ID Consult

 

In 1967, pediatric patients were vaccinated routinely against eight diseases with 10 vaccines: smallpox; diphtheria; tetanus and pertussis; polio serotypes 1, 2, and 3; measles; rubella; and mumps. Then in 1989, vaccine discovery took a dramatic upward trend. For the physicians and scientists involved in vaccine discovery, the driving force may have been a passion for scientific discovery and a humanitarian motivation, but what drove this major change in pediatric infectious diseases was economics.

KatarzynaBialasiewicz/Thinkstock

In 1989, I was fortunate to be part of the discovery team of the Haemophilus influenzae type b (Hib) polysaccharide and conjugate vaccines developed in Rochester, N.Y. Our team was led by David H. Smith, MD, and Porter Anderson, PhD – who later won the Lasker Prize for the significance of their work. Another team of scientists working at the National Institutes of Health was led by John Robbins, MD, and Rachel Schneerson, MD, where they concurrently developed a Hib conjugate vaccine using a different protein carrier and conjugation technology – they shared the Lasker Prize equally with Dr. Smith and Dr. Anderson.

I believe it was the success of the Hib conjugate vaccine that led to a renaissance in vaccine discovery that followed and continues to grow every year. The hiatus of more than 20 years between the introduction of the mumps vaccine in 1967 and that of the Hib vaccine in 1989 in my view was because the economic incentives to develop vaccines were absent. In fact, in the 1970s and early 1980s, vaccine manufacturers were drawing back from making vaccines because they were losing money selling them at a few dollars per dose.

Importantly, when the Hib conjugate vaccine was ready to be released, it had an unprecedented $15 per dose price. What followed was a big surprise to major pharmaceutical and vaccine companies: The Centers for Disease Control and Prevention and the American Academy of Pediatrics endorsed the use of the vaccine as routine. Private insurance companies were obliged to pay for vaccines as part of well-child care, and sales of the product proved profitable.

A trailblazing path had been created, and more and more vaccines have been discovered and come to market since then. Combination vaccines and vaccines for adolescents and adults have followed. The biggest blockbuster is Prevnar13 (actually 13 vaccines contained in a single combination), now with annual sales in excess of $7 billion worldwide and growing. Other vaccines with sales of a billion dollars or more are also on the market; anything in excess of $1 billion is considered a blockbuster in the pharmaceutical industry and gets the attention of CEOs (and investors) in a big way.

So now we have multiple large vaccine companies worldwide, and many smaller start-up vaccine companies as well. We have seen the introduction of vaccines in which not only infectious diseases are the target, but also more cancer prevention vaccines are coming to follow hepatitis B and human papillomavirus vaccines. Vaccines for other disease states – including autoimmune diseases, allergies, cardiovascular disease, diabetes, and many others – are in development. To me, this has been the most remarkable achievement of the past 50 years.
 

 

 

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute at Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. He has received funding awarded to his institution for vaccine research from GlaxoSmithKline, Merck, Pfizer, and Sanofi Pasteur. Email him at [email protected].

 

In 1967, pediatric patients were vaccinated routinely against eight diseases with 10 vaccines: smallpox; diphtheria; tetanus and pertussis; polio serotypes 1, 2, and 3; measles; rubella; and mumps. Then in 1989, vaccine discovery took a dramatic upward trend. For the physicians and scientists involved in vaccine discovery, the driving force may have been a passion for scientific discovery and a humanitarian motivation, but what drove this major change in pediatric infectious diseases was economics.

KatarzynaBialasiewicz/Thinkstock

In 1989, I was fortunate to be part of the discovery team of the Haemophilus influenzae type b (Hib) polysaccharide and conjugate vaccines developed in Rochester, N.Y. Our team was led by David H. Smith, MD, and Porter Anderson, PhD – who later won the Lasker Prize for the significance of their work. Another team of scientists working at the National Institutes of Health was led by John Robbins, MD, and Rachel Schneerson, MD, where they concurrently developed a Hib conjugate vaccine using a different protein carrier and conjugation technology – they shared the Lasker Prize equally with Dr. Smith and Dr. Anderson.

I believe it was the success of the Hib conjugate vaccine that led to a renaissance in vaccine discovery that followed and continues to grow every year. The hiatus of more than 20 years between the introduction of the mumps vaccine in 1967 and that of the Hib vaccine in 1989 in my view was because the economic incentives to develop vaccines were absent. In fact, in the 1970s and early 1980s, vaccine manufacturers were drawing back from making vaccines because they were losing money selling them at a few dollars per dose.

Importantly, when the Hib conjugate vaccine was ready to be released, it had an unprecedented $15 per dose price. What followed was a big surprise to major pharmaceutical and vaccine companies: The Centers for Disease Control and Prevention and the American Academy of Pediatrics endorsed the use of the vaccine as routine. Private insurance companies were obliged to pay for vaccines as part of well-child care, and sales of the product proved profitable.

A trailblazing path had been created, and more and more vaccines have been discovered and come to market since then. Combination vaccines and vaccines for adolescents and adults have followed. The biggest blockbuster is Prevnar13 (actually 13 vaccines contained in a single combination), now with annual sales in excess of $7 billion worldwide and growing. Other vaccines with sales of a billion dollars or more are also on the market; anything in excess of $1 billion is considered a blockbuster in the pharmaceutical industry and gets the attention of CEOs (and investors) in a big way.

So now we have multiple large vaccine companies worldwide, and many smaller start-up vaccine companies as well. We have seen the introduction of vaccines in which not only infectious diseases are the target, but also more cancer prevention vaccines are coming to follow hepatitis B and human papillomavirus vaccines. Vaccines for other disease states – including autoimmune diseases, allergies, cardiovascular disease, diabetes, and many others – are in development. To me, this has been the most remarkable achievement of the past 50 years.
 

 

 

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute at Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. He has received funding awarded to his institution for vaccine research from GlaxoSmithKline, Merck, Pfizer, and Sanofi Pasteur. Email him at [email protected].

 

In 1967, pediatric patients were vaccinated routinely against eight diseases with 10 vaccines: smallpox; diphtheria; tetanus and pertussis; polio serotypes 1, 2, and 3; measles; rubella; and mumps. Then in 1989, vaccine discovery took a dramatic upward trend. For the physicians and scientists involved in vaccine discovery, the driving force may have been a passion for scientific discovery and a humanitarian motivation, but what drove this major change in pediatric infectious diseases was economics.

KatarzynaBialasiewicz/Thinkstock

In 1989, I was fortunate to be part of the discovery team of the Haemophilus influenzae type b (Hib) polysaccharide and conjugate vaccines developed in Rochester, N.Y. Our team was led by David H. Smith, MD, and Porter Anderson, PhD – who later won the Lasker Prize for the significance of their work. Another team of scientists working at the National Institutes of Health was led by John Robbins, MD, and Rachel Schneerson, MD, where they concurrently developed a Hib conjugate vaccine using a different protein carrier and conjugation technology – they shared the Lasker Prize equally with Dr. Smith and Dr. Anderson.

I believe it was the success of the Hib conjugate vaccine that led to a renaissance in vaccine discovery that followed and continues to grow every year. The hiatus of more than 20 years between the introduction of the mumps vaccine in 1967 and that of the Hib vaccine in 1989 in my view was because the economic incentives to develop vaccines were absent. In fact, in the 1970s and early 1980s, vaccine manufacturers were drawing back from making vaccines because they were losing money selling them at a few dollars per dose.

Importantly, when the Hib conjugate vaccine was ready to be released, it had an unprecedented $15 per dose price. What followed was a big surprise to major pharmaceutical and vaccine companies: The Centers for Disease Control and Prevention and the American Academy of Pediatrics endorsed the use of the vaccine as routine. Private insurance companies were obliged to pay for vaccines as part of well-child care, and sales of the product proved profitable.

A trailblazing path had been created, and more and more vaccines have been discovered and come to market since then. Combination vaccines and vaccines for adolescents and adults have followed. The biggest blockbuster is Prevnar13 (actually 13 vaccines contained in a single combination), now with annual sales in excess of $7 billion worldwide and growing. Other vaccines with sales of a billion dollars or more are also on the market; anything in excess of $1 billion is considered a blockbuster in the pharmaceutical industry and gets the attention of CEOs (and investors) in a big way.

So now we have multiple large vaccine companies worldwide, and many smaller start-up vaccine companies as well. We have seen the introduction of vaccines in which not only infectious diseases are the target, but also more cancer prevention vaccines are coming to follow hepatitis B and human papillomavirus vaccines. Vaccines for other disease states – including autoimmune diseases, allergies, cardiovascular disease, diabetes, and many others – are in development. To me, this has been the most remarkable achievement of the past 50 years.
 

 

 

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute at Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. He has received funding awarded to his institution for vaccine research from GlaxoSmithKline, Merck, Pfizer, and Sanofi Pasteur. Email him at [email protected].

 

Malaria remains a major international public health concern. In 2015, the World Health Organization estimated that 212 million individuals were infected and that there were 429,000 deaths. This represents a 21% decline in incidence globally and a 29% decline in global mortality between 2010 and 2015. In 2016, malaria was endemic in 91 countries and territories, down from 108 in 2000. Although malaria has been eliminated from the United States since the early 1950s, approximately 1,700 cases are reported annually, most of which occur in returned travelers, according to the Centers for Disease Control and Prevention.

Courtesy NIAID

The elimination of malaria is multifaceted, including strategies for vector elimination, prevention of disease acquisition, early diagnosis, and effective treatment – a daunting challenge when one-half of the world’s population resides in an endemic area.

Five species of Plasmodium (P. falciparum, P. vivax, P. malariae, P. ovale, and, more recently, P. knowelsi) account for most of the infections in humans and are transmitted by the bite of an infected female Anopheles mosquito. The disease is rarely acquired by blood transfusion, by needle sharing, by organ transplantation, or congenitally. Once diagnosed, malaria can be treated; however, delay in initiating therapy can lead to both serious and fatal outcomes.
 

Treatment

Historically, drug development was driven by the need to protect the military. While quinine was isolated from the bark of the cinchona tree in 1820, chloroquine, proguanil, mefloquine, and atovaquone each were developed during or after a military conflict during 1945-1985. Tetracycline/doxycycline and clindamycin also have antimalarial activity. Use of any of these agents as monotherapy has led to drug resistance and treatment failure.

Artemisinin

Artemisinin (also known as qinghao su) and its derivatives are a new class of antimalarials derived from the sweet wormwood plant Artemisia annua. Initially developed in China in the 1970s, this class gained global attention in the 1990s. Artemisinin and its derivatives, artesunate, artemether, and dihydroartemisinin, are the most rapidly acting of all antimalarials and have the fastest parasite clearance time, rapid resolution of symptoms, and an excellent safety profile. They have activity against all Plasmodium species.

Because of artemisinins’ rapid elimination, they are used in combination with an agent that also kills blood parasites but has a slower elimination rate and a different mechanism of action. The goal is to prevent and delay the development of resistance and reduce recrudescence. The superiority of artemisinin-based combination therapy (ACT) over monotherapies has been documented.

In 2006, ACT was recommended as first-line therapy for treatment of uncomplicated P. falciparum and unknown species of Plasmodium malaria by the World Health Organization in malaria-endemic countries. Arthemeter/lumefantrine (Coartem), the first ACT in the United States, was licensed in 2009. Artesunate was recommended to replace quinine/quinidine for treatment of severe malaria in endemic countries in 2010. In the United States, intravenous artesunate is available through the CDC’s Investigational New Drug Application. To enroll a patient, contact the CDC Malaria Hotline at 770-488-7788. Treatment options in the United States include ACTs, but these currently are not first-line therapy. Refer to CDC.gov/malaria for specific treatment guidelines.

Resistance, always a concern, has remained limited to specific areas in Southeast Asia since reported in 2008. Monitoring drug efficacy, safety, quality of antimalarials is ongoing, as is discouraging monotherapy use of these agents. Globally, artemisinins are the mainstay of treatment. Spread of resistance would be a major setback for both malaria control and elimination.
 

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

 

Malaria remains a major international public health concern. In 2015, the World Health Organization estimated that 212 million individuals were infected and that there were 429,000 deaths. This represents a 21% decline in incidence globally and a 29% decline in global mortality between 2010 and 2015. In 2016, malaria was endemic in 91 countries and territories, down from 108 in 2000. Although malaria has been eliminated from the United States since the early 1950s, approximately 1,700 cases are reported annually, most of which occur in returned travelers, according to the Centers for Disease Control and Prevention.

Courtesy NIAID

The elimination of malaria is multifaceted, including strategies for vector elimination, prevention of disease acquisition, early diagnosis, and effective treatment – a daunting challenge when one-half of the world’s population resides in an endemic area.

Five species of Plasmodium (P. falciparum, P. vivax, P. malariae, P. ovale, and, more recently, P. knowelsi) account for most of the infections in humans and are transmitted by the bite of an infected female Anopheles mosquito. The disease is rarely acquired by blood transfusion, by needle sharing, by organ transplantation, or congenitally. Once diagnosed, malaria can be treated; however, delay in initiating therapy can lead to both serious and fatal outcomes.
 

Treatment

Historically, drug development was driven by the need to protect the military. While quinine was isolated from the bark of the cinchona tree in 1820, chloroquine, proguanil, mefloquine, and atovaquone each were developed during or after a military conflict during 1945-1985. Tetracycline/doxycycline and clindamycin also have antimalarial activity. Use of any of these agents as monotherapy has led to drug resistance and treatment failure.

Artemisinin

Artemisinin (also known as qinghao su) and its derivatives are a new class of antimalarials derived from the sweet wormwood plant Artemisia annua. Initially developed in China in the 1970s, this class gained global attention in the 1990s. Artemisinin and its derivatives, artesunate, artemether, and dihydroartemisinin, are the most rapidly acting of all antimalarials and have the fastest parasite clearance time, rapid resolution of symptoms, and an excellent safety profile. They have activity against all Plasmodium species.

Because of artemisinins’ rapid elimination, they are used in combination with an agent that also kills blood parasites but has a slower elimination rate and a different mechanism of action. The goal is to prevent and delay the development of resistance and reduce recrudescence. The superiority of artemisinin-based combination therapy (ACT) over monotherapies has been documented.

In 2006, ACT was recommended as first-line therapy for treatment of uncomplicated P. falciparum and unknown species of Plasmodium malaria by the World Health Organization in malaria-endemic countries. Arthemeter/lumefantrine (Coartem), the first ACT in the United States, was licensed in 2009. Artesunate was recommended to replace quinine/quinidine for treatment of severe malaria in endemic countries in 2010. In the United States, intravenous artesunate is available through the CDC’s Investigational New Drug Application. To enroll a patient, contact the CDC Malaria Hotline at 770-488-7788. Treatment options in the United States include ACTs, but these currently are not first-line therapy. Refer to CDC.gov/malaria for specific treatment guidelines.

Resistance, always a concern, has remained limited to specific areas in Southeast Asia since reported in 2008. Monitoring drug efficacy, safety, quality of antimalarials is ongoing, as is discouraging monotherapy use of these agents. Globally, artemisinins are the mainstay of treatment. Spread of resistance would be a major setback for both malaria control and elimination.
 

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

 

Malaria remains a major international public health concern. In 2015, the World Health Organization estimated that 212 million individuals were infected and that there were 429,000 deaths. This represents a 21% decline in incidence globally and a 29% decline in global mortality between 2010 and 2015. In 2016, malaria was endemic in 91 countries and territories, down from 108 in 2000. Although malaria has been eliminated from the United States since the early 1950s, approximately 1,700 cases are reported annually, most of which occur in returned travelers, according to the Centers for Disease Control and Prevention.

Courtesy NIAID

The elimination of malaria is multifaceted, including strategies for vector elimination, prevention of disease acquisition, early diagnosis, and effective treatment – a daunting challenge when one-half of the world’s population resides in an endemic area.

Five species of Plasmodium (P. falciparum, P. vivax, P. malariae, P. ovale, and, more recently, P. knowelsi) account for most of the infections in humans and are transmitted by the bite of an infected female Anopheles mosquito. The disease is rarely acquired by blood transfusion, by needle sharing, by organ transplantation, or congenitally. Once diagnosed, malaria can be treated; however, delay in initiating therapy can lead to both serious and fatal outcomes.
 

Treatment

Historically, drug development was driven by the need to protect the military. While quinine was isolated from the bark of the cinchona tree in 1820, chloroquine, proguanil, mefloquine, and atovaquone each were developed during or after a military conflict during 1945-1985. Tetracycline/doxycycline and clindamycin also have antimalarial activity. Use of any of these agents as monotherapy has led to drug resistance and treatment failure.

Artemisinin

Artemisinin (also known as qinghao su) and its derivatives are a new class of antimalarials derived from the sweet wormwood plant Artemisia annua. Initially developed in China in the 1970s, this class gained global attention in the 1990s. Artemisinin and its derivatives, artesunate, artemether, and dihydroartemisinin, are the most rapidly acting of all antimalarials and have the fastest parasite clearance time, rapid resolution of symptoms, and an excellent safety profile. They have activity against all Plasmodium species.

Because of artemisinins’ rapid elimination, they are used in combination with an agent that also kills blood parasites but has a slower elimination rate and a different mechanism of action. The goal is to prevent and delay the development of resistance and reduce recrudescence. The superiority of artemisinin-based combination therapy (ACT) over monotherapies has been documented.

In 2006, ACT was recommended as first-line therapy for treatment of uncomplicated P. falciparum and unknown species of Plasmodium malaria by the World Health Organization in malaria-endemic countries. Arthemeter/lumefantrine (Coartem), the first ACT in the United States, was licensed in 2009. Artesunate was recommended to replace quinine/quinidine for treatment of severe malaria in endemic countries in 2010. In the United States, intravenous artesunate is available through the CDC’s Investigational New Drug Application. To enroll a patient, contact the CDC Malaria Hotline at 770-488-7788. Treatment options in the United States include ACTs, but these currently are not first-line therapy. Refer to CDC.gov/malaria for specific treatment guidelines.

Resistance, always a concern, has remained limited to specific areas in Southeast Asia since reported in 2008. Monitoring drug efficacy, safety, quality of antimalarials is ongoing, as is discouraging monotherapy use of these agents. Globally, artemisinins are the mainstay of treatment. Spread of resistance would be a major setback for both malaria control and elimination.
 

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

 

In memory of Anne Marie Regan, CPNP, senior research coordinator, Pediatric HIV Program, Boston City Hospital

Our first child with perinatal HIV presented in 1985 at age 4 weeks with failure to thrive, vomiting, diarrhea, and thrush. Over the next several years, the number of HIV-infected infants grew exponentially, and by 1991, we were caring for more than 50 infants and children at Boston City Hospital.

Likewise, across the country, thousands more were being identified and cared for in pediatric programs. The complex nature of this disease required a novel approach. Replicated in multiple urban centers, we created a multidisciplinary program to address their needs, integrated with an National Institutes of Health–funded research agenda. We fought against the stigma facing those with HIV as well as the presumption that being a patient in the pediatric infectious diseases program implied a diagnosis of HIV. We advocated for access to care against a backdrop of fear of HIV acquisition in the medical community and supported our families who deemed HIV as a death sentence for themselves and their child. We worked with our colleagues in the prenatal program to expand HIV testing for pregnant women and to overcome their initial response, “Why test when the diagnosis just makes everyone sad?” We suffered the stresses of revealing each new diagnosis of HIV to a mother post partum (and the implication that she, too, was infected) and from our failures represented by infant deaths at a pace previously unknown to our infectious diseases program. Our team – made up of clinicians, socials workers, nurses and nurse practitioners, pharmacists, developmental specialists, pulmonologists, neurologists, and investigators – all worked in concert to provide the necessary care, but more importantly to gain the trust of our patients and families.

Antiretrovirals were marginally effective for HIV-infected infants and children at this time. Subsequently, we embarked on a national effort to prevent vertical transmission. We participated first in the study of pharmacokinetics of zidovudine (AZT) in newborns. We enrolled patients in ACTG 076 to test the hypothesis that treatment with AZT during pregnancy and labor, and in the infant, would reduce the risk of vertical transmission. Fifty U.S. and nine French sites enrolled 473 women between April 1991 and December 20, 1993. The results were spectacular; 8 of 100 infants in the AZT treatment group, compared with 25 out of 100 infants in the control group, developed HIV. By 1995, HIV testing was offered to all women at Boston Medical Center (formerly Boston City Hospital), and the promise of prevention of vertical transmission was reaching fruition. Between 1996 and 2016, approximately 500 HIV-infected women delivered at Boston Medical Center with vertical transmission identified in only 6 (1.2%) infants; without ACTG 076, we would have expected 125! In 2013, the Centers for Disease Control and Prevention reported that 70% of pregnant HIV-infected women received the complete 076 regimen, and 93% of mothers or infants received some part of the regimen. In 1992, 900 HIV-infected infants were diagnosed in the United States, and as many as 2,000 newborns were estimated to have been born infected with HIV; in 2015, 86 vertical transmissions were identified. This was, and remains, a remarkable accomplishment.

The successful interruption of HIV vertical transmission was a landmark turning point. Thousands of infants have been spared the burden of HIV disease, initially in high-income countries and now globally. Progress and success were possible only because of the brave HIV-infected women who volunteered for experimental protocols and the unsung nurses, nurse practitioners, social workers, and research teams that won the trust of these women and encouraged them to participate. There still is much to do to make it possible for all HIV-infected pregnant women to receive effective antiretroviral therapy. But we also can reflect back on the day we could imagine the end of the pediatric HIV epidemic and say we were part of it.
 

Dr. Pelton is chief of pediatric infectious diseases and coordinator of the maternal-child HIV program at Boston Medical Center. Ms. Moloney is a certified pediatric nurse practitioner in the division of pediatric infectious diseases. Dr. Pelton said he had no relevant financial disclosures, and Ms. Moloney is a speaker (on vaccines) for Sanofi Pasteur. Email them at [email protected].

 

In memory of Anne Marie Regan, CPNP, senior research coordinator, Pediatric HIV Program, Boston City Hospital

Our first child with perinatal HIV presented in 1985 at age 4 weeks with failure to thrive, vomiting, diarrhea, and thrush. Over the next several years, the number of HIV-infected infants grew exponentially, and by 1991, we were caring for more than 50 infants and children at Boston City Hospital.

Likewise, across the country, thousands more were being identified and cared for in pediatric programs. The complex nature of this disease required a novel approach. Replicated in multiple urban centers, we created a multidisciplinary program to address their needs, integrated with an National Institutes of Health–funded research agenda. We fought against the stigma facing those with HIV as well as the presumption that being a patient in the pediatric infectious diseases program implied a diagnosis of HIV. We advocated for access to care against a backdrop of fear of HIV acquisition in the medical community and supported our families who deemed HIV as a death sentence for themselves and their child. We worked with our colleagues in the prenatal program to expand HIV testing for pregnant women and to overcome their initial response, “Why test when the diagnosis just makes everyone sad?” We suffered the stresses of revealing each new diagnosis of HIV to a mother post partum (and the implication that she, too, was infected) and from our failures represented by infant deaths at a pace previously unknown to our infectious diseases program. Our team – made up of clinicians, socials workers, nurses and nurse practitioners, pharmacists, developmental specialists, pulmonologists, neurologists, and investigators – all worked in concert to provide the necessary care, but more importantly to gain the trust of our patients and families.

Antiretrovirals were marginally effective for HIV-infected infants and children at this time. Subsequently, we embarked on a national effort to prevent vertical transmission. We participated first in the study of pharmacokinetics of zidovudine (AZT) in newborns. We enrolled patients in ACTG 076 to test the hypothesis that treatment with AZT during pregnancy and labor, and in the infant, would reduce the risk of vertical transmission. Fifty U.S. and nine French sites enrolled 473 women between April 1991 and December 20, 1993. The results were spectacular; 8 of 100 infants in the AZT treatment group, compared with 25 out of 100 infants in the control group, developed HIV. By 1995, HIV testing was offered to all women at Boston Medical Center (formerly Boston City Hospital), and the promise of prevention of vertical transmission was reaching fruition. Between 1996 and 2016, approximately 500 HIV-infected women delivered at Boston Medical Center with vertical transmission identified in only 6 (1.2%) infants; without ACTG 076, we would have expected 125! In 2013, the Centers for Disease Control and Prevention reported that 70% of pregnant HIV-infected women received the complete 076 regimen, and 93% of mothers or infants received some part of the regimen. In 1992, 900 HIV-infected infants were diagnosed in the United States, and as many as 2,000 newborns were estimated to have been born infected with HIV; in 2015, 86 vertical transmissions were identified. This was, and remains, a remarkable accomplishment.

The successful interruption of HIV vertical transmission was a landmark turning point. Thousands of infants have been spared the burden of HIV disease, initially in high-income countries and now globally. Progress and success were possible only because of the brave HIV-infected women who volunteered for experimental protocols and the unsung nurses, nurse practitioners, social workers, and research teams that won the trust of these women and encouraged them to participate. There still is much to do to make it possible for all HIV-infected pregnant women to receive effective antiretroviral therapy. But we also can reflect back on the day we could imagine the end of the pediatric HIV epidemic and say we were part of it.
 

Dr. Pelton is chief of pediatric infectious diseases and coordinator of the maternal-child HIV program at Boston Medical Center. Ms. Moloney is a certified pediatric nurse practitioner in the division of pediatric infectious diseases. Dr. Pelton said he had no relevant financial disclosures, and Ms. Moloney is a speaker (on vaccines) for Sanofi Pasteur. Email them at [email protected].

 

In memory of Anne Marie Regan, CPNP, senior research coordinator, Pediatric HIV Program, Boston City Hospital

Our first child with perinatal HIV presented in 1985 at age 4 weeks with failure to thrive, vomiting, diarrhea, and thrush. Over the next several years, the number of HIV-infected infants grew exponentially, and by 1991, we were caring for more than 50 infants and children at Boston City Hospital.

Likewise, across the country, thousands more were being identified and cared for in pediatric programs. The complex nature of this disease required a novel approach. Replicated in multiple urban centers, we created a multidisciplinary program to address their needs, integrated with an National Institutes of Health–funded research agenda. We fought against the stigma facing those with HIV as well as the presumption that being a patient in the pediatric infectious diseases program implied a diagnosis of HIV. We advocated for access to care against a backdrop of fear of HIV acquisition in the medical community and supported our families who deemed HIV as a death sentence for themselves and their child. We worked with our colleagues in the prenatal program to expand HIV testing for pregnant women and to overcome their initial response, “Why test when the diagnosis just makes everyone sad?” We suffered the stresses of revealing each new diagnosis of HIV to a mother post partum (and the implication that she, too, was infected) and from our failures represented by infant deaths at a pace previously unknown to our infectious diseases program. Our team – made up of clinicians, socials workers, nurses and nurse practitioners, pharmacists, developmental specialists, pulmonologists, neurologists, and investigators – all worked in concert to provide the necessary care, but more importantly to gain the trust of our patients and families.

Antiretrovirals were marginally effective for HIV-infected infants and children at this time. Subsequently, we embarked on a national effort to prevent vertical transmission. We participated first in the study of pharmacokinetics of zidovudine (AZT) in newborns. We enrolled patients in ACTG 076 to test the hypothesis that treatment with AZT during pregnancy and labor, and in the infant, would reduce the risk of vertical transmission. Fifty U.S. and nine French sites enrolled 473 women between April 1991 and December 20, 1993. The results were spectacular; 8 of 100 infants in the AZT treatment group, compared with 25 out of 100 infants in the control group, developed HIV. By 1995, HIV testing was offered to all women at Boston Medical Center (formerly Boston City Hospital), and the promise of prevention of vertical transmission was reaching fruition. Between 1996 and 2016, approximately 500 HIV-infected women delivered at Boston Medical Center with vertical transmission identified in only 6 (1.2%) infants; without ACTG 076, we would have expected 125! In 2013, the Centers for Disease Control and Prevention reported that 70% of pregnant HIV-infected women received the complete 076 regimen, and 93% of mothers or infants received some part of the regimen. In 1992, 900 HIV-infected infants were diagnosed in the United States, and as many as 2,000 newborns were estimated to have been born infected with HIV; in 2015, 86 vertical transmissions were identified. This was, and remains, a remarkable accomplishment.

The successful interruption of HIV vertical transmission was a landmark turning point. Thousands of infants have been spared the burden of HIV disease, initially in high-income countries and now globally. Progress and success were possible only because of the brave HIV-infected women who volunteered for experimental protocols and the unsung nurses, nurse practitioners, social workers, and research teams that won the trust of these women and encouraged them to participate. There still is much to do to make it possible for all HIV-infected pregnant women to receive effective antiretroviral therapy. But we also can reflect back on the day we could imagine the end of the pediatric HIV epidemic and say we were part of it.
 

Dr. Pelton is chief of pediatric infectious diseases and coordinator of the maternal-child HIV program at Boston Medical Center. Ms. Moloney is a certified pediatric nurse practitioner in the division of pediatric infectious diseases. Dr. Pelton said he had no relevant financial disclosures, and Ms. Moloney is a speaker (on vaccines) for Sanofi Pasteur. Email them at [email protected].

 

I recently received a group text from a friend voicing her frustration that her neighbor had acquired chickens, and she shared a photo of some roaming freely in the front yard. Naturally, my response was related to the potential infectious disease exposure and infections. Another friend chimed in “fresh eggs, and these are free range chickens. They don’t get sick. ... Many people in my area have chickens.” Unbeknownst to my friends, they had helped me select the ID Consult topic for this month.

Nontyphoidal Salmonella bacteria are associated with a wide spectrum of infections which range from asymptomatic gastrointestinal carriage to bacteremia, meningitis, osteomyelitis, and focal infections. Invasive disease is seen most often in children younger than 5 years of age, persons aged 65 years or older, and individuals with hemoglobinopathies including sickle cell disease and those with immunodeficiencies. Annually, the Centers for Disease Control and Prevention estimates that nontyphoidal salmonellosis is responsible for 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths in the United States. Gastroenteritis is the most common manifestation of the disease and is characterized by abdominal cramps, diarrhea, and fever that develops 12-72 hours after exposure. It is usually self-limited. As previously reported in this column (June, 2017), Salmonella is one of the top two foodborne pathogens in the United States, and most outbreaks have been associated with consumption of contaminated food. But wait, contaminated food is not the only cause of some of our most recent outbreaks.

JasonJiron/Thinkstock

Salmonella is a zoonotic bacteria commonly found in the intestinal tract of several animals including poultry (chickens, ducks, geese, and turkeys), reptiles, and amphibians. Humans can acquire infection after both direct and indirect contact with infected animals. Most infected animals are asymptomatic and shed bacteria intermittently. Current U.S. outbreaks involve both pet turtles and poultry. Let’s stay focused on poultry.

Live poultry-associated salmonellosis (LPAS)

LPAS was first reported in the 1950s. More recent epidemiologic data was published by C. Basler et al. (Emerging Infect Dis. 2016;22[10]:1705-11). LPAS was defined as two or more culture confirmed human Salmonella infections with a combination of epidemiologic, laboratory, or traceback evidence linking illnesses to contact with live poultry. From 1990 to 2014, a total of 53 LPAS outbreaks in the United States were documented and associated with 2,630 illnesses, 387 hospitalizations, and 5 deaths. The median outbreak size involved 26 cases (range, 4-363) and 77% (41 of 53) were multistate. The median age of the patients was 9 years (range, less than 1 to 92 years), and 31% were aged 5 years or younger. Exposure to chicks and ducklings was reported in 85% and 38%, respectively. High-risk practices included keeping poultry inside of the home (46%), snuggling baby birds (49%), and kissing baby birds (13%). The median time from purchase of poultry to onset of illness was 17 days (range, 1-672), and 66% reported onset of illness less than 30 days after purchase. Almost 52% reported owning poultry for less than 1 year.

The number of outbreaks continued to increase. From 1990 to 2005, there were a total of 17 outbreaks, compared with 36 between 2006 and 2014. Historically, outbreaks occurred in children around Easter when brightly colored dyed chicks were purchased. In the above review, 80% of outbreaks began in February, March, or April with an average duration of 4.9 months (range, 1-12).

Salmonella isolates

Serotypes traditionally associated with foodborne outbreaks are not usually isolated in LPAS outbreaks. Most chicks are acquired from small mail order hatcheries that house multiple species, and the potential for comingling exists not only of birds but their pathogens. In contrast, commercial hatcheries typically are closed facilities with one breed. It is thought that this is one reason for multiple serotypes associated with backyard flock associated salmonellosis. In the 1990-2014 review, while S. montivideo was the most common serotype isolated (36%), 5 other serotypes also were reported.

Backyard flocks and LPAS

More recently outbreaks have been associated with backyard flocks occurring year round and affecting both adults and children in contrast to seasonal peaks. The first multistate backyard flock outbreak was documented in 2007. Currently, the CDC is investigating 10 separate multistate outbreaks that began on Jan. 4, 2017. It involves 48 states, 961 infected individuals, 215 hospitalizations, and 1 death. At least 5 salmonella serotypes have been isolated.

What about the hatcheries?

It’s estimated that 50 million live poultry are sold annually. Birds are shipped within 24 hours after hatching via the U.S. Postal Service in boxes containing up to 100 chicks. Delivery occurs within 72 hours of hatching. Approximately 20 mail order hatcheries provide the majority of poultry sold to the general public. The National Poultry Improvement Plan (NPIP) is a voluntary state and federal testing and certification program whose goal is to eliminate poultry disease from breeder flocks to prevent egg-transmitted and hatchery-disseminated diseases. All hatcheries may participate. They also may participate in the voluntary Salmonella monitoring program. Note participation is not mandatory.

Preventing future outbreaks: patient/parental education is mandatory

1. Make sure your parents know about the association of Salmonella and live poultry. Reinforce these are farm animals, not pets. Purchase birds from hatcheries that participate in NPIP and the Salmonella monitoring programs.

2. Chicks, ducklings, or other live poultry should not be taken to schools, day care facilities, or nursing homes. Poultry should not be allowed in the home or in areas where food or drink is being prepared or consumed.

3. Poultry should not be snuggled, kissed, or allowed to touch one’s mouth. Hand washing with soap and water should occur after touching live poultry or any object touched in areas where they live or roam.

4. Contact with live poultry should be avoided in those at risk for developing serious infections including persons aged 5 years or younger, 65 years or older, immunocompromised individuals, and those with hemoglobinopathies.

5. All equipment used to care for live birds should be washed outdoors. Owners should have designated shoes when caring for poultry which should never be worn inside the home.

Hopefully, the next time you see a patient with fever and diarrhea you will recall this topic and ask about their contact with live poultry.

Additional resources to facilitate discussions can be found at www.cdc.gov/salmonella.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

 

I recently received a group text from a friend voicing her frustration that her neighbor had acquired chickens, and she shared a photo of some roaming freely in the front yard. Naturally, my response was related to the potential infectious disease exposure and infections. Another friend chimed in “fresh eggs, and these are free range chickens. They don’t get sick. ... Many people in my area have chickens.” Unbeknownst to my friends, they had helped me select the ID Consult topic for this month.

Nontyphoidal Salmonella bacteria are associated with a wide spectrum of infections which range from asymptomatic gastrointestinal carriage to bacteremia, meningitis, osteomyelitis, and focal infections. Invasive disease is seen most often in children younger than 5 years of age, persons aged 65 years or older, and individuals with hemoglobinopathies including sickle cell disease and those with immunodeficiencies. Annually, the Centers for Disease Control and Prevention estimates that nontyphoidal salmonellosis is responsible for 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths in the United States. Gastroenteritis is the most common manifestation of the disease and is characterized by abdominal cramps, diarrhea, and fever that develops 12-72 hours after exposure. It is usually self-limited. As previously reported in this column (June, 2017), Salmonella is one of the top two foodborne pathogens in the United States, and most outbreaks have been associated with consumption of contaminated food. But wait, contaminated food is not the only cause of some of our most recent outbreaks.

JasonJiron/Thinkstock

Salmonella is a zoonotic bacteria commonly found in the intestinal tract of several animals including poultry (chickens, ducks, geese, and turkeys), reptiles, and amphibians. Humans can acquire infection after both direct and indirect contact with infected animals. Most infected animals are asymptomatic and shed bacteria intermittently. Current U.S. outbreaks involve both pet turtles and poultry. Let’s stay focused on poultry.

Live poultry-associated salmonellosis (LPAS)

LPAS was first reported in the 1950s. More recent epidemiologic data was published by C. Basler et al. (Emerging Infect Dis. 2016;22[10]:1705-11). LPAS was defined as two or more culture confirmed human Salmonella infections with a combination of epidemiologic, laboratory, or traceback evidence linking illnesses to contact with live poultry. From 1990 to 2014, a total of 53 LPAS outbreaks in the United States were documented and associated with 2,630 illnesses, 387 hospitalizations, and 5 deaths. The median outbreak size involved 26 cases (range, 4-363) and 77% (41 of 53) were multistate. The median age of the patients was 9 years (range, less than 1 to 92 years), and 31% were aged 5 years or younger. Exposure to chicks and ducklings was reported in 85% and 38%, respectively. High-risk practices included keeping poultry inside of the home (46%), snuggling baby birds (49%), and kissing baby birds (13%). The median time from purchase of poultry to onset of illness was 17 days (range, 1-672), and 66% reported onset of illness less than 30 days after purchase. Almost 52% reported owning poultry for less than 1 year.

The number of outbreaks continued to increase. From 1990 to 2005, there were a total of 17 outbreaks, compared with 36 between 2006 and 2014. Historically, outbreaks occurred in children around Easter when brightly colored dyed chicks were purchased. In the above review, 80% of outbreaks began in February, March, or April with an average duration of 4.9 months (range, 1-12).

Salmonella isolates

Serotypes traditionally associated with foodborne outbreaks are not usually isolated in LPAS outbreaks. Most chicks are acquired from small mail order hatcheries that house multiple species, and the potential for comingling exists not only of birds but their pathogens. In contrast, commercial hatcheries typically are closed facilities with one breed. It is thought that this is one reason for multiple serotypes associated with backyard flock associated salmonellosis. In the 1990-2014 review, while S. montivideo was the most common serotype isolated (36%), 5 other serotypes also were reported.

Backyard flocks and LPAS

More recently outbreaks have been associated with backyard flocks occurring year round and affecting both adults and children in contrast to seasonal peaks. The first multistate backyard flock outbreak was documented in 2007. Currently, the CDC is investigating 10 separate multistate outbreaks that began on Jan. 4, 2017. It involves 48 states, 961 infected individuals, 215 hospitalizations, and 1 death. At least 5 salmonella serotypes have been isolated.

What about the hatcheries?

It’s estimated that 50 million live poultry are sold annually. Birds are shipped within 24 hours after hatching via the U.S. Postal Service in boxes containing up to 100 chicks. Delivery occurs within 72 hours of hatching. Approximately 20 mail order hatcheries provide the majority of poultry sold to the general public. The National Poultry Improvement Plan (NPIP) is a voluntary state and federal testing and certification program whose goal is to eliminate poultry disease from breeder flocks to prevent egg-transmitted and hatchery-disseminated diseases. All hatcheries may participate. They also may participate in the voluntary Salmonella monitoring program. Note participation is not mandatory.

Preventing future outbreaks: patient/parental education is mandatory

1. Make sure your parents know about the association of Salmonella and live poultry. Reinforce these are farm animals, not pets. Purchase birds from hatcheries that participate in NPIP and the Salmonella monitoring programs.

2. Chicks, ducklings, or other live poultry should not be taken to schools, day care facilities, or nursing homes. Poultry should not be allowed in the home or in areas where food or drink is being prepared or consumed.

3. Poultry should not be snuggled, kissed, or allowed to touch one’s mouth. Hand washing with soap and water should occur after touching live poultry or any object touched in areas where they live or roam.

4. Contact with live poultry should be avoided in those at risk for developing serious infections including persons aged 5 years or younger, 65 years or older, immunocompromised individuals, and those with hemoglobinopathies.

5. All equipment used to care for live birds should be washed outdoors. Owners should have designated shoes when caring for poultry which should never be worn inside the home.

Hopefully, the next time you see a patient with fever and diarrhea you will recall this topic and ask about their contact with live poultry.

Additional resources to facilitate discussions can be found at www.cdc.gov/salmonella.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

 

I recently received a group text from a friend voicing her frustration that her neighbor had acquired chickens, and she shared a photo of some roaming freely in the front yard. Naturally, my response was related to the potential infectious disease exposure and infections. Another friend chimed in “fresh eggs, and these are free range chickens. They don’t get sick. ... Many people in my area have chickens.” Unbeknownst to my friends, they had helped me select the ID Consult topic for this month.

Nontyphoidal Salmonella bacteria are associated with a wide spectrum of infections which range from asymptomatic gastrointestinal carriage to bacteremia, meningitis, osteomyelitis, and focal infections. Invasive disease is seen most often in children younger than 5 years of age, persons aged 65 years or older, and individuals with hemoglobinopathies including sickle cell disease and those with immunodeficiencies. Annually, the Centers for Disease Control and Prevention estimates that nontyphoidal salmonellosis is responsible for 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths in the United States. Gastroenteritis is the most common manifestation of the disease and is characterized by abdominal cramps, diarrhea, and fever that develops 12-72 hours after exposure. It is usually self-limited. As previously reported in this column (June, 2017), Salmonella is one of the top two foodborne pathogens in the United States, and most outbreaks have been associated with consumption of contaminated food. But wait, contaminated food is not the only cause of some of our most recent outbreaks.

JasonJiron/Thinkstock

Salmonella is a zoonotic bacteria commonly found in the intestinal tract of several animals including poultry (chickens, ducks, geese, and turkeys), reptiles, and amphibians. Humans can acquire infection after both direct and indirect contact with infected animals. Most infected animals are asymptomatic and shed bacteria intermittently. Current U.S. outbreaks involve both pet turtles and poultry. Let’s stay focused on poultry.

Live poultry-associated salmonellosis (LPAS)

LPAS was first reported in the 1950s. More recent epidemiologic data was published by C. Basler et al. (Emerging Infect Dis. 2016;22[10]:1705-11). LPAS was defined as two or more culture confirmed human Salmonella infections with a combination of epidemiologic, laboratory, or traceback evidence linking illnesses to contact with live poultry. From 1990 to 2014, a total of 53 LPAS outbreaks in the United States were documented and associated with 2,630 illnesses, 387 hospitalizations, and 5 deaths. The median outbreak size involved 26 cases (range, 4-363) and 77% (41 of 53) were multistate. The median age of the patients was 9 years (range, less than 1 to 92 years), and 31% were aged 5 years or younger. Exposure to chicks and ducklings was reported in 85% and 38%, respectively. High-risk practices included keeping poultry inside of the home (46%), snuggling baby birds (49%), and kissing baby birds (13%). The median time from purchase of poultry to onset of illness was 17 days (range, 1-672), and 66% reported onset of illness less than 30 days after purchase. Almost 52% reported owning poultry for less than 1 year.

The number of outbreaks continued to increase. From 1990 to 2005, there were a total of 17 outbreaks, compared with 36 between 2006 and 2014. Historically, outbreaks occurred in children around Easter when brightly colored dyed chicks were purchased. In the above review, 80% of outbreaks began in February, March, or April with an average duration of 4.9 months (range, 1-12).

Salmonella isolates

Serotypes traditionally associated with foodborne outbreaks are not usually isolated in LPAS outbreaks. Most chicks are acquired from small mail order hatcheries that house multiple species, and the potential for comingling exists not only of birds but their pathogens. In contrast, commercial hatcheries typically are closed facilities with one breed. It is thought that this is one reason for multiple serotypes associated with backyard flock associated salmonellosis. In the 1990-2014 review, while S. montivideo was the most common serotype isolated (36%), 5 other serotypes also were reported.

Backyard flocks and LPAS

More recently outbreaks have been associated with backyard flocks occurring year round and affecting both adults and children in contrast to seasonal peaks. The first multistate backyard flock outbreak was documented in 2007. Currently, the CDC is investigating 10 separate multistate outbreaks that began on Jan. 4, 2017. It involves 48 states, 961 infected individuals, 215 hospitalizations, and 1 death. At least 5 salmonella serotypes have been isolated.

What about the hatcheries?

It’s estimated that 50 million live poultry are sold annually. Birds are shipped within 24 hours after hatching via the U.S. Postal Service in boxes containing up to 100 chicks. Delivery occurs within 72 hours of hatching. Approximately 20 mail order hatcheries provide the majority of poultry sold to the general public. The National Poultry Improvement Plan (NPIP) is a voluntary state and federal testing and certification program whose goal is to eliminate poultry disease from breeder flocks to prevent egg-transmitted and hatchery-disseminated diseases. All hatcheries may participate. They also may participate in the voluntary Salmonella monitoring program. Note participation is not mandatory.

Preventing future outbreaks: patient/parental education is mandatory

1. Make sure your parents know about the association of Salmonella and live poultry. Reinforce these are farm animals, not pets. Purchase birds from hatcheries that participate in NPIP and the Salmonella monitoring programs.

2. Chicks, ducklings, or other live poultry should not be taken to schools, day care facilities, or nursing homes. Poultry should not be allowed in the home or in areas where food or drink is being prepared or consumed.

3. Poultry should not be snuggled, kissed, or allowed to touch one’s mouth. Hand washing with soap and water should occur after touching live poultry or any object touched in areas where they live or roam.

4. Contact with live poultry should be avoided in those at risk for developing serious infections including persons aged 5 years or younger, 65 years or older, immunocompromised individuals, and those with hemoglobinopathies.

5. All equipment used to care for live birds should be washed outdoors. Owners should have designated shoes when caring for poultry which should never be worn inside the home.

Hopefully, the next time you see a patient with fever and diarrhea you will recall this topic and ask about their contact with live poultry.

Additional resources to facilitate discussions can be found at www.cdc.gov/salmonella.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

Alternative birthing practices, such as water births, placentophagia, and lotus births, are making news and gaining popularity. All three have been associated with sporadic, serious neonatal infections.

The U.S. prevalence of water births – delivering a baby underwater – is currently unknown, but in the United Kingdom the practice is common. According to a 2015 National Health Service maternity survey, approximately 9% of women who underwent vaginal delivery opted for water birth (Arch Dis Child Fetal Neonatal Ed. 2016 Jul;101[4]:F357-65). Both the Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives endorse this practice for healthy women with uncomplicated term pregnancies. According to a 2009 Cochrane Review, immersion during the first phase of labor reduces the use of epidural/spinal analgesia (Cochrane Database Syst Rev. 2009. doi: 10.1002/14651858.CD000111.pub3). The maternal benefits of delivery under water, though, have not been clearly defined.

JBrownInTheLight/Thinkstock

Another recent systematic review and meta-analysis that included 29 studies of water birth did not identify definitive evidence of neonatal harm, but benefits also were uncertain (Arch Dis Child Fetal Neonatal Ed. 2016 Jul;101[4]:F357-65). Investigators acknowledged that most of the studies of neonatal outcomes were small, observational, and included only low-risk mothers. Case reports document rare but potentially fatal complications in babies, including drowning, respiratory compromise from aspiration, cord rupture, and infection. One study showed increased rates of admission to a neonatal unit without difference in Apgar scores or infection rates (BMJ. 2004;328[7435]:314).

Legionella pneumophila is an uncommon pathogen in children, but cases of neonatal Legionnaires’ disease have been reported after water birth. Two affected babies born in Arizona in 2016 were successfully treated and survived (MMWR Morb Mortal Wkly Rep. 2017. doi: 10.15585/mmwr.mm6622a4). A baby born in Texas in 2014 died of sepsis and respiratory failure (Emerg Infect Dis. 2015. doi: 10.3201/eid2101.140846). Canadian investigators have reported fatal disseminated herpes simplex virus infection in an infant after water birth; the mother had herpetic whitlow and a recent blister concerning for HSV on her thigh (J Pediatric Infect Dis Soc. 2017 May 16. doi: 10.1093/jpids/pix035).

Admittedly, each of these cases might have been prevented by adherence to recommended infection control practices, and the absolute risk of infection after water birth is unknown and likely to be small. Still, neither the American Academy of Pediatrics nor the American College of Obstetricians and Gynecologists currently recommend the practice. ACOG suggests that “births occur on land, not in water” and has called for well-designed, prospective studies of the maternal and perinatal benefits and risks associated with immersion during labor and delivery (Obstet Gynecol. 2016;128:1198-9).

Placentophagia – consuming the placenta after birth – has been promoted by celebrity moms, including Katherine Heigl and Kourtney Kardashian. Placenta can be cooked, blended raw into a smoothie, or dehydrated and encapsulated.

Proponents of placentophagia claim health benefits of this practice, including improved mood and energy, and increased breast milk production. There are few published data to support these claims. A recent case report suggests the practice has the potential to harm the baby. In June 2017, Oregon public health authorities described a neonate with recurrent episodes of group B streptococcal (GBS) bacteremia. An identical strain of GBS was cultured from capsules containing the mother’s dehydrated placenta – she had consumed six of the capsules daily beginning a few days after the baby’s birth. According to the Morbidity and Mortality Weekly Report communication, “no standards exist for processing placenta for consumption” and the “placenta encapsulation process does not eradicate infectious pathogens per se. … Placenta capsule ingestion should be avoided”(MMWR Morb Mortal Wkly Rep. 2017;66:677-8. doi: 10.15585/mmwr.mm6625a4).

Finally, the ritual practice of umbilical cord nonseverance or lotus birth deserves a mention. In a lotus birth, the umbilical cord is left uncut, allowing the placenta to remain attached to the baby until the cord dries and naturally separates, generally 3-10 days after delivery. Describing a spiritual connection between the baby and the placenta, proponents claim lotus birth promotes bonding and allows for a gentler transition between intra- and extrauterine life.

A review of PubMed turned up no formal studies of this practice, but case reports describe complications such as neonatal idiopathic hepatitis and neonatal sepsis. The Royal College of Obstetricians and Gynaecologists has issued a warning about lotus births, advising that babies be monitored closely for infection. RCOG spokesperson Dr. Patrick O’Brien said in a 2008 statement, “If left for a period of time after the birth, there is a risk of infection in the placenta which can consequently spread to the baby. The placenta is particularly prone to infection as it contains blood. Within a short time after birth, once the umbilical cord has stopped pulsating, the placenta has no circulation and is essentially dead tissue.”

Interestingly, a quick scan of Etsy, the popular e-commerce website, turned up a number of lotus birth kits for sale. These generally contain a decorative cloth bag as well as an herb mix containing lavender and eucalyptus to promote drying and mask the smell of the decomposing placenta.

A friend of mine who recently delivered a baby did not choose any of these alternative birthing practices, but she told me that she understood why some women might. “Peer pressure,” she said. “There’s so much information on social media and on ‘mommy blogs.’ Some of the women posting have really strong opinions. … They can make you feel like a bad mom for not choosing what they call the most ‘natural’ option.”

In contrast, many pediatricians, me included, are not well informed about these practices and don’t routinely ask expectant moms about their plans. I propose that we can advocate for our patients-to-be by learning about these practices so that we can engage in an honest, respectful discussion about potential risks and benefits. For me, for now, the risks outweigh the benefits.

 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

Alternative birthing practices, such as water births, placentophagia, and lotus births, are making news and gaining popularity. All three have been associated with sporadic, serious neonatal infections.

The U.S. prevalence of water births – delivering a baby underwater – is currently unknown, but in the United Kingdom the practice is common. According to a 2015 National Health Service maternity survey, approximately 9% of women who underwent vaginal delivery opted for water birth (Arch Dis Child Fetal Neonatal Ed. 2016 Jul;101[4]:F357-65). Both the Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives endorse this practice for healthy women with uncomplicated term pregnancies. According to a 2009 Cochrane Review, immersion during the first phase of labor reduces the use of epidural/spinal analgesia (Cochrane Database Syst Rev. 2009. doi: 10.1002/14651858.CD000111.pub3). The maternal benefits of delivery under water, though, have not been clearly defined.

JBrownInTheLight/Thinkstock

Another recent systematic review and meta-analysis that included 29 studies of water birth did not identify definitive evidence of neonatal harm, but benefits also were uncertain (Arch Dis Child Fetal Neonatal Ed. 2016 Jul;101[4]:F357-65). Investigators acknowledged that most of the studies of neonatal outcomes were small, observational, and included only low-risk mothers. Case reports document rare but potentially fatal complications in babies, including drowning, respiratory compromise from aspiration, cord rupture, and infection. One study showed increased rates of admission to a neonatal unit without difference in Apgar scores or infection rates (BMJ. 2004;328[7435]:314).

Legionella pneumophila is an uncommon pathogen in children, but cases of neonatal Legionnaires’ disease have been reported after water birth. Two affected babies born in Arizona in 2016 were successfully treated and survived (MMWR Morb Mortal Wkly Rep. 2017. doi: 10.15585/mmwr.mm6622a4). A baby born in Texas in 2014 died of sepsis and respiratory failure (Emerg Infect Dis. 2015. doi: 10.3201/eid2101.140846). Canadian investigators have reported fatal disseminated herpes simplex virus infection in an infant after water birth; the mother had herpetic whitlow and a recent blister concerning for HSV on her thigh (J Pediatric Infect Dis Soc. 2017 May 16. doi: 10.1093/jpids/pix035).

Admittedly, each of these cases might have been prevented by adherence to recommended infection control practices, and the absolute risk of infection after water birth is unknown and likely to be small. Still, neither the American Academy of Pediatrics nor the American College of Obstetricians and Gynecologists currently recommend the practice. ACOG suggests that “births occur on land, not in water” and has called for well-designed, prospective studies of the maternal and perinatal benefits and risks associated with immersion during labor and delivery (Obstet Gynecol. 2016;128:1198-9).

Placentophagia – consuming the placenta after birth – has been promoted by celebrity moms, including Katherine Heigl and Kourtney Kardashian. Placenta can be cooked, blended raw into a smoothie, or dehydrated and encapsulated.

Proponents of placentophagia claim health benefits of this practice, including improved mood and energy, and increased breast milk production. There are few published data to support these claims. A recent case report suggests the practice has the potential to harm the baby. In June 2017, Oregon public health authorities described a neonate with recurrent episodes of group B streptococcal (GBS) bacteremia. An identical strain of GBS was cultured from capsules containing the mother’s dehydrated placenta – she had consumed six of the capsules daily beginning a few days after the baby’s birth. According to the Morbidity and Mortality Weekly Report communication, “no standards exist for processing placenta for consumption” and the “placenta encapsulation process does not eradicate infectious pathogens per se. … Placenta capsule ingestion should be avoided”(MMWR Morb Mortal Wkly Rep. 2017;66:677-8. doi: 10.15585/mmwr.mm6625a4).

Finally, the ritual practice of umbilical cord nonseverance or lotus birth deserves a mention. In a lotus birth, the umbilical cord is left uncut, allowing the placenta to remain attached to the baby until the cord dries and naturally separates, generally 3-10 days after delivery. Describing a spiritual connection between the baby and the placenta, proponents claim lotus birth promotes bonding and allows for a gentler transition between intra- and extrauterine life.

A review of PubMed turned up no formal studies of this practice, but case reports describe complications such as neonatal idiopathic hepatitis and neonatal sepsis. The Royal College of Obstetricians and Gynaecologists has issued a warning about lotus births, advising that babies be monitored closely for infection. RCOG spokesperson Dr. Patrick O’Brien said in a 2008 statement, “If left for a period of time after the birth, there is a risk of infection in the placenta which can consequently spread to the baby. The placenta is particularly prone to infection as it contains blood. Within a short time after birth, once the umbilical cord has stopped pulsating, the placenta has no circulation and is essentially dead tissue.”

Interestingly, a quick scan of Etsy, the popular e-commerce website, turned up a number of lotus birth kits for sale. These generally contain a decorative cloth bag as well as an herb mix containing lavender and eucalyptus to promote drying and mask the smell of the decomposing placenta.

A friend of mine who recently delivered a baby did not choose any of these alternative birthing practices, but she told me that she understood why some women might. “Peer pressure,” she said. “There’s so much information on social media and on ‘mommy blogs.’ Some of the women posting have really strong opinions. … They can make you feel like a bad mom for not choosing what they call the most ‘natural’ option.”

In contrast, many pediatricians, me included, are not well informed about these practices and don’t routinely ask expectant moms about their plans. I propose that we can advocate for our patients-to-be by learning about these practices so that we can engage in an honest, respectful discussion about potential risks and benefits. For me, for now, the risks outweigh the benefits.

 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

Alternative birthing practices, such as water births, placentophagia, and lotus births, are making news and gaining popularity. All three have been associated with sporadic, serious neonatal infections.

The U.S. prevalence of water births – delivering a baby underwater – is currently unknown, but in the United Kingdom the practice is common. According to a 2015 National Health Service maternity survey, approximately 9% of women who underwent vaginal delivery opted for water birth (Arch Dis Child Fetal Neonatal Ed. 2016 Jul;101[4]:F357-65). Both the Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives endorse this practice for healthy women with uncomplicated term pregnancies. According to a 2009 Cochrane Review, immersion during the first phase of labor reduces the use of epidural/spinal analgesia (Cochrane Database Syst Rev. 2009. doi: 10.1002/14651858.CD000111.pub3). The maternal benefits of delivery under water, though, have not been clearly defined.

JBrownInTheLight/Thinkstock

Another recent systematic review and meta-analysis that included 29 studies of water birth did not identify definitive evidence of neonatal harm, but benefits also were uncertain (Arch Dis Child Fetal Neonatal Ed. 2016 Jul;101[4]:F357-65). Investigators acknowledged that most of the studies of neonatal outcomes were small, observational, and included only low-risk mothers. Case reports document rare but potentially fatal complications in babies, including drowning, respiratory compromise from aspiration, cord rupture, and infection. One study showed increased rates of admission to a neonatal unit without difference in Apgar scores or infection rates (BMJ. 2004;328[7435]:314).

Legionella pneumophila is an uncommon pathogen in children, but cases of neonatal Legionnaires’ disease have been reported after water birth. Two affected babies born in Arizona in 2016 were successfully treated and survived (MMWR Morb Mortal Wkly Rep. 2017. doi: 10.15585/mmwr.mm6622a4). A baby born in Texas in 2014 died of sepsis and respiratory failure (Emerg Infect Dis. 2015. doi: 10.3201/eid2101.140846). Canadian investigators have reported fatal disseminated herpes simplex virus infection in an infant after water birth; the mother had herpetic whitlow and a recent blister concerning for HSV on her thigh (J Pediatric Infect Dis Soc. 2017 May 16. doi: 10.1093/jpids/pix035).

Admittedly, each of these cases might have been prevented by adherence to recommended infection control practices, and the absolute risk of infection after water birth is unknown and likely to be small. Still, neither the American Academy of Pediatrics nor the American College of Obstetricians and Gynecologists currently recommend the practice. ACOG suggests that “births occur on land, not in water” and has called for well-designed, prospective studies of the maternal and perinatal benefits and risks associated with immersion during labor and delivery (Obstet Gynecol. 2016;128:1198-9).

Placentophagia – consuming the placenta after birth – has been promoted by celebrity moms, including Katherine Heigl and Kourtney Kardashian. Placenta can be cooked, blended raw into a smoothie, or dehydrated and encapsulated.

Proponents of placentophagia claim health benefits of this practice, including improved mood and energy, and increased breast milk production. There are few published data to support these claims. A recent case report suggests the practice has the potential to harm the baby. In June 2017, Oregon public health authorities described a neonate with recurrent episodes of group B streptococcal (GBS) bacteremia. An identical strain of GBS was cultured from capsules containing the mother’s dehydrated placenta – she had consumed six of the capsules daily beginning a few days after the baby’s birth. According to the Morbidity and Mortality Weekly Report communication, “no standards exist for processing placenta for consumption” and the “placenta encapsulation process does not eradicate infectious pathogens per se. … Placenta capsule ingestion should be avoided”(MMWR Morb Mortal Wkly Rep. 2017;66:677-8. doi: 10.15585/mmwr.mm6625a4).

Finally, the ritual practice of umbilical cord nonseverance or lotus birth deserves a mention. In a lotus birth, the umbilical cord is left uncut, allowing the placenta to remain attached to the baby until the cord dries and naturally separates, generally 3-10 days after delivery. Describing a spiritual connection between the baby and the placenta, proponents claim lotus birth promotes bonding and allows for a gentler transition between intra- and extrauterine life.

A review of PubMed turned up no formal studies of this practice, but case reports describe complications such as neonatal idiopathic hepatitis and neonatal sepsis. The Royal College of Obstetricians and Gynaecologists has issued a warning about lotus births, advising that babies be monitored closely for infection. RCOG spokesperson Dr. Patrick O’Brien said in a 2008 statement, “If left for a period of time after the birth, there is a risk of infection in the placenta which can consequently spread to the baby. The placenta is particularly prone to infection as it contains blood. Within a short time after birth, once the umbilical cord has stopped pulsating, the placenta has no circulation and is essentially dead tissue.”

Interestingly, a quick scan of Etsy, the popular e-commerce website, turned up a number of lotus birth kits for sale. These generally contain a decorative cloth bag as well as an herb mix containing lavender and eucalyptus to promote drying and mask the smell of the decomposing placenta.

A friend of mine who recently delivered a baby did not choose any of these alternative birthing practices, but she told me that she understood why some women might. “Peer pressure,” she said. “There’s so much information on social media and on ‘mommy blogs.’ Some of the women posting have really strong opinions. … They can make you feel like a bad mom for not choosing what they call the most ‘natural’ option.”

In contrast, many pediatricians, me included, are not well informed about these practices and don’t routinely ask expectant moms about their plans. I propose that we can advocate for our patients-to-be by learning about these practices so that we can engage in an honest, respectful discussion about potential risks and benefits. For me, for now, the risks outweigh the benefits.

 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

 

In the Journal of Child and Adolescent Psychopharmacology’s July 2017 issue, a group of respected individuals representing diverse expertise published “guidelines” to support clinical management of pediatric acute-onset neuropsychiatric syndrome (PANS) and its subclass PANDAS (those associated with streptococcal infection). PANS represents an enigmatic clinical syndrome that includes abrupt onset of obsessive-compulsive disorder (OCD) or eating restriction in combination with anxiety, attention deficit, hyperkinesia, emotional lability, irritability, aggressive or oppositional behavior, or academic decline. Neurologic findings also may be present; these are most often motor or vocal tics, but choreiform movements of the finger (repetitive motions that are rapid, jerky, and involuntary), deteriorating penmanship, sleep disruptions, or urinary frequency also may be present. The clinical course most often is relapsing and remitting with overall improvement over months or years.

CDC/ Melissa Brower

These events are often, but not universally, associated with infections, both for the initial clinical presentation as well as the subsequent exacerbations. A spectrum of inciting infections, most often upper respiratory tract disease including rhinitis, sinusitis, and pharyngitis, are reported as precipitating events. Group A streptococcal (GAS) infection has been most commonly identified. The evidence for GAS includes retrospective studies of increases in antistreptolysin O (ASO), anti-DNAse B (ADB), or anticarbohydrate-specific antibody titers associated with OCD or tic exacerbations; epidemiologic studies linking GAS infections in the prior 3 months with OCD and tic disorders; and animal studies demonstrating neuropsychiatric changes after GAS immunizations. Other infectious agents, specifically Mycoplasma pneumoniae, influenza viruses, Lyme borreliosis, and sinus infections, also are suspected triggers for PANS. Definitive proof, however, of a causal relationship between infection and PANS or PANDAS remains lacking.

The PANS/PANDAS consortium made specific recommendations for the management of patients with this clinically diagnosed syndrome (J Child Adolesc Psychopharmacol. 2017 Apr 7. doi: 10.1089/cap.2016.0151).

Specific recommendations include:

1. Searching for a coexisting infectious etiology with history, exam, and appropriate laboratory testing (including ASO and ADB antibodies), and, when present, treating accordingly. Even in the absence of definitive evidence of GAS infection, they recommend an initial course of antimicrobial therapy such as that given to patients with rheumatic fever.

2. For children with PANDAS (PANS with either culture or serologic evidence of GAS), consider instituting long-term streptococcal prophylaxis. The data on its value is mixed; however, most studies find more than 40% (and as many as 75%) of exacerbations are associated with GAS, and at least one study reports a reduction in neuropsychiatric exacerbations in children on penicillin or azithromycin prophylaxis for a 1-year period. Such decisions should be individualized: In children with strong evidence of exacerbations linked to GAS, there was thought to be greater likelihood of benefit, while, in those with no evidence for prior GAS infection, the potential for benefit was thought to be insufficient to justify prophylaxis. Furthermore, the optimal duration of prophylaxis is unknown. The guidelines recommend up to 2 years, but individualization is appropriate since severe cases may warrant prolonged prophylaxis.

3. In children who present with PANDAS and a positive throat culture for GAS, follow-up should be the same as that given for rheumatic fever, with reculture at 2-7 days and retreatment if there is persistence of GAS.

4. Vigilance for GAS infection in family members is appropriate, including obtaining throat cultures from persons with pharyngitis and treating them promptly when results are positive.

5. When GAS infection is not identified, the clinician should search for alternative infectious agents, such as Mycoplasma pneumoniae (using polymerase chain reaction on throat or nasopharyngeal swab), influenza virus, or alternative infections such as sinusitis, and treat accordingly.

6. Children with PANS and PANDAS should be immunized according to Advisory Committee of Immunization Practices recommendations, which includes annual influenza immunization. The committee reported that symptom flares after immunization were uncommon, brief, and manageable with NSAIDs.

7. The committee suggested that optimization of serum vitamin D levels among children with PANS and PANDAS could be of benefit, despite limited evidence. The committee members recommended treating children with PANS/PANDAS with vitamin D₃ as needed to maintain serum 25-hydroxy vitamin D levels above 30 ng/mL. No benefit for adenotonsillectomy was identified. The committee recommended that tonsillectomy and/or adenoidectomy should limited to those with traditional indications (sleep apnea, failure to thrive, and abnormally large tonsils, etc.). The committee also found no evidence to suggest that probiotics modulate this condition.

These guidelines come with an important caveat. They represent a practical clinical approach for the management of infection in the context of PANS or PANDAS and rely heavily on the clinical experience of the members of the PANS/PANDAS Consortium. They provide criteria for the retrospective diagnosis of GAS infection and recommend treatment of GAS in all patients with newly diagnosed PANS. The suggested guidelines are supported by limited data and recognize that further prospective study of the mechanistic link between infection and PANS, clarification of the risk factors for development of PANS, and definitive study of the risks and benefits of antimicrobial prophylaxis are needed.

The consortium also has published two accompanying guidelines that address psychiatric (J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0145) and immunomodulatory management (J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0148) in the same issue of the Journal of Child and Adolescent Psychopharmacology.

 

Proposed criteria for documenting GAS infection in PANS pediatric patients

These are the criteria proposed by the consortium for documentation of active or prior GAS infection in children with PANS:

• A rise in serial antibody level, regardless of rapid test or culture result. This definition does not require clinical pharyngitis.
• Acute pharyngitis with a positive GAS throat culture, with or without a rising antibody level.
• Pharyngitis with characteristic palatal petechiae.
• Pharyngitis with a characteristic scarlatiniform rash.
• Pharyngitis without a throat swab or serology, but intimate (usually household) exposure to a proven GAS case.
• Asymptomatic pharyngeal colonization documented after an intimate exposure.
• Asymptomatic pharyngeal colonization after a negative throat swab documented within the prior 3-4 months.
• Single ASO or ADB antibody level within 6 months after the initial onset of neuropsychiatric symptoms may be accepted as positive if it is more than 95th percentile, using the laboratory’s normal standard for children of comparable age, or provisionally ASO greater than or equal to 1:480 or ADB greater than or equal to 1:1280.
• Both ASO and ADB are elevated at more than 80% percentile for age in the same serum sample within 6 months after the initial onset of neuropsychiatric symptoms.
• Culture-documented streptococcal dermatitis.

Source: J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0151.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he had no relevant financial disclosures. Email him at [email protected].

 

In the Journal of Child and Adolescent Psychopharmacology’s July 2017 issue, a group of respected individuals representing diverse expertise published “guidelines” to support clinical management of pediatric acute-onset neuropsychiatric syndrome (PANS) and its subclass PANDAS (those associated with streptococcal infection). PANS represents an enigmatic clinical syndrome that includes abrupt onset of obsessive-compulsive disorder (OCD) or eating restriction in combination with anxiety, attention deficit, hyperkinesia, emotional lability, irritability, aggressive or oppositional behavior, or academic decline. Neurologic findings also may be present; these are most often motor or vocal tics, but choreiform movements of the finger (repetitive motions that are rapid, jerky, and involuntary), deteriorating penmanship, sleep disruptions, or urinary frequency also may be present. The clinical course most often is relapsing and remitting with overall improvement over months or years.

CDC/ Melissa Brower

These events are often, but not universally, associated with infections, both for the initial clinical presentation as well as the subsequent exacerbations. A spectrum of inciting infections, most often upper respiratory tract disease including rhinitis, sinusitis, and pharyngitis, are reported as precipitating events. Group A streptococcal (GAS) infection has been most commonly identified. The evidence for GAS includes retrospective studies of increases in antistreptolysin O (ASO), anti-DNAse B (ADB), or anticarbohydrate-specific antibody titers associated with OCD or tic exacerbations; epidemiologic studies linking GAS infections in the prior 3 months with OCD and tic disorders; and animal studies demonstrating neuropsychiatric changes after GAS immunizations. Other infectious agents, specifically Mycoplasma pneumoniae, influenza viruses, Lyme borreliosis, and sinus infections, also are suspected triggers for PANS. Definitive proof, however, of a causal relationship between infection and PANS or PANDAS remains lacking.

The PANS/PANDAS consortium made specific recommendations for the management of patients with this clinically diagnosed syndrome (J Child Adolesc Psychopharmacol. 2017 Apr 7. doi: 10.1089/cap.2016.0151).

Specific recommendations include:

1. Searching for a coexisting infectious etiology with history, exam, and appropriate laboratory testing (including ASO and ADB antibodies), and, when present, treating accordingly. Even in the absence of definitive evidence of GAS infection, they recommend an initial course of antimicrobial therapy such as that given to patients with rheumatic fever.

2. For children with PANDAS (PANS with either culture or serologic evidence of GAS), consider instituting long-term streptococcal prophylaxis. The data on its value is mixed; however, most studies find more than 40% (and as many as 75%) of exacerbations are associated with GAS, and at least one study reports a reduction in neuropsychiatric exacerbations in children on penicillin or azithromycin prophylaxis for a 1-year period. Such decisions should be individualized: In children with strong evidence of exacerbations linked to GAS, there was thought to be greater likelihood of benefit, while, in those with no evidence for prior GAS infection, the potential for benefit was thought to be insufficient to justify prophylaxis. Furthermore, the optimal duration of prophylaxis is unknown. The guidelines recommend up to 2 years, but individualization is appropriate since severe cases may warrant prolonged prophylaxis.

3. In children who present with PANDAS and a positive throat culture for GAS, follow-up should be the same as that given for rheumatic fever, with reculture at 2-7 days and retreatment if there is persistence of GAS.

4. Vigilance for GAS infection in family members is appropriate, including obtaining throat cultures from persons with pharyngitis and treating them promptly when results are positive.

5. When GAS infection is not identified, the clinician should search for alternative infectious agents, such as Mycoplasma pneumoniae (using polymerase chain reaction on throat or nasopharyngeal swab), influenza virus, or alternative infections such as sinusitis, and treat accordingly.

6. Children with PANS and PANDAS should be immunized according to Advisory Committee of Immunization Practices recommendations, which includes annual influenza immunization. The committee reported that symptom flares after immunization were uncommon, brief, and manageable with NSAIDs.

7. The committee suggested that optimization of serum vitamin D levels among children with PANS and PANDAS could be of benefit, despite limited evidence. The committee members recommended treating children with PANS/PANDAS with vitamin D₃ as needed to maintain serum 25-hydroxy vitamin D levels above 30 ng/mL. No benefit for adenotonsillectomy was identified. The committee recommended that tonsillectomy and/or adenoidectomy should limited to those with traditional indications (sleep apnea, failure to thrive, and abnormally large tonsils, etc.). The committee also found no evidence to suggest that probiotics modulate this condition.

These guidelines come with an important caveat. They represent a practical clinical approach for the management of infection in the context of PANS or PANDAS and rely heavily on the clinical experience of the members of the PANS/PANDAS Consortium. They provide criteria for the retrospective diagnosis of GAS infection and recommend treatment of GAS in all patients with newly diagnosed PANS. The suggested guidelines are supported by limited data and recognize that further prospective study of the mechanistic link between infection and PANS, clarification of the risk factors for development of PANS, and definitive study of the risks and benefits of antimicrobial prophylaxis are needed.

The consortium also has published two accompanying guidelines that address psychiatric (J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0145) and immunomodulatory management (J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0148) in the same issue of the Journal of Child and Adolescent Psychopharmacology.

 

Proposed criteria for documenting GAS infection in PANS pediatric patients

These are the criteria proposed by the consortium for documentation of active or prior GAS infection in children with PANS:

• A rise in serial antibody level, regardless of rapid test or culture result. This definition does not require clinical pharyngitis.
• Acute pharyngitis with a positive GAS throat culture, with or without a rising antibody level.
• Pharyngitis with characteristic palatal petechiae.
• Pharyngitis with a characteristic scarlatiniform rash.
• Pharyngitis without a throat swab or serology, but intimate (usually household) exposure to a proven GAS case.
• Asymptomatic pharyngeal colonization documented after an intimate exposure.
• Asymptomatic pharyngeal colonization after a negative throat swab documented within the prior 3-4 months.
• Single ASO or ADB antibody level within 6 months after the initial onset of neuropsychiatric symptoms may be accepted as positive if it is more than 95th percentile, using the laboratory’s normal standard for children of comparable age, or provisionally ASO greater than or equal to 1:480 or ADB greater than or equal to 1:1280.
• Both ASO and ADB are elevated at more than 80% percentile for age in the same serum sample within 6 months after the initial onset of neuropsychiatric symptoms.
• Culture-documented streptococcal dermatitis.

Source: J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0151.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he had no relevant financial disclosures. Email him at [email protected].

 

In the Journal of Child and Adolescent Psychopharmacology’s July 2017 issue, a group of respected individuals representing diverse expertise published “guidelines” to support clinical management of pediatric acute-onset neuropsychiatric syndrome (PANS) and its subclass PANDAS (those associated with streptococcal infection). PANS represents an enigmatic clinical syndrome that includes abrupt onset of obsessive-compulsive disorder (OCD) or eating restriction in combination with anxiety, attention deficit, hyperkinesia, emotional lability, irritability, aggressive or oppositional behavior, or academic decline. Neurologic findings also may be present; these are most often motor or vocal tics, but choreiform movements of the finger (repetitive motions that are rapid, jerky, and involuntary), deteriorating penmanship, sleep disruptions, or urinary frequency also may be present. The clinical course most often is relapsing and remitting with overall improvement over months or years.

CDC/ Melissa Brower

These events are often, but not universally, associated with infections, both for the initial clinical presentation as well as the subsequent exacerbations. A spectrum of inciting infections, most often upper respiratory tract disease including rhinitis, sinusitis, and pharyngitis, are reported as precipitating events. Group A streptococcal (GAS) infection has been most commonly identified. The evidence for GAS includes retrospective studies of increases in antistreptolysin O (ASO), anti-DNAse B (ADB), or anticarbohydrate-specific antibody titers associated with OCD or tic exacerbations; epidemiologic studies linking GAS infections in the prior 3 months with OCD and tic disorders; and animal studies demonstrating neuropsychiatric changes after GAS immunizations. Other infectious agents, specifically Mycoplasma pneumoniae, influenza viruses, Lyme borreliosis, and sinus infections, also are suspected triggers for PANS. Definitive proof, however, of a causal relationship between infection and PANS or PANDAS remains lacking.

The PANS/PANDAS consortium made specific recommendations for the management of patients with this clinically diagnosed syndrome (J Child Adolesc Psychopharmacol. 2017 Apr 7. doi: 10.1089/cap.2016.0151).

Specific recommendations include:

1. Searching for a coexisting infectious etiology with history, exam, and appropriate laboratory testing (including ASO and ADB antibodies), and, when present, treating accordingly. Even in the absence of definitive evidence of GAS infection, they recommend an initial course of antimicrobial therapy such as that given to patients with rheumatic fever.

2. For children with PANDAS (PANS with either culture or serologic evidence of GAS), consider instituting long-term streptococcal prophylaxis. The data on its value is mixed; however, most studies find more than 40% (and as many as 75%) of exacerbations are associated with GAS, and at least one study reports a reduction in neuropsychiatric exacerbations in children on penicillin or azithromycin prophylaxis for a 1-year period. Such decisions should be individualized: In children with strong evidence of exacerbations linked to GAS, there was thought to be greater likelihood of benefit, while, in those with no evidence for prior GAS infection, the potential for benefit was thought to be insufficient to justify prophylaxis. Furthermore, the optimal duration of prophylaxis is unknown. The guidelines recommend up to 2 years, but individualization is appropriate since severe cases may warrant prolonged prophylaxis.

3. In children who present with PANDAS and a positive throat culture for GAS, follow-up should be the same as that given for rheumatic fever, with reculture at 2-7 days and retreatment if there is persistence of GAS.

4. Vigilance for GAS infection in family members is appropriate, including obtaining throat cultures from persons with pharyngitis and treating them promptly when results are positive.

5. When GAS infection is not identified, the clinician should search for alternative infectious agents, such as Mycoplasma pneumoniae (using polymerase chain reaction on throat or nasopharyngeal swab), influenza virus, or alternative infections such as sinusitis, and treat accordingly.

6. Children with PANS and PANDAS should be immunized according to Advisory Committee of Immunization Practices recommendations, which includes annual influenza immunization. The committee reported that symptom flares after immunization were uncommon, brief, and manageable with NSAIDs.

7. The committee suggested that optimization of serum vitamin D levels among children with PANS and PANDAS could be of benefit, despite limited evidence. The committee members recommended treating children with PANS/PANDAS with vitamin D₃ as needed to maintain serum 25-hydroxy vitamin D levels above 30 ng/mL. No benefit for adenotonsillectomy was identified. The committee recommended that tonsillectomy and/or adenoidectomy should limited to those with traditional indications (sleep apnea, failure to thrive, and abnormally large tonsils, etc.). The committee also found no evidence to suggest that probiotics modulate this condition.

These guidelines come with an important caveat. They represent a practical clinical approach for the management of infection in the context of PANS or PANDAS and rely heavily on the clinical experience of the members of the PANS/PANDAS Consortium. They provide criteria for the retrospective diagnosis of GAS infection and recommend treatment of GAS in all patients with newly diagnosed PANS. The suggested guidelines are supported by limited data and recognize that further prospective study of the mechanistic link between infection and PANS, clarification of the risk factors for development of PANS, and definitive study of the risks and benefits of antimicrobial prophylaxis are needed.

The consortium also has published two accompanying guidelines that address psychiatric (J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0145) and immunomodulatory management (J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0148) in the same issue of the Journal of Child and Adolescent Psychopharmacology.

 

Proposed criteria for documenting GAS infection in PANS pediatric patients

These are the criteria proposed by the consortium for documentation of active or prior GAS infection in children with PANS:

• A rise in serial antibody level, regardless of rapid test or culture result. This definition does not require clinical pharyngitis.
• Acute pharyngitis with a positive GAS throat culture, with or without a rising antibody level.
• Pharyngitis with characteristic palatal petechiae.
• Pharyngitis with a characteristic scarlatiniform rash.
• Pharyngitis without a throat swab or serology, but intimate (usually household) exposure to a proven GAS case.
• Asymptomatic pharyngeal colonization documented after an intimate exposure.
• Asymptomatic pharyngeal colonization after a negative throat swab documented within the prior 3-4 months.
• Single ASO or ADB antibody level within 6 months after the initial onset of neuropsychiatric symptoms may be accepted as positive if it is more than 95th percentile, using the laboratory’s normal standard for children of comparable age, or provisionally ASO greater than or equal to 1:480 or ADB greater than or equal to 1:1280.
• Both ASO and ADB are elevated at more than 80% percentile for age in the same serum sample within 6 months after the initial onset of neuropsychiatric symptoms.
• Culture-documented streptococcal dermatitis.

Source: J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0151.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he had no relevant financial disclosures. Email him at [email protected].

 

The baby looked perfect: healthy term male, weight at the 60th percentile, normal exam. The mother, a 26-year-old diagnosed with hepatitis C virus (HCV) infection during her pregnancy, looked alternately hopeful and horrified as I explained what implications her infection could have for her baby.

“Most babies will be fine,” I explained. “Of all mothers with hepatitis C infection, just under 6% will pass the infection on to their babies.” Transmission rates are twice as high in infants born to women with high HCV viral loads or those coinfected with HIV. The risk of transmission from women with undetectable HCV RNA is almost zero. Unfortunately, this mother did not fall into that category.

This scenario is increasingly common in exam rooms across the country. The Centers for Disease Control and Prevention (CDC) estimates that 3.5 million people in the United States are infected with HCV, but at least half do not know their infection status. Thanks in part to the heroin and prescription opioid epidemics, HCV infection is increasingly common among women of childbearing age. From 2009 to 2014, the prevalence of HCV infection among U.S. women giving birth nearly doubled, with the highest rates in Appalachian regions, according to the CDC. In Kentucky, where this mother and I live, HCV detection in women of childbearing age, defined as having a positive antibody or RNA test, increased more than 200% between 2009 and 2011, and the proportion of infants born to HCV-positive mothers increased 124%, according to the CDC. Referrals to my group’s practice for perinatal HCV exposure have exploded: some weeks, we’ll see as many as ten exposed babies in our outpatient office.

At that moment, however, I didn’t have time to be concerned about the numbers. My focus was one mother and her newborn baby.

“What if my baby is one of the unlucky ones who gets infected?” the mother asked, cuddling her infant. “What then?”

We know a lot about the course of hepatitis C in adults. An estimated 75%-86% of those infected will go on to develop chronic infection. Long-term sequelae include cirrhosis, liver failure, and hepatocellular carcinoma.

The course of HCV in children appears to be different. Twenty-five percent to 40% of vertically infected children will spontaneously clear their infection, most by 2 years of age. Occasionally, that might not happen until 7 years of age. Most who are chronically infected experience few symptoms, and fortunately cirrhosis and liver failure rarely present in childhood. In a large cohort of Italian children, half of whom were thought to be infected perinatally, less than 2% progressed to decompensated cirrhosis after 10 years of infection. According to the CDC, most children infected at birth “do well during childhood,” but more research is needed to understand the long-term effects of perinatal hepatitis C in children.

New antivirals have revolutionized the care of HCV-infected adults and now offer the hope of cure for up to 90%. None of these drugs are currently approved for use in children younger than 12 years, although clinical trials are underway. Because most cases of HCV in children are indolent, some children may not require treatment until adulthood.

July 28th was World Hepatitis Day and this year’s theme was Eliminate Hepatitis. To eliminate the problem of hepatitis C in children, pediatricians and others involved in the care of children need to get involved.

We need to know the scope of the problem

Since 2015, Kentucky has mandated reporting of all HCV-infected pregnant women and children through age 60 months, as well as all infants born to all HCV-infected women. At present though, there is substantial variability in state reporting requirements. We likely need a standardized case definition for perinatal HCV and national reporting criteria.

We need some clear guidance about testing during pregnancy

This should come from public health authorities, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists.

Jonathan Mermin, MD, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, has said, “Women are screened throughout pregnancy for many conditions that threaten their health. An expectant mother at risk for hepatitis C deserves to be tested. Knowing her status is the only way she can access the best hepatitis care and treatment – both for herself and her baby.” Yet, routine hepatitis C testing is not recommended during pregnancy, in part because there are no established interventions to prevent mother-to-child transmission of HCV. Instead, women are to be screened for risk factors and tested if they are present. As we learned with hepatitis B and HIV, risk factor screening is hard and misses individuals who are infected.

 

We need to ensure that HCV-exposed infants are identified and followed appropriately.

In a study of HCV-exposed infants born to women in Philadelphia, 84% did not receive adequate testing for HCV infection. In human terms, 537 children were born to HCV-positive mothers during the study period and 4 of 84 (5%) children tested were found to be infected. Assuming that 5% of HCV-exposed infants will develop chronic infection, 23 additional children were undiagnosed and, therefore, were not being followed for potential sequelae.

HCV-infected mothers in this study were more likely than non-infected mothers to be socioeconomically disadvantaged – specifically, unmarried, less educated, and publicly insured – suggesting that access to care may have played a role. When you add in drug use as a common risk factor for HCV infection, it is easy to understand why some at-risk infants are lost to follow-up.

Investigators in the Philadelphia study suggested that there might be more to the story. They proposed that pediatricians might be unaware of the need for testing because they had not been alerted to the mother’s HCV status by the obstetrician, the birthing hospital, or the mother herself. Finally, they theorized that many pediatricians “may be unaware or skeptical of the guidelines for testing children exposed to HCV.” This is a problem that we can solve.

I finished the visit with this mother by reassuring her that she could breastfeed her infant as planned as long as she did not have cracked or bleeding nipples. I also explained the schedule for testing. A 2002 National Institutes of Health consensus statement recommends that infants perinatally exposed to HCV have two HCV RNA tests between 2 and 6 months of age and/or be tested for HCV antibodies after 15 months. North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Practice Guidelines for Diagnosis and Management of Hepatitis C Infection in Infants, Children, and Adolescents recommend testing for HCV antibodies at 18 months of age (J Pediatr Gastroenterol Nutr. 2012 Jun;54[6]:838-55). If a family requests earlier testing, a serum HCV RNA test can be done as early as 2 months of age. If positive, NASPGHAN recommends testing after 12 months of age to evaluate for chronic infection.

My practice has adopted the National Institutes of Health consensus statement approach because many of the families we see experience significant anxiety about the diagnosis, and this mother was no exception. As noted in the expert guidelines, this was a situation in which “early exclusion of HCV infection is reassuring and may be worth the added expense.”

“So first test at 2 months?” she asked. “Until then, we can’t do anything but wait?”

It is estimated that there are 23,000 to 46,000 U.S. children living with HCV. The wait for pediatricians is over. HCV is a pediatric disease now, and we need to educate ourselves about diagnosis and management. A first step might be to begin asking expectant mothers and the mothers of newborns if they know their HCV status.

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

 

The baby looked perfect: healthy term male, weight at the 60th percentile, normal exam. The mother, a 26-year-old diagnosed with hepatitis C virus (HCV) infection during her pregnancy, looked alternately hopeful and horrified as I explained what implications her infection could have for her baby.

“Most babies will be fine,” I explained. “Of all mothers with hepatitis C infection, just under 6% will pass the infection on to their babies.” Transmission rates are twice as high in infants born to women with high HCV viral loads or those coinfected with HIV. The risk of transmission from women with undetectable HCV RNA is almost zero. Unfortunately, this mother did not fall into that category.

This scenario is increasingly common in exam rooms across the country. The Centers for Disease Control and Prevention (CDC) estimates that 3.5 million people in the United States are infected with HCV, but at least half do not know their infection status. Thanks in part to the heroin and prescription opioid epidemics, HCV infection is increasingly common among women of childbearing age. From 2009 to 2014, the prevalence of HCV infection among U.S. women giving birth nearly doubled, with the highest rates in Appalachian regions, according to the CDC. In Kentucky, where this mother and I live, HCV detection in women of childbearing age, defined as having a positive antibody or RNA test, increased more than 200% between 2009 and 2011, and the proportion of infants born to HCV-positive mothers increased 124%, according to the CDC. Referrals to my group’s practice for perinatal HCV exposure have exploded: some weeks, we’ll see as many as ten exposed babies in our outpatient office.

At that moment, however, I didn’t have time to be concerned about the numbers. My focus was one mother and her newborn baby.

“What if my baby is one of the unlucky ones who gets infected?” the mother asked, cuddling her infant. “What then?”

We know a lot about the course of hepatitis C in adults. An estimated 75%-86% of those infected will go on to develop chronic infection. Long-term sequelae include cirrhosis, liver failure, and hepatocellular carcinoma.

The course of HCV in children appears to be different. Twenty-five percent to 40% of vertically infected children will spontaneously clear their infection, most by 2 years of age. Occasionally, that might not happen until 7 years of age. Most who are chronically infected experience few symptoms, and fortunately cirrhosis and liver failure rarely present in childhood. In a large cohort of Italian children, half of whom were thought to be infected perinatally, less than 2% progressed to decompensated cirrhosis after 10 years of infection. According to the CDC, most children infected at birth “do well during childhood,” but more research is needed to understand the long-term effects of perinatal hepatitis C in children.

New antivirals have revolutionized the care of HCV-infected adults and now offer the hope of cure for up to 90%. None of these drugs are currently approved for use in children younger than 12 years, although clinical trials are underway. Because most cases of HCV in children are indolent, some children may not require treatment until adulthood.

July 28th was World Hepatitis Day and this year’s theme was Eliminate Hepatitis. To eliminate the problem of hepatitis C in children, pediatricians and others involved in the care of children need to get involved.

We need to know the scope of the problem

Since 2015, Kentucky has mandated reporting of all HCV-infected pregnant women and children through age 60 months, as well as all infants born to all HCV-infected women. At present though, there is substantial variability in state reporting requirements. We likely need a standardized case definition for perinatal HCV and national reporting criteria.

We need some clear guidance about testing during pregnancy

This should come from public health authorities, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists.

Jonathan Mermin, MD, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, has said, “Women are screened throughout pregnancy for many conditions that threaten their health. An expectant mother at risk for hepatitis C deserves to be tested. Knowing her status is the only way she can access the best hepatitis care and treatment – both for herself and her baby.” Yet, routine hepatitis C testing is not recommended during pregnancy, in part because there are no established interventions to prevent mother-to-child transmission of HCV. Instead, women are to be screened for risk factors and tested if they are present. As we learned with hepatitis B and HIV, risk factor screening is hard and misses individuals who are infected.

 

We need to ensure that HCV-exposed infants are identified and followed appropriately.

In a study of HCV-exposed infants born to women in Philadelphia, 84% did not receive adequate testing for HCV infection. In human terms, 537 children were born to HCV-positive mothers during the study period and 4 of 84 (5%) children tested were found to be infected. Assuming that 5% of HCV-exposed infants will develop chronic infection, 23 additional children were undiagnosed and, therefore, were not being followed for potential sequelae.

HCV-infected mothers in this study were more likely than non-infected mothers to be socioeconomically disadvantaged – specifically, unmarried, less educated, and publicly insured – suggesting that access to care may have played a role. When you add in drug use as a common risk factor for HCV infection, it is easy to understand why some at-risk infants are lost to follow-up.

Investigators in the Philadelphia study suggested that there might be more to the story. They proposed that pediatricians might be unaware of the need for testing because they had not been alerted to the mother’s HCV status by the obstetrician, the birthing hospital, or the mother herself. Finally, they theorized that many pediatricians “may be unaware or skeptical of the guidelines for testing children exposed to HCV.” This is a problem that we can solve.

I finished the visit with this mother by reassuring her that she could breastfeed her infant as planned as long as she did not have cracked or bleeding nipples. I also explained the schedule for testing. A 2002 National Institutes of Health consensus statement recommends that infants perinatally exposed to HCV have two HCV RNA tests between 2 and 6 months of age and/or be tested for HCV antibodies after 15 months. North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Practice Guidelines for Diagnosis and Management of Hepatitis C Infection in Infants, Children, and Adolescents recommend testing for HCV antibodies at 18 months of age (J Pediatr Gastroenterol Nutr. 2012 Jun;54[6]:838-55). If a family requests earlier testing, a serum HCV RNA test can be done as early as 2 months of age. If positive, NASPGHAN recommends testing after 12 months of age to evaluate for chronic infection.

My practice has adopted the National Institutes of Health consensus statement approach because many of the families we see experience significant anxiety about the diagnosis, and this mother was no exception. As noted in the expert guidelines, this was a situation in which “early exclusion of HCV infection is reassuring and may be worth the added expense.”

“So first test at 2 months?” she asked. “Until then, we can’t do anything but wait?”

It is estimated that there are 23,000 to 46,000 U.S. children living with HCV. The wait for pediatricians is over. HCV is a pediatric disease now, and we need to educate ourselves about diagnosis and management. A first step might be to begin asking expectant mothers and the mothers of newborns if they know their HCV status.

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

 

The baby looked perfect: healthy term male, weight at the 60th percentile, normal exam. The mother, a 26-year-old diagnosed with hepatitis C virus (HCV) infection during her pregnancy, looked alternately hopeful and horrified as I explained what implications her infection could have for her baby.

“Most babies will be fine,” I explained. “Of all mothers with hepatitis C infection, just under 6% will pass the infection on to their babies.” Transmission rates are twice as high in infants born to women with high HCV viral loads or those coinfected with HIV. The risk of transmission from women with undetectable HCV RNA is almost zero. Unfortunately, this mother did not fall into that category.

This scenario is increasingly common in exam rooms across the country. The Centers for Disease Control and Prevention (CDC) estimates that 3.5 million people in the United States are infected with HCV, but at least half do not know their infection status. Thanks in part to the heroin and prescription opioid epidemics, HCV infection is increasingly common among women of childbearing age. From 2009 to 2014, the prevalence of HCV infection among U.S. women giving birth nearly doubled, with the highest rates in Appalachian regions, according to the CDC. In Kentucky, where this mother and I live, HCV detection in women of childbearing age, defined as having a positive antibody or RNA test, increased more than 200% between 2009 and 2011, and the proportion of infants born to HCV-positive mothers increased 124%, according to the CDC. Referrals to my group’s practice for perinatal HCV exposure have exploded: some weeks, we’ll see as many as ten exposed babies in our outpatient office.

At that moment, however, I didn’t have time to be concerned about the numbers. My focus was one mother and her newborn baby.

“What if my baby is one of the unlucky ones who gets infected?” the mother asked, cuddling her infant. “What then?”

We know a lot about the course of hepatitis C in adults. An estimated 75%-86% of those infected will go on to develop chronic infection. Long-term sequelae include cirrhosis, liver failure, and hepatocellular carcinoma.

The course of HCV in children appears to be different. Twenty-five percent to 40% of vertically infected children will spontaneously clear their infection, most by 2 years of age. Occasionally, that might not happen until 7 years of age. Most who are chronically infected experience few symptoms, and fortunately cirrhosis and liver failure rarely present in childhood. In a large cohort of Italian children, half of whom were thought to be infected perinatally, less than 2% progressed to decompensated cirrhosis after 10 years of infection. According to the CDC, most children infected at birth “do well during childhood,” but more research is needed to understand the long-term effects of perinatal hepatitis C in children.

New antivirals have revolutionized the care of HCV-infected adults and now offer the hope of cure for up to 90%. None of these drugs are currently approved for use in children younger than 12 years, although clinical trials are underway. Because most cases of HCV in children are indolent, some children may not require treatment until adulthood.

July 28th was World Hepatitis Day and this year’s theme was Eliminate Hepatitis. To eliminate the problem of hepatitis C in children, pediatricians and others involved in the care of children need to get involved.

We need to know the scope of the problem

Since 2015, Kentucky has mandated reporting of all HCV-infected pregnant women and children through age 60 months, as well as all infants born to all HCV-infected women. At present though, there is substantial variability in state reporting requirements. We likely need a standardized case definition for perinatal HCV and national reporting criteria.

We need some clear guidance about testing during pregnancy

This should come from public health authorities, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists.

Jonathan Mermin, MD, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, has said, “Women are screened throughout pregnancy for many conditions that threaten their health. An expectant mother at risk for hepatitis C deserves to be tested. Knowing her status is the only way she can access the best hepatitis care and treatment – both for herself and her baby.” Yet, routine hepatitis C testing is not recommended during pregnancy, in part because there are no established interventions to prevent mother-to-child transmission of HCV. Instead, women are to be screened for risk factors and tested if they are present. As we learned with hepatitis B and HIV, risk factor screening is hard and misses individuals who are infected.

 

We need to ensure that HCV-exposed infants are identified and followed appropriately.

In a study of HCV-exposed infants born to women in Philadelphia, 84% did not receive adequate testing for HCV infection. In human terms, 537 children were born to HCV-positive mothers during the study period and 4 of 84 (5%) children tested were found to be infected. Assuming that 5% of HCV-exposed infants will develop chronic infection, 23 additional children were undiagnosed and, therefore, were not being followed for potential sequelae.

HCV-infected mothers in this study were more likely than non-infected mothers to be socioeconomically disadvantaged – specifically, unmarried, less educated, and publicly insured – suggesting that access to care may have played a role. When you add in drug use as a common risk factor for HCV infection, it is easy to understand why some at-risk infants are lost to follow-up.

Investigators in the Philadelphia study suggested that there might be more to the story. They proposed that pediatricians might be unaware of the need for testing because they had not been alerted to the mother’s HCV status by the obstetrician, the birthing hospital, or the mother herself. Finally, they theorized that many pediatricians “may be unaware or skeptical of the guidelines for testing children exposed to HCV.” This is a problem that we can solve.

I finished the visit with this mother by reassuring her that she could breastfeed her infant as planned as long as she did not have cracked or bleeding nipples. I also explained the schedule for testing. A 2002 National Institutes of Health consensus statement recommends that infants perinatally exposed to HCV have two HCV RNA tests between 2 and 6 months of age and/or be tested for HCV antibodies after 15 months. North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Practice Guidelines for Diagnosis and Management of Hepatitis C Infection in Infants, Children, and Adolescents recommend testing for HCV antibodies at 18 months of age (J Pediatr Gastroenterol Nutr. 2012 Jun;54[6]:838-55). If a family requests earlier testing, a serum HCV RNA test can be done as early as 2 months of age. If positive, NASPGHAN recommends testing after 12 months of age to evaluate for chronic infection.

My practice has adopted the National Institutes of Health consensus statement approach because many of the families we see experience significant anxiety about the diagnosis, and this mother was no exception. As noted in the expert guidelines, this was a situation in which “early exclusion of HCV infection is reassuring and may be worth the added expense.”

“So first test at 2 months?” she asked. “Until then, we can’t do anything but wait?”

It is estimated that there are 23,000 to 46,000 U.S. children living with HCV. The wait for pediatricians is over. HCV is a pediatric disease now, and we need to educate ourselves about diagnosis and management. A first step might be to begin asking expectant mothers and the mothers of newborns if they know their HCV status.

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

 

Are foodborne illness outbreaks more common now, or are we simply better at detection? Have the foods and sources associated with foodborne illness changed? Two recent Centers for Disease Control & Prevention reports provide insight.^1,2 In 2016, the Foodborne Diseases Active Surveillance Network (FoodNet) detected 24,029 infections, 5,212 hospitalizations, and 98 fatalities.¹ FoodNet has 10 sites serving 49 million people (15% of the U.S. population). These 2016 numbers changed only modestly from the 3 prior years.

The big two

The most frequent 2016 foodborne pathogens were Campylobacter and Salmonella, at approximately 8,000 illnesses each, detected by traditional cultures or culture-independent diagnostic tests (CIDTs). (See table.) CIDTs are relatively new molecular-based, mostly multiplex assays that test for more than a dozen pathogens in one assay.

Campylobacter-contaminated domestic food in 2016 was mostly raw/undercooked poultry or unpasteurized milk/fruit drinks. Campylobacter can be detected in up to 88% of chicken carcasses at processing plants and approximately 50% of raw chicken at grocery stores. However, Campylobacter from imported food most often came from fresh produce.²

Overall, Salmonella originated from diverse sources (eggs, poultry, meat, unpasteurized milk/juice/cheese, or raw fruits/vegetables/spices/nuts). But, in 2016, U.S. Salmonella outbreaks were from eggs, alfalfa sprouts, poultry, pistachios, and organic shake/meal products.

The runners-up

Most of the remainder of the 2016 foodborne illnesses were caused by Shigella, with nearly 3,000 cases; shigatoxin-producing Escherichia coli (STEC), with nearly 2,000 cases; and Cryptosporidium, also with nearly 2,000 cases. (See table.)

Hemolytic uremic syndrome (HUS)

HUS rates, mostly resulting from E. coli 0157 H7 in meat, did not vary from 2013 to 2016, with a total 62 pediatric HUS cases in FoodNet (0.56 /100,000 population). Slightly over half (56%) occurred in children under 5 years old at 1.18 per 100,000 population.

Does CIDT increase detection rates?

Detection of the “big two” did not change from 2013 to 2016 or over the past 2 decades. That said, Campylobacter detection was actually down 11% if considering only culture-confirmed cases. That is, if we do not count detections made exclusively by CIDT.

This is important because CIDT – now supplanting culture in many laboratories – identifies pathogens not likely detected by standard culture because culture is generally selective and CIDT is more sensitive. CIDT can increase detection rates (solo and multiple pathogens), even if illnesses do not really increase. The CDC suggested that this contributed to increased STEC and Yersinia detection in 2016. Some would not have been detected if only culture had been utilized.

Viable bacterial/viral isolates are not available from CIDT. A replicating pathogen is needed to characterize shifting/emerging pathogen strains (for example, analysis for mutations or new pathogens via sequencing or antimicrobial susceptibility testing).

To compensate, some CIDT-using laboratories perform “reflex cultures.” CIDT positive specimens also are cultured to provide viable isolates. However, this adds cost to an already costly CIDT test.

The role of imported food

Surveillance systems, such as the Foodborne Disease Outbreak Surveillance System, also track imported foodborne illness. Despite an approximately 50% decrease in overall U.S. foodborne outbreaks since 2000, imported food-related outbreaks increased to 195 during 2006-2014 from 54 during 1996-2004, with 10,685 illnesses, 1,017 hospitalizations, and 19 deaths since 2009. Also, imported food-related outbreaks rose from a mean 3 per year pre-2000 to a mean 18 per year during 2009-2014. Most imported food outbreaks (86% of total) had three causes: scombroid toxin (42% of total), Salmonella (33%), and hepatitis A virus (11%).

A foreign origin for approximately 19% of U.S.-consumed food makes it unsurprising that imported foods increasingly cause foodborne outbreaks. Much imported food is “outbreak prone.” Perhaps surprising is that a staggering 97% of fish/shellfish, 50% of fresh fruits, and 20% of fresh vegetables are imported, according to 2016 estimates by the U.S. Department of Agriculture.

Most imported food illnesses were from Salmonella (4,421 from 52 outbreaks), Cyclospora (2,533 from 33 outbreaks), hepatitis A virus (1,150 from 11 outbreaks), and Shigella (625 from 6 outbreaks). While eggs, ice cream, and poultry are notorious origins for Salmonella in domestic food, most imported Salmonella were from produce: fruits (26%), seeded vegetables (20%), sprouts (11%), nuts/seeds (10%), spices (7%), and herbs (2%).

Seafood/fish caused 55% of outbreaks but few illnesses per outbreak (median 3 illnesses/outbreak), so only 11% of total illnesses were caused by seafood/fish. In contrast, fresh produce caused only 33% of outbreaks but 84% of illnesses (median 40 illnesses/outbreak).

Geographic source, outbreak locations

The origin was known in 91% of outbreaks. Latin America and the Caribbean were most common, followed by Asia.³ Main contributing countries were Mexico (42 outbreaks), Indonesia (17) and Canada (11).

 

Contaminated fish/shellfish originated from all regions except Europe, most commonly from Asia (the majority of fish/shellfish outbreaks were from Indonesia, Vietnam, China, Philippines, Taiwan, and Thailand) with smaller contributions from the Bahamas and Ecuador.

Contaminated produce originated from all regions, mostly (64%) from Mexico and the Americas (Chile, Guatemala, and Honduras). All but one dairy outbreak originated in Latin America/the Caribbean.³ Outbreaks occurred in 31 states, most commonly California (30), Florida (25), and New York (16). Additionally, 43 (22%) were multistate outbreaks.

Conclusions

Outbreaks from domestic foods decreased, but those from imported foods increased. This makes sense given recent increases in outbreak-prone food imports, such as seafood/fish and produce.

To reduce overall foodborne illness outbreaks, governmental agencies need to:

• Develop/enforce regulations that promote proper growing, handling, and processing of foods.
• Strengthen surveillance networks and share standard culture and molecular detection/characterization protocols to identify outbreaks as close to real time as possible.
• Ensure rapid traceability not only to country of origin but to an exact farm or seafood/fish harvesting entity.
• Provide rapid public knowledge of outbreaks and origins, plus outbreak-specific recommendations to control/minimize resultant illnesses.

Individuals can help protect themselves by avoiding inadequately washed or incompletely cooked foods or foods of uncertain origin.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at [email protected].

References

1. MMWR. 2017 Apr 21;66(15):397-403.

2. Emerg Infect Dis. 2017 Mar;23(3):525-8.

3. Technical appendix in Emerg Infect Dis. 2017 Mar;23(3):525-8.

 

Are foodborne illness outbreaks more common now, or are we simply better at detection? Have the foods and sources associated with foodborne illness changed? Two recent Centers for Disease Control & Prevention reports provide insight.^1,2 In 2016, the Foodborne Diseases Active Surveillance Network (FoodNet) detected 24,029 infections, 5,212 hospitalizations, and 98 fatalities.¹ FoodNet has 10 sites serving 49 million people (15% of the U.S. population). These 2016 numbers changed only modestly from the 3 prior years.

The big two

The most frequent 2016 foodborne pathogens were Campylobacter and Salmonella, at approximately 8,000 illnesses each, detected by traditional cultures or culture-independent diagnostic tests (CIDTs). (See table.) CIDTs are relatively new molecular-based, mostly multiplex assays that test for more than a dozen pathogens in one assay.

Campylobacter-contaminated domestic food in 2016 was mostly raw/undercooked poultry or unpasteurized milk/fruit drinks. Campylobacter can be detected in up to 88% of chicken carcasses at processing plants and approximately 50% of raw chicken at grocery stores. However, Campylobacter from imported food most often came from fresh produce.²

Overall, Salmonella originated from diverse sources (eggs, poultry, meat, unpasteurized milk/juice/cheese, or raw fruits/vegetables/spices/nuts). But, in 2016, U.S. Salmonella outbreaks were from eggs, alfalfa sprouts, poultry, pistachios, and organic shake/meal products.

The runners-up

Most of the remainder of the 2016 foodborne illnesses were caused by Shigella, with nearly 3,000 cases; shigatoxin-producing Escherichia coli (STEC), with nearly 2,000 cases; and Cryptosporidium, also with nearly 2,000 cases. (See table.)

Hemolytic uremic syndrome (HUS)

HUS rates, mostly resulting from E. coli 0157 H7 in meat, did not vary from 2013 to 2016, with a total 62 pediatric HUS cases in FoodNet (0.56 /100,000 population). Slightly over half (56%) occurred in children under 5 years old at 1.18 per 100,000 population.

Does CIDT increase detection rates?

Detection of the “big two” did not change from 2013 to 2016 or over the past 2 decades. That said, Campylobacter detection was actually down 11% if considering only culture-confirmed cases. That is, if we do not count detections made exclusively by CIDT.

This is important because CIDT – now supplanting culture in many laboratories – identifies pathogens not likely detected by standard culture because culture is generally selective and CIDT is more sensitive. CIDT can increase detection rates (solo and multiple pathogens), even if illnesses do not really increase. The CDC suggested that this contributed to increased STEC and Yersinia detection in 2016. Some would not have been detected if only culture had been utilized.

Viable bacterial/viral isolates are not available from CIDT. A replicating pathogen is needed to characterize shifting/emerging pathogen strains (for example, analysis for mutations or new pathogens via sequencing or antimicrobial susceptibility testing).

To compensate, some CIDT-using laboratories perform “reflex cultures.” CIDT positive specimens also are cultured to provide viable isolates. However, this adds cost to an already costly CIDT test.

The role of imported food

Surveillance systems, such as the Foodborne Disease Outbreak Surveillance System, also track imported foodborne illness. Despite an approximately 50% decrease in overall U.S. foodborne outbreaks since 2000, imported food-related outbreaks increased to 195 during 2006-2014 from 54 during 1996-2004, with 10,685 illnesses, 1,017 hospitalizations, and 19 deaths since 2009. Also, imported food-related outbreaks rose from a mean 3 per year pre-2000 to a mean 18 per year during 2009-2014. Most imported food outbreaks (86% of total) had three causes: scombroid toxin (42% of total), Salmonella (33%), and hepatitis A virus (11%).

A foreign origin for approximately 19% of U.S.-consumed food makes it unsurprising that imported foods increasingly cause foodborne outbreaks. Much imported food is “outbreak prone.” Perhaps surprising is that a staggering 97% of fish/shellfish, 50% of fresh fruits, and 20% of fresh vegetables are imported, according to 2016 estimates by the U.S. Department of Agriculture.

Most imported food illnesses were from Salmonella (4,421 from 52 outbreaks), Cyclospora (2,533 from 33 outbreaks), hepatitis A virus (1,150 from 11 outbreaks), and Shigella (625 from 6 outbreaks). While eggs, ice cream, and poultry are notorious origins for Salmonella in domestic food, most imported Salmonella were from produce: fruits (26%), seeded vegetables (20%), sprouts (11%), nuts/seeds (10%), spices (7%), and herbs (2%).

Seafood/fish caused 55% of outbreaks but few illnesses per outbreak (median 3 illnesses/outbreak), so only 11% of total illnesses were caused by seafood/fish. In contrast, fresh produce caused only 33% of outbreaks but 84% of illnesses (median 40 illnesses/outbreak).

Geographic source, outbreak locations

The origin was known in 91% of outbreaks. Latin America and the Caribbean were most common, followed by Asia.³ Main contributing countries were Mexico (42 outbreaks), Indonesia (17) and Canada (11).

 

Contaminated fish/shellfish originated from all regions except Europe, most commonly from Asia (the majority of fish/shellfish outbreaks were from Indonesia, Vietnam, China, Philippines, Taiwan, and Thailand) with smaller contributions from the Bahamas and Ecuador.

Contaminated produce originated from all regions, mostly (64%) from Mexico and the Americas (Chile, Guatemala, and Honduras). All but one dairy outbreak originated in Latin America/the Caribbean.³ Outbreaks occurred in 31 states, most commonly California (30), Florida (25), and New York (16). Additionally, 43 (22%) were multistate outbreaks.

Conclusions

Outbreaks from domestic foods decreased, but those from imported foods increased. This makes sense given recent increases in outbreak-prone food imports, such as seafood/fish and produce.

To reduce overall foodborne illness outbreaks, governmental agencies need to:

• Develop/enforce regulations that promote proper growing, handling, and processing of foods.
• Strengthen surveillance networks and share standard culture and molecular detection/characterization protocols to identify outbreaks as close to real time as possible.
• Ensure rapid traceability not only to country of origin but to an exact farm or seafood/fish harvesting entity.
• Provide rapid public knowledge of outbreaks and origins, plus outbreak-specific recommendations to control/minimize resultant illnesses.

Individuals can help protect themselves by avoiding inadequately washed or incompletely cooked foods or foods of uncertain origin.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at [email protected].

References

1. MMWR. 2017 Apr 21;66(15):397-403.

2. Emerg Infect Dis. 2017 Mar;23(3):525-8.

3. Technical appendix in Emerg Infect Dis. 2017 Mar;23(3):525-8.

 

Are foodborne illness outbreaks more common now, or are we simply better at detection? Have the foods and sources associated with foodborne illness changed? Two recent Centers for Disease Control & Prevention reports provide insight.^1,2 In 2016, the Foodborne Diseases Active Surveillance Network (FoodNet) detected 24,029 infections, 5,212 hospitalizations, and 98 fatalities.¹ FoodNet has 10 sites serving 49 million people (15% of the U.S. population). These 2016 numbers changed only modestly from the 3 prior years.

The big two

The most frequent 2016 foodborne pathogens were Campylobacter and Salmonella, at approximately 8,000 illnesses each, detected by traditional cultures or culture-independent diagnostic tests (CIDTs). (See table.) CIDTs are relatively new molecular-based, mostly multiplex assays that test for more than a dozen pathogens in one assay.

Campylobacter-contaminated domestic food in 2016 was mostly raw/undercooked poultry or unpasteurized milk/fruit drinks. Campylobacter can be detected in up to 88% of chicken carcasses at processing plants and approximately 50% of raw chicken at grocery stores. However, Campylobacter from imported food most often came from fresh produce.²

Overall, Salmonella originated from diverse sources (eggs, poultry, meat, unpasteurized milk/juice/cheese, or raw fruits/vegetables/spices/nuts). But, in 2016, U.S. Salmonella outbreaks were from eggs, alfalfa sprouts, poultry, pistachios, and organic shake/meal products.

The runners-up

Most of the remainder of the 2016 foodborne illnesses were caused by Shigella, with nearly 3,000 cases; shigatoxin-producing Escherichia coli (STEC), with nearly 2,000 cases; and Cryptosporidium, also with nearly 2,000 cases. (See table.)

Hemolytic uremic syndrome (HUS)

HUS rates, mostly resulting from E. coli 0157 H7 in meat, did not vary from 2013 to 2016, with a total 62 pediatric HUS cases in FoodNet (0.56 /100,000 population). Slightly over half (56%) occurred in children under 5 years old at 1.18 per 100,000 population.

Does CIDT increase detection rates?

Detection of the “big two” did not change from 2013 to 2016 or over the past 2 decades. That said, Campylobacter detection was actually down 11% if considering only culture-confirmed cases. That is, if we do not count detections made exclusively by CIDT.

This is important because CIDT – now supplanting culture in many laboratories – identifies pathogens not likely detected by standard culture because culture is generally selective and CIDT is more sensitive. CIDT can increase detection rates (solo and multiple pathogens), even if illnesses do not really increase. The CDC suggested that this contributed to increased STEC and Yersinia detection in 2016. Some would not have been detected if only culture had been utilized.

Viable bacterial/viral isolates are not available from CIDT. A replicating pathogen is needed to characterize shifting/emerging pathogen strains (for example, analysis for mutations or new pathogens via sequencing or antimicrobial susceptibility testing).

To compensate, some CIDT-using laboratories perform “reflex cultures.” CIDT positive specimens also are cultured to provide viable isolates. However, this adds cost to an already costly CIDT test.

The role of imported food

Surveillance systems, such as the Foodborne Disease Outbreak Surveillance System, also track imported foodborne illness. Despite an approximately 50% decrease in overall U.S. foodborne outbreaks since 2000, imported food-related outbreaks increased to 195 during 2006-2014 from 54 during 1996-2004, with 10,685 illnesses, 1,017 hospitalizations, and 19 deaths since 2009. Also, imported food-related outbreaks rose from a mean 3 per year pre-2000 to a mean 18 per year during 2009-2014. Most imported food outbreaks (86% of total) had three causes: scombroid toxin (42% of total), Salmonella (33%), and hepatitis A virus (11%).

A foreign origin for approximately 19% of U.S.-consumed food makes it unsurprising that imported foods increasingly cause foodborne outbreaks. Much imported food is “outbreak prone.” Perhaps surprising is that a staggering 97% of fish/shellfish, 50% of fresh fruits, and 20% of fresh vegetables are imported, according to 2016 estimates by the U.S. Department of Agriculture.

Most imported food illnesses were from Salmonella (4,421 from 52 outbreaks), Cyclospora (2,533 from 33 outbreaks), hepatitis A virus (1,150 from 11 outbreaks), and Shigella (625 from 6 outbreaks). While eggs, ice cream, and poultry are notorious origins for Salmonella in domestic food, most imported Salmonella were from produce: fruits (26%), seeded vegetables (20%), sprouts (11%), nuts/seeds (10%), spices (7%), and herbs (2%).

Seafood/fish caused 55% of outbreaks but few illnesses per outbreak (median 3 illnesses/outbreak), so only 11% of total illnesses were caused by seafood/fish. In contrast, fresh produce caused only 33% of outbreaks but 84% of illnesses (median 40 illnesses/outbreak).

Geographic source, outbreak locations

The origin was known in 91% of outbreaks. Latin America and the Caribbean were most common, followed by Asia.³ Main contributing countries were Mexico (42 outbreaks), Indonesia (17) and Canada (11).

 

Contaminated fish/shellfish originated from all regions except Europe, most commonly from Asia (the majority of fish/shellfish outbreaks were from Indonesia, Vietnam, China, Philippines, Taiwan, and Thailand) with smaller contributions from the Bahamas and Ecuador.

Contaminated produce originated from all regions, mostly (64%) from Mexico and the Americas (Chile, Guatemala, and Honduras). All but one dairy outbreak originated in Latin America/the Caribbean.³ Outbreaks occurred in 31 states, most commonly California (30), Florida (25), and New York (16). Additionally, 43 (22%) were multistate outbreaks.

Conclusions

Outbreaks from domestic foods decreased, but those from imported foods increased. This makes sense given recent increases in outbreak-prone food imports, such as seafood/fish and produce.

To reduce overall foodborne illness outbreaks, governmental agencies need to:

• Develop/enforce regulations that promote proper growing, handling, and processing of foods.
• Strengthen surveillance networks and share standard culture and molecular detection/characterization protocols to identify outbreaks as close to real time as possible.
• Ensure rapid traceability not only to country of origin but to an exact farm or seafood/fish harvesting entity.
• Provide rapid public knowledge of outbreaks and origins, plus outbreak-specific recommendations to control/minimize resultant illnesses.

Individuals can help protect themselves by avoiding inadequately washed or incompletely cooked foods or foods of uncertain origin.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at [email protected].

References

1. MMWR. 2017 Apr 21;66(15):397-403.

2. Emerg Infect Dis. 2017 Mar;23(3):525-8.

3. Technical appendix in Emerg Infect Dis. 2017 Mar;23(3):525-8.

 

There are several things you should know about necessary vaccinations, and sometimes potential supply problems, if your families will be traveling internationally.

Yellow fever and vaccine supply

Yellow fever is caused by a Flavivirus transmitted by the bite of an infected mosquito. It occurs in sub-Saharan Africa and in tropical areas in South America. Multiple factors determine a traveler’s risk for acquisition, including destination, season, duration of potential exposure, activities, and the local transmission rate. The majority of those infected are asymptomatic or have minimal clinical symptoms. The incubation period is 3-6 days, which is then followed by an influenza-like illness. Approximately 15% of infected individuals develop more serious symptoms including jaundice, hemorrhagic symptoms, shock, and, ultimately, multiorgan system failure with a fatality rate of 90%. There is no specific treatment.

Prevention is avoidance of mosquito bites and receipt of yellow fever vaccine (YF-Vax). It is a relatively safe vaccine and indicated for use in persons at least 9 months of age. There are a few situations in which it can be administered to patients as young as 6 months. The vaccine becomes valid 10 days after administration, and it must be documented on an International Certificate of Vaccination or Prophylaxis card (Yellow Card).

Previously, vaccine boosters were required every 10 years. However, the duration of immunity was extensively reviewed by the World Health Organization and effective July 11, 2016, boosters are no longer required. A single dose of vaccine is now valid for the lifetime of the individual. This includes those persons vaccinated prior to July 11, 2016. Since it is a live vaccine, administration is contraindicated in certain individuals. Exemption letters are provided for those who have a medical contraindication.

Caution is advised in persons receiving their initial dose of YF-VAX who are older than 60 years of age because they have an increased risk of serious side effects. This is not a concern for the pediatrician. The vaccine can only be administered at state approved facilities. It is one vaccine that is not only recommended, but may be required for entry into certain countries. Go to www.cdc.gov/yellowfever for a complete list.

Sanofi Pasteur is the only U.S. manufacturer of YF-VAX. Production has ceased until mid-2018, when a new manufacturing facility will open. Current supplies are anticipated to be depleted by mid-2017, and orders have been limited to 5 doses per month. Sanofi Pasteur, in conjunction with the Food and Drug Administration, will make Stamaril – a yellow fever vaccine manufactured by the company in France and licensed in over 70 countries – available to U.S. travelers through an Expanded Access Investigational New Drug Application. Details on how and when this program will be operational are forthcoming. What is known is that, nationwide, there will be a limited number of sites administering Stamaril. Once finalized, a list of locations will be posted on the CDC Yellow Fever site.

How does this affect your patients? If travel to a yellow fever risk area is anticipated, they should not delay in seeking pretravel advice and immunizations until the last minute. Individual clinic inventories will not be stable. Postponing a trip or changing destinations is preferred if the vaccine is not available. Yellow fever exemption letters are only provided for those persons who have a medical contraindication to receive YF-VAX.
 

Zika, dengue, and chikungunya

These three Flaviviruses all are transmitted by mosquitoes and can present with fever, rash, and headache. Their distribution is overlapping in several parts of the world. Most infected people are asymptomatic. If symptoms develop, they usually are self-limited. Disease prevention is by mosquito avoidance. There are no preventive vaccines.

Zika virus is the only one associated with a congenital syndrome. It is characterized by brain abnormalities with or without microcephaly, neural tube defects, and ocular abnormalities.

Guidelines for the evaluation and management of Zika virus–exposed infants were initially published in January, 2016, with the most recent update published in August 2016 (MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65[33]:870-8).

Preliminary data from the U.S. Zika pregnancy registry of 442 completed pregnancies between Jan. 15 to Sept. 22, 2016, identified birth defects in 26 fetuses/ infants (6%). There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%) asymptomatic and 10 of 167 (6%) symptomatic women. There were no birth defects in infants when exposure occurred after the first trimester. Of the 26 affected infants, 4 had microcephaly and no neuroimaging and 3 (12%) had no fetal or infant testing. Approximately 41% (82/442) of infants did not have Zika virus testing (JAMA. 2017 Jan 3;317[1]:59-68).

It is unclear why testing was not performed. One concern is that the pediatrician may not have been aware of the maternal Zika virus exposure or test results. It may behoove us to begin asking questions about parental international travel to provide optimal management for our patients. We also should be familiar with the current guidelines for evaluating any potentially exposed infants, which include postnatal neuroimaging, Zika virus testing, a comprehensive newborn examination including neurologic exam, and a standard newborn hearing screen prior to hospital discharge.

Regardless of maternal Zika virus test results, infants with any clinical findings suggestive of congenital Zika virus syndrome and possible maternal exposure based on epidemiologic link also should be tested. Zika virus travel alerts and the most up to date information can be found on the Centers for Disease Control and Prevention website (www. cdc.gov/Zika).

CDC/Molly Kurnit, M.P.H.

 

Measles

Although endemic measles was eliminated in the United States in 2000, it is still common in many countries in Europe, Africa, and the Pacific. Most cases in the United States occur in unvaccinated individuals, with 78 cases reported in 2016. As of March 25, 2017, 28 cases have been reported. At least 10 countries – including Belgium, France, Italy, Germany, Portugal, and Thailand – have reported outbreaks of measles since April 2017. As reminder, all children aged 6-11 months should receive one dose of MMR and those 12 months or older should receive two doses of MMR at least 28 days apart if international travel is planned. Adults born after 1956 also should have received two doses of MMR prior to international travel.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported having no relevant financial disclosures.

 

There are several things you should know about necessary vaccinations, and sometimes potential supply problems, if your families will be traveling internationally.

Yellow fever and vaccine supply

Yellow fever is caused by a Flavivirus transmitted by the bite of an infected mosquito. It occurs in sub-Saharan Africa and in tropical areas in South America. Multiple factors determine a traveler’s risk for acquisition, including destination, season, duration of potential exposure, activities, and the local transmission rate. The majority of those infected are asymptomatic or have minimal clinical symptoms. The incubation period is 3-6 days, which is then followed by an influenza-like illness. Approximately 15% of infected individuals develop more serious symptoms including jaundice, hemorrhagic symptoms, shock, and, ultimately, multiorgan system failure with a fatality rate of 90%. There is no specific treatment.

Prevention is avoidance of mosquito bites and receipt of yellow fever vaccine (YF-Vax). It is a relatively safe vaccine and indicated for use in persons at least 9 months of age. There are a few situations in which it can be administered to patients as young as 6 months. The vaccine becomes valid 10 days after administration, and it must be documented on an International Certificate of Vaccination or Prophylaxis card (Yellow Card).

Previously, vaccine boosters were required every 10 years. However, the duration of immunity was extensively reviewed by the World Health Organization and effective July 11, 2016, boosters are no longer required. A single dose of vaccine is now valid for the lifetime of the individual. This includes those persons vaccinated prior to July 11, 2016. Since it is a live vaccine, administration is contraindicated in certain individuals. Exemption letters are provided for those who have a medical contraindication.

Caution is advised in persons receiving their initial dose of YF-VAX who are older than 60 years of age because they have an increased risk of serious side effects. This is not a concern for the pediatrician. The vaccine can only be administered at state approved facilities. It is one vaccine that is not only recommended, but may be required for entry into certain countries. Go to www.cdc.gov/yellowfever for a complete list.

Sanofi Pasteur is the only U.S. manufacturer of YF-VAX. Production has ceased until mid-2018, when a new manufacturing facility will open. Current supplies are anticipated to be depleted by mid-2017, and orders have been limited to 5 doses per month. Sanofi Pasteur, in conjunction with the Food and Drug Administration, will make Stamaril – a yellow fever vaccine manufactured by the company in France and licensed in over 70 countries – available to U.S. travelers through an Expanded Access Investigational New Drug Application. Details on how and when this program will be operational are forthcoming. What is known is that, nationwide, there will be a limited number of sites administering Stamaril. Once finalized, a list of locations will be posted on the CDC Yellow Fever site.

How does this affect your patients? If travel to a yellow fever risk area is anticipated, they should not delay in seeking pretravel advice and immunizations until the last minute. Individual clinic inventories will not be stable. Postponing a trip or changing destinations is preferred if the vaccine is not available. Yellow fever exemption letters are only provided for those persons who have a medical contraindication to receive YF-VAX.
 

Zika, dengue, and chikungunya

These three Flaviviruses all are transmitted by mosquitoes and can present with fever, rash, and headache. Their distribution is overlapping in several parts of the world. Most infected people are asymptomatic. If symptoms develop, they usually are self-limited. Disease prevention is by mosquito avoidance. There are no preventive vaccines.

Zika virus is the only one associated with a congenital syndrome. It is characterized by brain abnormalities with or without microcephaly, neural tube defects, and ocular abnormalities.

Guidelines for the evaluation and management of Zika virus–exposed infants were initially published in January, 2016, with the most recent update published in August 2016 (MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65[33]:870-8).

Preliminary data from the U.S. Zika pregnancy registry of 442 completed pregnancies between Jan. 15 to Sept. 22, 2016, identified birth defects in 26 fetuses/ infants (6%). There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%) asymptomatic and 10 of 167 (6%) symptomatic women. There were no birth defects in infants when exposure occurred after the first trimester. Of the 26 affected infants, 4 had microcephaly and no neuroimaging and 3 (12%) had no fetal or infant testing. Approximately 41% (82/442) of infants did not have Zika virus testing (JAMA. 2017 Jan 3;317[1]:59-68).

It is unclear why testing was not performed. One concern is that the pediatrician may not have been aware of the maternal Zika virus exposure or test results. It may behoove us to begin asking questions about parental international travel to provide optimal management for our patients. We also should be familiar with the current guidelines for evaluating any potentially exposed infants, which include postnatal neuroimaging, Zika virus testing, a comprehensive newborn examination including neurologic exam, and a standard newborn hearing screen prior to hospital discharge.

Regardless of maternal Zika virus test results, infants with any clinical findings suggestive of congenital Zika virus syndrome and possible maternal exposure based on epidemiologic link also should be tested. Zika virus travel alerts and the most up to date information can be found on the Centers for Disease Control and Prevention website (www. cdc.gov/Zika).

CDC/Molly Kurnit, M.P.H.

 

Measles

Although endemic measles was eliminated in the United States in 2000, it is still common in many countries in Europe, Africa, and the Pacific. Most cases in the United States occur in unvaccinated individuals, with 78 cases reported in 2016. As of March 25, 2017, 28 cases have been reported. At least 10 countries – including Belgium, France, Italy, Germany, Portugal, and Thailand – have reported outbreaks of measles since April 2017. As reminder, all children aged 6-11 months should receive one dose of MMR and those 12 months or older should receive two doses of MMR at least 28 days apart if international travel is planned. Adults born after 1956 also should have received two doses of MMR prior to international travel.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported having no relevant financial disclosures.

 

There are several things you should know about necessary vaccinations, and sometimes potential supply problems, if your families will be traveling internationally.

Yellow fever and vaccine supply

Yellow fever is caused by a Flavivirus transmitted by the bite of an infected mosquito. It occurs in sub-Saharan Africa and in tropical areas in South America. Multiple factors determine a traveler’s risk for acquisition, including destination, season, duration of potential exposure, activities, and the local transmission rate. The majority of those infected are asymptomatic or have minimal clinical symptoms. The incubation period is 3-6 days, which is then followed by an influenza-like illness. Approximately 15% of infected individuals develop more serious symptoms including jaundice, hemorrhagic symptoms, shock, and, ultimately, multiorgan system failure with a fatality rate of 90%. There is no specific treatment.

Prevention is avoidance of mosquito bites and receipt of yellow fever vaccine (YF-Vax). It is a relatively safe vaccine and indicated for use in persons at least 9 months of age. There are a few situations in which it can be administered to patients as young as 6 months. The vaccine becomes valid 10 days after administration, and it must be documented on an International Certificate of Vaccination or Prophylaxis card (Yellow Card).

Previously, vaccine boosters were required every 10 years. However, the duration of immunity was extensively reviewed by the World Health Organization and effective July 11, 2016, boosters are no longer required. A single dose of vaccine is now valid for the lifetime of the individual. This includes those persons vaccinated prior to July 11, 2016. Since it is a live vaccine, administration is contraindicated in certain individuals. Exemption letters are provided for those who have a medical contraindication.

Caution is advised in persons receiving their initial dose of YF-VAX who are older than 60 years of age because they have an increased risk of serious side effects. This is not a concern for the pediatrician. The vaccine can only be administered at state approved facilities. It is one vaccine that is not only recommended, but may be required for entry into certain countries. Go to www.cdc.gov/yellowfever for a complete list.

Sanofi Pasteur is the only U.S. manufacturer of YF-VAX. Production has ceased until mid-2018, when a new manufacturing facility will open. Current supplies are anticipated to be depleted by mid-2017, and orders have been limited to 5 doses per month. Sanofi Pasteur, in conjunction with the Food and Drug Administration, will make Stamaril – a yellow fever vaccine manufactured by the company in France and licensed in over 70 countries – available to U.S. travelers through an Expanded Access Investigational New Drug Application. Details on how and when this program will be operational are forthcoming. What is known is that, nationwide, there will be a limited number of sites administering Stamaril. Once finalized, a list of locations will be posted on the CDC Yellow Fever site.

How does this affect your patients? If travel to a yellow fever risk area is anticipated, they should not delay in seeking pretravel advice and immunizations until the last minute. Individual clinic inventories will not be stable. Postponing a trip or changing destinations is preferred if the vaccine is not available. Yellow fever exemption letters are only provided for those persons who have a medical contraindication to receive YF-VAX.
 

Zika, dengue, and chikungunya

These three Flaviviruses all are transmitted by mosquitoes and can present with fever, rash, and headache. Their distribution is overlapping in several parts of the world. Most infected people are asymptomatic. If symptoms develop, they usually are self-limited. Disease prevention is by mosquito avoidance. There are no preventive vaccines.

Zika virus is the only one associated with a congenital syndrome. It is characterized by brain abnormalities with or without microcephaly, neural tube defects, and ocular abnormalities.

Guidelines for the evaluation and management of Zika virus–exposed infants were initially published in January, 2016, with the most recent update published in August 2016 (MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65[33]:870-8).

Preliminary data from the U.S. Zika pregnancy registry of 442 completed pregnancies between Jan. 15 to Sept. 22, 2016, identified birth defects in 26 fetuses/ infants (6%). There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%) asymptomatic and 10 of 167 (6%) symptomatic women. There were no birth defects in infants when exposure occurred after the first trimester. Of the 26 affected infants, 4 had microcephaly and no neuroimaging and 3 (12%) had no fetal or infant testing. Approximately 41% (82/442) of infants did not have Zika virus testing (JAMA. 2017 Jan 3;317[1]:59-68).

It is unclear why testing was not performed. One concern is that the pediatrician may not have been aware of the maternal Zika virus exposure or test results. It may behoove us to begin asking questions about parental international travel to provide optimal management for our patients. We also should be familiar with the current guidelines for evaluating any potentially exposed infants, which include postnatal neuroimaging, Zika virus testing, a comprehensive newborn examination including neurologic exam, and a standard newborn hearing screen prior to hospital discharge.

Regardless of maternal Zika virus test results, infants with any clinical findings suggestive of congenital Zika virus syndrome and possible maternal exposure based on epidemiologic link also should be tested. Zika virus travel alerts and the most up to date information can be found on the Centers for Disease Control and Prevention website (www. cdc.gov/Zika).

CDC/Molly Kurnit, M.P.H.

 

Measles

Although endemic measles was eliminated in the United States in 2000, it is still common in many countries in Europe, Africa, and the Pacific. Most cases in the United States occur in unvaccinated individuals, with 78 cases reported in 2016. As of March 25, 2017, 28 cases have been reported. At least 10 countries – including Belgium, France, Italy, Germany, Portugal, and Thailand – have reported outbreaks of measles since April 2017. As reminder, all children aged 6-11 months should receive one dose of MMR and those 12 months or older should receive two doses of MMR at least 28 days apart if international travel is planned. Adults born after 1956 also should have received two doses of MMR prior to international travel.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported having no relevant financial disclosures.

 

In December 2016, the results of a randomized, controlled trial of 5-day vs. 10-day amoxicillin/clavulanate treatment of acute otitis media (AOM) in children aged 6-23 months was reported by Hoberman et al. in the New England Journal of Medicine (NEJM).¹ Predefined criteria for clinical failure were used that considered both symptoms and signs of AOM, assessed on days 12-14 after start of treatment with 5 vs. 10 days of treatment with the antibiotic. The conclusion reached was clear: The clinical failure rate for the 5-day regimen was 34% vs. 16% in the 10-day group, supporting a preference for the 10-day treatment.

I was surprised. The clinical failure rate for the 5-day regimen seemed very high for treatment with amoxicillin/clavulanate. If it is 34% with amoxicillin/clavulanate, then what would it have been with amoxicillin, as recommended by the American Academy of Pediatrics?

The result was not consistent with a systematic review that included 49 trials containing 12,045 participants.² In that meta-analysis, the risk of treatment failure was statistically higher with short courses of antibiotics (odds ratio, 1.34; 95% confidence interval, 1.15-1.55) at 1 month after initiation of therapy (21% failure with short-course treatment and 18% with long course; absolute difference of 3% between groups) but clinically, only marginally significant. The meta-analysis included many trials with antibiotics that likely were much less effective against the major bacteria that cause AOM, compared with amoxicillin/clavulanate. While all systematic reviews and meta-analyses suffer from potential inclusion of studies that are poorly designed, the wealth of data from these types of studies offers the advantage of seeing bigger trends and consistencies.

So, why did the systematic review conclude that there was a minimal difference between shortened treatments and the standard 10-day when the NEJM study reported such a striking difference?

In Rochester, N.Y., we have been conducting a longitudinal, prospective study of AOM that is NIH-sponsored to better understand the immune response to AOM, especially in otitis-prone children.^3,4 In that study we are treating all children aged 6-23 months with amoxicillin/clavulanate using the same dose as used in the study by Hoberman et al. We have two exceptions: If the child has a second AOM within 30 days of a prior episode or they have an eardrum rupture, we treat for 10 days.⁵ Our clinical failure rate is 6%. Why is the failure rate in Rochester so much lower than that in Pittsburgh and Bardstown, Ky., where the Hoberman et al. study was done?

One possibility is an important difference in our study design, compared with that of the NEJM study. All the children in our prospective study have a tympanocentesis to confirm the clinical diagnosis, and our research has shown that tympanocentesis results in immediate relief of ear pain and reduces the frequency of antibiotic treatment failure about twofold, compared with children diagnosed and treated by the same physicians in the same clinic practice.⁶ So, if the tympanocentesis is factored out of the equation, the Rochester clinical failure comes out to 14% for 5-day treatment. Why would the children in Rochester not getting a tympanocentesis, being treated with the same antibiotic, same dose, and same definition of clinical failure, during the same time frame, and having the same bacteria with the same antibiotic resistance rates have a clinical failure rate of 14%, compared with the 34% in the NEJM study?

Next question: Why would 10 days of treatment result in better clinical success than 5 days? As an infectious disease expert, my answer would be that the longer treatment must have been more frequently successful in killing the causative bacteria. But that is puzzling because, in studies where tympanocentesis was performed to confirm the clinical diagnosis of AOM and a second tympanocentesis was done 3-5 days later to confirm microbiological eradication of the causative bacteria (so-called double tap studies), it was found that the bacteria were killed in 3-5 days unless they were resistant to the antibiotic used.⁷ Using an antibiotic longer if the organism is resistant to that antibiotic does not work.

Next question: How does a clinical failure rate of 34% fit according to past studies of shortened course antibiotic treatment of AOM? Besides the systematic review and meta-analysis noted above, in many countries outside the United States the 5-day regimen is standard, so, if health care providers were seeing a 34% failure rate, that would have been noticeable for sure.⁸ So, if health care providers were seeing a 34% failure rate, would that not have been noticeable? And would not a 16% failure rate, nearly 1 of 5 cases, be noticeable for children treated for 10 days?

Was there something different about the children who were in the Hoberman et al. study and the children treated in countries outside the United States and in our practice in Rochester? My group has collaborated and published on studies of AOM with the Pittsburgh and Kentucky groups, and we have not found significant site to site differences in outcomes, demonstrating that a population difference is unlikely.^9-11

Next question: How does a clinical failure rate of 16% fit according to past studies of 10 days’ antibiotic treatment of AOM? It is on target with the meta-analysis and two other recent studies in the NEJM.^12,13 However, if the failure rate was 16% with amoxicillin/clavulanate (which is effective against beta-lactamase–producing Haemophilus influenzae and Moraxella catarrhalis, whereas amoxicillin is not), then the predicted failure rate with amoxicillin for 10 days should be double (34%) or triple (51%) had amoxicillin been used as recommended by the AAP in light of the bacterial resistance of otopathogens. That calculation is based on the prevalence of beta-lactamase–producing H. influenzae and M. catarrhalis in the Pittsburgh and Kentucky populations, the same prevalence seen in the Rochester population.” ¹⁴

So, I conclude that this wonderful study does not convince me to change my practice from standard use of 5-day amoxicillin/clavulanate treatment of AOM. Besides, outside of a study setting, most parents don’t give the full 10-day treatment. They stop when their child seems normal (a few days after starting treatment) and save the remainder of the medicine in the refrigerator for the next illness to save a trip to the doctor. Plus, in this column, I did not even get into the issue of disturbing the microbiome with longer courses of antibiotic treatment, a topic for a future discussion.

 

References

1. N Engl J Med. 2016 Dec 22;375(25):2446-56.

2. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD001095.

3. Pediatr Infect Dis J. 2016 Sep;35(9):1027-32.

4. Pediatr Infect Dis J. 2016 Sep;35(9):1033-9.

5. Otolaryngol Head Neck Surg. 2001 Apr;124(4):381-7.

6. Pediatr Infect Dis J. 2013 May;32(5):473-8.

7. Pediatr Infect Dis J. 2006 Mar;25(3):211-8.

8. Pediatr Infect Dis J. 2000 Sep;19(9):929-37.

9. Pediatr Infect Dis J. 1999 Aug;18(8):741-4.

10. Clin Pediatr (Phila). 2008 Nov;47(9):901-6.

11. Drugs. 2012 Oct 22;72(15):1991-7.

12. N Engl J Med. 2011 Jan 13;364(2):105-15.

13. N Engl J Med. 2011 Jan 13;364(2):116-26.

14. Pediatr Infect Dis J. 2016 Aug;35(8):901-6.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. He has no disclosures.

 

In December 2016, the results of a randomized, controlled trial of 5-day vs. 10-day amoxicillin/clavulanate treatment of acute otitis media (AOM) in children aged 6-23 months was reported by Hoberman et al. in the New England Journal of Medicine (NEJM).¹ Predefined criteria for clinical failure were used that considered both symptoms and signs of AOM, assessed on days 12-14 after start of treatment with 5 vs. 10 days of treatment with the antibiotic. The conclusion reached was clear: The clinical failure rate for the 5-day regimen was 34% vs. 16% in the 10-day group, supporting a preference for the 10-day treatment.

I was surprised. The clinical failure rate for the 5-day regimen seemed very high for treatment with amoxicillin/clavulanate. If it is 34% with amoxicillin/clavulanate, then what would it have been with amoxicillin, as recommended by the American Academy of Pediatrics?

The result was not consistent with a systematic review that included 49 trials containing 12,045 participants.² In that meta-analysis, the risk of treatment failure was statistically higher with short courses of antibiotics (odds ratio, 1.34; 95% confidence interval, 1.15-1.55) at 1 month after initiation of therapy (21% failure with short-course treatment and 18% with long course; absolute difference of 3% between groups) but clinically, only marginally significant. The meta-analysis included many trials with antibiotics that likely were much less effective against the major bacteria that cause AOM, compared with amoxicillin/clavulanate. While all systematic reviews and meta-analyses suffer from potential inclusion of studies that are poorly designed, the wealth of data from these types of studies offers the advantage of seeing bigger trends and consistencies.

So, why did the systematic review conclude that there was a minimal difference between shortened treatments and the standard 10-day when the NEJM study reported such a striking difference?

In Rochester, N.Y., we have been conducting a longitudinal, prospective study of AOM that is NIH-sponsored to better understand the immune response to AOM, especially in otitis-prone children.^3,4 In that study we are treating all children aged 6-23 months with amoxicillin/clavulanate using the same dose as used in the study by Hoberman et al. We have two exceptions: If the child has a second AOM within 30 days of a prior episode or they have an eardrum rupture, we treat for 10 days.⁵ Our clinical failure rate is 6%. Why is the failure rate in Rochester so much lower than that in Pittsburgh and Bardstown, Ky., where the Hoberman et al. study was done?

One possibility is an important difference in our study design, compared with that of the NEJM study. All the children in our prospective study have a tympanocentesis to confirm the clinical diagnosis, and our research has shown that tympanocentesis results in immediate relief of ear pain and reduces the frequency of antibiotic treatment failure about twofold, compared with children diagnosed and treated by the same physicians in the same clinic practice.⁶ So, if the tympanocentesis is factored out of the equation, the Rochester clinical failure comes out to 14% for 5-day treatment. Why would the children in Rochester not getting a tympanocentesis, being treated with the same antibiotic, same dose, and same definition of clinical failure, during the same time frame, and having the same bacteria with the same antibiotic resistance rates have a clinical failure rate of 14%, compared with the 34% in the NEJM study?

Next question: Why would 10 days of treatment result in better clinical success than 5 days? As an infectious disease expert, my answer would be that the longer treatment must have been more frequently successful in killing the causative bacteria. But that is puzzling because, in studies where tympanocentesis was performed to confirm the clinical diagnosis of AOM and a second tympanocentesis was done 3-5 days later to confirm microbiological eradication of the causative bacteria (so-called double tap studies), it was found that the bacteria were killed in 3-5 days unless they were resistant to the antibiotic used.⁷ Using an antibiotic longer if the organism is resistant to that antibiotic does not work.

Next question: How does a clinical failure rate of 34% fit according to past studies of shortened course antibiotic treatment of AOM? Besides the systematic review and meta-analysis noted above, in many countries outside the United States the 5-day regimen is standard, so, if health care providers were seeing a 34% failure rate, that would have been noticeable for sure.⁸ So, if health care providers were seeing a 34% failure rate, would that not have been noticeable? And would not a 16% failure rate, nearly 1 of 5 cases, be noticeable for children treated for 10 days?

Was there something different about the children who were in the Hoberman et al. study and the children treated in countries outside the United States and in our practice in Rochester? My group has collaborated and published on studies of AOM with the Pittsburgh and Kentucky groups, and we have not found significant site to site differences in outcomes, demonstrating that a population difference is unlikely.^9-11

Next question: How does a clinical failure rate of 16% fit according to past studies of 10 days’ antibiotic treatment of AOM? It is on target with the meta-analysis and two other recent studies in the NEJM.^12,13 However, if the failure rate was 16% with amoxicillin/clavulanate (which is effective against beta-lactamase–producing Haemophilus influenzae and Moraxella catarrhalis, whereas amoxicillin is not), then the predicted failure rate with amoxicillin for 10 days should be double (34%) or triple (51%) had amoxicillin been used as recommended by the AAP in light of the bacterial resistance of otopathogens. That calculation is based on the prevalence of beta-lactamase–producing H. influenzae and M. catarrhalis in the Pittsburgh and Kentucky populations, the same prevalence seen in the Rochester population.” ¹⁴

So, I conclude that this wonderful study does not convince me to change my practice from standard use of 5-day amoxicillin/clavulanate treatment of AOM. Besides, outside of a study setting, most parents don’t give the full 10-day treatment. They stop when their child seems normal (a few days after starting treatment) and save the remainder of the medicine in the refrigerator for the next illness to save a trip to the doctor. Plus, in this column, I did not even get into the issue of disturbing the microbiome with longer courses of antibiotic treatment, a topic for a future discussion.

 

References

1. N Engl J Med. 2016 Dec 22;375(25):2446-56.

2. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD001095.

3. Pediatr Infect Dis J. 2016 Sep;35(9):1027-32.

4. Pediatr Infect Dis J. 2016 Sep;35(9):1033-9.

5. Otolaryngol Head Neck Surg. 2001 Apr;124(4):381-7.

6. Pediatr Infect Dis J. 2013 May;32(5):473-8.

7. Pediatr Infect Dis J. 2006 Mar;25(3):211-8.

8. Pediatr Infect Dis J. 2000 Sep;19(9):929-37.

9. Pediatr Infect Dis J. 1999 Aug;18(8):741-4.

10. Clin Pediatr (Phila). 2008 Nov;47(9):901-6.

11. Drugs. 2012 Oct 22;72(15):1991-7.

12. N Engl J Med. 2011 Jan 13;364(2):105-15.

13. N Engl J Med. 2011 Jan 13;364(2):116-26.

14. Pediatr Infect Dis J. 2016 Aug;35(8):901-6.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. He has no disclosures.

 

In December 2016, the results of a randomized, controlled trial of 5-day vs. 10-day amoxicillin/clavulanate treatment of acute otitis media (AOM) in children aged 6-23 months was reported by Hoberman et al. in the New England Journal of Medicine (NEJM).¹ Predefined criteria for clinical failure were used that considered both symptoms and signs of AOM, assessed on days 12-14 after start of treatment with 5 vs. 10 days of treatment with the antibiotic. The conclusion reached was clear: The clinical failure rate for the 5-day regimen was 34% vs. 16% in the 10-day group, supporting a preference for the 10-day treatment.

I was surprised. The clinical failure rate for the 5-day regimen seemed very high for treatment with amoxicillin/clavulanate. If it is 34% with amoxicillin/clavulanate, then what would it have been with amoxicillin, as recommended by the American Academy of Pediatrics?

The result was not consistent with a systematic review that included 49 trials containing 12,045 participants.² In that meta-analysis, the risk of treatment failure was statistically higher with short courses of antibiotics (odds ratio, 1.34; 95% confidence interval, 1.15-1.55) at 1 month after initiation of therapy (21% failure with short-course treatment and 18% with long course; absolute difference of 3% between groups) but clinically, only marginally significant. The meta-analysis included many trials with antibiotics that likely were much less effective against the major bacteria that cause AOM, compared with amoxicillin/clavulanate. While all systematic reviews and meta-analyses suffer from potential inclusion of studies that are poorly designed, the wealth of data from these types of studies offers the advantage of seeing bigger trends and consistencies.

So, why did the systematic review conclude that there was a minimal difference between shortened treatments and the standard 10-day when the NEJM study reported such a striking difference?

In Rochester, N.Y., we have been conducting a longitudinal, prospective study of AOM that is NIH-sponsored to better understand the immune response to AOM, especially in otitis-prone children.^3,4 In that study we are treating all children aged 6-23 months with amoxicillin/clavulanate using the same dose as used in the study by Hoberman et al. We have two exceptions: If the child has a second AOM within 30 days of a prior episode or they have an eardrum rupture, we treat for 10 days.⁵ Our clinical failure rate is 6%. Why is the failure rate in Rochester so much lower than that in Pittsburgh and Bardstown, Ky., where the Hoberman et al. study was done?

One possibility is an important difference in our study design, compared with that of the NEJM study. All the children in our prospective study have a tympanocentesis to confirm the clinical diagnosis, and our research has shown that tympanocentesis results in immediate relief of ear pain and reduces the frequency of antibiotic treatment failure about twofold, compared with children diagnosed and treated by the same physicians in the same clinic practice.⁶ So, if the tympanocentesis is factored out of the equation, the Rochester clinical failure comes out to 14% for 5-day treatment. Why would the children in Rochester not getting a tympanocentesis, being treated with the same antibiotic, same dose, and same definition of clinical failure, during the same time frame, and having the same bacteria with the same antibiotic resistance rates have a clinical failure rate of 14%, compared with the 34% in the NEJM study?

Next question: Why would 10 days of treatment result in better clinical success than 5 days? As an infectious disease expert, my answer would be that the longer treatment must have been more frequently successful in killing the causative bacteria. But that is puzzling because, in studies where tympanocentesis was performed to confirm the clinical diagnosis of AOM and a second tympanocentesis was done 3-5 days later to confirm microbiological eradication of the causative bacteria (so-called double tap studies), it was found that the bacteria were killed in 3-5 days unless they were resistant to the antibiotic used.⁷ Using an antibiotic longer if the organism is resistant to that antibiotic does not work.

Next question: How does a clinical failure rate of 34% fit according to past studies of shortened course antibiotic treatment of AOM? Besides the systematic review and meta-analysis noted above, in many countries outside the United States the 5-day regimen is standard, so, if health care providers were seeing a 34% failure rate, that would have been noticeable for sure.⁸ So, if health care providers were seeing a 34% failure rate, would that not have been noticeable? And would not a 16% failure rate, nearly 1 of 5 cases, be noticeable for children treated for 10 days?

Was there something different about the children who were in the Hoberman et al. study and the children treated in countries outside the United States and in our practice in Rochester? My group has collaborated and published on studies of AOM with the Pittsburgh and Kentucky groups, and we have not found significant site to site differences in outcomes, demonstrating that a population difference is unlikely.^9-11

Next question: How does a clinical failure rate of 16% fit according to past studies of 10 days’ antibiotic treatment of AOM? It is on target with the meta-analysis and two other recent studies in the NEJM.^12,13 However, if the failure rate was 16% with amoxicillin/clavulanate (which is effective against beta-lactamase–producing Haemophilus influenzae and Moraxella catarrhalis, whereas amoxicillin is not), then the predicted failure rate with amoxicillin for 10 days should be double (34%) or triple (51%) had amoxicillin been used as recommended by the AAP in light of the bacterial resistance of otopathogens. That calculation is based on the prevalence of beta-lactamase–producing H. influenzae and M. catarrhalis in the Pittsburgh and Kentucky populations, the same prevalence seen in the Rochester population.” ¹⁴

So, I conclude that this wonderful study does not convince me to change my practice from standard use of 5-day amoxicillin/clavulanate treatment of AOM. Besides, outside of a study setting, most parents don’t give the full 10-day treatment. They stop when their child seems normal (a few days after starting treatment) and save the remainder of the medicine in the refrigerator for the next illness to save a trip to the doctor. Plus, in this column, I did not even get into the issue of disturbing the microbiome with longer courses of antibiotic treatment, a topic for a future discussion.

 

References

1. N Engl J Med. 2016 Dec 22;375(25):2446-56.

2. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD001095.

3. Pediatr Infect Dis J. 2016 Sep;35(9):1027-32.

4. Pediatr Infect Dis J. 2016 Sep;35(9):1033-9.

5. Otolaryngol Head Neck Surg. 2001 Apr;124(4):381-7.

6. Pediatr Infect Dis J. 2013 May;32(5):473-8.

7. Pediatr Infect Dis J. 2006 Mar;25(3):211-8.

8. Pediatr Infect Dis J. 2000 Sep;19(9):929-37.

9. Pediatr Infect Dis J. 1999 Aug;18(8):741-4.

10. Clin Pediatr (Phila). 2008 Nov;47(9):901-6.

11. Drugs. 2012 Oct 22;72(15):1991-7.

12. N Engl J Med. 2011 Jan 13;364(2):105-15.

13. N Engl J Med. 2011 Jan 13;364(2):116-26.

14. Pediatr Infect Dis J. 2016 Aug;35(8):901-6.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. He has no disclosures.