Pediatrics

There are over 3700 types of mosquitoes worldwide and over 200 types in the continental United States, of which only 12 are associated with transmitting diseases to humans. The majority are just a nuisance. Since they cannot readily be distinguished, strategies to prevent any bites are recommended.

West Nile Virus

In the US, West Nile virus (WNV) is the leading cause of neuroinvasive arboviral disease. Just hearing the name took me back to New York in 1999 when sightings of dead birds around the city and boroughs were reported daily. The virus was isolated that same year. The enzootic circle occurs between mosquitoes and birds, which are the primary vertebrate host via the bite of Culex mosquitoes. After a bite from an infected mosquito, humans are usually a dead-end host since the level and duration of viremia needed to infect another mosquito is insufficient.

Human-to-human transmission is documented through blood transfusion and solid organ transplantation. Vertical transmission is rarely described. Initially isolated in New York, WNV quickly spread across North America and has been isolated in every continent except Antarctica. Most cases occur in the summer and autumn.

Most infected individuals are asymptomatic. Those who do develop symptoms have fever, headache, myalgia, arthralgia, nausea, vomiting, and a transient rash. Less than 1% develop meningitis/encephalitis symptoms similar to other causes of aseptic meningitis. Those with encephalitis in addition to fever and headache may have altered mental status and focal neurologic deficits including flaccid paralysis or movement disorders.

Detection of anti-WNV IgM antibodies (AB) in serum or CSF is the most common way to make the diagnosis. IgM AB usually is present within 3-8 days after onset of symptoms and persists up to 90 days. Data from ArboNET, the national arboviral surveillance system managed by Centers for Disease Control and Prevention and state health departments, reveal that from 1999 to 2022 there were 56,575 cases of WNV including 28,684 cases of neuroinvasive disease. In 2023 there were 2,406 and 1,599 cases, respectively. Those historic totals for WNV are 10 times greater than the totals for all the other etiologies of neuroinvasive arboviral diseases in the US combined (Jamestown Canyon, LaCrosse, St. Louis, and Eastern Equine encephalitis n = 1813).

Remember to include WNV in your differential of a febrile patient with neurologic symptoms, mosquito bites, blood transfusions, and organ transplantation. Treatment is supportive care.

The US began screening all blood donations for WNV in 2003. Organ donor screening is not universal.

Dengue

Dengue, another arbovirus, is transmitted by bites of infected Aedes aegypti and Aedes albopictus mosquitoes, which prefer to feed during the daytime. There are four dengue virus serotypes: DENV-1 DENV-2, DENV-3 and DENV-4. In endemic areas, all four serotypes are usually co-circulating and people can be infected by each one.

Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Long-term immunity is type specific. Heterologous protection lasts only a few months. Dengue is endemic throughout the tropics and subtropics of Asia, Africa, and the Americas. Approximately 53% of the world’s population live in an area where dengue transmission can occur. In the US, most cases are reported from Puerto Rico. Dengue is endemic in the following US territories: Puerto Rico, US Virgin Islands, American Samoa, and free associated states. Most cases reported on the mainland are travel related. However, locally acquired dengue has been reported. From 2010 to 2023 Hawaii reported 250 cases, Florida 438, and Texas 40 locally acquired cases. During that same period, Puerto Rico reported more than 32,000 cases. It is the leading cause of febrile illness for travelers returning from the Caribbean, Latin America, and South Asia. Peru is currently experiencing an outbreak with more than 25,000 cases reported since January 2024. Most cases of dengue occur in adolescents and young adults. Severe disease occurs most often in infants, those with underlying chronic disease, pregnant women, and persons infected with dengue for the second time.

Symptoms range from a mild febrile illness to severe disease associated with hemorrhage and shock. Onset is usually 7-10 days after infection and symptoms include high fever, severe headache, retro-orbital pain, arthralgia and myalgias, nausea, and vomiting; some may develop a generalized rash.

The World Health Organization (WHO) classifies dengue as 1) dengue with or without warning signs for progression of disease and 2) severe dengue. Warning signs for disease progression include abdominal pain or tenderness, persistent vomiting, fluid accumulation (e.g., ascites, pericardial or pleural effusion), mucosal bleeding, restlessness, postural hypotension, liver enlargement greater than 2 cm. Severe dengue is defined as any sign of severe plasma leakage leading to shock, severe bleeding or organ failure, or fluid accumulation with respiratory distress. Management is supportive care.

Prevention: In the US, Dengvaxia, a live attenuated tetravalent vaccine, is approved for use in children aged 9–16 years with laboratory-confirmed previous dengue virus infection and living in areas where dengue is endemic. It is administered at 0, 6, and 12 months. It is not available for purchase on the mainland. Continued control of the vector and personal protection is necessary to prevent recurrent infections.
 

CHIKV

Chikungunya (CHIKV), which means “that which bends up” in the Mkonde language of Tanzania, refers to the appearance of the person with severe usually symmetric arthralgias characteristic for this infection that otherwise is often clinically confused with dengue and Zika. It too is transmitted by A. aegypti and A. albopictus and is prevalent in tropical Africa, Asia, Central and South America, and the Caribbean. Like dengue it is predominantly an urban disease. The WHO reported the first case in the Western Hemisphere in Saint Martin in December 2013. By August 2014, 31 additional territories and Caribbean or South American countries reported 576,535 suspected cases. Florida first reported locally acquired CHIKV in June 2014. By December an additional 11 cases had been identified. Texas reported one case in 2015. Diagnosis is with IgM ab or PCR. Treatment is supportive with most recovering from acute illness within 2 weeks. Data in adults indicate 40-52% may develop chronic or recurrent joint pain.

Prevention: IXCHIQ, a live attenuated vaccine, was licensed in November 2023 and recommended by the CDC in February 2024 for use in persons at least 18 years of age with travel to destinations where there is a CHIKV outbreak. It may be considered for persons traveling to a country or territory without an outbreak but with evidence of CHIKV transmission among humans within the last 5 years and those staying in endemic areas for a cumulative period of at least 6 months over a 2-year period. Specific recommendations for lab workers and persons older than 65 years were also made. This is good news for your older patients who may be participating in mission trips, volunteering, studying abroad, or just vacationing in an endemic area. Adolescent vaccine trials are ongoing and pediatric trials will soon be initiated. In addition, vector control and use of personal protective measures cannot be emphasized enough.

There are several other mosquito borne diseases, however our discussion here is limited to three. Why these three? WNV as a reminder that it is the most common neuroinvasive agent in the US. Dengue and CHIKV because they are not endemic in the US so they might not routinely be considered in febrile patients; both diseases have been reported and acquired on the mainland and your patients may travel to an endemic area and return home with an unwanted souvenir. You will be ready for them.

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

Suggested Reading

Chikungunya. Centers for Disease Control and Prevention. 2024. https://www.cdc.gov/vaccines/acip/recommendations.html.

Fagrem AC et al. West Nile and Other Nationally Notifiable Arboviral Diseases–United States, 2021. MMWR Morb Mortal Wkly Rep. 2023 Aug 25;72(34):901-906.

Fever in Returned Travelers, Travel Medicine (Fourth Edition). 2019. doi: 10.1016/B978-0-323-54696-6.00056-2.

Paz-Baily et al. Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021 MMWR Recomm Rep. 2021 Dec 17;70(6):1-16).

Staples JE and Fischer M. Chikungunya virus in the Americas — what a vectorborne pathogen can do. N Engl J Med. 2014 Sep 4;371(10):887-9.

Mosquitoes and Diseases A-Z, Centers for Disease Control and Prevention. https://www.cdc.gov/mosquitoes/about/diseases.html.

There are over 3700 types of mosquitoes worldwide and over 200 types in the continental United States, of which only 12 are associated with transmitting diseases to humans. The majority are just a nuisance. Since they cannot readily be distinguished, strategies to prevent any bites are recommended.

West Nile Virus

In the US, West Nile virus (WNV) is the leading cause of neuroinvasive arboviral disease. Just hearing the name took me back to New York in 1999 when sightings of dead birds around the city and boroughs were reported daily. The virus was isolated that same year. The enzootic circle occurs between mosquitoes and birds, which are the primary vertebrate host via the bite of Culex mosquitoes. After a bite from an infected mosquito, humans are usually a dead-end host since the level and duration of viremia needed to infect another mosquito is insufficient.

Human-to-human transmission is documented through blood transfusion and solid organ transplantation. Vertical transmission is rarely described. Initially isolated in New York, WNV quickly spread across North America and has been isolated in every continent except Antarctica. Most cases occur in the summer and autumn.

Most infected individuals are asymptomatic. Those who do develop symptoms have fever, headache, myalgia, arthralgia, nausea, vomiting, and a transient rash. Less than 1% develop meningitis/encephalitis symptoms similar to other causes of aseptic meningitis. Those with encephalitis in addition to fever and headache may have altered mental status and focal neurologic deficits including flaccid paralysis or movement disorders.

Detection of anti-WNV IgM antibodies (AB) in serum or CSF is the most common way to make the diagnosis. IgM AB usually is present within 3-8 days after onset of symptoms and persists up to 90 days. Data from ArboNET, the national arboviral surveillance system managed by Centers for Disease Control and Prevention and state health departments, reveal that from 1999 to 2022 there were 56,575 cases of WNV including 28,684 cases of neuroinvasive disease. In 2023 there were 2,406 and 1,599 cases, respectively. Those historic totals for WNV are 10 times greater than the totals for all the other etiologies of neuroinvasive arboviral diseases in the US combined (Jamestown Canyon, LaCrosse, St. Louis, and Eastern Equine encephalitis n = 1813).

Remember to include WNV in your differential of a febrile patient with neurologic symptoms, mosquito bites, blood transfusions, and organ transplantation. Treatment is supportive care.

The US began screening all blood donations for WNV in 2003. Organ donor screening is not universal.

Dengue

Dengue, another arbovirus, is transmitted by bites of infected Aedes aegypti and Aedes albopictus mosquitoes, which prefer to feed during the daytime. There are four dengue virus serotypes: DENV-1 DENV-2, DENV-3 and DENV-4. In endemic areas, all four serotypes are usually co-circulating and people can be infected by each one.

Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Long-term immunity is type specific. Heterologous protection lasts only a few months. Dengue is endemic throughout the tropics and subtropics of Asia, Africa, and the Americas. Approximately 53% of the world’s population live in an area where dengue transmission can occur. In the US, most cases are reported from Puerto Rico. Dengue is endemic in the following US territories: Puerto Rico, US Virgin Islands, American Samoa, and free associated states. Most cases reported on the mainland are travel related. However, locally acquired dengue has been reported. From 2010 to 2023 Hawaii reported 250 cases, Florida 438, and Texas 40 locally acquired cases. During that same period, Puerto Rico reported more than 32,000 cases. It is the leading cause of febrile illness for travelers returning from the Caribbean, Latin America, and South Asia. Peru is currently experiencing an outbreak with more than 25,000 cases reported since January 2024. Most cases of dengue occur in adolescents and young adults. Severe disease occurs most often in infants, those with underlying chronic disease, pregnant women, and persons infected with dengue for the second time.

Symptoms range from a mild febrile illness to severe disease associated with hemorrhage and shock. Onset is usually 7-10 days after infection and symptoms include high fever, severe headache, retro-orbital pain, arthralgia and myalgias, nausea, and vomiting; some may develop a generalized rash.

The World Health Organization (WHO) classifies dengue as 1) dengue with or without warning signs for progression of disease and 2) severe dengue. Warning signs for disease progression include abdominal pain or tenderness, persistent vomiting, fluid accumulation (e.g., ascites, pericardial or pleural effusion), mucosal bleeding, restlessness, postural hypotension, liver enlargement greater than 2 cm. Severe dengue is defined as any sign of severe plasma leakage leading to shock, severe bleeding or organ failure, or fluid accumulation with respiratory distress. Management is supportive care.

Prevention: In the US, Dengvaxia, a live attenuated tetravalent vaccine, is approved for use in children aged 9–16 years with laboratory-confirmed previous dengue virus infection and living in areas where dengue is endemic. It is administered at 0, 6, and 12 months. It is not available for purchase on the mainland. Continued control of the vector and personal protection is necessary to prevent recurrent infections.
 

CHIKV

Chikungunya (CHIKV), which means “that which bends up” in the Mkonde language of Tanzania, refers to the appearance of the person with severe usually symmetric arthralgias characteristic for this infection that otherwise is often clinically confused with dengue and Zika. It too is transmitted by A. aegypti and A. albopictus and is prevalent in tropical Africa, Asia, Central and South America, and the Caribbean. Like dengue it is predominantly an urban disease. The WHO reported the first case in the Western Hemisphere in Saint Martin in December 2013. By August 2014, 31 additional territories and Caribbean or South American countries reported 576,535 suspected cases. Florida first reported locally acquired CHIKV in June 2014. By December an additional 11 cases had been identified. Texas reported one case in 2015. Diagnosis is with IgM ab or PCR. Treatment is supportive with most recovering from acute illness within 2 weeks. Data in adults indicate 40-52% may develop chronic or recurrent joint pain.

Prevention: IXCHIQ, a live attenuated vaccine, was licensed in November 2023 and recommended by the CDC in February 2024 for use in persons at least 18 years of age with travel to destinations where there is a CHIKV outbreak. It may be considered for persons traveling to a country or territory without an outbreak but with evidence of CHIKV transmission among humans within the last 5 years and those staying in endemic areas for a cumulative period of at least 6 months over a 2-year period. Specific recommendations for lab workers and persons older than 65 years were also made. This is good news for your older patients who may be participating in mission trips, volunteering, studying abroad, or just vacationing in an endemic area. Adolescent vaccine trials are ongoing and pediatric trials will soon be initiated. In addition, vector control and use of personal protective measures cannot be emphasized enough.

There are several other mosquito borne diseases, however our discussion here is limited to three. Why these three? WNV as a reminder that it is the most common neuroinvasive agent in the US. Dengue and CHIKV because they are not endemic in the US so they might not routinely be considered in febrile patients; both diseases have been reported and acquired on the mainland and your patients may travel to an endemic area and return home with an unwanted souvenir. You will be ready for them.

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

Suggested Reading

Chikungunya. Centers for Disease Control and Prevention. 2024. https://www.cdc.gov/vaccines/acip/recommendations.html.

Fagrem AC et al. West Nile and Other Nationally Notifiable Arboviral Diseases–United States, 2021. MMWR Morb Mortal Wkly Rep. 2023 Aug 25;72(34):901-906.

Fever in Returned Travelers, Travel Medicine (Fourth Edition). 2019. doi: 10.1016/B978-0-323-54696-6.00056-2.

Paz-Baily et al. Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021 MMWR Recomm Rep. 2021 Dec 17;70(6):1-16).

Staples JE and Fischer M. Chikungunya virus in the Americas — what a vectorborne pathogen can do. N Engl J Med. 2014 Sep 4;371(10):887-9.

Mosquitoes and Diseases A-Z, Centers for Disease Control and Prevention. https://www.cdc.gov/mosquitoes/about/diseases.html.

There are over 3700 types of mosquitoes worldwide and over 200 types in the continental United States, of which only 12 are associated with transmitting diseases to humans. The majority are just a nuisance. Since they cannot readily be distinguished, strategies to prevent any bites are recommended.

West Nile Virus

In the US, West Nile virus (WNV) is the leading cause of neuroinvasive arboviral disease. Just hearing the name took me back to New York in 1999 when sightings of dead birds around the city and boroughs were reported daily. The virus was isolated that same year. The enzootic circle occurs between mosquitoes and birds, which are the primary vertebrate host via the bite of Culex mosquitoes. After a bite from an infected mosquito, humans are usually a dead-end host since the level and duration of viremia needed to infect another mosquito is insufficient.

Human-to-human transmission is documented through blood transfusion and solid organ transplantation. Vertical transmission is rarely described. Initially isolated in New York, WNV quickly spread across North America and has been isolated in every continent except Antarctica. Most cases occur in the summer and autumn.

Most infected individuals are asymptomatic. Those who do develop symptoms have fever, headache, myalgia, arthralgia, nausea, vomiting, and a transient rash. Less than 1% develop meningitis/encephalitis symptoms similar to other causes of aseptic meningitis. Those with encephalitis in addition to fever and headache may have altered mental status and focal neurologic deficits including flaccid paralysis or movement disorders.

Detection of anti-WNV IgM antibodies (AB) in serum or CSF is the most common way to make the diagnosis. IgM AB usually is present within 3-8 days after onset of symptoms and persists up to 90 days. Data from ArboNET, the national arboviral surveillance system managed by Centers for Disease Control and Prevention and state health departments, reveal that from 1999 to 2022 there were 56,575 cases of WNV including 28,684 cases of neuroinvasive disease. In 2023 there were 2,406 and 1,599 cases, respectively. Those historic totals for WNV are 10 times greater than the totals for all the other etiologies of neuroinvasive arboviral diseases in the US combined (Jamestown Canyon, LaCrosse, St. Louis, and Eastern Equine encephalitis n = 1813).

Remember to include WNV in your differential of a febrile patient with neurologic symptoms, mosquito bites, blood transfusions, and organ transplantation. Treatment is supportive care.

The US began screening all blood donations for WNV in 2003. Organ donor screening is not universal.

Dengue

Dengue, another arbovirus, is transmitted by bites of infected Aedes aegypti and Aedes albopictus mosquitoes, which prefer to feed during the daytime. There are four dengue virus serotypes: DENV-1 DENV-2, DENV-3 and DENV-4. In endemic areas, all four serotypes are usually co-circulating and people can be infected by each one.

Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Long-term immunity is type specific. Heterologous protection lasts only a few months. Dengue is endemic throughout the tropics and subtropics of Asia, Africa, and the Americas. Approximately 53% of the world’s population live in an area where dengue transmission can occur. In the US, most cases are reported from Puerto Rico. Dengue is endemic in the following US territories: Puerto Rico, US Virgin Islands, American Samoa, and free associated states. Most cases reported on the mainland are travel related. However, locally acquired dengue has been reported. From 2010 to 2023 Hawaii reported 250 cases, Florida 438, and Texas 40 locally acquired cases. During that same period, Puerto Rico reported more than 32,000 cases. It is the leading cause of febrile illness for travelers returning from the Caribbean, Latin America, and South Asia. Peru is currently experiencing an outbreak with more than 25,000 cases reported since January 2024. Most cases of dengue occur in adolescents and young adults. Severe disease occurs most often in infants, those with underlying chronic disease, pregnant women, and persons infected with dengue for the second time.

Symptoms range from a mild febrile illness to severe disease associated with hemorrhage and shock. Onset is usually 7-10 days after infection and symptoms include high fever, severe headache, retro-orbital pain, arthralgia and myalgias, nausea, and vomiting; some may develop a generalized rash.

The World Health Organization (WHO) classifies dengue as 1) dengue with or without warning signs for progression of disease and 2) severe dengue. Warning signs for disease progression include abdominal pain or tenderness, persistent vomiting, fluid accumulation (e.g., ascites, pericardial or pleural effusion), mucosal bleeding, restlessness, postural hypotension, liver enlargement greater than 2 cm. Severe dengue is defined as any sign of severe plasma leakage leading to shock, severe bleeding or organ failure, or fluid accumulation with respiratory distress. Management is supportive care.

Prevention: In the US, Dengvaxia, a live attenuated tetravalent vaccine, is approved for use in children aged 9–16 years with laboratory-confirmed previous dengue virus infection and living in areas where dengue is endemic. It is administered at 0, 6, and 12 months. It is not available for purchase on the mainland. Continued control of the vector and personal protection is necessary to prevent recurrent infections.
 

CHIKV

Chikungunya (CHIKV), which means “that which bends up” in the Mkonde language of Tanzania, refers to the appearance of the person with severe usually symmetric arthralgias characteristic for this infection that otherwise is often clinically confused with dengue and Zika. It too is transmitted by A. aegypti and A. albopictus and is prevalent in tropical Africa, Asia, Central and South America, and the Caribbean. Like dengue it is predominantly an urban disease. The WHO reported the first case in the Western Hemisphere in Saint Martin in December 2013. By August 2014, 31 additional territories and Caribbean or South American countries reported 576,535 suspected cases. Florida first reported locally acquired CHIKV in June 2014. By December an additional 11 cases had been identified. Texas reported one case in 2015. Diagnosis is with IgM ab or PCR. Treatment is supportive with most recovering from acute illness within 2 weeks. Data in adults indicate 40-52% may develop chronic or recurrent joint pain.

Prevention: IXCHIQ, a live attenuated vaccine, was licensed in November 2023 and recommended by the CDC in February 2024 for use in persons at least 18 years of age with travel to destinations where there is a CHIKV outbreak. It may be considered for persons traveling to a country or territory without an outbreak but with evidence of CHIKV transmission among humans within the last 5 years and those staying in endemic areas for a cumulative period of at least 6 months over a 2-year period. Specific recommendations for lab workers and persons older than 65 years were also made. This is good news for your older patients who may be participating in mission trips, volunteering, studying abroad, or just vacationing in an endemic area. Adolescent vaccine trials are ongoing and pediatric trials will soon be initiated. In addition, vector control and use of personal protective measures cannot be emphasized enough.

There are several other mosquito borne diseases, however our discussion here is limited to three. Why these three? WNV as a reminder that it is the most common neuroinvasive agent in the US. Dengue and CHIKV because they are not endemic in the US so they might not routinely be considered in febrile patients; both diseases have been reported and acquired on the mainland and your patients may travel to an endemic area and return home with an unwanted souvenir. You will be ready for them.

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

Suggested Reading

Chikungunya. Centers for Disease Control and Prevention. 2024. https://www.cdc.gov/vaccines/acip/recommendations.html.

Fagrem AC et al. West Nile and Other Nationally Notifiable Arboviral Diseases–United States, 2021. MMWR Morb Mortal Wkly Rep. 2023 Aug 25;72(34):901-906.

Fever in Returned Travelers, Travel Medicine (Fourth Edition). 2019. doi: 10.1016/B978-0-323-54696-6.00056-2.

Paz-Baily et al. Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021 MMWR Recomm Rep. 2021 Dec 17;70(6):1-16).

Staples JE and Fischer M. Chikungunya virus in the Americas — what a vectorborne pathogen can do. N Engl J Med. 2014 Sep 4;371(10):887-9.

Mosquitoes and Diseases A-Z, Centers for Disease Control and Prevention. https://www.cdc.gov/mosquitoes/about/diseases.html.

With rates of syphilis rising quickly in the United States and elsewhere, clinicians are having to up their game when it comes to diagnosing and treating an infection that they may not be paying enough attention to.

More than 200,000 cases of syphilis were reported in the United States in 2022, which is the highest number since 1950 and is a 17.3% increase over 2021, according to the latest figures from the Centers for Disease Control and Prevention (CDC). The rate of infection has increased almost every year since a historic low in 2001.

And the trend is not limited to the United States. Last year, the infection rate in the United Kingdom hit a 50-year high, said David Mabey, BCh, DM, from the London School of Hygiene and Tropical Medicine. Syphilis and other sexually transmitted infections are also a major problem in low- and middle-income countries, he added, although good data are not always available.

Many of today’s healthcare professionals have little experience with the disease, shared Ina Park, MD, a sexually transmitted infections specialist at the University of California at San Francisco. “An entire generation of physicians — including myself — did not see any cases until we were well out of our training,” Dr. Park reported. “We’re really playing catch-up.”
 

A Centuries-Old Ailment

Dr. Park offered some advice on the challenges of diagnosing what can be an elusive infection at the Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver. That advice boiled down to one simple rule: “Test, test, test.”

Because syphilis can mimic so many other conditions and can have long periods of latency, it can be easily missed or even misdiagnosed by experienced physicians, said Dr. Park. Clinicians need to keep it front of mind and have a lower threshold for testing, even if there are no obvious symptoms.

Following the CDC’s new recommendations for syphilis screening will help, she noted; every sexually active patient aged between 15 and 44 years who lives in a county with a syphilis infection rate of 4.6 per 100,000 people or higher should get the test. And clinicians should remain vigilant, even in areas with a lower prevalence. “If you can’t account for new symptoms in a sexually active patient, order a test,” said Dr. Park.
 

Complicated Cases

The lack of experience with syphilis affects not just diagnosis but also treatment, particularly for complex cases, said Khalil Ghanem, MD, PhD, from the Johns Hopkins University School of Medicine in Baltimore. “When you don’t have to deal with something for a while, you forget how to deal with it,” he added.

At CROI, Dr. Ghanem offered suggestions for how to navigate complicated cases of ocular syphilis, otic syphilis, and neurosyphilis, and how to interpret test results when a patient’s antigen titers are being “unruly.”

With potential ocular or otic syphilis, you shouldn’t wait for a specialist like an ophthalmologist to weigh in but instead refer the patient directly to the emergency department because of the risk that the symptoms may become irreversible and result in permanent blindness or deafness. “You don’t want to dilly-dally with those conditions,” Dr. Ghanem said.

Closely monitoring a patient’s rapid plasma regain and venereal disease research laboratory antigen levels is the only way to manage syphilis and to determine whether the infection is responding to treatment, he noted, but sometimes those titers “don’t do what you think they should be doing” and fail to decline or even go up after treatment.

“You don’t know if they went up because the patient was re-infected, or they developed neurosyphilis, or there was a problem at the lab,” he said. “It can be challenging to interpret.”

To decipher confusing test results, Dr. Ghanem recommended getting a detailed history to understand whether a patient is at risk for reinfection, whether there are signs of neurosyphilis or other complications, whether pregnancy is possible, and so on. “Based on the answers, you can determine what the most rational approach to treatment would be,” he shared.
 

Drug Shortages

Efforts to get the infection under control have become more complicated. Last summer, Pfizer announced that it had run out of penicillin G benzathine (Bicillin), an injectable, long-acting drug that is one of the main treatments for syphilis and the only one that can be given to pregnant people. Supplies for children ran out at the end of June 2023, and supplies for adults were gone by the end of September.

Because Pfizer is the only company that manufactures penicillin G benzathine, there is no one to pick up the slack in the short-term, so the shortage is expected to continue until at least the middle of 2024.

In response, the US Food and Drug Administration has temporarily allowed the use of benzylpenicillin benzathine (Extencilline), a French formulation that has not been approved in the United States, until supplies of penicillin G benzathine are stabilized.

The shortage has shone a spotlight on the important issue of a lack of alternatives for the treatment of syphilis during pregnancy, which increases the risk for congenital syphilis. “Hopefully, this pushes the National Institutes of Health and others to step up their game on studies for alternative drugs for use in pregnancy,” Dr. Ghanem said.
 

A version of this article appeared on Medscape.com.

With rates of syphilis rising quickly in the United States and elsewhere, clinicians are having to up their game when it comes to diagnosing and treating an infection that they may not be paying enough attention to.

More than 200,000 cases of syphilis were reported in the United States in 2022, which is the highest number since 1950 and is a 17.3% increase over 2021, according to the latest figures from the Centers for Disease Control and Prevention (CDC). The rate of infection has increased almost every year since a historic low in 2001.

And the trend is not limited to the United States. Last year, the infection rate in the United Kingdom hit a 50-year high, said David Mabey, BCh, DM, from the London School of Hygiene and Tropical Medicine. Syphilis and other sexually transmitted infections are also a major problem in low- and middle-income countries, he added, although good data are not always available.

Many of today’s healthcare professionals have little experience with the disease, shared Ina Park, MD, a sexually transmitted infections specialist at the University of California at San Francisco. “An entire generation of physicians — including myself — did not see any cases until we were well out of our training,” Dr. Park reported. “We’re really playing catch-up.”
 

A Centuries-Old Ailment

Dr. Park offered some advice on the challenges of diagnosing what can be an elusive infection at the Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver. That advice boiled down to one simple rule: “Test, test, test.”

Because syphilis can mimic so many other conditions and can have long periods of latency, it can be easily missed or even misdiagnosed by experienced physicians, said Dr. Park. Clinicians need to keep it front of mind and have a lower threshold for testing, even if there are no obvious symptoms.

Following the CDC’s new recommendations for syphilis screening will help, she noted; every sexually active patient aged between 15 and 44 years who lives in a county with a syphilis infection rate of 4.6 per 100,000 people or higher should get the test. And clinicians should remain vigilant, even in areas with a lower prevalence. “If you can’t account for new symptoms in a sexually active patient, order a test,” said Dr. Park.
 

Complicated Cases

The lack of experience with syphilis affects not just diagnosis but also treatment, particularly for complex cases, said Khalil Ghanem, MD, PhD, from the Johns Hopkins University School of Medicine in Baltimore. “When you don’t have to deal with something for a while, you forget how to deal with it,” he added.

At CROI, Dr. Ghanem offered suggestions for how to navigate complicated cases of ocular syphilis, otic syphilis, and neurosyphilis, and how to interpret test results when a patient’s antigen titers are being “unruly.”

With potential ocular or otic syphilis, you shouldn’t wait for a specialist like an ophthalmologist to weigh in but instead refer the patient directly to the emergency department because of the risk that the symptoms may become irreversible and result in permanent blindness or deafness. “You don’t want to dilly-dally with those conditions,” Dr. Ghanem said.

Closely monitoring a patient’s rapid plasma regain and venereal disease research laboratory antigen levels is the only way to manage syphilis and to determine whether the infection is responding to treatment, he noted, but sometimes those titers “don’t do what you think they should be doing” and fail to decline or even go up after treatment.

“You don’t know if they went up because the patient was re-infected, or they developed neurosyphilis, or there was a problem at the lab,” he said. “It can be challenging to interpret.”

To decipher confusing test results, Dr. Ghanem recommended getting a detailed history to understand whether a patient is at risk for reinfection, whether there are signs of neurosyphilis or other complications, whether pregnancy is possible, and so on. “Based on the answers, you can determine what the most rational approach to treatment would be,” he shared.
 

Drug Shortages

Efforts to get the infection under control have become more complicated. Last summer, Pfizer announced that it had run out of penicillin G benzathine (Bicillin), an injectable, long-acting drug that is one of the main treatments for syphilis and the only one that can be given to pregnant people. Supplies for children ran out at the end of June 2023, and supplies for adults were gone by the end of September.

Because Pfizer is the only company that manufactures penicillin G benzathine, there is no one to pick up the slack in the short-term, so the shortage is expected to continue until at least the middle of 2024.

In response, the US Food and Drug Administration has temporarily allowed the use of benzylpenicillin benzathine (Extencilline), a French formulation that has not been approved in the United States, until supplies of penicillin G benzathine are stabilized.

The shortage has shone a spotlight on the important issue of a lack of alternatives for the treatment of syphilis during pregnancy, which increases the risk for congenital syphilis. “Hopefully, this pushes the National Institutes of Health and others to step up their game on studies for alternative drugs for use in pregnancy,” Dr. Ghanem said.
 

A version of this article appeared on Medscape.com.

With rates of syphilis rising quickly in the United States and elsewhere, clinicians are having to up their game when it comes to diagnosing and treating an infection that they may not be paying enough attention to.

More than 200,000 cases of syphilis were reported in the United States in 2022, which is the highest number since 1950 and is a 17.3% increase over 2021, according to the latest figures from the Centers for Disease Control and Prevention (CDC). The rate of infection has increased almost every year since a historic low in 2001.

And the trend is not limited to the United States. Last year, the infection rate in the United Kingdom hit a 50-year high, said David Mabey, BCh, DM, from the London School of Hygiene and Tropical Medicine. Syphilis and other sexually transmitted infections are also a major problem in low- and middle-income countries, he added, although good data are not always available.

Many of today’s healthcare professionals have little experience with the disease, shared Ina Park, MD, a sexually transmitted infections specialist at the University of California at San Francisco. “An entire generation of physicians — including myself — did not see any cases until we were well out of our training,” Dr. Park reported. “We’re really playing catch-up.”
 

A Centuries-Old Ailment

Dr. Park offered some advice on the challenges of diagnosing what can be an elusive infection at the Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver. That advice boiled down to one simple rule: “Test, test, test.”

Because syphilis can mimic so many other conditions and can have long periods of latency, it can be easily missed or even misdiagnosed by experienced physicians, said Dr. Park. Clinicians need to keep it front of mind and have a lower threshold for testing, even if there are no obvious symptoms.

Following the CDC’s new recommendations for syphilis screening will help, she noted; every sexually active patient aged between 15 and 44 years who lives in a county with a syphilis infection rate of 4.6 per 100,000 people or higher should get the test. And clinicians should remain vigilant, even in areas with a lower prevalence. “If you can’t account for new symptoms in a sexually active patient, order a test,” said Dr. Park.
 

Complicated Cases

The lack of experience with syphilis affects not just diagnosis but also treatment, particularly for complex cases, said Khalil Ghanem, MD, PhD, from the Johns Hopkins University School of Medicine in Baltimore. “When you don’t have to deal with something for a while, you forget how to deal with it,” he added.

At CROI, Dr. Ghanem offered suggestions for how to navigate complicated cases of ocular syphilis, otic syphilis, and neurosyphilis, and how to interpret test results when a patient’s antigen titers are being “unruly.”

With potential ocular or otic syphilis, you shouldn’t wait for a specialist like an ophthalmologist to weigh in but instead refer the patient directly to the emergency department because of the risk that the symptoms may become irreversible and result in permanent blindness or deafness. “You don’t want to dilly-dally with those conditions,” Dr. Ghanem said.

Closely monitoring a patient’s rapid plasma regain and venereal disease research laboratory antigen levels is the only way to manage syphilis and to determine whether the infection is responding to treatment, he noted, but sometimes those titers “don’t do what you think they should be doing” and fail to decline or even go up after treatment.

“You don’t know if they went up because the patient was re-infected, or they developed neurosyphilis, or there was a problem at the lab,” he said. “It can be challenging to interpret.”

To decipher confusing test results, Dr. Ghanem recommended getting a detailed history to understand whether a patient is at risk for reinfection, whether there are signs of neurosyphilis or other complications, whether pregnancy is possible, and so on. “Based on the answers, you can determine what the most rational approach to treatment would be,” he shared.
 

Drug Shortages

Efforts to get the infection under control have become more complicated. Last summer, Pfizer announced that it had run out of penicillin G benzathine (Bicillin), an injectable, long-acting drug that is one of the main treatments for syphilis and the only one that can be given to pregnant people. Supplies for children ran out at the end of June 2023, and supplies for adults were gone by the end of September.

Because Pfizer is the only company that manufactures penicillin G benzathine, there is no one to pick up the slack in the short-term, so the shortage is expected to continue until at least the middle of 2024.

In response, the US Food and Drug Administration has temporarily allowed the use of benzylpenicillin benzathine (Extencilline), a French formulation that has not been approved in the United States, until supplies of penicillin G benzathine are stabilized.

The shortage has shone a spotlight on the important issue of a lack of alternatives for the treatment of syphilis during pregnancy, which increases the risk for congenital syphilis. “Hopefully, this pushes the National Institutes of Health and others to step up their game on studies for alternative drugs for use in pregnancy,” Dr. Ghanem said.
 

A version of this article appeared on Medscape.com.

The new RSV antibody treatment for babies has been highly effective in its first season, according to a first look at data from four children’s hospitals.

Babies who received the new preventive treatment for RSV shortly after birth were 90% less likely to be severely sickened with the potentially deadly respiratory illness, according to the new estimate published by the Centers for Disease Control and Prevention. It is the first real-world evaluation of Beyfortus (the generic name is nirsevimab), which was approved by the Food and Drug Administration last July.

RSV is a seasonal illness that affects more people — particularly infants and the elderly — in the fall and winter. Symptoms are usually mild in healthy adults, but infants are particularly at risk of getting bronchiolitis, which results in exhausting wheezing and coughing in babies due to swelling in their airways and lungs. Babies who are hospitalized may need fluids and medical devices to help them breathe.

RSV peaked this season from November to January, with more than 10,000 monthly diagnoses reported to the CDC. 

The new CDC analysis was conducted among about 700 babies hospitalized for severe respiratory problems from October to the end of February. Among the babies in the study, 407 were diagnosed with RSV and 292 tested negative. The researchers found that 1% of babies in the study who were diagnosed with RSV had received Beyfortus, while the remaining babies who were positive for the virus had not. 

Among the babies hospitalized for other severe respiratory problems, 18% had received Beyfortus. Overall, just 59 babies among the nearly 700 in the study received Beyfortus, perhaps reflecting the short supply of the medicine the first season it was available. The report authors noted that babies in the study who did receive Beyfortus also tended to have high-risk medical conditions.

The number of babies nationwide who received Beyfortus during this first season of availability is unclear, but a January CDC survey showed that 4 in 10 parents said their babies under 8 months old had received the treatment. The Wall Street Journal reported recently that a shortage last fall resulted from underestimated demand and from production plans that were set before the CDC decided to recommend that all infants under 8 months old receive Beyfortus if their mothers did not get a maternal vaccine that can protect infants from RSV.

Both the antibody treatment for infants and the maternal vaccine were shown in clinical trials to be about 80% effective at preventing severe illness stemming from RSV.

The authors of the latest CDC report concluded that “this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.”

A version of this article appeared on WebMD.com.

The new RSV antibody treatment for babies has been highly effective in its first season, according to a first look at data from four children’s hospitals.

Babies who received the new preventive treatment for RSV shortly after birth were 90% less likely to be severely sickened with the potentially deadly respiratory illness, according to the new estimate published by the Centers for Disease Control and Prevention. It is the first real-world evaluation of Beyfortus (the generic name is nirsevimab), which was approved by the Food and Drug Administration last July.

RSV is a seasonal illness that affects more people — particularly infants and the elderly — in the fall and winter. Symptoms are usually mild in healthy adults, but infants are particularly at risk of getting bronchiolitis, which results in exhausting wheezing and coughing in babies due to swelling in their airways and lungs. Babies who are hospitalized may need fluids and medical devices to help them breathe.

RSV peaked this season from November to January, with more than 10,000 monthly diagnoses reported to the CDC. 

The new CDC analysis was conducted among about 700 babies hospitalized for severe respiratory problems from October to the end of February. Among the babies in the study, 407 were diagnosed with RSV and 292 tested negative. The researchers found that 1% of babies in the study who were diagnosed with RSV had received Beyfortus, while the remaining babies who were positive for the virus had not. 

Among the babies hospitalized for other severe respiratory problems, 18% had received Beyfortus. Overall, just 59 babies among the nearly 700 in the study received Beyfortus, perhaps reflecting the short supply of the medicine the first season it was available. The report authors noted that babies in the study who did receive Beyfortus also tended to have high-risk medical conditions.

The number of babies nationwide who received Beyfortus during this first season of availability is unclear, but a January CDC survey showed that 4 in 10 parents said their babies under 8 months old had received the treatment. The Wall Street Journal reported recently that a shortage last fall resulted from underestimated demand and from production plans that were set before the CDC decided to recommend that all infants under 8 months old receive Beyfortus if their mothers did not get a maternal vaccine that can protect infants from RSV.

Both the antibody treatment for infants and the maternal vaccine were shown in clinical trials to be about 80% effective at preventing severe illness stemming from RSV.

The authors of the latest CDC report concluded that “this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.”

A version of this article appeared on WebMD.com.

The new RSV antibody treatment for babies has been highly effective in its first season, according to a first look at data from four children’s hospitals.

Babies who received the new preventive treatment for RSV shortly after birth were 90% less likely to be severely sickened with the potentially deadly respiratory illness, according to the new estimate published by the Centers for Disease Control and Prevention. It is the first real-world evaluation of Beyfortus (the generic name is nirsevimab), which was approved by the Food and Drug Administration last July.

RSV is a seasonal illness that affects more people — particularly infants and the elderly — in the fall and winter. Symptoms are usually mild in healthy adults, but infants are particularly at risk of getting bronchiolitis, which results in exhausting wheezing and coughing in babies due to swelling in their airways and lungs. Babies who are hospitalized may need fluids and medical devices to help them breathe.

RSV peaked this season from November to January, with more than 10,000 monthly diagnoses reported to the CDC. 

The new CDC analysis was conducted among about 700 babies hospitalized for severe respiratory problems from October to the end of February. Among the babies in the study, 407 were diagnosed with RSV and 292 tested negative. The researchers found that 1% of babies in the study who were diagnosed with RSV had received Beyfortus, while the remaining babies who were positive for the virus had not. 

Among the babies hospitalized for other severe respiratory problems, 18% had received Beyfortus. Overall, just 59 babies among the nearly 700 in the study received Beyfortus, perhaps reflecting the short supply of the medicine the first season it was available. The report authors noted that babies in the study who did receive Beyfortus also tended to have high-risk medical conditions.

The number of babies nationwide who received Beyfortus during this first season of availability is unclear, but a January CDC survey showed that 4 in 10 parents said their babies under 8 months old had received the treatment. The Wall Street Journal reported recently that a shortage last fall resulted from underestimated demand and from production plans that were set before the CDC decided to recommend that all infants under 8 months old receive Beyfortus if their mothers did not get a maternal vaccine that can protect infants from RSV.

Both the antibody treatment for infants and the maternal vaccine were shown in clinical trials to be about 80% effective at preventing severe illness stemming from RSV.

The authors of the latest CDC report concluded that “this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.”

A version of this article appeared on WebMD.com.

Bullying, heavy social media use, experimentation with drugs and alcohol: These are the well-described hazards of adolescence. We have growing knowledge of the risks associated with these experiences and which youth are more vulnerable to these risks. Developmentally, adolescence is a time of critical brain development marked by heightened sensitivity to social approval and limited impulse control. Adolescents also have growing autonomy from parents alongside a stronger need for time with friends (the new peer home away from the parental home). These factors alone make adolescence a period of heightened sensitivity to these experiences, but some youth have greater vulnerability to develop psychopathology such as anxiety, depression, eating disorders, or addiction after exposure to these common experiences. Pediatricians can assess these broader vulnerabilities during well child visits of pre- and early teens and offer patients and their parents strategies for minimizing risk and cultivating resilience.

Bullying

Bullying, both verbal and physical, has long been an unwelcome part of youth. Cellphones and social media have brought bullying into the 21st century. Cyberbullying has meant that targeted youth are no longer safe after school and it carries higher risk of self-harm and suicidality than the analog version. No child benefits from bullying, but some children are more vulnerable to develop an anxiety or mood disorder, self-injury, or suicidality, whereas others experience stress and distress, but are able to adaptively seek support from friends and adults and stay on track developmentally, even to flourish. There is evidence that girls and LGBTQ youth are more commonly bullied and at higher risk for depression, self-harm, and suicidality as a consequence of cyberbullying. Youth already suffering from a psychiatric illness or substance abuse who are bullied are at higher risk for self-harm and suicidality than that of their bullied peers. Youth whose parents score high on measures of distress and family dysfunction also face higher risk of self-harm and suicidality after bullying.¹

Social Media

Unlike bullying, social media has been a force only in 21st century life, with Facebook starting in 2004 and cellphones in common use by adolescents in the past 2 decades. While there are potential benefits of social media use, such as stronger connections to supportive peers for isolated LGBTQ youth or youth who live in rural areas, there are also risks. Of course, social media carries the risk of cyberbullying. It also carries the risk for very heavy patterns of use that can interfere with physical activity, adequate sleep, academic performance, and healthy in-person social activities. There is robust emerging evidence that heavy users have higher rates of mood disorders and anxiety symptoms, although it is unclear whether social media exacerbates, or more social media use is the result of depression and/or anxiety. Adolescents’ desire for social acceptance makes them especially sensitive to the social rewards of “likes” and they are thus vulnerable to becoming heavy users. Adolescent girls who are heavy users are vulnerable to developing a disordered body image and eating disorders. Those youth with especially low levels of impulse control, such as those with ADHD, have greater risk of developing problematic use.^2-4

Substance Use and Abuse

Exploration of alcohol and drug use has been a common experience, and hazard, of adolescence for many generations. As a result, we have richer knowledge of those factors that are associated with risk of and protection against that use progressing to a use disorder. Earlier age at first experimentation appears to be independently correlated with increased risk of developing a substance use disorder. Every pediatrician should be aware of a family history of substance use disorders, especially alcohol, as they are strongly associated with higher risk. Youth with temperaments that are sensation seeking, externalizing and impulsive are at higher risk. Youth with anxiety and mood disorders and untreated attention deficit disorders are at higher risk. Youth whose parents have high levels of conflict or “permissive” parenting styles are at higher risk as are those who as children experienced abuse or neglect.^5-7

Minimizing Risk and Cultivating Resilience

Protective factors balance these risks: adequate sleep; positive relationships with friends and parents; and confidence in their academic, athletic, or social abilities all are correlated with good outcomes after bullying, drug and alcohol use, and social media use. These teenagers are meaningfully connected to caring adults and peers, have a future orientation, and typically have higher self-esteem. Youth whose parents balance attunement with rules and expectations (“authoritative” parenting) appear to be at lower risk of poor mental health outcomes associated with heavy social media use as well as other risk behaviors. These parents have clear rules and expectations, including about drugs and alcohol, and enforce rules reasonably calmly and consistently. Youth whose families eat dinner together at least three times weekly, who attend schools that offer a wide range of after-school activities, and who learn to use problem-focused coping skills rather than emotion-focused coping skills are protected against poor mental health outcomes in the face of these challenges.

While bullying is a stressor, social media and substances may seem like ways of managing stress and connecting with peers. There are youth with clear vulnerabilities to the risks associated with each of them. Shared factors include vulnerable temperaments, high conflict or permissive parenting, family history of substance use disorders or preexisting psychiatric illness. Pediatricians are in a unique position to raise teenagers’ awareness of their specific vulnerabilities. Talk about the heightened risk of experimentation with alcohol or drugs in your patients who are in treatment for an anxiety or mood disorder. Help them cultivate critical thinking — an adolescent specialty — around marketing and peer pressure. Remind them that social media companies make money from keeping them online longer. Then help them identify what strategies are in their control, such as limiting their time online. What else could they be doing with their time that they actually enjoy? Remind them about the value of protecting time for adequate sleep, regular exercise, and sitting down for dinner with their family. Ask about their nourishing relationships with peers and adults and talk about the value of protecting time for them. Ask your patients and their parents about how they face stress, emphasizing their ability to locate what is within their control. While awareness of feelings is important, learning to manage intense emotions is more connected to healthy habits of sleep and exercise and strategies to get support or pivot to engaging activities. Discussing this openly models for parents how to bear difficulty alongside their children without becoming distressed or punitive themselves. Talk with worried parents about the value of regular meals together, shared physical activities, and supporting time for their children’s emerging interests and hobbies. Equipping your patients and their parents with knowledge about their particular vulnerabilities, reminders about what is known about these risks, and all that is in their power to build resilience, may be as meaningful a public health intervention as asking them about biking with helmets and using seat belts.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Zych I et al. Protective Factors Against Bullying and Cyberbullying: A Systematic Review of Meta-Analyses. Aggress Violent Behav. 2019;45:4-19. doi: 10.1016/j.avb.2018.06.008.

2. Office of the Surgeon General. Social Media and Youth Mental Health: The U.S. Surgeon General’s Advisory. 2023. https://www.ncbi.nlm.nih.gov/books/NBK594761/.

3. Uhls Y et al. Benefits and Costs of Social Media in Adolescence. Pediatrics. 2017 Nov;140(Suppl 2):S67-S70. doi: 10.1542/peds.2016-1758E.

4. Health Advisory on Social Media Use in Adolescence. American Psychological Association (2023).

5. Sloboda Z et al. Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention, Substance Use and Misuse, Subst Use Misuse. 2012 Jun-Jul;47(8-9):944-62. doi: 10.3109/10826084.2012.663280.

6. O’Connell M et al. Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press and US Department of Health and Human Services, Substance Abuse and Mental Health Administration. 2009 (https://nap.nationalacademies.org/catalog/12480/preventing-mental-emotional-and-behavioral-disorders-among-young-people-progress).

7. Staiger P et al. Can Emotion-Focused Coping Help Explain the Link Between Posttraumatic Stress Disorder Severity and Triggers for Substance Use in Young Adults? J Subst Abuse Treat. 2009 Mar;36(2):220-6. doi: 10.1016/j.jsat.2008.05.008.

Bullying, heavy social media use, experimentation with drugs and alcohol: These are the well-described hazards of adolescence. We have growing knowledge of the risks associated with these experiences and which youth are more vulnerable to these risks. Developmentally, adolescence is a time of critical brain development marked by heightened sensitivity to social approval and limited impulse control. Adolescents also have growing autonomy from parents alongside a stronger need for time with friends (the new peer home away from the parental home). These factors alone make adolescence a period of heightened sensitivity to these experiences, but some youth have greater vulnerability to develop psychopathology such as anxiety, depression, eating disorders, or addiction after exposure to these common experiences. Pediatricians can assess these broader vulnerabilities during well child visits of pre- and early teens and offer patients and their parents strategies for minimizing risk and cultivating resilience.

Bullying

Bullying, both verbal and physical, has long been an unwelcome part of youth. Cellphones and social media have brought bullying into the 21st century. Cyberbullying has meant that targeted youth are no longer safe after school and it carries higher risk of self-harm and suicidality than the analog version. No child benefits from bullying, but some children are more vulnerable to develop an anxiety or mood disorder, self-injury, or suicidality, whereas others experience stress and distress, but are able to adaptively seek support from friends and adults and stay on track developmentally, even to flourish. There is evidence that girls and LGBTQ youth are more commonly bullied and at higher risk for depression, self-harm, and suicidality as a consequence of cyberbullying. Youth already suffering from a psychiatric illness or substance abuse who are bullied are at higher risk for self-harm and suicidality than that of their bullied peers. Youth whose parents score high on measures of distress and family dysfunction also face higher risk of self-harm and suicidality after bullying.¹

Social Media

Unlike bullying, social media has been a force only in 21st century life, with Facebook starting in 2004 and cellphones in common use by adolescents in the past 2 decades. While there are potential benefits of social media use, such as stronger connections to supportive peers for isolated LGBTQ youth or youth who live in rural areas, there are also risks. Of course, social media carries the risk of cyberbullying. It also carries the risk for very heavy patterns of use that can interfere with physical activity, adequate sleep, academic performance, and healthy in-person social activities. There is robust emerging evidence that heavy users have higher rates of mood disorders and anxiety symptoms, although it is unclear whether social media exacerbates, or more social media use is the result of depression and/or anxiety. Adolescents’ desire for social acceptance makes them especially sensitive to the social rewards of “likes” and they are thus vulnerable to becoming heavy users. Adolescent girls who are heavy users are vulnerable to developing a disordered body image and eating disorders. Those youth with especially low levels of impulse control, such as those with ADHD, have greater risk of developing problematic use.^2-4

Substance Use and Abuse

Exploration of alcohol and drug use has been a common experience, and hazard, of adolescence for many generations. As a result, we have richer knowledge of those factors that are associated with risk of and protection against that use progressing to a use disorder. Earlier age at first experimentation appears to be independently correlated with increased risk of developing a substance use disorder. Every pediatrician should be aware of a family history of substance use disorders, especially alcohol, as they are strongly associated with higher risk. Youth with temperaments that are sensation seeking, externalizing and impulsive are at higher risk. Youth with anxiety and mood disorders and untreated attention deficit disorders are at higher risk. Youth whose parents have high levels of conflict or “permissive” parenting styles are at higher risk as are those who as children experienced abuse or neglect.^5-7

Minimizing Risk and Cultivating Resilience

Protective factors balance these risks: adequate sleep; positive relationships with friends and parents; and confidence in their academic, athletic, or social abilities all are correlated with good outcomes after bullying, drug and alcohol use, and social media use. These teenagers are meaningfully connected to caring adults and peers, have a future orientation, and typically have higher self-esteem. Youth whose parents balance attunement with rules and expectations (“authoritative” parenting) appear to be at lower risk of poor mental health outcomes associated with heavy social media use as well as other risk behaviors. These parents have clear rules and expectations, including about drugs and alcohol, and enforce rules reasonably calmly and consistently. Youth whose families eat dinner together at least three times weekly, who attend schools that offer a wide range of after-school activities, and who learn to use problem-focused coping skills rather than emotion-focused coping skills are protected against poor mental health outcomes in the face of these challenges.

While bullying is a stressor, social media and substances may seem like ways of managing stress and connecting with peers. There are youth with clear vulnerabilities to the risks associated with each of them. Shared factors include vulnerable temperaments, high conflict or permissive parenting, family history of substance use disorders or preexisting psychiatric illness. Pediatricians are in a unique position to raise teenagers’ awareness of their specific vulnerabilities. Talk about the heightened risk of experimentation with alcohol or drugs in your patients who are in treatment for an anxiety or mood disorder. Help them cultivate critical thinking — an adolescent specialty — around marketing and peer pressure. Remind them that social media companies make money from keeping them online longer. Then help them identify what strategies are in their control, such as limiting their time online. What else could they be doing with their time that they actually enjoy? Remind them about the value of protecting time for adequate sleep, regular exercise, and sitting down for dinner with their family. Ask about their nourishing relationships with peers and adults and talk about the value of protecting time for them. Ask your patients and their parents about how they face stress, emphasizing their ability to locate what is within their control. While awareness of feelings is important, learning to manage intense emotions is more connected to healthy habits of sleep and exercise and strategies to get support or pivot to engaging activities. Discussing this openly models for parents how to bear difficulty alongside their children without becoming distressed or punitive themselves. Talk with worried parents about the value of regular meals together, shared physical activities, and supporting time for their children’s emerging interests and hobbies. Equipping your patients and their parents with knowledge about their particular vulnerabilities, reminders about what is known about these risks, and all that is in their power to build resilience, may be as meaningful a public health intervention as asking them about biking with helmets and using seat belts.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Zych I et al. Protective Factors Against Bullying and Cyberbullying: A Systematic Review of Meta-Analyses. Aggress Violent Behav. 2019;45:4-19. doi: 10.1016/j.avb.2018.06.008.

2. Office of the Surgeon General. Social Media and Youth Mental Health: The U.S. Surgeon General’s Advisory. 2023. https://www.ncbi.nlm.nih.gov/books/NBK594761/.

3. Uhls Y et al. Benefits and Costs of Social Media in Adolescence. Pediatrics. 2017 Nov;140(Suppl 2):S67-S70. doi: 10.1542/peds.2016-1758E.

4. Health Advisory on Social Media Use in Adolescence. American Psychological Association (2023).

5. Sloboda Z et al. Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention, Substance Use and Misuse, Subst Use Misuse. 2012 Jun-Jul;47(8-9):944-62. doi: 10.3109/10826084.2012.663280.

6. O’Connell M et al. Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press and US Department of Health and Human Services, Substance Abuse and Mental Health Administration. 2009 (https://nap.nationalacademies.org/catalog/12480/preventing-mental-emotional-and-behavioral-disorders-among-young-people-progress).

7. Staiger P et al. Can Emotion-Focused Coping Help Explain the Link Between Posttraumatic Stress Disorder Severity and Triggers for Substance Use in Young Adults? J Subst Abuse Treat. 2009 Mar;36(2):220-6. doi: 10.1016/j.jsat.2008.05.008.

Bullying, heavy social media use, experimentation with drugs and alcohol: These are the well-described hazards of adolescence. We have growing knowledge of the risks associated with these experiences and which youth are more vulnerable to these risks. Developmentally, adolescence is a time of critical brain development marked by heightened sensitivity to social approval and limited impulse control. Adolescents also have growing autonomy from parents alongside a stronger need for time with friends (the new peer home away from the parental home). These factors alone make adolescence a period of heightened sensitivity to these experiences, but some youth have greater vulnerability to develop psychopathology such as anxiety, depression, eating disorders, or addiction after exposure to these common experiences. Pediatricians can assess these broader vulnerabilities during well child visits of pre- and early teens and offer patients and their parents strategies for minimizing risk and cultivating resilience.

Bullying

Bullying, both verbal and physical, has long been an unwelcome part of youth. Cellphones and social media have brought bullying into the 21st century. Cyberbullying has meant that targeted youth are no longer safe after school and it carries higher risk of self-harm and suicidality than the analog version. No child benefits from bullying, but some children are more vulnerable to develop an anxiety or mood disorder, self-injury, or suicidality, whereas others experience stress and distress, but are able to adaptively seek support from friends and adults and stay on track developmentally, even to flourish. There is evidence that girls and LGBTQ youth are more commonly bullied and at higher risk for depression, self-harm, and suicidality as a consequence of cyberbullying. Youth already suffering from a psychiatric illness or substance abuse who are bullied are at higher risk for self-harm and suicidality than that of their bullied peers. Youth whose parents score high on measures of distress and family dysfunction also face higher risk of self-harm and suicidality after bullying.¹

Social Media

Unlike bullying, social media has been a force only in 21st century life, with Facebook starting in 2004 and cellphones in common use by adolescents in the past 2 decades. While there are potential benefits of social media use, such as stronger connections to supportive peers for isolated LGBTQ youth or youth who live in rural areas, there are also risks. Of course, social media carries the risk of cyberbullying. It also carries the risk for very heavy patterns of use that can interfere with physical activity, adequate sleep, academic performance, and healthy in-person social activities. There is robust emerging evidence that heavy users have higher rates of mood disorders and anxiety symptoms, although it is unclear whether social media exacerbates, or more social media use is the result of depression and/or anxiety. Adolescents’ desire for social acceptance makes them especially sensitive to the social rewards of “likes” and they are thus vulnerable to becoming heavy users. Adolescent girls who are heavy users are vulnerable to developing a disordered body image and eating disorders. Those youth with especially low levels of impulse control, such as those with ADHD, have greater risk of developing problematic use.^2-4

Substance Use and Abuse

Exploration of alcohol and drug use has been a common experience, and hazard, of adolescence for many generations. As a result, we have richer knowledge of those factors that are associated with risk of and protection against that use progressing to a use disorder. Earlier age at first experimentation appears to be independently correlated with increased risk of developing a substance use disorder. Every pediatrician should be aware of a family history of substance use disorders, especially alcohol, as they are strongly associated with higher risk. Youth with temperaments that are sensation seeking, externalizing and impulsive are at higher risk. Youth with anxiety and mood disorders and untreated attention deficit disorders are at higher risk. Youth whose parents have high levels of conflict or “permissive” parenting styles are at higher risk as are those who as children experienced abuse or neglect.^5-7

Minimizing Risk and Cultivating Resilience

Protective factors balance these risks: adequate sleep; positive relationships with friends and parents; and confidence in their academic, athletic, or social abilities all are correlated with good outcomes after bullying, drug and alcohol use, and social media use. These teenagers are meaningfully connected to caring adults and peers, have a future orientation, and typically have higher self-esteem. Youth whose parents balance attunement with rules and expectations (“authoritative” parenting) appear to be at lower risk of poor mental health outcomes associated with heavy social media use as well as other risk behaviors. These parents have clear rules and expectations, including about drugs and alcohol, and enforce rules reasonably calmly and consistently. Youth whose families eat dinner together at least three times weekly, who attend schools that offer a wide range of after-school activities, and who learn to use problem-focused coping skills rather than emotion-focused coping skills are protected against poor mental health outcomes in the face of these challenges.

While bullying is a stressor, social media and substances may seem like ways of managing stress and connecting with peers. There are youth with clear vulnerabilities to the risks associated with each of them. Shared factors include vulnerable temperaments, high conflict or permissive parenting, family history of substance use disorders or preexisting psychiatric illness. Pediatricians are in a unique position to raise teenagers’ awareness of their specific vulnerabilities. Talk about the heightened risk of experimentation with alcohol or drugs in your patients who are in treatment for an anxiety or mood disorder. Help them cultivate critical thinking — an adolescent specialty — around marketing and peer pressure. Remind them that social media companies make money from keeping them online longer. Then help them identify what strategies are in their control, such as limiting their time online. What else could they be doing with their time that they actually enjoy? Remind them about the value of protecting time for adequate sleep, regular exercise, and sitting down for dinner with their family. Ask about their nourishing relationships with peers and adults and talk about the value of protecting time for them. Ask your patients and their parents about how they face stress, emphasizing their ability to locate what is within their control. While awareness of feelings is important, learning to manage intense emotions is more connected to healthy habits of sleep and exercise and strategies to get support or pivot to engaging activities. Discussing this openly models for parents how to bear difficulty alongside their children without becoming distressed or punitive themselves. Talk with worried parents about the value of regular meals together, shared physical activities, and supporting time for their children’s emerging interests and hobbies. Equipping your patients and their parents with knowledge about their particular vulnerabilities, reminders about what is known about these risks, and all that is in their power to build resilience, may be as meaningful a public health intervention as asking them about biking with helmets and using seat belts.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Zych I et al. Protective Factors Against Bullying and Cyberbullying: A Systematic Review of Meta-Analyses. Aggress Violent Behav. 2019;45:4-19. doi: 10.1016/j.avb.2018.06.008.

2. Office of the Surgeon General. Social Media and Youth Mental Health: The U.S. Surgeon General’s Advisory. 2023. https://www.ncbi.nlm.nih.gov/books/NBK594761/.

3. Uhls Y et al. Benefits and Costs of Social Media in Adolescence. Pediatrics. 2017 Nov;140(Suppl 2):S67-S70. doi: 10.1542/peds.2016-1758E.

4. Health Advisory on Social Media Use in Adolescence. American Psychological Association (2023).

5. Sloboda Z et al. Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention, Substance Use and Misuse, Subst Use Misuse. 2012 Jun-Jul;47(8-9):944-62. doi: 10.3109/10826084.2012.663280.

6. O’Connell M et al. Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press and US Department of Health and Human Services, Substance Abuse and Mental Health Administration. 2009 (https://nap.nationalacademies.org/catalog/12480/preventing-mental-emotional-and-behavioral-disorders-among-young-people-progress).

7. Staiger P et al. Can Emotion-Focused Coping Help Explain the Link Between Posttraumatic Stress Disorder Severity and Triggers for Substance Use in Young Adults? J Subst Abuse Treat. 2009 Mar;36(2):220-6. doi: 10.1016/j.jsat.2008.05.008.

A phase 3 trial of a maternal vaccine candidate for respiratory syncytial virus (RSV) has been stopped early because the risk for preterm births is higher in the candidate vaccine group than in the placebo group.

By the time enrollment was stopped on February 25, 2022 because of the safety signal of preterm birth, 5328 pregnant women had been vaccinated, about half of the intended 10,000 enrollees. Of these, 3557 received the candidate vaccine RSV prefusion F protein–based maternal vaccine, and another 1771 received a placebo.

Data from the trial, sponsored by GSK, were immediately made available when recruitment and vaccination were stopped, and investigation of the preterm birth risk followed. Results of that analysis, led by Ilse Dieussaert, IR, vice president for vaccine development at GSK in Wavre, Belgium, are published online on March 13 in The New England Journal of Medicine. 

“We have discontinued our work on this RSV maternal candidate vaccine, and we are closing out all ongoing trials with the exception of the MAT-015 follow-on study to monitor subsequent pregnancies,” a GSK spokesperson said in an interview.

The trial was conducted in pregnant women aged 18-49 years to assess the efficacy and safety of the vaccine. The women were randomly assigned 2:1 to receive the candidate vaccine or placebo between 24 and 34 weeks’ gestation.
 

Preterm Births

The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract infection in infants from birth to 6 months and safety in infants from birth to 12 months.

According to the data, preterm birth occurred in 6.8% of the infants in the vaccine group and in 4.9% of those in the placebo group (relative risk [RR], 1.37; 95% CI, 1.08-1.74; P = .01). Neonatal death occurred in 0.4% in the vaccine group and 0.2% in the placebo group (RR, 2.16; 95% CI, 0.62-7.56; P = .23).

To date, only one RSV vaccine (Abrysvo, Pfizer) has been approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection.

“It was a very big deal that this trial was stopped, and the new candidate won’t get approval.” said Aaron E. Glatt, MD, chair of the Department of Medicine and chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.
 

Only One RSV Vaccine Approved in Pregnancy

Dr. Glatt pointed out the GSK vaccine is like the maternal vaccine that did get approved. “The data clearly show that there was a slight but increased risk in preterm labor,” Dr. Glatt said, “and while not as clearly shown, there was an increase in neonatal death in the group of very small numbers, but any neonatal death is of concern.”

The implications were disturbing, he added, “You’re giving this vaccine to prevent neonatal death.” Though the Pfizer vaccine that was granted approval had a very slight increase in premature birth, the risk wasn’t statistically significant, he pointed out, “and it showed similar benefits in preventing neonatal illness, which can be fatal.”

Dr. Glatt said that there is still a lingering concern with the approved vaccine, and he explained that most clinicians will give it closer to the end of the recommended time window of 34 weeks. “This way, even if there is a slight increase in premature term labor, you’re probably not going to have a serious outcome because the baby will be far enough along.”

A difference in the incidence of preterm birth between the experimental vaccine and placebo groups was predominantly found in low- and middle-income countries, according to Dieussaert’s team, “where approximately 50% of the trial population was enrolled and where the medical need for maternal RSV vaccines is the greatest.”

The RR was 1.56 (95% CI, 1.17-2.10) for low- and middle-income countries and 1.04 (95% CI, 0.68-1.58) for high-income countries. 

“If a smaller percentage of participants from low- and middle-income countries had been enrolled in our trial, the RR for preterm birth in the vaccine group as compared with the placebo group might have been reduced in the overall trial population,” they reported.

The authors explained that the data do not reveal the cause of the higher risk for preterm birth in the vaccine group.

“We do not know what caused the signal,” the company’s spokesperson added. “GSK completed all the necessary steps of product development including preclinical toxicology studies and clinical studies in nonpregnant women prior to starting the studies in pregnant women. There were no safety signals identified in any of the earlier parts of the clinical testing. There have been no safety signals identified in the other phase 3 trials for this vaccine candidate.”

Researchers did not find a correlation between preterm births in the treatment vs control groups with gestational age at the time of vaccination or with particular vaccine clinical trial material lots, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or time between study vaccination and delivery, the GSK spokesperson said.

The spokesperson noted that the halted vaccine is different from GSK’s currently approved adjuvanted RSV vaccine (Arexvy) for adults aged 60 years or older.

What’s Next for Other Vaccines

Maternal vaccines have been effective in preventing other diseases in infants, such as tetanus, influenza, and pertussis, but RSV is a very hard virus to make a vaccine for, Dr. Glatt shared.

The need is great to have more than one option for a maternal RSV vaccine, he added, to address any potential supply concerns.

“People have to realize how serious RSV can be in infants,” he said. “It can be a fatal disease. This can be a serious illness even in healthy children.”

A version of this article appeared on Medscape.com.

A phase 3 trial of a maternal vaccine candidate for respiratory syncytial virus (RSV) has been stopped early because the risk for preterm births is higher in the candidate vaccine group than in the placebo group.

By the time enrollment was stopped on February 25, 2022 because of the safety signal of preterm birth, 5328 pregnant women had been vaccinated, about half of the intended 10,000 enrollees. Of these, 3557 received the candidate vaccine RSV prefusion F protein–based maternal vaccine, and another 1771 received a placebo.

Data from the trial, sponsored by GSK, were immediately made available when recruitment and vaccination were stopped, and investigation of the preterm birth risk followed. Results of that analysis, led by Ilse Dieussaert, IR, vice president for vaccine development at GSK in Wavre, Belgium, are published online on March 13 in The New England Journal of Medicine. 

“We have discontinued our work on this RSV maternal candidate vaccine, and we are closing out all ongoing trials with the exception of the MAT-015 follow-on study to monitor subsequent pregnancies,” a GSK spokesperson said in an interview.

The trial was conducted in pregnant women aged 18-49 years to assess the efficacy and safety of the vaccine. The women were randomly assigned 2:1 to receive the candidate vaccine or placebo between 24 and 34 weeks’ gestation.
 

Preterm Births

The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract infection in infants from birth to 6 months and safety in infants from birth to 12 months.

According to the data, preterm birth occurred in 6.8% of the infants in the vaccine group and in 4.9% of those in the placebo group (relative risk [RR], 1.37; 95% CI, 1.08-1.74; P = .01). Neonatal death occurred in 0.4% in the vaccine group and 0.2% in the placebo group (RR, 2.16; 95% CI, 0.62-7.56; P = .23).

To date, only one RSV vaccine (Abrysvo, Pfizer) has been approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection.

“It was a very big deal that this trial was stopped, and the new candidate won’t get approval.” said Aaron E. Glatt, MD, chair of the Department of Medicine and chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.
 

Only One RSV Vaccine Approved in Pregnancy

Dr. Glatt pointed out the GSK vaccine is like the maternal vaccine that did get approved. “The data clearly show that there was a slight but increased risk in preterm labor,” Dr. Glatt said, “and while not as clearly shown, there was an increase in neonatal death in the group of very small numbers, but any neonatal death is of concern.”

The implications were disturbing, he added, “You’re giving this vaccine to prevent neonatal death.” Though the Pfizer vaccine that was granted approval had a very slight increase in premature birth, the risk wasn’t statistically significant, he pointed out, “and it showed similar benefits in preventing neonatal illness, which can be fatal.”

Dr. Glatt said that there is still a lingering concern with the approved vaccine, and he explained that most clinicians will give it closer to the end of the recommended time window of 34 weeks. “This way, even if there is a slight increase in premature term labor, you’re probably not going to have a serious outcome because the baby will be far enough along.”

A difference in the incidence of preterm birth between the experimental vaccine and placebo groups was predominantly found in low- and middle-income countries, according to Dieussaert’s team, “where approximately 50% of the trial population was enrolled and where the medical need for maternal RSV vaccines is the greatest.”

The RR was 1.56 (95% CI, 1.17-2.10) for low- and middle-income countries and 1.04 (95% CI, 0.68-1.58) for high-income countries. 

“If a smaller percentage of participants from low- and middle-income countries had been enrolled in our trial, the RR for preterm birth in the vaccine group as compared with the placebo group might have been reduced in the overall trial population,” they reported.

The authors explained that the data do not reveal the cause of the higher risk for preterm birth in the vaccine group.

“We do not know what caused the signal,” the company’s spokesperson added. “GSK completed all the necessary steps of product development including preclinical toxicology studies and clinical studies in nonpregnant women prior to starting the studies in pregnant women. There were no safety signals identified in any of the earlier parts of the clinical testing. There have been no safety signals identified in the other phase 3 trials for this vaccine candidate.”

Researchers did not find a correlation between preterm births in the treatment vs control groups with gestational age at the time of vaccination or with particular vaccine clinical trial material lots, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or time between study vaccination and delivery, the GSK spokesperson said.

The spokesperson noted that the halted vaccine is different from GSK’s currently approved adjuvanted RSV vaccine (Arexvy) for adults aged 60 years or older.

What’s Next for Other Vaccines

Maternal vaccines have been effective in preventing other diseases in infants, such as tetanus, influenza, and pertussis, but RSV is a very hard virus to make a vaccine for, Dr. Glatt shared.

The need is great to have more than one option for a maternal RSV vaccine, he added, to address any potential supply concerns.

“People have to realize how serious RSV can be in infants,” he said. “It can be a fatal disease. This can be a serious illness even in healthy children.”

A version of this article appeared on Medscape.com.

A phase 3 trial of a maternal vaccine candidate for respiratory syncytial virus (RSV) has been stopped early because the risk for preterm births is higher in the candidate vaccine group than in the placebo group.

By the time enrollment was stopped on February 25, 2022 because of the safety signal of preterm birth, 5328 pregnant women had been vaccinated, about half of the intended 10,000 enrollees. Of these, 3557 received the candidate vaccine RSV prefusion F protein–based maternal vaccine, and another 1771 received a placebo.

Data from the trial, sponsored by GSK, were immediately made available when recruitment and vaccination were stopped, and investigation of the preterm birth risk followed. Results of that analysis, led by Ilse Dieussaert, IR, vice president for vaccine development at GSK in Wavre, Belgium, are published online on March 13 in The New England Journal of Medicine. 

“We have discontinued our work on this RSV maternal candidate vaccine, and we are closing out all ongoing trials with the exception of the MAT-015 follow-on study to monitor subsequent pregnancies,” a GSK spokesperson said in an interview.

The trial was conducted in pregnant women aged 18-49 years to assess the efficacy and safety of the vaccine. The women were randomly assigned 2:1 to receive the candidate vaccine or placebo between 24 and 34 weeks’ gestation.
 

Preterm Births

The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract infection in infants from birth to 6 months and safety in infants from birth to 12 months.

According to the data, preterm birth occurred in 6.8% of the infants in the vaccine group and in 4.9% of those in the placebo group (relative risk [RR], 1.37; 95% CI, 1.08-1.74; P = .01). Neonatal death occurred in 0.4% in the vaccine group and 0.2% in the placebo group (RR, 2.16; 95% CI, 0.62-7.56; P = .23).

To date, only one RSV vaccine (Abrysvo, Pfizer) has been approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection.

“It was a very big deal that this trial was stopped, and the new candidate won’t get approval.” said Aaron E. Glatt, MD, chair of the Department of Medicine and chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.
 

Only One RSV Vaccine Approved in Pregnancy

Dr. Glatt pointed out the GSK vaccine is like the maternal vaccine that did get approved. “The data clearly show that there was a slight but increased risk in preterm labor,” Dr. Glatt said, “and while not as clearly shown, there was an increase in neonatal death in the group of very small numbers, but any neonatal death is of concern.”

The implications were disturbing, he added, “You’re giving this vaccine to prevent neonatal death.” Though the Pfizer vaccine that was granted approval had a very slight increase in premature birth, the risk wasn’t statistically significant, he pointed out, “and it showed similar benefits in preventing neonatal illness, which can be fatal.”

Dr. Glatt said that there is still a lingering concern with the approved vaccine, and he explained that most clinicians will give it closer to the end of the recommended time window of 34 weeks. “This way, even if there is a slight increase in premature term labor, you’re probably not going to have a serious outcome because the baby will be far enough along.”

A difference in the incidence of preterm birth between the experimental vaccine and placebo groups was predominantly found in low- and middle-income countries, according to Dieussaert’s team, “where approximately 50% of the trial population was enrolled and where the medical need for maternal RSV vaccines is the greatest.”

The RR was 1.56 (95% CI, 1.17-2.10) for low- and middle-income countries and 1.04 (95% CI, 0.68-1.58) for high-income countries. 

“If a smaller percentage of participants from low- and middle-income countries had been enrolled in our trial, the RR for preterm birth in the vaccine group as compared with the placebo group might have been reduced in the overall trial population,” they reported.

The authors explained that the data do not reveal the cause of the higher risk for preterm birth in the vaccine group.

“We do not know what caused the signal,” the company’s spokesperson added. “GSK completed all the necessary steps of product development including preclinical toxicology studies and clinical studies in nonpregnant women prior to starting the studies in pregnant women. There were no safety signals identified in any of the earlier parts of the clinical testing. There have been no safety signals identified in the other phase 3 trials for this vaccine candidate.”

Researchers did not find a correlation between preterm births in the treatment vs control groups with gestational age at the time of vaccination or with particular vaccine clinical trial material lots, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or time between study vaccination and delivery, the GSK spokesperson said.

The spokesperson noted that the halted vaccine is different from GSK’s currently approved adjuvanted RSV vaccine (Arexvy) for adults aged 60 years or older.

What’s Next for Other Vaccines

Maternal vaccines have been effective in preventing other diseases in infants, such as tetanus, influenza, and pertussis, but RSV is a very hard virus to make a vaccine for, Dr. Glatt shared.

The need is great to have more than one option for a maternal RSV vaccine, he added, to address any potential supply concerns.

“People have to realize how serious RSV can be in infants,” he said. “It can be a fatal disease. This can be a serious illness even in healthy children.”

A version of this article appeared on Medscape.com.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Skipping meals, mood and anxiety disorders, as well as vaping and substance use, all raise the risk for frequent recurrent headaches in children and adolescents, new data from a population-based study showed.

Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.

“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.

The findings were published online in Neurology.
 

Negative Consequences

Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.

Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.

To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.

In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.

For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.

The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.

Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.

“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.

Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.

Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.

In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).

Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).

Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.

One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
 

Prioritize Questions About Lifestyle?

In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”

One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.

The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

A study found that 94% of best-selling baby cleansers contain allergens, despite their hypoallergenic claims.

METHODOLOGY:

• Many baby cleansers are marketed as “hypoallergenic,” but these claims are not validated. 
• This study assessed the potential allergens and marketing claims in best-selling baby cleansers. 
• The researchers collected ingredients and marketing claims of the top 50 best-selling baby body wash products sold on Amazon on April 4, 2023. 
• Ingredient lists were checked for potential allergens using the 2020 American Contact Dermatitis Society (ACDS) core allergen series, which lists 90 common allergens for adults and children.

TAKEAWAY:

• In the 50 cleansers tested, 10 allergens were identified. Overall, 94% of the cleansers contained at least one allergen, averaging 2.9 allergens per product; cocamidopropyl betaine  (72%), fragrance (64%), and sodium benzoate (54%) were the most common allergens. 
• All cleansers had at least five marketing claims, with an average of 10.9 claims per product; the most common claims were “paraben-free” (88%), “phthalate-free” (84%), “tear-free” (74%), and “hypoallergenic” or “allergy-tested” (74%). 
• There was no significant difference in the number of allergens in the cleansers marketed as “hypoallergenic” or “allergy tested” compared with cleansers that did not have these claims (P = .843).
• Fewer allergens were found in cleansers endorsed by the National Eczema Association (P = .004) or labeled “synthetic fragrance-free” (P = .003).
• There was a positive correlation between a greater number of allergens and an increased number of marketing claims (r = 0.547, P < .001) and a negative correlation between cost and number of allergens (r = −0.450, P = .001).

IN PRACTICE:

Because marketing claims like “hypoallergenic” may be misleading, “clinicians should counsel parents to carefully examine cleanser ingredients or consider selecting cleansers” endorsed by the National Eczema Association or another international eczema organization, especially for infants and children with a history of atopic dermatitis, the authors wrote. 

SOURCE:

The study, led by Sasan D. Noveir, BA, from the University of California, Los Angeles, and coauthors from the division of dermatology at UCLA, was published online in Pediatric Dermatology.

LIMITATIONS:

The study only evaluated top-selling products from a single online source at a specific time, which may limit generalizability. Potential allergens not included in the ACDS core series may be present.

DISCLOSURES:

The study did not disclose any funding source. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A study found that 94% of best-selling baby cleansers contain allergens, despite their hypoallergenic claims.

METHODOLOGY:

• Many baby cleansers are marketed as “hypoallergenic,” but these claims are not validated. 
• This study assessed the potential allergens and marketing claims in best-selling baby cleansers. 
• The researchers collected ingredients and marketing claims of the top 50 best-selling baby body wash products sold on Amazon on April 4, 2023. 
• Ingredient lists were checked for potential allergens using the 2020 American Contact Dermatitis Society (ACDS) core allergen series, which lists 90 common allergens for adults and children.

TAKEAWAY:

• In the 50 cleansers tested, 10 allergens were identified. Overall, 94% of the cleansers contained at least one allergen, averaging 2.9 allergens per product; cocamidopropyl betaine  (72%), fragrance (64%), and sodium benzoate (54%) were the most common allergens. 
• All cleansers had at least five marketing claims, with an average of 10.9 claims per product; the most common claims were “paraben-free” (88%), “phthalate-free” (84%), “tear-free” (74%), and “hypoallergenic” or “allergy-tested” (74%). 
• There was no significant difference in the number of allergens in the cleansers marketed as “hypoallergenic” or “allergy tested” compared with cleansers that did not have these claims (P = .843).
• Fewer allergens were found in cleansers endorsed by the National Eczema Association (P = .004) or labeled “synthetic fragrance-free” (P = .003).
• There was a positive correlation between a greater number of allergens and an increased number of marketing claims (r = 0.547, P < .001) and a negative correlation between cost and number of allergens (r = −0.450, P = .001).

IN PRACTICE:

Because marketing claims like “hypoallergenic” may be misleading, “clinicians should counsel parents to carefully examine cleanser ingredients or consider selecting cleansers” endorsed by the National Eczema Association or another international eczema organization, especially for infants and children with a history of atopic dermatitis, the authors wrote. 

SOURCE:

The study, led by Sasan D. Noveir, BA, from the University of California, Los Angeles, and coauthors from the division of dermatology at UCLA, was published online in Pediatric Dermatology.

LIMITATIONS:

The study only evaluated top-selling products from a single online source at a specific time, which may limit generalizability. Potential allergens not included in the ACDS core series may be present.

DISCLOSURES:

The study did not disclose any funding source. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A study found that 94% of best-selling baby cleansers contain allergens, despite their hypoallergenic claims.

METHODOLOGY:

• Many baby cleansers are marketed as “hypoallergenic,” but these claims are not validated. 
• This study assessed the potential allergens and marketing claims in best-selling baby cleansers. 
• The researchers collected ingredients and marketing claims of the top 50 best-selling baby body wash products sold on Amazon on April 4, 2023. 
• Ingredient lists were checked for potential allergens using the 2020 American Contact Dermatitis Society (ACDS) core allergen series, which lists 90 common allergens for adults and children.

TAKEAWAY:

• In the 50 cleansers tested, 10 allergens were identified. Overall, 94% of the cleansers contained at least one allergen, averaging 2.9 allergens per product; cocamidopropyl betaine  (72%), fragrance (64%), and sodium benzoate (54%) were the most common allergens. 
• All cleansers had at least five marketing claims, with an average of 10.9 claims per product; the most common claims were “paraben-free” (88%), “phthalate-free” (84%), “tear-free” (74%), and “hypoallergenic” or “allergy-tested” (74%). 
• There was no significant difference in the number of allergens in the cleansers marketed as “hypoallergenic” or “allergy tested” compared with cleansers that did not have these claims (P = .843).
• Fewer allergens were found in cleansers endorsed by the National Eczema Association (P = .004) or labeled “synthetic fragrance-free” (P = .003).
• There was a positive correlation between a greater number of allergens and an increased number of marketing claims (r = 0.547, P < .001) and a negative correlation between cost and number of allergens (r = −0.450, P = .001).

IN PRACTICE:

Because marketing claims like “hypoallergenic” may be misleading, “clinicians should counsel parents to carefully examine cleanser ingredients or consider selecting cleansers” endorsed by the National Eczema Association or another international eczema organization, especially for infants and children with a history of atopic dermatitis, the authors wrote. 

SOURCE:

The study, led by Sasan D. Noveir, BA, from the University of California, Los Angeles, and coauthors from the division of dermatology at UCLA, was published online in Pediatric Dermatology.

LIMITATIONS:

The study only evaluated top-selling products from a single online source at a specific time, which may limit generalizability. Potential allergens not included in the ACDS core series may be present.

DISCLOSURES:

The study did not disclose any funding source. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Hand, foot, and mouth disease (HFMD) is a viral infection that commonly affects children under the age of five. It is primarily caused by coxsackieviruses and other enterovirus species.¹ While it predominantly affects children, it is important to note that it can also affect adults. Although it is not a life threatening infection, it can cause a painful rash and is highly contagious. The infection is easily spread in multiple ways, including via respiratory droplets, contact with vesicular or nasal secretions, or through fecal-oral transmission. Most cases occur during the summer and fall seasons but individuals can be infected at any time of the year.

HFMD typically starts with a few days of non-specific viral symptoms, such as fever, cough, sore throat, and fatigue. It is then followed by an eruption of intraoral macules and vesicles and a widespread distribution of oval shaped macules that predominantly involve the hands and feet.¹ Both children and adults can present atypically. Atypical presentations include vesicles and bullae on extensor surfaces such as the forearms, as well as eruptions on the face or buttocks.² Other atypical morphologies include eczema herpeticum-like, Gianotti-Crosti-like, and purpuric/petechiae.³ Atypical hand, food, and mouth disease cases are often caused by coxsackievirus A6, however other strains of coxsackievirus can also cause atypical symptoms.^2,3

Our 35-year-old female patient presented with eroded papules and vesicles around the mouth. A diagnosis of atypical HFMD was made clinically in the following days when the patient developed the more classic intraoral and acral macules and vesicles.

Vanessa Ortega, Dr. Brooke Resh Sateesh, and Dr. Justin Gordon

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Centers for Disease Control and Prevention. (2023, June 20). Symptoms of hand, foot, and mouth disease.

2. Drago F et al. J Am Acad Dermatol. 2017 Aug;77(2):e51-6. doi: 10.1016/j.jaad.2017.03.046.

3. Starkey SY et al. Pediatr Dermatol. 2024 Jan-Feb;41(1):23-7. doi: 10.1111/pde.15461.

Hand, foot, and mouth disease (HFMD) is a viral infection that commonly affects children under the age of five. It is primarily caused by coxsackieviruses and other enterovirus species.¹ While it predominantly affects children, it is important to note that it can also affect adults. Although it is not a life threatening infection, it can cause a painful rash and is highly contagious. The infection is easily spread in multiple ways, including via respiratory droplets, contact with vesicular or nasal secretions, or through fecal-oral transmission. Most cases occur during the summer and fall seasons but individuals can be infected at any time of the year.

HFMD typically starts with a few days of non-specific viral symptoms, such as fever, cough, sore throat, and fatigue. It is then followed by an eruption of intraoral macules and vesicles and a widespread distribution of oval shaped macules that predominantly involve the hands and feet.¹ Both children and adults can present atypically. Atypical presentations include vesicles and bullae on extensor surfaces such as the forearms, as well as eruptions on the face or buttocks.² Other atypical morphologies include eczema herpeticum-like, Gianotti-Crosti-like, and purpuric/petechiae.³ Atypical hand, food, and mouth disease cases are often caused by coxsackievirus A6, however other strains of coxsackievirus can also cause atypical symptoms.^2,3

Our 35-year-old female patient presented with eroded papules and vesicles around the mouth. A diagnosis of atypical HFMD was made clinically in the following days when the patient developed the more classic intraoral and acral macules and vesicles.

Vanessa Ortega, Dr. Brooke Resh Sateesh, and Dr. Justin Gordon

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Centers for Disease Control and Prevention. (2023, June 20). Symptoms of hand, foot, and mouth disease.

2. Drago F et al. J Am Acad Dermatol. 2017 Aug;77(2):e51-6. doi: 10.1016/j.jaad.2017.03.046.

3. Starkey SY et al. Pediatr Dermatol. 2024 Jan-Feb;41(1):23-7. doi: 10.1111/pde.15461.

Hand, foot, and mouth disease (HFMD) is a viral infection that commonly affects children under the age of five. It is primarily caused by coxsackieviruses and other enterovirus species.¹ While it predominantly affects children, it is important to note that it can also affect adults. Although it is not a life threatening infection, it can cause a painful rash and is highly contagious. The infection is easily spread in multiple ways, including via respiratory droplets, contact with vesicular or nasal secretions, or through fecal-oral transmission. Most cases occur during the summer and fall seasons but individuals can be infected at any time of the year.

HFMD typically starts with a few days of non-specific viral symptoms, such as fever, cough, sore throat, and fatigue. It is then followed by an eruption of intraoral macules and vesicles and a widespread distribution of oval shaped macules that predominantly involve the hands and feet.¹ Both children and adults can present atypically. Atypical presentations include vesicles and bullae on extensor surfaces such as the forearms, as well as eruptions on the face or buttocks.² Other atypical morphologies include eczema herpeticum-like, Gianotti-Crosti-like, and purpuric/petechiae.³ Atypical hand, food, and mouth disease cases are often caused by coxsackievirus A6, however other strains of coxsackievirus can also cause atypical symptoms.^2,3

Our 35-year-old female patient presented with eroded papules and vesicles around the mouth. A diagnosis of atypical HFMD was made clinically in the following days when the patient developed the more classic intraoral and acral macules and vesicles.

Vanessa Ortega, Dr. Brooke Resh Sateesh, and Dr. Justin Gordon

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Centers for Disease Control and Prevention. (2023, June 20). Symptoms of hand, foot, and mouth disease.

2. Drago F et al. J Am Acad Dermatol. 2017 Aug;77(2):e51-6. doi: 10.1016/j.jaad.2017.03.046.

3. Starkey SY et al. Pediatr Dermatol. 2024 Jan-Feb;41(1):23-7. doi: 10.1111/pde.15461.

TOPLINE:

Researchers have developed a tool that uses artificial intelligence (AI) to identify acute otitis media in children based on otoscopic videos. It may improve diagnosis of ear infections in primary care settings, the developers said.

METHODOLOGY:

• The developers relied on otoscopic videos of the tympanic membrane captured on smartphones connected to scopes.
• Their analysis focused on 1151 videos from 635 children, most younger than 3 years old, who were seen for sick or well visits at outpatient clinics in Pennsylvania from 2018 to 2023.
• The tool was trained to differentiate between patients who did and did not have acute otitis media.

TAKEAWAY:

• Out of an original pool of 1561 videos, 410 were excluded due to obstruction by cerumen. In the remaining videos, experts identified acute otitis media in 305 videos (26.5%) and no acute otitis media in 846 videos (73.5%).
• The tool achieved a sensitivity of 93.8% and specificity of 93.5%, with bulging of the tympanic membrane being the most indicative feature of acute otitis media, present in 100% of diagnosed cases, according to the researchers.
• Feedback from 60 parents was largely positive, with 80% wanting the tool to be used during future visits.

IN PRACTICE:

Based on the diagnostic accuracy of clinicians in other studies, “The algorithm exhibited higher accuracy than pediatricians, primary care physicians, and advance practice clinicians and, accordingly, could reasonably be used in these settings to aid with decisions regarding treatment,” the authors of the study wrote. “More accurate diagnosis of [acute otitis media] may help reduce unnecessary prescriptions of antimicrobials in young children,” they added.

Studies directly comparing the performance of the tool vs clinicians are still needed, however, according to an editorial accompanying the journal article.

“While the data from this study show the model’s accuracy (94%) is superior to historical accuracy of clinicians in diagnosing acute otitis media (84% or less), these data come from different studies not using the same definition for accuracy,” wrote Hojjat Salmasian, MD, MPH, PhD, and Lisa Biggs, MD, with Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. “If we assume the model is confirmed to be highly accurate and free from bias, this model could truly transform care for patients with suspected acute otitis media.”

SOURCE:

Alejandro Hoberman, MD, with the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, was the corresponding author of the study. It was published online in JAMA Pediatrics .

LIMITATIONS:

The study used convenience sampling and did not include external validation of the tool. The researchers lacked information about participant demographics and the reason for their clinic visit.

DISCLOSURES:

Three authors of the study are listed as inventors on a patent for a tool to diagnose acute otitis media. Two authors with Dcipher Analytics disclosed fees from the University of Pittsburgh for their work on an application programming interface during the study. The research was supported by the Department of Pediatrics at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have developed a tool that uses artificial intelligence (AI) to identify acute otitis media in children based on otoscopic videos. It may improve diagnosis of ear infections in primary care settings, the developers said.

METHODOLOGY:

• The developers relied on otoscopic videos of the tympanic membrane captured on smartphones connected to scopes.
• Their analysis focused on 1151 videos from 635 children, most younger than 3 years old, who were seen for sick or well visits at outpatient clinics in Pennsylvania from 2018 to 2023.
• The tool was trained to differentiate between patients who did and did not have acute otitis media.

TAKEAWAY:

• Out of an original pool of 1561 videos, 410 were excluded due to obstruction by cerumen. In the remaining videos, experts identified acute otitis media in 305 videos (26.5%) and no acute otitis media in 846 videos (73.5%).
• The tool achieved a sensitivity of 93.8% and specificity of 93.5%, with bulging of the tympanic membrane being the most indicative feature of acute otitis media, present in 100% of diagnosed cases, according to the researchers.
• Feedback from 60 parents was largely positive, with 80% wanting the tool to be used during future visits.

IN PRACTICE:

Based on the diagnostic accuracy of clinicians in other studies, “The algorithm exhibited higher accuracy than pediatricians, primary care physicians, and advance practice clinicians and, accordingly, could reasonably be used in these settings to aid with decisions regarding treatment,” the authors of the study wrote. “More accurate diagnosis of [acute otitis media] may help reduce unnecessary prescriptions of antimicrobials in young children,” they added.

Studies directly comparing the performance of the tool vs clinicians are still needed, however, according to an editorial accompanying the journal article.

“While the data from this study show the model’s accuracy (94%) is superior to historical accuracy of clinicians in diagnosing acute otitis media (84% or less), these data come from different studies not using the same definition for accuracy,” wrote Hojjat Salmasian, MD, MPH, PhD, and Lisa Biggs, MD, with Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. “If we assume the model is confirmed to be highly accurate and free from bias, this model could truly transform care for patients with suspected acute otitis media.”

SOURCE:

Alejandro Hoberman, MD, with the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, was the corresponding author of the study. It was published online in JAMA Pediatrics .

LIMITATIONS:

The study used convenience sampling and did not include external validation of the tool. The researchers lacked information about participant demographics and the reason for their clinic visit.

DISCLOSURES:

Three authors of the study are listed as inventors on a patent for a tool to diagnose acute otitis media. Two authors with Dcipher Analytics disclosed fees from the University of Pittsburgh for their work on an application programming interface during the study. The research was supported by the Department of Pediatrics at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Researchers have developed a tool that uses artificial intelligence (AI) to identify acute otitis media in children based on otoscopic videos. It may improve diagnosis of ear infections in primary care settings, the developers said.

METHODOLOGY:

• The developers relied on otoscopic videos of the tympanic membrane captured on smartphones connected to scopes.
• Their analysis focused on 1151 videos from 635 children, most younger than 3 years old, who were seen for sick or well visits at outpatient clinics in Pennsylvania from 2018 to 2023.
• The tool was trained to differentiate between patients who did and did not have acute otitis media.

TAKEAWAY:

• Out of an original pool of 1561 videos, 410 were excluded due to obstruction by cerumen. In the remaining videos, experts identified acute otitis media in 305 videos (26.5%) and no acute otitis media in 846 videos (73.5%).
• The tool achieved a sensitivity of 93.8% and specificity of 93.5%, with bulging of the tympanic membrane being the most indicative feature of acute otitis media, present in 100% of diagnosed cases, according to the researchers.
• Feedback from 60 parents was largely positive, with 80% wanting the tool to be used during future visits.

IN PRACTICE:

Based on the diagnostic accuracy of clinicians in other studies, “The algorithm exhibited higher accuracy than pediatricians, primary care physicians, and advance practice clinicians and, accordingly, could reasonably be used in these settings to aid with decisions regarding treatment,” the authors of the study wrote. “More accurate diagnosis of [acute otitis media] may help reduce unnecessary prescriptions of antimicrobials in young children,” they added.

Studies directly comparing the performance of the tool vs clinicians are still needed, however, according to an editorial accompanying the journal article.

“While the data from this study show the model’s accuracy (94%) is superior to historical accuracy of clinicians in diagnosing acute otitis media (84% or less), these data come from different studies not using the same definition for accuracy,” wrote Hojjat Salmasian, MD, MPH, PhD, and Lisa Biggs, MD, with Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. “If we assume the model is confirmed to be highly accurate and free from bias, this model could truly transform care for patients with suspected acute otitis media.”

SOURCE:

Alejandro Hoberman, MD, with the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, was the corresponding author of the study. It was published online in JAMA Pediatrics .

LIMITATIONS:

The study used convenience sampling and did not include external validation of the tool. The researchers lacked information about participant demographics and the reason for their clinic visit.

DISCLOSURES:

Three authors of the study are listed as inventors on a patent for a tool to diagnose acute otitis media. Two authors with Dcipher Analytics disclosed fees from the University of Pittsburgh for their work on an application programming interface during the study. The research was supported by the Department of Pediatrics at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A wise medical precept is attributed to Theodore Woodward, MD (1914-2005): “When you hear hoofbeats, think of horses, not zebras.” Primary care pediatricians, however, often find themselves confronting so-called rare or uncommon diseases (“zebras”) in their offices. The pressing challenge is to know when to suspect them. How can one reconcile the need to dispel uncertainty with the use of diagnostic tests that can be costly and invasive? When can the desire to reassure parents mean delaying the detection of a potentially treatable condition?

“It may seem like wordplay, but it’s not uncommon to have a rare disease,” noted Alejandro Fainboim, MD, a specialist in rare diseases and head of the Multivalent Day Hospital at the Ricardo Gutiérrez Children’s Hospital in Buenos Aires, Argentina. “And pediatricians are the first line of defense in detecting these types of pathologies. To make the diagnosis, we have to consider them. And to consider them, we must be knowledgeable. That’s why sometimes, ignorance slows down the diagnosis,” Dr. Fainboim made his remarks during an online seminar organized for the press on the eve of Rare Disease Day, which is commemorated on February 29th.

There are more than 8000 rare diseases, which generally are defined as those affecting fewer than five people per 10,000. But collectively, one in every 13 people has one of these diseases, and one in every two diagnosed patients is a child. Dr. Fainboim emphasized that most of these rare diseases are severe or very severe, hereditary, degenerative, and potentially fatal. And although they are pediatric pathologies, some manifest later in adulthood.

“The major problem we pediatricians face is that we’re handed a model from adults to solve pediatric diseases. So, signs and symptoms are described that we won’t find early on, but we have to anticipate and learn to decode some that are hidden,” he remarked.

Diagnostic delays and repeated consultations with various doctors before identification are common. Dr. Fainboim added that in industrialized countries, the diagnosis of these diseases takes between 5 and 10 years, and in low-income countries, up to 30 years or more. However, “this has improved significantly in recent years,” he said.
 

Unnoticed Signs

Specialists who treat patients with rare diseases often feel that there were obvious signs that went unnoticed and should have aroused the suspicion of the primary care physician. An example is paroxysmal nocturnal hemoglobinuria, which affects 13-14 people per million inhabitants and can appear at any age, although the incidence is higher in the third decade of life.

“In my 50 years as a doctor, I’ve seen seven or eight patients with paroxysmal nocturnal hemoglobinuria,” said Elsa Nucifora, MD, a hematologist at the Italian Hospital of Buenos Aires, Argentina. But “the diagnosis is so easy” that doctors could make it if they “were to think instead of acting automatically because they’re in a hurry,” she added. The diagnosis should be considered “every time anemia occurs in a young person, with certain characteristics, instead of giving them iron like everyone else and ‘we’ll see later’…the diagnosis is in two or three steps, so it’s not complicated.”

Similar situations occur with more than 1000 neuromuscular diseases involving mutations in more than 600 genes, including spinal muscular atrophy and muscular dystrophies.

“What are the most common manifestations? The hypotonic infant, the child who walks late, who falls frequently, who can’t climb stairs, who later may have difficulty breathing, who loses strength: These are presentations often unrecognized by doctors not in the specialty,” said Alberto Dubrovsky, MD, director of the Department of Neurology and the Neuromuscular Diseases Unit at the Favaloro University Neuroscience Institute in Buenos Aires, Argentina, during the seminar. “And considering that these diseases are diagnosed based on genetic mutations that need to be known to search for and request them, we are faced with a truly complex scenario that requires subspecialization.”

In a study recently published in the Argentine Archives of Pediatrics, Dr. Dubrovsky and colleagues interviewed 112 families of Argentine patients with molecular diagnoses of spinal muscular atrophy types I, II, and III and found that in 75%-85% of cases, the first signs of the disease (such as hypotonia, developmental delay, inability to achieve bipedal standing, or frequent falls) were recognized by parents. For type I, the most severe and early onset, in only 17.5% of cases did a neonatologist or pediatrician first notice something. Of the 72 patients with types II and III, where routine checks are less frequent than in the first months of life, only one doctor detected the first signs of the disease before parents or other relatives.

In the same study, the median time elapsed between the first sign and confirmed molecular diagnosis was 2, 10, and 31.5 months for types I, II, and III, respectively. The delay “is primarily due to the lack of clinical suspicion on the part of the intervening physician, who often dismisses or misinterprets the signs reported by parents, as reflected in the alternative diagnoses invoked,” the authors wrote.

“I don’t even ask for suspicion of a specific rare disease because that requires specialization. What I ask for is a kind of recognition or realization that something is happening and then request a consultation with the specialist to ensure proper care,” said Dr. Dubrovsky.

In another study conducted among 70 Argentine patients under age 13 years who were diagnosed with Duchenne muscular dystrophy (one of the most severe forms of muscular dystrophy), 82% of the pediatricians who were initially consulted for any problem in motor agility that parents, other relatives, or teachers had detected dismissed the observation. “They’re told to wait, that it will mature a little more,” said Dr. Dubrovsky. This explains why the time to diagnosis in Argentina from the first signs is around 2 years. The delays are unfortunate because “today we have treatments capable of interfering with the disease’s progression slope, reducing its progression, or eventually stopping it,” he said.

“Do you mind that primary care pediatricians don’t notice or dismiss signs and symptoms strongly suggestive of one of these rare diseases? Does it frustrate you?” this news organization asked asked Dr. Dubrovsky. “Sometimes it does make me angry, but many times it’s understood that there can’t be highly trained specialists everywhere to realize and request diagnostic tests. One must consider the circumstances in each case, and that’s why we work in education,” he replied.
 

Rules and Experience

In an interview, Dr. Fainboim highlighted key factors that should prompt a pediatrician’s suspicion. One is common symptoms expressed in a more intense or complicated way or when many symptoms coexist in the same patient, even if each one separately is benign or not so severe.

Dr. Fainboim also recommended establishing a therapeutic alliance with parents. “We shouldn’t undermine what parents say, especially those who have other children and already know what normal child development is like. This is a very important milestone.

“We have to strengthen the suspicion clue, and for that, we rely on standards and our experience, which we keep refining. As Wilde said, experience is the sum of our mistakes. But there’s no universal answer. Not all families are the same. Not all diseases manifest in the same way. And unless there’s an imminent risk to life or function, one can wait and take the time to evaluate it. For example, if I have a child with slowed developmental milestones, what I have to do is teach how to stimulate them or send them for stimulation with another professional. And I observe the response to this initial basic treatment. If I see no response, the alarms start to grow louder,” said Dr. Fainboim.

Pablo Barvosa, MD, the principal physician in the outpatient area of the Juan P. Garrahan Pediatric Hospital in Buenos Aires, Argentina, and a member of the Working Group on Genetics and Rare Diseases of the Argentine Society of Pediatrics, told this news organization about other factors that should be considered for detecting these pathologies. Dr. Barvosa did not participate in the online seminar.

“Patients with rare diseases have common symptoms. What needs to be done is to prioritize those symptoms that behave abnormally, that have an unusual evolution compared with normal situations. For example, children who go into a coma after a fasting episode or after eating a certain food,” he said.

Dr. Barvosa also suggested considering when patients belong to certain communities where there is a lot of endogamy, due to the higher incidence of hereditary diseases. “Attention should be heightened when parents are cousins or relatives,” he pointed out.

“My view is that doctors should think more and better, be rational, sequential. If a disease is treated and resolved, but we find out that the child had 26 previous hospitalizations in the last 2 years, something is wrong. We have to look at the patient’s and family’s life histories. If a mother had 15 miscarriages, that’s a warning sign. We have to find a common thread. Be a sharp-witted pediatrician,” said Dr. Barvosa.

The suspicion and diagnosis of a rare disease can be devastating for families and painful for the professional, but even if there is no specific treatment, “something can always be done for patients,” he added.

And in certain circumstances, identifying a rare disease can reverse the ominous “stamp” of a wrong diagnosis. Dr. Barvosa commented on the case of a 7-year-old boy he attended at the hospital in 2014. The boy presented as quadriplegic, with no mobility in his limbs, and the parents were convinced he had that condition because he had fallen from the roof of the house. Although imaging techniques did not show a spinal injury, it was assumed to be a case of spinal cord injury without radiographic abnormality. But something caught Dr. Barvosa’s attention: The boy had well-developed abdominal muscles, as if he were an athlete. So, he requested an electromyogram, and the muscle was found to be in permanent contraction.

“The patient didn’t have a spinal cord injury: He had Isaacs’ syndrome,” said Dr. Barvosa. The syndrome also is known as acquired neuromyotonia, a rare condition of hyperexcitability of peripheral nerves that activate muscle fibers. “That is treated with anticonvulsants, such as phenytoin. Within a week, he was walking again, and shortly after, he was playing soccer. When I presented the case at a conference, I cried with emotion. That’s why the pediatrician must be insistent, be like the gadfly that stings in the ear” when there are clinical elements that don’t quite fit into a clear diagnosis, he added.

In recent publications, Dr. Dubrovsky has reported receiving fees for consultations or research from PTC, Sarepta, Biogen, Sanofi Genzyme, Takeda Avexis, Novartis, Raffo, and Roche. Dr. Nucifora has received fees from Jansen LATAM. Dr. Fainboim reported receiving fees from Sanofi. Dr. Barvosa has declared no relevant financial conflicts of interest. The webinar was organized by Urban Comunicaciones.
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A wise medical precept is attributed to Theodore Woodward, MD (1914-2005): “When you hear hoofbeats, think of horses, not zebras.” Primary care pediatricians, however, often find themselves confronting so-called rare or uncommon diseases (“zebras”) in their offices. The pressing challenge is to know when to suspect them. How can one reconcile the need to dispel uncertainty with the use of diagnostic tests that can be costly and invasive? When can the desire to reassure parents mean delaying the detection of a potentially treatable condition?

“It may seem like wordplay, but it’s not uncommon to have a rare disease,” noted Alejandro Fainboim, MD, a specialist in rare diseases and head of the Multivalent Day Hospital at the Ricardo Gutiérrez Children’s Hospital in Buenos Aires, Argentina. “And pediatricians are the first line of defense in detecting these types of pathologies. To make the diagnosis, we have to consider them. And to consider them, we must be knowledgeable. That’s why sometimes, ignorance slows down the diagnosis,” Dr. Fainboim made his remarks during an online seminar organized for the press on the eve of Rare Disease Day, which is commemorated on February 29th.

There are more than 8000 rare diseases, which generally are defined as those affecting fewer than five people per 10,000. But collectively, one in every 13 people has one of these diseases, and one in every two diagnosed patients is a child. Dr. Fainboim emphasized that most of these rare diseases are severe or very severe, hereditary, degenerative, and potentially fatal. And although they are pediatric pathologies, some manifest later in adulthood.

“The major problem we pediatricians face is that we’re handed a model from adults to solve pediatric diseases. So, signs and symptoms are described that we won’t find early on, but we have to anticipate and learn to decode some that are hidden,” he remarked.

Diagnostic delays and repeated consultations with various doctors before identification are common. Dr. Fainboim added that in industrialized countries, the diagnosis of these diseases takes between 5 and 10 years, and in low-income countries, up to 30 years or more. However, “this has improved significantly in recent years,” he said.
 

Unnoticed Signs

Specialists who treat patients with rare diseases often feel that there were obvious signs that went unnoticed and should have aroused the suspicion of the primary care physician. An example is paroxysmal nocturnal hemoglobinuria, which affects 13-14 people per million inhabitants and can appear at any age, although the incidence is higher in the third decade of life.

“In my 50 years as a doctor, I’ve seen seven or eight patients with paroxysmal nocturnal hemoglobinuria,” said Elsa Nucifora, MD, a hematologist at the Italian Hospital of Buenos Aires, Argentina. But “the diagnosis is so easy” that doctors could make it if they “were to think instead of acting automatically because they’re in a hurry,” she added. The diagnosis should be considered “every time anemia occurs in a young person, with certain characteristics, instead of giving them iron like everyone else and ‘we’ll see later’…the diagnosis is in two or three steps, so it’s not complicated.”

Similar situations occur with more than 1000 neuromuscular diseases involving mutations in more than 600 genes, including spinal muscular atrophy and muscular dystrophies.

“What are the most common manifestations? The hypotonic infant, the child who walks late, who falls frequently, who can’t climb stairs, who later may have difficulty breathing, who loses strength: These are presentations often unrecognized by doctors not in the specialty,” said Alberto Dubrovsky, MD, director of the Department of Neurology and the Neuromuscular Diseases Unit at the Favaloro University Neuroscience Institute in Buenos Aires, Argentina, during the seminar. “And considering that these diseases are diagnosed based on genetic mutations that need to be known to search for and request them, we are faced with a truly complex scenario that requires subspecialization.”

In a study recently published in the Argentine Archives of Pediatrics, Dr. Dubrovsky and colleagues interviewed 112 families of Argentine patients with molecular diagnoses of spinal muscular atrophy types I, II, and III and found that in 75%-85% of cases, the first signs of the disease (such as hypotonia, developmental delay, inability to achieve bipedal standing, or frequent falls) were recognized by parents. For type I, the most severe and early onset, in only 17.5% of cases did a neonatologist or pediatrician first notice something. Of the 72 patients with types II and III, where routine checks are less frequent than in the first months of life, only one doctor detected the first signs of the disease before parents or other relatives.

In the same study, the median time elapsed between the first sign and confirmed molecular diagnosis was 2, 10, and 31.5 months for types I, II, and III, respectively. The delay “is primarily due to the lack of clinical suspicion on the part of the intervening physician, who often dismisses or misinterprets the signs reported by parents, as reflected in the alternative diagnoses invoked,” the authors wrote.

“I don’t even ask for suspicion of a specific rare disease because that requires specialization. What I ask for is a kind of recognition or realization that something is happening and then request a consultation with the specialist to ensure proper care,” said Dr. Dubrovsky.

In another study conducted among 70 Argentine patients under age 13 years who were diagnosed with Duchenne muscular dystrophy (one of the most severe forms of muscular dystrophy), 82% of the pediatricians who were initially consulted for any problem in motor agility that parents, other relatives, or teachers had detected dismissed the observation. “They’re told to wait, that it will mature a little more,” said Dr. Dubrovsky. This explains why the time to diagnosis in Argentina from the first signs is around 2 years. The delays are unfortunate because “today we have treatments capable of interfering with the disease’s progression slope, reducing its progression, or eventually stopping it,” he said.

“Do you mind that primary care pediatricians don’t notice or dismiss signs and symptoms strongly suggestive of one of these rare diseases? Does it frustrate you?” this news organization asked asked Dr. Dubrovsky. “Sometimes it does make me angry, but many times it’s understood that there can’t be highly trained specialists everywhere to realize and request diagnostic tests. One must consider the circumstances in each case, and that’s why we work in education,” he replied.
 

Rules and Experience

In an interview, Dr. Fainboim highlighted key factors that should prompt a pediatrician’s suspicion. One is common symptoms expressed in a more intense or complicated way or when many symptoms coexist in the same patient, even if each one separately is benign or not so severe.

Dr. Fainboim also recommended establishing a therapeutic alliance with parents. “We shouldn’t undermine what parents say, especially those who have other children and already know what normal child development is like. This is a very important milestone.

“We have to strengthen the suspicion clue, and for that, we rely on standards and our experience, which we keep refining. As Wilde said, experience is the sum of our mistakes. But there’s no universal answer. Not all families are the same. Not all diseases manifest in the same way. And unless there’s an imminent risk to life or function, one can wait and take the time to evaluate it. For example, if I have a child with slowed developmental milestones, what I have to do is teach how to stimulate them or send them for stimulation with another professional. And I observe the response to this initial basic treatment. If I see no response, the alarms start to grow louder,” said Dr. Fainboim.

Pablo Barvosa, MD, the principal physician in the outpatient area of the Juan P. Garrahan Pediatric Hospital in Buenos Aires, Argentina, and a member of the Working Group on Genetics and Rare Diseases of the Argentine Society of Pediatrics, told this news organization about other factors that should be considered for detecting these pathologies. Dr. Barvosa did not participate in the online seminar.

“Patients with rare diseases have common symptoms. What needs to be done is to prioritize those symptoms that behave abnormally, that have an unusual evolution compared with normal situations. For example, children who go into a coma after a fasting episode or after eating a certain food,” he said.

Dr. Barvosa also suggested considering when patients belong to certain communities where there is a lot of endogamy, due to the higher incidence of hereditary diseases. “Attention should be heightened when parents are cousins or relatives,” he pointed out.

“My view is that doctors should think more and better, be rational, sequential. If a disease is treated and resolved, but we find out that the child had 26 previous hospitalizations in the last 2 years, something is wrong. We have to look at the patient’s and family’s life histories. If a mother had 15 miscarriages, that’s a warning sign. We have to find a common thread. Be a sharp-witted pediatrician,” said Dr. Barvosa.

The suspicion and diagnosis of a rare disease can be devastating for families and painful for the professional, but even if there is no specific treatment, “something can always be done for patients,” he added.

And in certain circumstances, identifying a rare disease can reverse the ominous “stamp” of a wrong diagnosis. Dr. Barvosa commented on the case of a 7-year-old boy he attended at the hospital in 2014. The boy presented as quadriplegic, with no mobility in his limbs, and the parents were convinced he had that condition because he had fallen from the roof of the house. Although imaging techniques did not show a spinal injury, it was assumed to be a case of spinal cord injury without radiographic abnormality. But something caught Dr. Barvosa’s attention: The boy had well-developed abdominal muscles, as if he were an athlete. So, he requested an electromyogram, and the muscle was found to be in permanent contraction.

“The patient didn’t have a spinal cord injury: He had Isaacs’ syndrome,” said Dr. Barvosa. The syndrome also is known as acquired neuromyotonia, a rare condition of hyperexcitability of peripheral nerves that activate muscle fibers. “That is treated with anticonvulsants, such as phenytoin. Within a week, he was walking again, and shortly after, he was playing soccer. When I presented the case at a conference, I cried with emotion. That’s why the pediatrician must be insistent, be like the gadfly that stings in the ear” when there are clinical elements that don’t quite fit into a clear diagnosis, he added.

In recent publications, Dr. Dubrovsky has reported receiving fees for consultations or research from PTC, Sarepta, Biogen, Sanofi Genzyme, Takeda Avexis, Novartis, Raffo, and Roche. Dr. Nucifora has received fees from Jansen LATAM. Dr. Fainboim reported receiving fees from Sanofi. Dr. Barvosa has declared no relevant financial conflicts of interest. The webinar was organized by Urban Comunicaciones.
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A wise medical precept is attributed to Theodore Woodward, MD (1914-2005): “When you hear hoofbeats, think of horses, not zebras.” Primary care pediatricians, however, often find themselves confronting so-called rare or uncommon diseases (“zebras”) in their offices. The pressing challenge is to know when to suspect them. How can one reconcile the need to dispel uncertainty with the use of diagnostic tests that can be costly and invasive? When can the desire to reassure parents mean delaying the detection of a potentially treatable condition?

“It may seem like wordplay, but it’s not uncommon to have a rare disease,” noted Alejandro Fainboim, MD, a specialist in rare diseases and head of the Multivalent Day Hospital at the Ricardo Gutiérrez Children’s Hospital in Buenos Aires, Argentina. “And pediatricians are the first line of defense in detecting these types of pathologies. To make the diagnosis, we have to consider them. And to consider them, we must be knowledgeable. That’s why sometimes, ignorance slows down the diagnosis,” Dr. Fainboim made his remarks during an online seminar organized for the press on the eve of Rare Disease Day, which is commemorated on February 29th.

There are more than 8000 rare diseases, which generally are defined as those affecting fewer than five people per 10,000. But collectively, one in every 13 people has one of these diseases, and one in every two diagnosed patients is a child. Dr. Fainboim emphasized that most of these rare diseases are severe or very severe, hereditary, degenerative, and potentially fatal. And although they are pediatric pathologies, some manifest later in adulthood.

“The major problem we pediatricians face is that we’re handed a model from adults to solve pediatric diseases. So, signs and symptoms are described that we won’t find early on, but we have to anticipate and learn to decode some that are hidden,” he remarked.

Diagnostic delays and repeated consultations with various doctors before identification are common. Dr. Fainboim added that in industrialized countries, the diagnosis of these diseases takes between 5 and 10 years, and in low-income countries, up to 30 years or more. However, “this has improved significantly in recent years,” he said.
 

Unnoticed Signs

Specialists who treat patients with rare diseases often feel that there were obvious signs that went unnoticed and should have aroused the suspicion of the primary care physician. An example is paroxysmal nocturnal hemoglobinuria, which affects 13-14 people per million inhabitants and can appear at any age, although the incidence is higher in the third decade of life.

“In my 50 years as a doctor, I’ve seen seven or eight patients with paroxysmal nocturnal hemoglobinuria,” said Elsa Nucifora, MD, a hematologist at the Italian Hospital of Buenos Aires, Argentina. But “the diagnosis is so easy” that doctors could make it if they “were to think instead of acting automatically because they’re in a hurry,” she added. The diagnosis should be considered “every time anemia occurs in a young person, with certain characteristics, instead of giving them iron like everyone else and ‘we’ll see later’…the diagnosis is in two or three steps, so it’s not complicated.”

Similar situations occur with more than 1000 neuromuscular diseases involving mutations in more than 600 genes, including spinal muscular atrophy and muscular dystrophies.

“What are the most common manifestations? The hypotonic infant, the child who walks late, who falls frequently, who can’t climb stairs, who later may have difficulty breathing, who loses strength: These are presentations often unrecognized by doctors not in the specialty,” said Alberto Dubrovsky, MD, director of the Department of Neurology and the Neuromuscular Diseases Unit at the Favaloro University Neuroscience Institute in Buenos Aires, Argentina, during the seminar. “And considering that these diseases are diagnosed based on genetic mutations that need to be known to search for and request them, we are faced with a truly complex scenario that requires subspecialization.”

In a study recently published in the Argentine Archives of Pediatrics, Dr. Dubrovsky and colleagues interviewed 112 families of Argentine patients with molecular diagnoses of spinal muscular atrophy types I, II, and III and found that in 75%-85% of cases, the first signs of the disease (such as hypotonia, developmental delay, inability to achieve bipedal standing, or frequent falls) were recognized by parents. For type I, the most severe and early onset, in only 17.5% of cases did a neonatologist or pediatrician first notice something. Of the 72 patients with types II and III, where routine checks are less frequent than in the first months of life, only one doctor detected the first signs of the disease before parents or other relatives.

In the same study, the median time elapsed between the first sign and confirmed molecular diagnosis was 2, 10, and 31.5 months for types I, II, and III, respectively. The delay “is primarily due to the lack of clinical suspicion on the part of the intervening physician, who often dismisses or misinterprets the signs reported by parents, as reflected in the alternative diagnoses invoked,” the authors wrote.

“I don’t even ask for suspicion of a specific rare disease because that requires specialization. What I ask for is a kind of recognition or realization that something is happening and then request a consultation with the specialist to ensure proper care,” said Dr. Dubrovsky.

In another study conducted among 70 Argentine patients under age 13 years who were diagnosed with Duchenne muscular dystrophy (one of the most severe forms of muscular dystrophy), 82% of the pediatricians who were initially consulted for any problem in motor agility that parents, other relatives, or teachers had detected dismissed the observation. “They’re told to wait, that it will mature a little more,” said Dr. Dubrovsky. This explains why the time to diagnosis in Argentina from the first signs is around 2 years. The delays are unfortunate because “today we have treatments capable of interfering with the disease’s progression slope, reducing its progression, or eventually stopping it,” he said.

“Do you mind that primary care pediatricians don’t notice or dismiss signs and symptoms strongly suggestive of one of these rare diseases? Does it frustrate you?” this news organization asked asked Dr. Dubrovsky. “Sometimes it does make me angry, but many times it’s understood that there can’t be highly trained specialists everywhere to realize and request diagnostic tests. One must consider the circumstances in each case, and that’s why we work in education,” he replied.
 

Rules and Experience

In an interview, Dr. Fainboim highlighted key factors that should prompt a pediatrician’s suspicion. One is common symptoms expressed in a more intense or complicated way or when many symptoms coexist in the same patient, even if each one separately is benign or not so severe.

Dr. Fainboim also recommended establishing a therapeutic alliance with parents. “We shouldn’t undermine what parents say, especially those who have other children and already know what normal child development is like. This is a very important milestone.

“We have to strengthen the suspicion clue, and for that, we rely on standards and our experience, which we keep refining. As Wilde said, experience is the sum of our mistakes. But there’s no universal answer. Not all families are the same. Not all diseases manifest in the same way. And unless there’s an imminent risk to life or function, one can wait and take the time to evaluate it. For example, if I have a child with slowed developmental milestones, what I have to do is teach how to stimulate them or send them for stimulation with another professional. And I observe the response to this initial basic treatment. If I see no response, the alarms start to grow louder,” said Dr. Fainboim.

Pablo Barvosa, MD, the principal physician in the outpatient area of the Juan P. Garrahan Pediatric Hospital in Buenos Aires, Argentina, and a member of the Working Group on Genetics and Rare Diseases of the Argentine Society of Pediatrics, told this news organization about other factors that should be considered for detecting these pathologies. Dr. Barvosa did not participate in the online seminar.

“Patients with rare diseases have common symptoms. What needs to be done is to prioritize those symptoms that behave abnormally, that have an unusual evolution compared with normal situations. For example, children who go into a coma after a fasting episode or after eating a certain food,” he said.

Dr. Barvosa also suggested considering when patients belong to certain communities where there is a lot of endogamy, due to the higher incidence of hereditary diseases. “Attention should be heightened when parents are cousins or relatives,” he pointed out.

“My view is that doctors should think more and better, be rational, sequential. If a disease is treated and resolved, but we find out that the child had 26 previous hospitalizations in the last 2 years, something is wrong. We have to look at the patient’s and family’s life histories. If a mother had 15 miscarriages, that’s a warning sign. We have to find a common thread. Be a sharp-witted pediatrician,” said Dr. Barvosa.

The suspicion and diagnosis of a rare disease can be devastating for families and painful for the professional, but even if there is no specific treatment, “something can always be done for patients,” he added.

And in certain circumstances, identifying a rare disease can reverse the ominous “stamp” of a wrong diagnosis. Dr. Barvosa commented on the case of a 7-year-old boy he attended at the hospital in 2014. The boy presented as quadriplegic, with no mobility in his limbs, and the parents were convinced he had that condition because he had fallen from the roof of the house. Although imaging techniques did not show a spinal injury, it was assumed to be a case of spinal cord injury without radiographic abnormality. But something caught Dr. Barvosa’s attention: The boy had well-developed abdominal muscles, as if he were an athlete. So, he requested an electromyogram, and the muscle was found to be in permanent contraction.

“The patient didn’t have a spinal cord injury: He had Isaacs’ syndrome,” said Dr. Barvosa. The syndrome also is known as acquired neuromyotonia, a rare condition of hyperexcitability of peripheral nerves that activate muscle fibers. “That is treated with anticonvulsants, such as phenytoin. Within a week, he was walking again, and shortly after, he was playing soccer. When I presented the case at a conference, I cried with emotion. That’s why the pediatrician must be insistent, be like the gadfly that stings in the ear” when there are clinical elements that don’t quite fit into a clear diagnosis, he added.

In recent publications, Dr. Dubrovsky has reported receiving fees for consultations or research from PTC, Sarepta, Biogen, Sanofi Genzyme, Takeda Avexis, Novartis, Raffo, and Roche. Dr. Nucifora has received fees from Jansen LATAM. Dr. Fainboim reported receiving fees from Sanofi. Dr. Barvosa has declared no relevant financial conflicts of interest. The webinar was organized by Urban Comunicaciones.
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.