdB), as well as the CD-specific antigen glutamate dehydrogenase (GDH). GDH is found in both toxin and nontoxin producing CD strains. Compared with CCNA or toxigenic culture, these assays have more rapid turnaround time, are less labor-intensive, and don’t require special laboratory expertise for interpretation. However, recently, it has become clear that the EIA toxin assays lack sufficient sensitivity for use as the sole diagnostic test for CDI. On the other hand, the GDH EIA’s better sensitivity, compared with the toxin EIAs, is counterbalanced by its inability to distinguish between toxigenic and nontoxigenic CD. So, the best EIA approach combines GDH, TcdA, and/or TcdB testing.
More recently, CD testing via nucleic acid amplification tests (NAATs), usually by polymerase chain reaction testing (PCR), has become available. Although developed more than 15 years ago, it has been improved. The potentially high sensitivity and specificity of PCR might make it the optimal CD test just when we need it because of recent changes in epidemiology and severity of CDI: The increase in community-acquired CD cases that are not associated with antibiotics, and the emergence of a fluoroquinolone-resistant epidemic strain (Anaerobe 2003;9:289-94).
In addition to PCR’s high sensitivity and specificity, other advantages include short turnaround time and ease of performance with minimal hands-on time. The main downside is cost, which can be 3-10 times more than EIA.
A nice paper summarizing the pros and cons of various CD tests and a treatment algorithm taking into account a multistep testing approach was recently published (Clin. Infect. Dis. 2011;52:1451-7).
At our institution, we use GDH EIA plus the toxin A&B EIA tests to screen symptomatic children older than 1 year of age. We reserve PCR as a "tiebreaker" for those with positive GDH but negative for both toxins. In this scenario, if the PCR is positive and ongoing symptoms are consistent with CDI, treatment is warranted. Keep in mind, however, that successfully treated CDI patients may have persistent but asymptomatic CD colonization (and detectable toxin by PCR) for several weeks after treatment. So PCR is not necessarily reliable in those patients. A study at our institution is currently actively assessing physician understanding and comfort with evolving CD diagnostic and treatment modalities, including our recent implementation of the two-step method.
While we now have more precise CD testing tools for older children, infants younger than 1 year of age should not routinely be tested or treated for CDI. They should be evaluated for other, more likely causes of diarrhea. And we likely will not have clearer guidelines in this area anytime soon.
Dr. Harrison is a professor of pediatrics and pediatric infectious diseases and Dr. Klatte is a second-year fellow in pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Neither Dr. Harrison nor Dr. Klatte has any relevant financial disclosures.
CDC Seeks Public Input on Tough Vaccine Decisions
At the next meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP), the group will need to decide whether to recommend routine meningococcal conjugate vaccine (MCV) use in infants. Because other federal committees recently suggested that the CDC engage the public before such decisions, the agency developed a new information-gathering process involving consumers. This took the form of focus group meetings designed to be open and to elicit input from those who might hold differing opinions about vaccines.
Over the summer, four pilot group meetings were held in Concord N.H., Chicago, Seattle, and Denver. There were about 100 attendees in Chicago and Seattle, and about half that number each in New Hampshire and Denver. Participants included provaccine groups such as the Meningitis Angels, who passionately support routine meningococcal immunization for young infants, representatives of the antivaccine group, who call themselves the National Vaccine Information Center, as well as more or less "neutral" individuals recruited through local health departments. They were asked a series of hypothetical questions about their opinions on use of new/future vaccines and the extent that they’d be willing to support and pay for such vaccines. The answers would likely apply to MCV.
Insights from these focus groups will likely play a role in ACIP’s October discussions of routine infant immunization against meningococcal disease. The decision is complicated because of three potentially competing vaccine formulations that are not currently interchangeable and with potentially different schedules:
• Sanofi-Pasteur’s MenACWY-D (Menactra) is currently licensed starting at 9 months of age in select high-risk groups, but could be expanded to all infants.
• Novartis’ MenACWY-CRM (Menveo) was recently approved for children ages 2 years and above, but is before the U.S. Food and Drug Administration (FDA) for licensure at 2, 4, and 6 months of age.
• A not yet licensed GlaxoSmithKline’s HibMenCY (MenHibRix) is a combination vaccine containing Haemophilus influenzae type b and meningococcal type A and C antigens. GSK is seeking licensure for use down to 2 months of age.
In June, ACIP recommended Sanofi-Pasteur’s quadrivalent MenACWY-D for specific high-risk children aged 9-23 months, such as travelers to meningococcal disease-endemic areas, infants with complement deficiencies, those in outbreak situations, and HIV-infected infants with other indications for vaccination. The committee postponed voting on whether 9- to 23-month-olds with functional or anatomic asplenia, including sickle cell disease, should receive this vaccine. This was due to data that pneumococcal geometric mean titers were reduced when MenACWY-D was given at the same time as pneumococcal conjugate vaccine (PCV-7). The clinical impact of such lower titers (that are still in the protective range) are unclear, but pneumococcus is a higher threat than meningococcus for these groups.
So what is the rationale for waiting until 9 months of age to begin MCV? For one, it avoids the need for a potential extra injection at 2, 4, and 6 months, and there are only two, not four doses. Also, none of the candidate MCVs contains meningococcal serotype B, the most common serotype affecting children less than 3 years of age. Several manufacturers are working on a B serogroup vaccine, which is years away from release. Lastly, the absolute number of annually prevented deaths (about five per year) would be relatively small among those less than 9 months of age.
What is the rationale for giving MCV at 2 months of age? Because children aged less than 3 years have the highest attack rate for invasive meningococcal disease (about 50% serogroup B and 50% of the other serogroups combined), it also makes sense to start MCV as early as possible to maximize reduction of nonserogroup-B invasive meningococcal disease. And if one used the GSK combo DTaP-Hep B- IPV vaccine plus Hib MenCY, there would not be additional injections at 2, 4, and 6 months.
So if the licensures for use in 2-month-olds come through soon as is expected, ACIP will need to address routine infant MCV immunization. Consider the complexity. It’s unlikely that Sanofi’s MenACWY-D will be licensed for this age soon, so it remains a candidate only for routine first dosing at 9 months of age. It would become almost obsolete if ACIP recommends routine 2, 4, and 6 month MCV dosing. However, a 2, 4, and 6 month recommendation raises added questions. Should the GSK HibMenCY be preferred over the Novartis MenACWY-CRM (which does not contain Hib) if both are FDA approved for 2-month-olds? And what impact would use of HibMenCY have on the use of Sanofi’s combo DTaP-Hib-IPV vaccine? You wouldn’t use HibMenCY with DTaP-Hib-IPV, because that would be a double dose of Hib vaccine.
So which approach would you use in your practice? It is something to consider. If ACIP recommends both for initial dosing at 2 months, vaccine buying groups may be making decisions for clinicians based on price and package deals. Regardless, it will further complicate the vaccine schedule. And if it is complicated for us, parents are going to be even less likely to understand if their child is "up to date."
The CDC organized the focus groups to help inform those decisions. One question was "Which type of disease do you think should be given priority when it comes to developing new vaccines?" Choices were those diseases that affect many people but aren’t severe; those that are relatively rare but if contracted can cause severe disability or death; or equal priority for both. The attendees had varied opinions, but 26% in Concord and 59% in Seattle chose the rare/severe option, while 34% in Chicago to 48% in Concord chose "equal priority for both."
They also asked, "How many children need to get a severe illness in a typical year in the United States to make it a good idea that children be vaccinated?" Options were 1 in 100, 1 in 1,000, 1 in 10,000, 1 in 100,000, or 1 in 1 million. While each option was picked by at least some participants, the 1 in 100 option was a frequent choice, ranging from 23% in Denver to 57% in Chicago.
When asked what they believed ACIP should recommend for MCV, most – ranging from 53% in Seattle to 86% in Chicago – chose "add the meningococcal vaccine to the schedule for infants/children, and recommend all children be vaccinated." The other choices were less popular. The "no ACIP or CDC recommendation, but add to the Vaccines for Children program" was chosen by 8%-31%, and "no ACIP/CDC recommendation and do not add to the VFC program" was chosen by 7%-21%.
And as for what they would be willing to pay out of pocket, the largest subset in Chicago (44%) and Concord (53%) agreed to pay the highest priced option for those cities (more than $150), while in Denver and Seattle, 31% and 34%, respectively, actually appeared willing to pay more than $500.
Of course, these are very small samples of likely biased data from subsets of the public having high interest in vaccines (positive or negative attitudes). Still, I think it’s a very interesting new direction the CDC has taken to elicit this kind of information when planning to discuss difficult vaccine policy decisions. At the very least, it improves transparency, which should hopefully help us when talking with our patients about new vaccine recommendations and the complicated schedules, whatever they may be.
Dr. Christopher J. Harrison is a professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison receives grant funding from GlaxoSmithKline for research trials of MMR.
At the next meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP), the group will need to decide whether to recommend routine meningococcal conjugate vaccine (MCV) use in infants. Because other federal committees recently suggested that the CDC engage the public before such decisions, the agency developed a new information-gathering process involving consumers. This took the form of focus group meetings designed to be open and to elicit input from those who might hold differing opinions about vaccines.
Over the summer, four pilot group meetings were held in Concord N.H., Chicago, Seattle, and Denver. There were about 100 attendees in Chicago and Seattle, and about half that number each in New Hampshire and Denver. Participants included provaccine groups such as the Meningitis Angels, who passionately support routine meningococcal immunization for young infants, representatives of the antivaccine group, who call themselves the National Vaccine Information Center, as well as more or less "neutral" individuals recruited through local health departments. They were asked a series of hypothetical questions about their opinions on use of new/future vaccines and the extent that they’d be willing to support and pay for such vaccines. The answers would likely apply to MCV.
Insights from these focus groups will likely play a role in ACIP’s October discussions of routine infant immunization against meningococcal disease. The decision is complicated because of three potentially competing vaccine formulations that are not currently interchangeable and with potentially different schedules:
• Sanofi-Pasteur’s MenACWY-D (Menactra) is currently licensed starting at 9 months of age in select high-risk groups, but could be expanded to all infants.
• Novartis’ MenACWY-CRM (Menveo) was recently approved for children ages 2 years and above, but is before the U.S. Food and Drug Administration (FDA) for licensure at 2, 4, and 6 months of age.
• A not yet licensed GlaxoSmithKline’s HibMenCY (MenHibRix) is a combination vaccine containing Haemophilus influenzae type b and meningococcal type A and C antigens. GSK is seeking licensure for use down to 2 months of age.
In June, ACIP recommended Sanofi-Pasteur’s quadrivalent MenACWY-D for specific high-risk children aged 9-23 months, such as travelers to meningococcal disease-endemic areas, infants with complement deficiencies, those in outbreak situations, and HIV-infected infants with other indications for vaccination. The committee postponed voting on whether 9- to 23-month-olds with functional or anatomic asplenia, including sickle cell disease, should receive this vaccine. This was due to data that pneumococcal geometric mean titers were reduced when MenACWY-D was given at the same time as pneumococcal conjugate vaccine (PCV-7). The clinical impact of such lower titers (that are still in the protective range) are unclear, but pneumococcus is a higher threat than meningococcus for these groups.
So what is the rationale for waiting until 9 months of age to begin MCV? For one, it avoids the need for a potential extra injection at 2, 4, and 6 months, and there are only two, not four doses. Also, none of the candidate MCVs contains meningococcal serotype B, the most common serotype affecting children less than 3 years of age. Several manufacturers are working on a B serogroup vaccine, which is years away from release. Lastly, the absolute number of annually prevented deaths (about five per year) would be relatively small among those less than 9 months of age.
What is the rationale for giving MCV at 2 months of age? Because children aged less than 3 years have the highest attack rate for invasive meningococcal disease (about 50% serogroup B and 50% of the other serogroups combined), it also makes sense to start MCV as early as possible to maximize reduction of nonserogroup-B invasive meningococcal disease. And if one used the GSK combo DTaP-Hep B- IPV vaccine plus Hib MenCY, there would not be additional injections at 2, 4, and 6 months.
So if the licensures for use in 2-month-olds come through soon as is expected, ACIP will need to address routine infant MCV immunization. Consider the complexity. It’s unlikely that Sanofi’s MenACWY-D will be licensed for this age soon, so it remains a candidate only for routine first dosing at 9 months of age. It would become almost obsolete if ACIP recommends routine 2, 4, and 6 month MCV dosing. However, a 2, 4, and 6 month recommendation raises added questions. Should the GSK HibMenCY be preferred over the Novartis MenACWY-CRM (which does not contain Hib) if both are FDA approved for 2-month-olds? And what impact would use of HibMenCY have on the use of Sanofi’s combo DTaP-Hib-IPV vaccine? You wouldn’t use HibMenCY with DTaP-Hib-IPV, because that would be a double dose of Hib vaccine.
So which approach would you use in your practice? It is something to consider. If ACIP recommends both for initial dosing at 2 months, vaccine buying groups may be making decisions for clinicians based on price and package deals. Regardless, it will further complicate the vaccine schedule. And if it is complicated for us, parents are going to be even less likely to understand if their child is "up to date."
The CDC organized the focus groups to help inform those decisions. One question was "Which type of disease do you think should be given priority when it comes to developing new vaccines?" Choices were those diseases that affect many people but aren’t severe; those that are relatively rare but if contracted can cause severe disability or death; or equal priority for both. The attendees had varied opinions, but 26% in Concord and 59% in Seattle chose the rare/severe option, while 34% in Chicago to 48% in Concord chose "equal priority for both."
They also asked, "How many children need to get a severe illness in a typical year in the United States to make it a good idea that children be vaccinated?" Options were 1 in 100, 1 in 1,000, 1 in 10,000, 1 in 100,000, or 1 in 1 million. While each option was picked by at least some participants, the 1 in 100 option was a frequent choice, ranging from 23% in Denver to 57% in Chicago.
When asked what they believed ACIP should recommend for MCV, most – ranging from 53% in Seattle to 86% in Chicago – chose "add the meningococcal vaccine to the schedule for infants/children, and recommend all children be vaccinated." The other choices were less popular. The "no ACIP or CDC recommendation, but add to the Vaccines for Children program" was chosen by 8%-31%, and "no ACIP/CDC recommendation and do not add to the VFC program" was chosen by 7%-21%.
And as for what they would be willing to pay out of pocket, the largest subset in Chicago (44%) and Concord (53%) agreed to pay the highest priced option for those cities (more than $150), while in Denver and Seattle, 31% and 34%, respectively, actually appeared willing to pay more than $500.
Of course, these are very small samples of likely biased data from subsets of the public having high interest in vaccines (positive or negative attitudes). Still, I think it’s a very interesting new direction the CDC has taken to elicit this kind of information when planning to discuss difficult vaccine policy decisions. At the very least, it improves transparency, which should hopefully help us when talking with our patients about new vaccine recommendations and the complicated schedules, whatever they may be.
Dr. Christopher J. Harrison is a professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison receives grant funding from GlaxoSmithKline for research trials of MMR.
At the next meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP), the group will need to decide whether to recommend routine meningococcal conjugate vaccine (MCV) use in infants. Because other federal committees recently suggested that the CDC engage the public before such decisions, the agency developed a new information-gathering process involving consumers. This took the form of focus group meetings designed to be open and to elicit input from those who might hold differing opinions about vaccines.
Over the summer, four pilot group meetings were held in Concord N.H., Chicago, Seattle, and Denver. There were about 100 attendees in Chicago and Seattle, and about half that number each in New Hampshire and Denver. Participants included provaccine groups such as the Meningitis Angels, who passionately support routine meningococcal immunization for young infants, representatives of the antivaccine group, who call themselves the National Vaccine Information Center, as well as more or less "neutral" individuals recruited through local health departments. They were asked a series of hypothetical questions about their opinions on use of new/future vaccines and the extent that they’d be willing to support and pay for such vaccines. The answers would likely apply to MCV.
Insights from these focus groups will likely play a role in ACIP’s October discussions of routine infant immunization against meningococcal disease. The decision is complicated because of three potentially competing vaccine formulations that are not currently interchangeable and with potentially different schedules:
• Sanofi-Pasteur’s MenACWY-D (Menactra) is currently licensed starting at 9 months of age in select high-risk groups, but could be expanded to all infants.
• Novartis’ MenACWY-CRM (Menveo) was recently approved for children ages 2 years and above, but is before the U.S. Food and Drug Administration (FDA) for licensure at 2, 4, and 6 months of age.
• A not yet licensed GlaxoSmithKline’s HibMenCY (MenHibRix) is a combination vaccine containing Haemophilus influenzae type b and meningococcal type A and C antigens. GSK is seeking licensure for use down to 2 months of age.
In June, ACIP recommended Sanofi-Pasteur’s quadrivalent MenACWY-D for specific high-risk children aged 9-23 months, such as travelers to meningococcal disease-endemic areas, infants with complement deficiencies, those in outbreak situations, and HIV-infected infants with other indications for vaccination. The committee postponed voting on whether 9- to 23-month-olds with functional or anatomic asplenia, including sickle cell disease, should receive this vaccine. This was due to data that pneumococcal geometric mean titers were reduced when MenACWY-D was given at the same time as pneumococcal conjugate vaccine (PCV-7). The clinical impact of such lower titers (that are still in the protective range) are unclear, but pneumococcus is a higher threat than meningococcus for these groups.
So what is the rationale for waiting until 9 months of age to begin MCV? For one, it avoids the need for a potential extra injection at 2, 4, and 6 months, and there are only two, not four doses. Also, none of the candidate MCVs contains meningococcal serotype B, the most common serotype affecting children less than 3 years of age. Several manufacturers are working on a B serogroup vaccine, which is years away from release. Lastly, the absolute number of annually prevented deaths (about five per year) would be relatively small among those less than 9 months of age.
What is the rationale for giving MCV at 2 months of age? Because children aged less than 3 years have the highest attack rate for invasive meningococcal disease (about 50% serogroup B and 50% of the other serogroups combined), it also makes sense to start MCV as early as possible to maximize reduction of nonserogroup-B invasive meningococcal disease. And if one used the GSK combo DTaP-Hep B- IPV vaccine plus Hib MenCY, there would not be additional injections at 2, 4, and 6 months.
So if the licensures for use in 2-month-olds come through soon as is expected, ACIP will need to address routine infant MCV immunization. Consider the complexity. It’s unlikely that Sanofi’s MenACWY-D will be licensed for this age soon, so it remains a candidate only for routine first dosing at 9 months of age. It would become almost obsolete if ACIP recommends routine 2, 4, and 6 month MCV dosing. However, a 2, 4, and 6 month recommendation raises added questions. Should the GSK HibMenCY be preferred over the Novartis MenACWY-CRM (which does not contain Hib) if both are FDA approved for 2-month-olds? And what impact would use of HibMenCY have on the use of Sanofi’s combo DTaP-Hib-IPV vaccine? You wouldn’t use HibMenCY with DTaP-Hib-IPV, because that would be a double dose of Hib vaccine.
So which approach would you use in your practice? It is something to consider. If ACIP recommends both for initial dosing at 2 months, vaccine buying groups may be making decisions for clinicians based on price and package deals. Regardless, it will further complicate the vaccine schedule. And if it is complicated for us, parents are going to be even less likely to understand if their child is "up to date."
The CDC organized the focus groups to help inform those decisions. One question was "Which type of disease do you think should be given priority when it comes to developing new vaccines?" Choices were those diseases that affect many people but aren’t severe; those that are relatively rare but if contracted can cause severe disability or death; or equal priority for both. The attendees had varied opinions, but 26% in Concord and 59% in Seattle chose the rare/severe option, while 34% in Chicago to 48% in Concord chose "equal priority for both."
They also asked, "How many children need to get a severe illness in a typical year in the United States to make it a good idea that children be vaccinated?" Options were 1 in 100, 1 in 1,000, 1 in 10,000, 1 in 100,000, or 1 in 1 million. While each option was picked by at least some participants, the 1 in 100 option was a frequent choice, ranging from 23% in Denver to 57% in Chicago.
When asked what they believed ACIP should recommend for MCV, most – ranging from 53% in Seattle to 86% in Chicago – chose "add the meningococcal vaccine to the schedule for infants/children, and recommend all children be vaccinated." The other choices were less popular. The "no ACIP or CDC recommendation, but add to the Vaccines for Children program" was chosen by 8%-31%, and "no ACIP/CDC recommendation and do not add to the VFC program" was chosen by 7%-21%.
And as for what they would be willing to pay out of pocket, the largest subset in Chicago (44%) and Concord (53%) agreed to pay the highest priced option for those cities (more than $150), while in Denver and Seattle, 31% and 34%, respectively, actually appeared willing to pay more than $500.
Of course, these are very small samples of likely biased data from subsets of the public having high interest in vaccines (positive or negative attitudes). Still, I think it’s a very interesting new direction the CDC has taken to elicit this kind of information when planning to discuss difficult vaccine policy decisions. At the very least, it improves transparency, which should hopefully help us when talking with our patients about new vaccine recommendations and the complicated schedules, whatever they may be.
Dr. Christopher J. Harrison is a professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison receives grant funding from GlaxoSmithKline for research trials of MMR.
Watch for Foodborne Illness
The recent Escherichia coli outbreak in Germany reminds us yet again about the threat of foodborne illness and the need for awareness about the clinical manifestations, the treatment, and the public health implications. On June 14, a 2-year-old boy became the first child and the 37th person to die in Germany's ongoing E. coli outbreak. Here in the United States, the Centers for Disease Control and Prevention estimates 48 million people – 1 in every 6 Americans – become ill, 128,000 are hospitalized, and 3,000 die of foodborne illness annually. About half of all foodborne illness occurs in children, who are particularly vulnerable because of their immature immune systems, lower body weight, and reduced stomach acid production.
Norovirus has become the most common recognized foodborne pathogen, causing about 5 million illnesses a year, followed by nontyphoidal Salmonella, with just over 1 million annual cases, and Clostridium perfringens, at just under 1 million, according to the CDC. Norovirus illness is usually mild, but it did cause an estimated 149 annual deaths. Nontyphoidal Salmonella is the most common serious cause of foodborne illness with an estimated 378 annual deaths, followed by Toxoplasma gondii (327 deaths) and Listeria monocytogenes (255 deaths).
The following foodborne illnesses are frequent causes of morbidity in children. Information on the possible foodborne sources and the effects of infection are from a report compiled by the Pew Health Group in collaboration with the Center for Foodborne Illness Research and Prevention.
▸ Salmonella. These infections occur in approximately 75 children/100,000 under age 4 years, according to the CDC. It is commonly associated with foods of animal origin, including beef, poultry, milk, and eggs, or cross-contamination from these with other foods. Typical symptoms include diarrhea, fever, and abdominal cramps. More serious short-term manifestations can include colitis, meningitis, septicemia, and death. Treatment involves rehydration as needed.
In general, antibiotic therapy is not warranted, but in immunocompromised hosts and children younger than age 6 months, antimicrobial therapy may be beneficial. In such settings, ceftriaxone is effective when susceptible, specifically in high-risk populations.
▸ Shigella. This infection occurs in about 28/100,000 children under age 4 years and 26/100,000 for those aged 4-11 years, according to the CDC. It is often associated with vegetables harvested in fields contaminated with sewage; flies that breed in infected feces and contaminate the food; and drinking, swimming, or playing in contaminated water. Short-term effects include high fever, diarrhea that is often bloody, stomach cramps, and seizures in children less than age 2 years. Reactive or chronic arthritis can be a postinfectious sequelae.
Treatment includes rehydration as necessary, and antibiotics for severe disease or dysentery, particularly in those with underlying immunosuppression. Ceftriaxone and ciprofloxacin are effective, although the latter is not licensed for use in young children. Resistance to amoxicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) is common. Treatment of mild cases may be indicated to shorten the duration of excretion.
▸ Campylobacter. This infection affects 29/100,000 children under age 4 years, similar in incidence to Shigella. Foodborne sources included raw or undercooked poultry or foods cross-contaminated by poultry, unpasteurized milk, and contaminated water. Symptoms include diarrhea (sometimes bloody), cramping, abdominal pain, urinary tract infection, fever, and meningitis. Campylobacter is also associated with Guillain-Barré syndrome or reactive/chronic arthritis. Again, treatment involves rehydration as necessary. Macrolides (azithromycin or erythromycin) can shorten duration of illness and prevent relapse.
▸ E. coli or other shiga toxin–producing strains. This foodborne infection has been in the headlines lately, and affects about 4/100,000 children between 4 and 11 years of age. Typical food sources include ground beef and other meats, green leafy vegetables, unpasteurized juices or raw milk, or soft cheeses made from raw milk. Symptoms include severe stomach cramps, diarrhea (often bloody), and vomiting. Hemolytic-uremic syndrome occurs in about 15% of children with E. coli 0157:H7 infection. This can result in long-term kidney damage as well as death.
In general, antibiotics have not been shown to benefit patients. Early reports of increased risk of hemolytic-uremic syndrome with antibiotic treatment have not been confirmed. As with the others, rehydration and supportive therapy are the mainstays of treatment.
▸ Listeria. This infection occurs in about 0.76/100,000 children under age 4 years, according to the CDC. About one-third of all cases involve pregnant women. Common food sources include uncooked meats, particularly cold cuts and hot dogs, as well as smoked seafood, raw milk, soft cheeses made from raw milk, and vegetables grown in contaminated soil or fertilizer. Symptoms include fever, muscle aches, nausea, and diarrhea. Headaches, stiff neck, confusion, loss of balance, and seizures can result if infection spreads to the nervous system.
For invasive disease, ampicillin plus an aminoglycoside is recommended. For penicillin-allergic patients, TMP-SMZ or high-dose vancomycin can be used. Cephalosporins are generally inactive. In the majority of patients with febrile gastroenteritis, the illness is self-limited (typical duration, 2 days or less) and therefore, generally no antibiotic treatment is necessary.
In pregnant women, listerial febrile gastroenteritis can lead to fetal death, premature birth, or infected newborns. Oral ampicillin or TMP-SMZ can be given for several days in immunocompromised or pregnant patients with listerial febrile gastroenteritis, particularly if they are still symptomatic once the culture result is known.
The recent Escherichia coli outbreak in Germany reminds us yet again about the threat of foodborne illness and the need for awareness about the clinical manifestations, the treatment, and the public health implications. On June 14, a 2-year-old boy became the first child and the 37th person to die in Germany's ongoing E. coli outbreak. Here in the United States, the Centers for Disease Control and Prevention estimates 48 million people – 1 in every 6 Americans – become ill, 128,000 are hospitalized, and 3,000 die of foodborne illness annually. About half of all foodborne illness occurs in children, who are particularly vulnerable because of their immature immune systems, lower body weight, and reduced stomach acid production.
Norovirus has become the most common recognized foodborne pathogen, causing about 5 million illnesses a year, followed by nontyphoidal Salmonella, with just over 1 million annual cases, and Clostridium perfringens, at just under 1 million, according to the CDC. Norovirus illness is usually mild, but it did cause an estimated 149 annual deaths. Nontyphoidal Salmonella is the most common serious cause of foodborne illness with an estimated 378 annual deaths, followed by Toxoplasma gondii (327 deaths) and Listeria monocytogenes (255 deaths).
The following foodborne illnesses are frequent causes of morbidity in children. Information on the possible foodborne sources and the effects of infection are from a report compiled by the Pew Health Group in collaboration with the Center for Foodborne Illness Research and Prevention.
▸ Salmonella. These infections occur in approximately 75 children/100,000 under age 4 years, according to the CDC. It is commonly associated with foods of animal origin, including beef, poultry, milk, and eggs, or cross-contamination from these with other foods. Typical symptoms include diarrhea, fever, and abdominal cramps. More serious short-term manifestations can include colitis, meningitis, septicemia, and death. Treatment involves rehydration as needed.
In general, antibiotic therapy is not warranted, but in immunocompromised hosts and children younger than age 6 months, antimicrobial therapy may be beneficial. In such settings, ceftriaxone is effective when susceptible, specifically in high-risk populations.
▸ Shigella. This infection occurs in about 28/100,000 children under age 4 years and 26/100,000 for those aged 4-11 years, according to the CDC. It is often associated with vegetables harvested in fields contaminated with sewage; flies that breed in infected feces and contaminate the food; and drinking, swimming, or playing in contaminated water. Short-term effects include high fever, diarrhea that is often bloody, stomach cramps, and seizures in children less than age 2 years. Reactive or chronic arthritis can be a postinfectious sequelae.
Treatment includes rehydration as necessary, and antibiotics for severe disease or dysentery, particularly in those with underlying immunosuppression. Ceftriaxone and ciprofloxacin are effective, although the latter is not licensed for use in young children. Resistance to amoxicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) is common. Treatment of mild cases may be indicated to shorten the duration of excretion.
▸ Campylobacter. This infection affects 29/100,000 children under age 4 years, similar in incidence to Shigella. Foodborne sources included raw or undercooked poultry or foods cross-contaminated by poultry, unpasteurized milk, and contaminated water. Symptoms include diarrhea (sometimes bloody), cramping, abdominal pain, urinary tract infection, fever, and meningitis. Campylobacter is also associated with Guillain-Barré syndrome or reactive/chronic arthritis. Again, treatment involves rehydration as necessary. Macrolides (azithromycin or erythromycin) can shorten duration of illness and prevent relapse.
▸ E. coli or other shiga toxin–producing strains. This foodborne infection has been in the headlines lately, and affects about 4/100,000 children between 4 and 11 years of age. Typical food sources include ground beef and other meats, green leafy vegetables, unpasteurized juices or raw milk, or soft cheeses made from raw milk. Symptoms include severe stomach cramps, diarrhea (often bloody), and vomiting. Hemolytic-uremic syndrome occurs in about 15% of children with E. coli 0157:H7 infection. This can result in long-term kidney damage as well as death.
In general, antibiotics have not been shown to benefit patients. Early reports of increased risk of hemolytic-uremic syndrome with antibiotic treatment have not been confirmed. As with the others, rehydration and supportive therapy are the mainstays of treatment.
▸ Listeria. This infection occurs in about 0.76/100,000 children under age 4 years, according to the CDC. About one-third of all cases involve pregnant women. Common food sources include uncooked meats, particularly cold cuts and hot dogs, as well as smoked seafood, raw milk, soft cheeses made from raw milk, and vegetables grown in contaminated soil or fertilizer. Symptoms include fever, muscle aches, nausea, and diarrhea. Headaches, stiff neck, confusion, loss of balance, and seizures can result if infection spreads to the nervous system.
For invasive disease, ampicillin plus an aminoglycoside is recommended. For penicillin-allergic patients, TMP-SMZ or high-dose vancomycin can be used. Cephalosporins are generally inactive. In the majority of patients with febrile gastroenteritis, the illness is self-limited (typical duration, 2 days or less) and therefore, generally no antibiotic treatment is necessary.
In pregnant women, listerial febrile gastroenteritis can lead to fetal death, premature birth, or infected newborns. Oral ampicillin or TMP-SMZ can be given for several days in immunocompromised or pregnant patients with listerial febrile gastroenteritis, particularly if they are still symptomatic once the culture result is known.
The recent Escherichia coli outbreak in Germany reminds us yet again about the threat of foodborne illness and the need for awareness about the clinical manifestations, the treatment, and the public health implications. On June 14, a 2-year-old boy became the first child and the 37th person to die in Germany's ongoing E. coli outbreak. Here in the United States, the Centers for Disease Control and Prevention estimates 48 million people – 1 in every 6 Americans – become ill, 128,000 are hospitalized, and 3,000 die of foodborne illness annually. About half of all foodborne illness occurs in children, who are particularly vulnerable because of their immature immune systems, lower body weight, and reduced stomach acid production.
Norovirus has become the most common recognized foodborne pathogen, causing about 5 million illnesses a year, followed by nontyphoidal Salmonella, with just over 1 million annual cases, and Clostridium perfringens, at just under 1 million, according to the CDC. Norovirus illness is usually mild, but it did cause an estimated 149 annual deaths. Nontyphoidal Salmonella is the most common serious cause of foodborne illness with an estimated 378 annual deaths, followed by Toxoplasma gondii (327 deaths) and Listeria monocytogenes (255 deaths).
The following foodborne illnesses are frequent causes of morbidity in children. Information on the possible foodborne sources and the effects of infection are from a report compiled by the Pew Health Group in collaboration with the Center for Foodborne Illness Research and Prevention.
▸ Salmonella. These infections occur in approximately 75 children/100,000 under age 4 years, according to the CDC. It is commonly associated with foods of animal origin, including beef, poultry, milk, and eggs, or cross-contamination from these with other foods. Typical symptoms include diarrhea, fever, and abdominal cramps. More serious short-term manifestations can include colitis, meningitis, septicemia, and death. Treatment involves rehydration as needed.
In general, antibiotic therapy is not warranted, but in immunocompromised hosts and children younger than age 6 months, antimicrobial therapy may be beneficial. In such settings, ceftriaxone is effective when susceptible, specifically in high-risk populations.
▸ Shigella. This infection occurs in about 28/100,000 children under age 4 years and 26/100,000 for those aged 4-11 years, according to the CDC. It is often associated with vegetables harvested in fields contaminated with sewage; flies that breed in infected feces and contaminate the food; and drinking, swimming, or playing in contaminated water. Short-term effects include high fever, diarrhea that is often bloody, stomach cramps, and seizures in children less than age 2 years. Reactive or chronic arthritis can be a postinfectious sequelae.
Treatment includes rehydration as necessary, and antibiotics for severe disease or dysentery, particularly in those with underlying immunosuppression. Ceftriaxone and ciprofloxacin are effective, although the latter is not licensed for use in young children. Resistance to amoxicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) is common. Treatment of mild cases may be indicated to shorten the duration of excretion.
▸ Campylobacter. This infection affects 29/100,000 children under age 4 years, similar in incidence to Shigella. Foodborne sources included raw or undercooked poultry or foods cross-contaminated by poultry, unpasteurized milk, and contaminated water. Symptoms include diarrhea (sometimes bloody), cramping, abdominal pain, urinary tract infection, fever, and meningitis. Campylobacter is also associated with Guillain-Barré syndrome or reactive/chronic arthritis. Again, treatment involves rehydration as necessary. Macrolides (azithromycin or erythromycin) can shorten duration of illness and prevent relapse.
▸ E. coli or other shiga toxin–producing strains. This foodborne infection has been in the headlines lately, and affects about 4/100,000 children between 4 and 11 years of age. Typical food sources include ground beef and other meats, green leafy vegetables, unpasteurized juices or raw milk, or soft cheeses made from raw milk. Symptoms include severe stomach cramps, diarrhea (often bloody), and vomiting. Hemolytic-uremic syndrome occurs in about 15% of children with E. coli 0157:H7 infection. This can result in long-term kidney damage as well as death.
In general, antibiotics have not been shown to benefit patients. Early reports of increased risk of hemolytic-uremic syndrome with antibiotic treatment have not been confirmed. As with the others, rehydration and supportive therapy are the mainstays of treatment.
▸ Listeria. This infection occurs in about 0.76/100,000 children under age 4 years, according to the CDC. About one-third of all cases involve pregnant women. Common food sources include uncooked meats, particularly cold cuts and hot dogs, as well as smoked seafood, raw milk, soft cheeses made from raw milk, and vegetables grown in contaminated soil or fertilizer. Symptoms include fever, muscle aches, nausea, and diarrhea. Headaches, stiff neck, confusion, loss of balance, and seizures can result if infection spreads to the nervous system.
For invasive disease, ampicillin plus an aminoglycoside is recommended. For penicillin-allergic patients, TMP-SMZ or high-dose vancomycin can be used. Cephalosporins are generally inactive. In the majority of patients with febrile gastroenteritis, the illness is self-limited (typical duration, 2 days or less) and therefore, generally no antibiotic treatment is necessary.
In pregnant women, listerial febrile gastroenteritis can lead to fetal death, premature birth, or infected newborns. Oral ampicillin or TMP-SMZ can be given for several days in immunocompromised or pregnant patients with listerial febrile gastroenteritis, particularly if they are still symptomatic once the culture result is known.
Unreliable Herd Immunity Leads to More Measles
The Centers for Disease Control and Prevention's summary of the alarming 118 U.S. cases of measles in 2011 reports that nearly all were caused by scattered inadvertent measles introduction from measles-endemic countries. This importation resulted from U.S. residents returning or immigrants coming from endemic countries. A dozen or so imported cases of measles are not unexpected or new. Every year, cases of imported measles occur.
So why is there an increase in the number of transmitted cases in the United States? Increased vulnerability to ongoing transmission is now possible because herd immunity has become unreliable.
Herd immunity in the past was often discussed in the context of protecting the less than 5% of the community who are too young (less than 12 months old) to receive MMR vaccine or who have true contraindications to vaccine. For measles, reliable herd immunity requires approximately 90% of the community to be immune to measles. To achieve this, we need 95% of the community immunized because approximately 5% of immunized children fail to become immune from a single immunization.
This became clear during the 1990s measles outbreaks and led to a recommendation for two doses, the second dose at 4–6 years of age. That controlled measles outbreaks until the past 2 years, when measles has been increasingly reported. Partly, this is due to the increase in the number of countries with endemic measles, including developed countries, most notably France, as reported in MMWR (2011:60;666-8). So the number of imported cases likely increased. But if herd immunity is strong, secondary cases should not be frequent.
What is new, and has directly led to many cases, is an increase in the number of geographic clusters of unvaccinated children due to parents delaying or refusing measles vaccine. In those areas, secondary cases are occurring at a rate not seen in decades. It's not that the overall national measles immunization rate is that much lower. The overall rate of one dose of MMR vaccine is near 90%, and two-dose coverage is around 80%.
The problem is that the extra geographically clustered 5% who choose to delay or avoid MMR vaccine permit transmission from imported cases mostly among unvaccinated children. In those areas, herd immunity is broken. Just this relatively small shift in local immunization density breaks down herd immunity to measles.
Why is it so? Measles is one of the three most contagious infections, being transmitted via airborne particles. Further, during the first 3 days of measles the presentation is a nonspecific febrile upper respiratory tract infection. So persons with measles often do not restrict their activity and may expose many people via normal activities or even in the reception rooms at medical facilities.
It is not until the third day or perhaps the fourth day of contagion and fever that the classic symptoms of cough, coryza, and nonpurulent conjunctivitis (the 3 C's) begin to appear, along with the beginnings of a maculopapular rash starting on the head. Because most clinicians under 60 years of age have little if any experience with measles, measles may go initially undiagnosed. This leads to additional exposures.
So imported measles added to focal weak spots in herd immunity to measles is the mechanism for increasing measles cases in the United States. Now children whose parents choose to avoid measles vaccine because the disease “is gone” or because of unfounded fears of adverse effects are no longer safe from disease. Note that 105 of the 118 (89%) cases were unvaccinated. And parents who would wish to vaccinate their children but cannot because of age or true contraindication also can no longer rely on herd immunity to protect their children.
This is a call to action. First, we should continue to be strong advocates for on-time MMR vaccination. We are unlikely to convince adamant antivaccine parents, but perhaps we can sway those who are merely conflicted by the false and discredited information promulgated by antivaccine groups.
Second, each of us needs to be aware of whether measles has occurred in our practice area, or in areas where our patients are planning to travel. If there is an expectation of possible exposure, consider administering the second MMR dose anytime more than 1 month after the first dose. And if the child is 9–12 months of age, consider giving a first dose prior to the usual 12 months of age. This will not be a valid dose per current Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics recommendations, but it may save the child from an illness with risks for both immediate and long-term severe pulmonary or neurological complications.
Third, don't miss the disease if it shows up in your patient. Be hypervigilant for the three C's plus high fever, and classic morbilliform rash.
Measles is in the air and until herd immunity is restored, expect cases in every major city in the United States. Hopefully, we as pediatric clinicians, in partnership with our local health departments, can make a difference and minimize these outbreaks.
The Centers for Disease Control and Prevention's summary of the alarming 118 U.S. cases of measles in 2011 reports that nearly all were caused by scattered inadvertent measles introduction from measles-endemic countries. This importation resulted from U.S. residents returning or immigrants coming from endemic countries. A dozen or so imported cases of measles are not unexpected or new. Every year, cases of imported measles occur.
So why is there an increase in the number of transmitted cases in the United States? Increased vulnerability to ongoing transmission is now possible because herd immunity has become unreliable.
Herd immunity in the past was often discussed in the context of protecting the less than 5% of the community who are too young (less than 12 months old) to receive MMR vaccine or who have true contraindications to vaccine. For measles, reliable herd immunity requires approximately 90% of the community to be immune to measles. To achieve this, we need 95% of the community immunized because approximately 5% of immunized children fail to become immune from a single immunization.
This became clear during the 1990s measles outbreaks and led to a recommendation for two doses, the second dose at 4–6 years of age. That controlled measles outbreaks until the past 2 years, when measles has been increasingly reported. Partly, this is due to the increase in the number of countries with endemic measles, including developed countries, most notably France, as reported in MMWR (2011:60;666-8). So the number of imported cases likely increased. But if herd immunity is strong, secondary cases should not be frequent.
What is new, and has directly led to many cases, is an increase in the number of geographic clusters of unvaccinated children due to parents delaying or refusing measles vaccine. In those areas, secondary cases are occurring at a rate not seen in decades. It's not that the overall national measles immunization rate is that much lower. The overall rate of one dose of MMR vaccine is near 90%, and two-dose coverage is around 80%.
The problem is that the extra geographically clustered 5% who choose to delay or avoid MMR vaccine permit transmission from imported cases mostly among unvaccinated children. In those areas, herd immunity is broken. Just this relatively small shift in local immunization density breaks down herd immunity to measles.
Why is it so? Measles is one of the three most contagious infections, being transmitted via airborne particles. Further, during the first 3 days of measles the presentation is a nonspecific febrile upper respiratory tract infection. So persons with measles often do not restrict their activity and may expose many people via normal activities or even in the reception rooms at medical facilities.
It is not until the third day or perhaps the fourth day of contagion and fever that the classic symptoms of cough, coryza, and nonpurulent conjunctivitis (the 3 C's) begin to appear, along with the beginnings of a maculopapular rash starting on the head. Because most clinicians under 60 years of age have little if any experience with measles, measles may go initially undiagnosed. This leads to additional exposures.
So imported measles added to focal weak spots in herd immunity to measles is the mechanism for increasing measles cases in the United States. Now children whose parents choose to avoid measles vaccine because the disease “is gone” or because of unfounded fears of adverse effects are no longer safe from disease. Note that 105 of the 118 (89%) cases were unvaccinated. And parents who would wish to vaccinate their children but cannot because of age or true contraindication also can no longer rely on herd immunity to protect their children.
This is a call to action. First, we should continue to be strong advocates for on-time MMR vaccination. We are unlikely to convince adamant antivaccine parents, but perhaps we can sway those who are merely conflicted by the false and discredited information promulgated by antivaccine groups.
Second, each of us needs to be aware of whether measles has occurred in our practice area, or in areas where our patients are planning to travel. If there is an expectation of possible exposure, consider administering the second MMR dose anytime more than 1 month after the first dose. And if the child is 9–12 months of age, consider giving a first dose prior to the usual 12 months of age. This will not be a valid dose per current Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics recommendations, but it may save the child from an illness with risks for both immediate and long-term severe pulmonary or neurological complications.
Third, don't miss the disease if it shows up in your patient. Be hypervigilant for the three C's plus high fever, and classic morbilliform rash.
Measles is in the air and until herd immunity is restored, expect cases in every major city in the United States. Hopefully, we as pediatric clinicians, in partnership with our local health departments, can make a difference and minimize these outbreaks.
The Centers for Disease Control and Prevention's summary of the alarming 118 U.S. cases of measles in 2011 reports that nearly all were caused by scattered inadvertent measles introduction from measles-endemic countries. This importation resulted from U.S. residents returning or immigrants coming from endemic countries. A dozen or so imported cases of measles are not unexpected or new. Every year, cases of imported measles occur.
So why is there an increase in the number of transmitted cases in the United States? Increased vulnerability to ongoing transmission is now possible because herd immunity has become unreliable.
Herd immunity in the past was often discussed in the context of protecting the less than 5% of the community who are too young (less than 12 months old) to receive MMR vaccine or who have true contraindications to vaccine. For measles, reliable herd immunity requires approximately 90% of the community to be immune to measles. To achieve this, we need 95% of the community immunized because approximately 5% of immunized children fail to become immune from a single immunization.
This became clear during the 1990s measles outbreaks and led to a recommendation for two doses, the second dose at 4–6 years of age. That controlled measles outbreaks until the past 2 years, when measles has been increasingly reported. Partly, this is due to the increase in the number of countries with endemic measles, including developed countries, most notably France, as reported in MMWR (2011:60;666-8). So the number of imported cases likely increased. But if herd immunity is strong, secondary cases should not be frequent.
What is new, and has directly led to many cases, is an increase in the number of geographic clusters of unvaccinated children due to parents delaying or refusing measles vaccine. In those areas, secondary cases are occurring at a rate not seen in decades. It's not that the overall national measles immunization rate is that much lower. The overall rate of one dose of MMR vaccine is near 90%, and two-dose coverage is around 80%.
The problem is that the extra geographically clustered 5% who choose to delay or avoid MMR vaccine permit transmission from imported cases mostly among unvaccinated children. In those areas, herd immunity is broken. Just this relatively small shift in local immunization density breaks down herd immunity to measles.
Why is it so? Measles is one of the three most contagious infections, being transmitted via airborne particles. Further, during the first 3 days of measles the presentation is a nonspecific febrile upper respiratory tract infection. So persons with measles often do not restrict their activity and may expose many people via normal activities or even in the reception rooms at medical facilities.
It is not until the third day or perhaps the fourth day of contagion and fever that the classic symptoms of cough, coryza, and nonpurulent conjunctivitis (the 3 C's) begin to appear, along with the beginnings of a maculopapular rash starting on the head. Because most clinicians under 60 years of age have little if any experience with measles, measles may go initially undiagnosed. This leads to additional exposures.
So imported measles added to focal weak spots in herd immunity to measles is the mechanism for increasing measles cases in the United States. Now children whose parents choose to avoid measles vaccine because the disease “is gone” or because of unfounded fears of adverse effects are no longer safe from disease. Note that 105 of the 118 (89%) cases were unvaccinated. And parents who would wish to vaccinate their children but cannot because of age or true contraindication also can no longer rely on herd immunity to protect their children.
This is a call to action. First, we should continue to be strong advocates for on-time MMR vaccination. We are unlikely to convince adamant antivaccine parents, but perhaps we can sway those who are merely conflicted by the false and discredited information promulgated by antivaccine groups.
Second, each of us needs to be aware of whether measles has occurred in our practice area, or in areas where our patients are planning to travel. If there is an expectation of possible exposure, consider administering the second MMR dose anytime more than 1 month after the first dose. And if the child is 9–12 months of age, consider giving a first dose prior to the usual 12 months of age. This will not be a valid dose per current Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics recommendations, but it may save the child from an illness with risks for both immediate and long-term severe pulmonary or neurological complications.
Third, don't miss the disease if it shows up in your patient. Be hypervigilant for the three C's plus high fever, and classic morbilliform rash.
Measles is in the air and until herd immunity is restored, expect cases in every major city in the United States. Hopefully, we as pediatric clinicians, in partnership with our local health departments, can make a difference and minimize these outbreaks.