Pediatrics

Photo by Bill Branson

Childhood cancer survivors (CCSs) who were diagnosed in the 1990s have a lower risk of subsequent malignancies than CCSs diagnosed in the 1970s, according to research published in JAMA.

The data suggest this outcome is associated with a reduction in the overall use and median dose of therapeutic radiation over time.

Past research has shown an association between therapeutic radiation and the development of subsequent neoplasms in CCSs. Studies have also linked specific chemotherapeutic agents to subsequent neoplasms.

This information has been used to modify childhood cancer treatment over time, with the hope of reducing the risk of subsequent neoplasms while maintaining or improving 5-year survival.

To assess the effects of these treatment modifications, Gregory Armstrong, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted a study of CCSs.

The researchers evaluated 23,603 five-year CCSs (mean age at diagnosis, 7.7 years) treated at pediatric hospitals in the US and Canada from 1970 through 1999, with follow-up through December 2015.

The most common initial diagnoses were acute lymphoblastic leukemia (35.1%), Hodgkin lymphoma (11.1%), and astrocytoma (9.6%).

Subsequent neoplasms, malignancies

At a mean follow-up of 20.5 years, 1639 CCSs had experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 non-melanoma skin cancers. The most common neoplasms were breast and thyroid cancers.

The 15-year cumulative incidence of subsequent neoplasms decreased by decade of diagnosis. The incidence was 2.9% for patients diagnosed in the 1970s, 2.4% for those diagnosed in the ’80s, and 1.5% for those diagnosed in the ’90s. For the 1970s vs 1980s, the P value was 0.02. For the 1970s vs 1990s and for the 1980s vs 1990s, the P value was <0.001.

The 15-year cumulative incidence of subsequent malignancies also decreased by decade of diagnosis—2.1% for the ’70s, 1.7% for the ’80s, and 1.3% for the ’90s. The P value was <0.001 for the ’70s vs the ’90s and the ’80s vs the ’90s.

Risk factors

In multivariable analyses, female CCSs had a higher rate of subsequent neoplasms (including malignancies) than males.

In addition, high doses of alkylating agents and platinum agents were associated with increased rates of subsequent malignancies.

The researchers noted that, although there was a decrease in the median cumulative dose of alkylating agents over time, the proportion of CCSs receiving these agents increased. And both the median cumulative dose of platinum agents and the proportion of CCSs receiving these agents increased from the ’70s to the ’90s.

Finally, therapeutic radiation was associated with increased rates of subsequent malignant neoplasms, meningiomas, and non-melanoma skin cancers.

This corresponded with the researchers’ findings that the proportion of individuals receiving radiation and the median dose of radiation both decreased over time.

The proportion of individuals receiving any radiation therapy was 77.7% in the ’70s, 56.7% in the ’80s, and 36.8% in the ’90s. The median dose of radiation was 30.0 Gy in the ’70s, 24.0 Gy in the ’80s, and 26.0 Gy in the ’90s.

“The most ominous late effect of pediatric cancer treatment is a second malignancy,” Dr Armstrong said. “This study shows efforts to reduce the late effects of treatment are paying off. The risk of second cancers for survivors increases with age, so it is good to see the reduction emerging early in survivorship while survivors are still young.”

Photo by Bill Branson

Childhood cancer survivors (CCSs) who were diagnosed in the 1990s have a lower risk of subsequent malignancies than CCSs diagnosed in the 1970s, according to research published in JAMA.

The data suggest this outcome is associated with a reduction in the overall use and median dose of therapeutic radiation over time.

Past research has shown an association between therapeutic radiation and the development of subsequent neoplasms in CCSs. Studies have also linked specific chemotherapeutic agents to subsequent neoplasms.

This information has been used to modify childhood cancer treatment over time, with the hope of reducing the risk of subsequent neoplasms while maintaining or improving 5-year survival.

To assess the effects of these treatment modifications, Gregory Armstrong, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted a study of CCSs.

The researchers evaluated 23,603 five-year CCSs (mean age at diagnosis, 7.7 years) treated at pediatric hospitals in the US and Canada from 1970 through 1999, with follow-up through December 2015.

The most common initial diagnoses were acute lymphoblastic leukemia (35.1%), Hodgkin lymphoma (11.1%), and astrocytoma (9.6%).

Subsequent neoplasms, malignancies

At a mean follow-up of 20.5 years, 1639 CCSs had experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 non-melanoma skin cancers. The most common neoplasms were breast and thyroid cancers.

The 15-year cumulative incidence of subsequent neoplasms decreased by decade of diagnosis. The incidence was 2.9% for patients diagnosed in the 1970s, 2.4% for those diagnosed in the ’80s, and 1.5% for those diagnosed in the ’90s. For the 1970s vs 1980s, the P value was 0.02. For the 1970s vs 1990s and for the 1980s vs 1990s, the P value was <0.001.

The 15-year cumulative incidence of subsequent malignancies also decreased by decade of diagnosis—2.1% for the ’70s, 1.7% for the ’80s, and 1.3% for the ’90s. The P value was <0.001 for the ’70s vs the ’90s and the ’80s vs the ’90s.

Risk factors

In multivariable analyses, female CCSs had a higher rate of subsequent neoplasms (including malignancies) than males.

In addition, high doses of alkylating agents and platinum agents were associated with increased rates of subsequent malignancies.

The researchers noted that, although there was a decrease in the median cumulative dose of alkylating agents over time, the proportion of CCSs receiving these agents increased. And both the median cumulative dose of platinum agents and the proportion of CCSs receiving these agents increased from the ’70s to the ’90s.

Finally, therapeutic radiation was associated with increased rates of subsequent malignant neoplasms, meningiomas, and non-melanoma skin cancers.

This corresponded with the researchers’ findings that the proportion of individuals receiving radiation and the median dose of radiation both decreased over time.

The proportion of individuals receiving any radiation therapy was 77.7% in the ’70s, 56.7% in the ’80s, and 36.8% in the ’90s. The median dose of radiation was 30.0 Gy in the ’70s, 24.0 Gy in the ’80s, and 26.0 Gy in the ’90s.

“The most ominous late effect of pediatric cancer treatment is a second malignancy,” Dr Armstrong said. “This study shows efforts to reduce the late effects of treatment are paying off. The risk of second cancers for survivors increases with age, so it is good to see the reduction emerging early in survivorship while survivors are still young.”

Photo by Bill Branson

Childhood cancer survivors (CCSs) who were diagnosed in the 1990s have a lower risk of subsequent malignancies than CCSs diagnosed in the 1970s, according to research published in JAMA.

The data suggest this outcome is associated with a reduction in the overall use and median dose of therapeutic radiation over time.

Past research has shown an association between therapeutic radiation and the development of subsequent neoplasms in CCSs. Studies have also linked specific chemotherapeutic agents to subsequent neoplasms.

This information has been used to modify childhood cancer treatment over time, with the hope of reducing the risk of subsequent neoplasms while maintaining or improving 5-year survival.

To assess the effects of these treatment modifications, Gregory Armstrong, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted a study of CCSs.

The researchers evaluated 23,603 five-year CCSs (mean age at diagnosis, 7.7 years) treated at pediatric hospitals in the US and Canada from 1970 through 1999, with follow-up through December 2015.

The most common initial diagnoses were acute lymphoblastic leukemia (35.1%), Hodgkin lymphoma (11.1%), and astrocytoma (9.6%).

Subsequent neoplasms, malignancies

At a mean follow-up of 20.5 years, 1639 CCSs had experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 non-melanoma skin cancers. The most common neoplasms were breast and thyroid cancers.

The 15-year cumulative incidence of subsequent neoplasms decreased by decade of diagnosis. The incidence was 2.9% for patients diagnosed in the 1970s, 2.4% for those diagnosed in the ’80s, and 1.5% for those diagnosed in the ’90s. For the 1970s vs 1980s, the P value was 0.02. For the 1970s vs 1990s and for the 1980s vs 1990s, the P value was <0.001.

The 15-year cumulative incidence of subsequent malignancies also decreased by decade of diagnosis—2.1% for the ’70s, 1.7% for the ’80s, and 1.3% for the ’90s. The P value was <0.001 for the ’70s vs the ’90s and the ’80s vs the ’90s.

Risk factors

In multivariable analyses, female CCSs had a higher rate of subsequent neoplasms (including malignancies) than males.

In addition, high doses of alkylating agents and platinum agents were associated with increased rates of subsequent malignancies.

The researchers noted that, although there was a decrease in the median cumulative dose of alkylating agents over time, the proportion of CCSs receiving these agents increased. And both the median cumulative dose of platinum agents and the proportion of CCSs receiving these agents increased from the ’70s to the ’90s.

Finally, therapeutic radiation was associated with increased rates of subsequent malignant neoplasms, meningiomas, and non-melanoma skin cancers.

This corresponded with the researchers’ findings that the proportion of individuals receiving radiation and the median dose of radiation both decreased over time.

The proportion of individuals receiving any radiation therapy was 77.7% in the ’70s, 56.7% in the ’80s, and 36.8% in the ’90s. The median dose of radiation was 30.0 Gy in the ’70s, 24.0 Gy in the ’80s, and 26.0 Gy in the ’90s.

“The most ominous late effect of pediatric cancer treatment is a second malignancy,” Dr Armstrong said. “This study shows efforts to reduce the late effects of treatment are paying off. The risk of second cancers for survivors increases with age, so it is good to see the reduction emerging early in survivorship while survivors are still young.”

EVIDENCE SUMMARY

A 2010 meta-analysis evaluated 14 RCTs investigating the effectiveness of giving sweet solutions before immunization in 1707 healthy term infants from beyond the neonatal period to 12 months of age.¹ Intervention groups received 0.25 to 10 mL (median, 2 mL) of 12% to 75% sucrose or 30% to 40% glucose orally 2 minutes before one to 4 injections (one study used 3 oral doses every 30 seconds, and one study added topical EMLA cream). Control groups received water or nothing (plus topical placebo in one study).

Pooled outcome data for crying duration from 6 studies (5 sucrose, one glucose; 716 injections) showed no significant difference between groups. When 2 studies with widely differing results using 12% sucrose were removed, however, a statistically significant weighted mean difference of 12 seconds less crying favored sweet solutions (3 sucrose, one glucose; 568 injections; 95% confidence interval, −23 to −0.78).

Differences among studies in volumes and concentrations of sweet solutions used prevented investigators from ascertaining optimal dosing.

Sucrose solution significantly reduces crying time compared with placebo

A 2014 double-blind RCT evaluated sucrose solutions compared with sterile water in older infants.² One nurse gave 2 mL of a 75% sucrose solution, a 25% sucrose solution, or sterile water orally over 15 seconds immediately before administering diphtheria, tetanus, acellular pertussis/Haemophilus influenzae type b/inactivated poliovirus (DTaP/Hib/IPV), pneumococcal, and hepatitis A vaccines to 537 healthy 16- to 19-month-old infants simultaneously in the right and left deltoids. Parents cuddled the infant over one shoulder while a distracting noise was made. Pacifiers (5 infants) and pretreatment paracetamol (8 infants) were permitted.

Infants receiving sucrose solutions showed significantly reduced total crying times compared with controls (75% sucrose, 43 seconds; 25% sucrose, 62 seconds; placebo, 120 seconds; P<.001 for 75% sucrose compared with other solutions; P<.001 for 25% sucrose compared with placebo).

Glucose also shortens crying

A 2012 double-blind RCT compared glucose solution with sterile water before vaccination in 120 healthy infants 2 months of age.³ Parents used a syringe to apply 2 mL of a 25% glucose solution or sterile water over 30 seconds to the lateral side of the infant’s tongue immediately before injection of DTaP/Hib/IPV vaccine into the right thigh followed by injection of hepatitis B vaccine into the left thigh.

Infants lay on the examination table in the supine position with the head elevated. Parents weren’t permitted to use a pacifier or bottle, or swaddle, cuddle, or restrain the infant during the procedure, but they were allowed to lift and calm the infant 15 seconds after the injections. Mean full-lung crying time and mean total crying time were significantly shorter in the treatment group (TABLE³).

EVIDENCE SUMMARY

A 2010 meta-analysis evaluated 14 RCTs investigating the effectiveness of giving sweet solutions before immunization in 1707 healthy term infants from beyond the neonatal period to 12 months of age.¹ Intervention groups received 0.25 to 10 mL (median, 2 mL) of 12% to 75% sucrose or 30% to 40% glucose orally 2 minutes before one to 4 injections (one study used 3 oral doses every 30 seconds, and one study added topical EMLA cream). Control groups received water or nothing (plus topical placebo in one study).

Pooled outcome data for crying duration from 6 studies (5 sucrose, one glucose; 716 injections) showed no significant difference between groups. When 2 studies with widely differing results using 12% sucrose were removed, however, a statistically significant weighted mean difference of 12 seconds less crying favored sweet solutions (3 sucrose, one glucose; 568 injections; 95% confidence interval, −23 to −0.78).

Differences among studies in volumes and concentrations of sweet solutions used prevented investigators from ascertaining optimal dosing.

Sucrose solution significantly reduces crying time compared with placebo

A 2014 double-blind RCT evaluated sucrose solutions compared with sterile water in older infants.² One nurse gave 2 mL of a 75% sucrose solution, a 25% sucrose solution, or sterile water orally over 15 seconds immediately before administering diphtheria, tetanus, acellular pertussis/Haemophilus influenzae type b/inactivated poliovirus (DTaP/Hib/IPV), pneumococcal, and hepatitis A vaccines to 537 healthy 16- to 19-month-old infants simultaneously in the right and left deltoids. Parents cuddled the infant over one shoulder while a distracting noise was made. Pacifiers (5 infants) and pretreatment paracetamol (8 infants) were permitted.

Infants receiving sucrose solutions showed significantly reduced total crying times compared with controls (75% sucrose, 43 seconds; 25% sucrose, 62 seconds; placebo, 120 seconds; P<.001 for 75% sucrose compared with other solutions; P<.001 for 25% sucrose compared with placebo).

Glucose also shortens crying

A 2012 double-blind RCT compared glucose solution with sterile water before vaccination in 120 healthy infants 2 months of age.³ Parents used a syringe to apply 2 mL of a 25% glucose solution or sterile water over 30 seconds to the lateral side of the infant’s tongue immediately before injection of DTaP/Hib/IPV vaccine into the right thigh followed by injection of hepatitis B vaccine into the left thigh.

Infants lay on the examination table in the supine position with the head elevated. Parents weren’t permitted to use a pacifier or bottle, or swaddle, cuddle, or restrain the infant during the procedure, but they were allowed to lift and calm the infant 15 seconds after the injections. Mean full-lung crying time and mean total crying time were significantly shorter in the treatment group (TABLE³).

EVIDENCE SUMMARY

A 2010 meta-analysis evaluated 14 RCTs investigating the effectiveness of giving sweet solutions before immunization in 1707 healthy term infants from beyond the neonatal period to 12 months of age.¹ Intervention groups received 0.25 to 10 mL (median, 2 mL) of 12% to 75% sucrose or 30% to 40% glucose orally 2 minutes before one to 4 injections (one study used 3 oral doses every 30 seconds, and one study added topical EMLA cream). Control groups received water or nothing (plus topical placebo in one study).

Pooled outcome data for crying duration from 6 studies (5 sucrose, one glucose; 716 injections) showed no significant difference between groups. When 2 studies with widely differing results using 12% sucrose were removed, however, a statistically significant weighted mean difference of 12 seconds less crying favored sweet solutions (3 sucrose, one glucose; 568 injections; 95% confidence interval, −23 to −0.78).

Differences among studies in volumes and concentrations of sweet solutions used prevented investigators from ascertaining optimal dosing.

Sucrose solution significantly reduces crying time compared with placebo

A 2014 double-blind RCT evaluated sucrose solutions compared with sterile water in older infants.² One nurse gave 2 mL of a 75% sucrose solution, a 25% sucrose solution, or sterile water orally over 15 seconds immediately before administering diphtheria, tetanus, acellular pertussis/Haemophilus influenzae type b/inactivated poliovirus (DTaP/Hib/IPV), pneumococcal, and hepatitis A vaccines to 537 healthy 16- to 19-month-old infants simultaneously in the right and left deltoids. Parents cuddled the infant over one shoulder while a distracting noise was made. Pacifiers (5 infants) and pretreatment paracetamol (8 infants) were permitted.

Infants receiving sucrose solutions showed significantly reduced total crying times compared with controls (75% sucrose, 43 seconds; 25% sucrose, 62 seconds; placebo, 120 seconds; P<.001 for 75% sucrose compared with other solutions; P<.001 for 25% sucrose compared with placebo).

Glucose also shortens crying

A 2012 double-blind RCT compared glucose solution with sterile water before vaccination in 120 healthy infants 2 months of age.³ Parents used a syringe to apply 2 mL of a 25% glucose solution or sterile water over 30 seconds to the lateral side of the infant’s tongue immediately before injection of DTaP/Hib/IPV vaccine into the right thigh followed by injection of hepatitis B vaccine into the left thigh.

Infants lay on the examination table in the supine position with the head elevated. Parents weren’t permitted to use a pacifier or bottle, or swaddle, cuddle, or restrain the infant during the procedure, but they were allowed to lift and calm the infant 15 seconds after the injections. Mean full-lung crying time and mean total crying time were significantly shorter in the treatment group (TABLE³).

A 4-month-old girl was brought to our clinic with a 4-week history of blisters on her arms and legs. The eruption started on her right posterior and lateral calf and then appeared on her left calf and bilateral elbows. Other than the blisters, the girl appeared well and was eating and growing normally. Her parents said she had not been in contact with anyone with a similar rash or itching. They also denied recent outdoor activities, camping trips, or environmental exposures.

The child had been previously treated with topical and oral steroids and oral antibiotics by a pediatrician, but the rash barely improved. On physical examination, she was afebrile with well-demarcated erythematous papules and plaques with bullae, and erosions with honey-colored crusts. The rash was distributed symmetrically on the bilateral posterior and lateral lower legs and lateral upper arms (FIGURE).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Allergic contact dermatitis from a car seat

The appearance and distribution of the rash on the infant’s posterior and lateral lower legs and lateral upper arms prompted us to conclude that this was a case of allergic contact dermatitis from a car seat, along with secondary impetiginization.

The incidence of car seat contact dermatitis is unknown, although it is suspected to be both under-recognized and under-reported. In fact, the number of cases may be on the rise,¹ given the increasing number of synthetic liners now being used in car seats, high chairs, and other infant support products.

The distribution of car seat dermatitis typically involves areas in direct contact with the car seat, such as the elbows, upper lateral or posterior thighs, and lower lateral legs.More common in summer months. Car seat dermatitis is commonly reported in warmer months, when an infant’s skin is more likely to be in direct contact with the car seat and sweating is increased.¹ In the acute setting, clinical morphology usually takes the form of inflamed papules or vesicles, while in chronic presentations, lichenified eczematous plaques may be seen. Distribution is typically symmetric and involves areas in direct contact with the car seat, such as the elbows, upper lateral or posterior thighs, lower lateral legs, and sometimes, the occipital scalp.¹ The presence of a secondary infection or autoeczematization can complicate the clinical presentation.

Which car seat materials are to blame? Previous reports have described the shiny, nylon-like material overlying the car seat cushion as the cause of the contact allergy, but no specific allergens have yet been identified.¹ Attempts at identifying specific allergens in car seat liners have been thwarted by the proprietary nature of manufacturers’ formulas and the unwillingness of companies to divulge the chemicals used in the manufacture of their car seats. Potential allergens include bromine, chlorine, and flame-retardants.¹ These allergens differ from the usual contact allergens in children and adolescents, which include nickel sulfate, cobalt chloride, potassium dichromate, fragrance mix, thimerosal, neomycin sulfate, and para-tertiary-butylphenol formaldehyde resin.²

Differential includes other conditions with blisters, plaques

The differential diagnosis includes eczema herpeticum, bullous impetigo, and psoriasis.

Infants with eczema herpeticum usually have eczematous plaques in locations such as the cheeks, neck, antecubital fossa, popliteal fossa, and ankles, with numerous “punched-out” shallow erosions. Children with extensive eczema herpeticum can be systemically ill.

Bullous impetigo is seen as flaccid bullae in infants, which can easily rupture and leave behind superficial erosions. These blisters tend to appear on normal skin. (This is quite different from the thick, erythematous plaques seen in contact dermatitis.) In patients with superficial erosions, a polymerase chain reaction test for the herpes virus and a bacterial culture should be obtained.

Psoriasis often presents with well-demarcated erythematous plaques with overlying silver scale. Although it can be symmetric on extensor surfaces, the weeping vesicles with acute onset that were seen in this case would be unusual.

Look for a pattern. The well-demarcated symmetric plaques corresponding directly to areas in contact with the car seat should be a strong clue for contact dermatitis. While patch testing for relevant chemicals is often indicated in patients for whom there is a clinical suspicion of a contact allergy,^3,4 we did not perform such testing because the specific chemicals involved in car seat manufacturing are unknown.

Topical steroids and avoidance of the allergen help resolve the rash

The mainstay of treatment for allergic contact dermatitis is avoiding the contact allergen. In car seat contact dermatitis, parents should be counseled to avoid contact between the child’s bare skin and the car seat liner. Given that the precise allergen is unknown, it is impossible to know if a new car seat would contain the same material. Instead, we recommend covering the car seat with a cotton blanket to avoid irritation/allergens.

Depending on the extent of the rash, the patient should be treated with a mid- or high-potency topical steroid until the erythema and blistering resolve.^5-8 A 3-week prednisone taper can also be considered for severe cases. For patients who have >25% of their body surface involved, oral steroids are recommended.⁶ Any secondary infection should be treated with topical and oral antibiotics, as appropriate.

Our patient. Due to the extent and severity of the eruption, we put the patient on a 3-week oral prednisone taper and advised the parents to apply clobetasol 0.05% ointment to the affected areas 2 times a day. We also prescribed a 7-day course of cephalexin 50 mg/kg divided in 3 doses a day and topical mupirocin ointment (to be applied 2 times a day) for the secondary impetiginization.

We advised the parents to use a cotton blanket over the baby’s car seat to prevent further outbreaks. The eruption resolved within 2 months. 

CORRESPONDENCE
Karolyn A. Wanat, MD, Department of Dermatology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 40000 PFP, Iowa City, IA 52242; karolyn-wanat@uiowa.edu.

A 4-month-old girl was brought to our clinic with a 4-week history of blisters on her arms and legs. The eruption started on her right posterior and lateral calf and then appeared on her left calf and bilateral elbows. Other than the blisters, the girl appeared well and was eating and growing normally. Her parents said she had not been in contact with anyone with a similar rash or itching. They also denied recent outdoor activities, camping trips, or environmental exposures.

The child had been previously treated with topical and oral steroids and oral antibiotics by a pediatrician, but the rash barely improved. On physical examination, she was afebrile with well-demarcated erythematous papules and plaques with bullae, and erosions with honey-colored crusts. The rash was distributed symmetrically on the bilateral posterior and lateral lower legs and lateral upper arms (FIGURE).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Allergic contact dermatitis from a car seat

The appearance and distribution of the rash on the infant’s posterior and lateral lower legs and lateral upper arms prompted us to conclude that this was a case of allergic contact dermatitis from a car seat, along with secondary impetiginization.

The incidence of car seat contact dermatitis is unknown, although it is suspected to be both under-recognized and under-reported. In fact, the number of cases may be on the rise,¹ given the increasing number of synthetic liners now being used in car seats, high chairs, and other infant support products.

The distribution of car seat dermatitis typically involves areas in direct contact with the car seat, such as the elbows, upper lateral or posterior thighs, and lower lateral legs.More common in summer months. Car seat dermatitis is commonly reported in warmer months, when an infant’s skin is more likely to be in direct contact with the car seat and sweating is increased.¹ In the acute setting, clinical morphology usually takes the form of inflamed papules or vesicles, while in chronic presentations, lichenified eczematous plaques may be seen. Distribution is typically symmetric and involves areas in direct contact with the car seat, such as the elbows, upper lateral or posterior thighs, lower lateral legs, and sometimes, the occipital scalp.¹ The presence of a secondary infection or autoeczematization can complicate the clinical presentation.

Which car seat materials are to blame? Previous reports have described the shiny, nylon-like material overlying the car seat cushion as the cause of the contact allergy, but no specific allergens have yet been identified.¹ Attempts at identifying specific allergens in car seat liners have been thwarted by the proprietary nature of manufacturers’ formulas and the unwillingness of companies to divulge the chemicals used in the manufacture of their car seats. Potential allergens include bromine, chlorine, and flame-retardants.¹ These allergens differ from the usual contact allergens in children and adolescents, which include nickel sulfate, cobalt chloride, potassium dichromate, fragrance mix, thimerosal, neomycin sulfate, and para-tertiary-butylphenol formaldehyde resin.²

Differential includes other conditions with blisters, plaques

The differential diagnosis includes eczema herpeticum, bullous impetigo, and psoriasis.

Infants with eczema herpeticum usually have eczematous plaques in locations such as the cheeks, neck, antecubital fossa, popliteal fossa, and ankles, with numerous “punched-out” shallow erosions. Children with extensive eczema herpeticum can be systemically ill.

Bullous impetigo is seen as flaccid bullae in infants, which can easily rupture and leave behind superficial erosions. These blisters tend to appear on normal skin. (This is quite different from the thick, erythematous plaques seen in contact dermatitis.) In patients with superficial erosions, a polymerase chain reaction test for the herpes virus and a bacterial culture should be obtained.

Psoriasis often presents with well-demarcated erythematous plaques with overlying silver scale. Although it can be symmetric on extensor surfaces, the weeping vesicles with acute onset that were seen in this case would be unusual.

Look for a pattern. The well-demarcated symmetric plaques corresponding directly to areas in contact with the car seat should be a strong clue for contact dermatitis. While patch testing for relevant chemicals is often indicated in patients for whom there is a clinical suspicion of a contact allergy,^3,4 we did not perform such testing because the specific chemicals involved in car seat manufacturing are unknown.

Topical steroids and avoidance of the allergen help resolve the rash

The mainstay of treatment for allergic contact dermatitis is avoiding the contact allergen. In car seat contact dermatitis, parents should be counseled to avoid contact between the child’s bare skin and the car seat liner. Given that the precise allergen is unknown, it is impossible to know if a new car seat would contain the same material. Instead, we recommend covering the car seat with a cotton blanket to avoid irritation/allergens.

Depending on the extent of the rash, the patient should be treated with a mid- or high-potency topical steroid until the erythema and blistering resolve.^5-8 A 3-week prednisone taper can also be considered for severe cases. For patients who have >25% of their body surface involved, oral steroids are recommended.⁶ Any secondary infection should be treated with topical and oral antibiotics, as appropriate.

Our patient. Due to the extent and severity of the eruption, we put the patient on a 3-week oral prednisone taper and advised the parents to apply clobetasol 0.05% ointment to the affected areas 2 times a day. We also prescribed a 7-day course of cephalexin 50 mg/kg divided in 3 doses a day and topical mupirocin ointment (to be applied 2 times a day) for the secondary impetiginization.

We advised the parents to use a cotton blanket over the baby’s car seat to prevent further outbreaks. The eruption resolved within 2 months. 

CORRESPONDENCE
Karolyn A. Wanat, MD, Department of Dermatology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 40000 PFP, Iowa City, IA 52242; karolyn-wanat@uiowa.edu.

A 4-month-old girl was brought to our clinic with a 4-week history of blisters on her arms and legs. The eruption started on her right posterior and lateral calf and then appeared on her left calf and bilateral elbows. Other than the blisters, the girl appeared well and was eating and growing normally. Her parents said she had not been in contact with anyone with a similar rash or itching. They also denied recent outdoor activities, camping trips, or environmental exposures.

The child had been previously treated with topical and oral steroids and oral antibiotics by a pediatrician, but the rash barely improved. On physical examination, she was afebrile with well-demarcated erythematous papules and plaques with bullae, and erosions with honey-colored crusts. The rash was distributed symmetrically on the bilateral posterior and lateral lower legs and lateral upper arms (FIGURE).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Allergic contact dermatitis from a car seat

The appearance and distribution of the rash on the infant’s posterior and lateral lower legs and lateral upper arms prompted us to conclude that this was a case of allergic contact dermatitis from a car seat, along with secondary impetiginization.

The incidence of car seat contact dermatitis is unknown, although it is suspected to be both under-recognized and under-reported. In fact, the number of cases may be on the rise,¹ given the increasing number of synthetic liners now being used in car seats, high chairs, and other infant support products.

The distribution of car seat dermatitis typically involves areas in direct contact with the car seat, such as the elbows, upper lateral or posterior thighs, and lower lateral legs.More common in summer months. Car seat dermatitis is commonly reported in warmer months, when an infant’s skin is more likely to be in direct contact with the car seat and sweating is increased.¹ In the acute setting, clinical morphology usually takes the form of inflamed papules or vesicles, while in chronic presentations, lichenified eczematous plaques may be seen. Distribution is typically symmetric and involves areas in direct contact with the car seat, such as the elbows, upper lateral or posterior thighs, lower lateral legs, and sometimes, the occipital scalp.¹ The presence of a secondary infection or autoeczematization can complicate the clinical presentation.

Which car seat materials are to blame? Previous reports have described the shiny, nylon-like material overlying the car seat cushion as the cause of the contact allergy, but no specific allergens have yet been identified.¹ Attempts at identifying specific allergens in car seat liners have been thwarted by the proprietary nature of manufacturers’ formulas and the unwillingness of companies to divulge the chemicals used in the manufacture of their car seats. Potential allergens include bromine, chlorine, and flame-retardants.¹ These allergens differ from the usual contact allergens in children and adolescents, which include nickel sulfate, cobalt chloride, potassium dichromate, fragrance mix, thimerosal, neomycin sulfate, and para-tertiary-butylphenol formaldehyde resin.²

Differential includes other conditions with blisters, plaques

The differential diagnosis includes eczema herpeticum, bullous impetigo, and psoriasis.

Infants with eczema herpeticum usually have eczematous plaques in locations such as the cheeks, neck, antecubital fossa, popliteal fossa, and ankles, with numerous “punched-out” shallow erosions. Children with extensive eczema herpeticum can be systemically ill.

Bullous impetigo is seen as flaccid bullae in infants, which can easily rupture and leave behind superficial erosions. These blisters tend to appear on normal skin. (This is quite different from the thick, erythematous plaques seen in contact dermatitis.) In patients with superficial erosions, a polymerase chain reaction test for the herpes virus and a bacterial culture should be obtained.

Psoriasis often presents with well-demarcated erythematous plaques with overlying silver scale. Although it can be symmetric on extensor surfaces, the weeping vesicles with acute onset that were seen in this case would be unusual.

Look for a pattern. The well-demarcated symmetric plaques corresponding directly to areas in contact with the car seat should be a strong clue for contact dermatitis. While patch testing for relevant chemicals is often indicated in patients for whom there is a clinical suspicion of a contact allergy,^3,4 we did not perform such testing because the specific chemicals involved in car seat manufacturing are unknown.

Topical steroids and avoidance of the allergen help resolve the rash

The mainstay of treatment for allergic contact dermatitis is avoiding the contact allergen. In car seat contact dermatitis, parents should be counseled to avoid contact between the child’s bare skin and the car seat liner. Given that the precise allergen is unknown, it is impossible to know if a new car seat would contain the same material. Instead, we recommend covering the car seat with a cotton blanket to avoid irritation/allergens.

Depending on the extent of the rash, the patient should be treated with a mid- or high-potency topical steroid until the erythema and blistering resolve.^5-8 A 3-week prednisone taper can also be considered for severe cases. For patients who have >25% of their body surface involved, oral steroids are recommended.⁶ Any secondary infection should be treated with topical and oral antibiotics, as appropriate.

Our patient. Due to the extent and severity of the eruption, we put the patient on a 3-week oral prednisone taper and advised the parents to apply clobetasol 0.05% ointment to the affected areas 2 times a day. We also prescribed a 7-day course of cephalexin 50 mg/kg divided in 3 doses a day and topical mupirocin ointment (to be applied 2 times a day) for the secondary impetiginization.

We advised the parents to use a cotton blanket over the baby’s car seat to prevent further outbreaks. The eruption resolved within 2 months. 

CORRESPONDENCE
Karolyn A. Wanat, MD, Department of Dermatology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 40000 PFP, Iowa City, IA 52242; karolyn-wanat@uiowa.edu.

 

The burden of serious infection is quite high among children who have systemic lupus erythematosus, with a “striking” preponderance of bacterial pneumonia, according to a report published in Arthritis Care & Research.

Infections are known to be commonplace among systemic lupus erythematosus (SLE) patients in general, and the increased risk is attributed both to the disease and to immunosuppressant therapies. However, most information on this topic comes from studies of adult patients seen at individual academic medical centers, said Linda T. Hiraki, MD, ScD, of the division of rheumatology at The Hospital for Sick Children, Toronto, and her associates.

To examine the nationwide prevalence of serious infections among children with SLE, they analyzed administrative data from a Medicaid database. They focused on 3,500 patients aged 5-18 years, including 1,297 who also had lupus nephritis, who were enrolled in Medicaid during 2000-2006 and followed for a mean of 2.6 years. This yielded a cumulative follow-up of more than 10,100 person-years (Arthritis Care Res. 2017 Feb 19. doi: 10.1002/acr.23219).

Courtesy Wikimedia Commons/doktorinternet/Creative Commons License

A total of 593 of these children had 1,053 serious infections requiring hospitalization during the study period, including 326 children with concurrent lupus nephritis who had 624 infections. A total of 17% of the entire study population and 25% of the subset with lupus nephritis developed at least one such infection. A substantial proportion – 18% of the overall cohort and 21% of those with lupus nephritis – had three or more serious infections requiring hospitalization during the relatively short follow-up, Dr. Hiraki and her associates noted.

The overall incidence was 10.4 serious infections per 100 person-years, and it was 17.65 per 100 person-years in the subset of patients who had lupus nephritis. By comparison, this overall rate is nearly four times higher than that reported for children with juvenile idiopathic arthritis, and the incidence among children with concomitant lupus nephritis is more than six times higher.

Infection rates were markedly higher among African American (incidence rate ratio [IRR], 1.83) and Native American (IRR, 1.81) children, compared with white children. They also were higher in early adolescence (ages 9-12 years) than earlier in childhood (ages 5-8 years), the investigators said.

Most of the infections (87%) were bacterial, whereas 11% were viral and 1.3% were fungal. (The remaining amount was unknown in the data because of too few numbers for federal reporting.) The most frequent bacterial infections were pneumonia (438 cases), followed by bacteremia (274 cases) and cellulitis (272 cases). Herpes zoster was the most frequent viral infection, accounting for 81 cases. The investigators noted that the low rate of fungal infections may be an artifact of the study protocol, which excluded, for technical reasons, cases of systemic candidiasis.

Not surprisingly, the rate of serious infection was higher among children with a high comorbidity burden than among healthier children.

Overall, the risk of serious infection was 59% higher for SLE patients who took corticosteroids during the study’s 6-month baseline period, in which 67% of patients took them (minimum of 20 mg/day of prednisone equivalent). However, the risk of serious infection was no different between those who used immunosuppressants (31%) or didn’t use them during that period.

A total of 26 children died within 30 days of hospital admission for a serious infection, for an overall mortality of 4.4% among children who developed serious infections. In comparison, 1.6% in the total cohort of 3,500 died. More than half of the children who died had concomitant lupus nephritis. In addition, 77% of those who died were taking corticosteroids when they developed the infections.

It is difficult to distinguish whether the high infection rate could be attributed to SLE itself or to its treatments. More studies are needed to further investigate this, as well as to address the disproportionate incidence among nonwhite children and any potential benefits from prophylactic use of antibiotics and vaccinations, Dr. Hiraki and her associates said.

The Canadian Institutes of Health Research, the Lupus Foundation of America, the Rheumatology Research Foundation, and the National Institutes of Health supported the study. Dr. Hiraki and her associates reported having no relevant disclosures.

 

 

The burden of serious infection is quite high among children who have systemic lupus erythematosus, with a “striking” preponderance of bacterial pneumonia, according to a report published in Arthritis Care & Research.

Infections are known to be commonplace among systemic lupus erythematosus (SLE) patients in general, and the increased risk is attributed both to the disease and to immunosuppressant therapies. However, most information on this topic comes from studies of adult patients seen at individual academic medical centers, said Linda T. Hiraki, MD, ScD, of the division of rheumatology at The Hospital for Sick Children, Toronto, and her associates.

To examine the nationwide prevalence of serious infections among children with SLE, they analyzed administrative data from a Medicaid database. They focused on 3,500 patients aged 5-18 years, including 1,297 who also had lupus nephritis, who were enrolled in Medicaid during 2000-2006 and followed for a mean of 2.6 years. This yielded a cumulative follow-up of more than 10,100 person-years (Arthritis Care Res. 2017 Feb 19. doi: 10.1002/acr.23219).

Courtesy Wikimedia Commons/doktorinternet/Creative Commons License

A total of 593 of these children had 1,053 serious infections requiring hospitalization during the study period, including 326 children with concurrent lupus nephritis who had 624 infections. A total of 17% of the entire study population and 25% of the subset with lupus nephritis developed at least one such infection. A substantial proportion – 18% of the overall cohort and 21% of those with lupus nephritis – had three or more serious infections requiring hospitalization during the relatively short follow-up, Dr. Hiraki and her associates noted.

The overall incidence was 10.4 serious infections per 100 person-years, and it was 17.65 per 100 person-years in the subset of patients who had lupus nephritis. By comparison, this overall rate is nearly four times higher than that reported for children with juvenile idiopathic arthritis, and the incidence among children with concomitant lupus nephritis is more than six times higher.

Infection rates were markedly higher among African American (incidence rate ratio [IRR], 1.83) and Native American (IRR, 1.81) children, compared with white children. They also were higher in early adolescence (ages 9-12 years) than earlier in childhood (ages 5-8 years), the investigators said.

Most of the infections (87%) were bacterial, whereas 11% were viral and 1.3% were fungal. (The remaining amount was unknown in the data because of too few numbers for federal reporting.) The most frequent bacterial infections were pneumonia (438 cases), followed by bacteremia (274 cases) and cellulitis (272 cases). Herpes zoster was the most frequent viral infection, accounting for 81 cases. The investigators noted that the low rate of fungal infections may be an artifact of the study protocol, which excluded, for technical reasons, cases of systemic candidiasis.

Not surprisingly, the rate of serious infection was higher among children with a high comorbidity burden than among healthier children.

Overall, the risk of serious infection was 59% higher for SLE patients who took corticosteroids during the study’s 6-month baseline period, in which 67% of patients took them (minimum of 20 mg/day of prednisone equivalent). However, the risk of serious infection was no different between those who used immunosuppressants (31%) or didn’t use them during that period.

A total of 26 children died within 30 days of hospital admission for a serious infection, for an overall mortality of 4.4% among children who developed serious infections. In comparison, 1.6% in the total cohort of 3,500 died. More than half of the children who died had concomitant lupus nephritis. In addition, 77% of those who died were taking corticosteroids when they developed the infections.

It is difficult to distinguish whether the high infection rate could be attributed to SLE itself or to its treatments. More studies are needed to further investigate this, as well as to address the disproportionate incidence among nonwhite children and any potential benefits from prophylactic use of antibiotics and vaccinations, Dr. Hiraki and her associates said.

The Canadian Institutes of Health Research, the Lupus Foundation of America, the Rheumatology Research Foundation, and the National Institutes of Health supported the study. Dr. Hiraki and her associates reported having no relevant disclosures.

 

 

The burden of serious infection is quite high among children who have systemic lupus erythematosus, with a “striking” preponderance of bacterial pneumonia, according to a report published in Arthritis Care & Research.

Infections are known to be commonplace among systemic lupus erythematosus (SLE) patients in general, and the increased risk is attributed both to the disease and to immunosuppressant therapies. However, most information on this topic comes from studies of adult patients seen at individual academic medical centers, said Linda T. Hiraki, MD, ScD, of the division of rheumatology at The Hospital for Sick Children, Toronto, and her associates.

To examine the nationwide prevalence of serious infections among children with SLE, they analyzed administrative data from a Medicaid database. They focused on 3,500 patients aged 5-18 years, including 1,297 who also had lupus nephritis, who were enrolled in Medicaid during 2000-2006 and followed for a mean of 2.6 years. This yielded a cumulative follow-up of more than 10,100 person-years (Arthritis Care Res. 2017 Feb 19. doi: 10.1002/acr.23219).

Courtesy Wikimedia Commons/doktorinternet/Creative Commons License

A total of 593 of these children had 1,053 serious infections requiring hospitalization during the study period, including 326 children with concurrent lupus nephritis who had 624 infections. A total of 17% of the entire study population and 25% of the subset with lupus nephritis developed at least one such infection. A substantial proportion – 18% of the overall cohort and 21% of those with lupus nephritis – had three or more serious infections requiring hospitalization during the relatively short follow-up, Dr. Hiraki and her associates noted.

The overall incidence was 10.4 serious infections per 100 person-years, and it was 17.65 per 100 person-years in the subset of patients who had lupus nephritis. By comparison, this overall rate is nearly four times higher than that reported for children with juvenile idiopathic arthritis, and the incidence among children with concomitant lupus nephritis is more than six times higher.

Infection rates were markedly higher among African American (incidence rate ratio [IRR], 1.83) and Native American (IRR, 1.81) children, compared with white children. They also were higher in early adolescence (ages 9-12 years) than earlier in childhood (ages 5-8 years), the investigators said.

Most of the infections (87%) were bacterial, whereas 11% were viral and 1.3% were fungal. (The remaining amount was unknown in the data because of too few numbers for federal reporting.) The most frequent bacterial infections were pneumonia (438 cases), followed by bacteremia (274 cases) and cellulitis (272 cases). Herpes zoster was the most frequent viral infection, accounting for 81 cases. The investigators noted that the low rate of fungal infections may be an artifact of the study protocol, which excluded, for technical reasons, cases of systemic candidiasis.

Not surprisingly, the rate of serious infection was higher among children with a high comorbidity burden than among healthier children.

Overall, the risk of serious infection was 59% higher for SLE patients who took corticosteroids during the study’s 6-month baseline period, in which 67% of patients took them (minimum of 20 mg/day of prednisone equivalent). However, the risk of serious infection was no different between those who used immunosuppressants (31%) or didn’t use them during that period.

A total of 26 children died within 30 days of hospital admission for a serious infection, for an overall mortality of 4.4% among children who developed serious infections. In comparison, 1.6% in the total cohort of 3,500 died. More than half of the children who died had concomitant lupus nephritis. In addition, 77% of those who died were taking corticosteroids when they developed the infections.

It is difficult to distinguish whether the high infection rate could be attributed to SLE itself or to its treatments. More studies are needed to further investigate this, as well as to address the disproportionate incidence among nonwhite children and any potential benefits from prophylactic use of antibiotics and vaccinations, Dr. Hiraki and her associates said.

The Canadian Institutes of Health Research, the Lupus Foundation of America, the Rheumatology Research Foundation, and the National Institutes of Health supported the study. Dr. Hiraki and her associates reported having no relevant disclosures.

 

 

Progress continues to be made on creating a Zika vaccine, but taking any of the current candidates all the way through clinical trials and into production could take another few years, according to the latest information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

“As we all know, there is no vaccine for Zika, but there are a number of vaccines that have been developed over the last century or so for other flaviviruses, [such as] dengue, yellow fever, Japanese encephalitis, [West Nile], and we know a great deal about flaviviruses in general and the pathology that they have,” explained Gerald R. Kovacs, PhD, of the Biomedical Advanced Research and Development Authority (BARDA). “What we’re doing is using our lessons learned and working with the epidemiologists, with the clinicians, with the nonclinical development people, and using those lessons to develop new vaccines for Zika.”

Aunt_Spray/Thinkstock

Currently, Zika vaccine development is in the first of three “aims,” according to Dr. Kovacs. The first aim, which began last year and is expected to continue into 2018, is to evaluate available vaccine candidates to assess safety, efficacy, and immunogenicity, while also identifying protective immune correlates during the period of most frequent disease incidence.

By next year, the second aim should begin to take shape, which will be the deployment of available vaccines under an appropriate regulatory mechanism to U.S. populations at high risk of exposure.

Finally, by 2020, Dr. Kovacs explained that the government hopes to be partnering with industry to commercialize a Zika vaccine and make it available for broad distribution.

The vaccines being looked at include an inactivated whole-virus vaccine, a live attenuated vaccine that utilizes flavichimeras, a recombinant vaccine, and nucleic acid vaccines, including DNA and mRNA varieties. While each have their pros and cons, only the inactivated whole-virus and live attenuated virus vaccines have licensed human flavivirus vaccines already available for protection against Japanese encephalitis, tick-borne encephalitis, yellow fever, and dengue.

The Zika Purified Inactivated Vaccine (ZPIV) has two candidates in “advanced development,” one by Sanofi Pasteur and the other by Takeda. Currently, the Walter Reed Army Institute of Research and the National Institute of Allergy and Infectious Diseases are conducting phase I clinical trials on both ZPIV candidates to determine their safety and immunogenicity profiles and gathering information on regimen, dosing, and prior flavi immunity. ZPIV has already proven to be fully protective in mice and nonhuman primates. Both the Sanofi and Takeda ZPIVs are expected to enter phase II testing by the middle of next year, and phase III testing at some point in 2019 or 2020.

“Human challenge was discussed at a consultation that the [National Institutes of Health] held a couple of months ago [and] in a nutshell, what the committee found was that there isn’t sufficient information right now on Zika relative to its pathology and how it’s transmitted from humans to humans to support a human clinical study at this time,” said Dr. Kovacs. “But they will, as we accrue more information about this disease, revisit the potential of doing this type of study.”

Dr. Kovacs also highlighted the need for manufacturers to stay in the game as long as possible, urging them not to be discouraged by dwindling interest and funding regarding the Zika vaccine initiative.

“We can develop as many vaccines as possible, but what’s necessary is for these manufacturers to stay in for the long haul,” he explained. “With cuts in funding and less and less enthusiasm for Zika, it becomes challenging for the U.S. government to continue to engage with manufacturers on these types of products [but] we hope that all of our partners will continue on their endeavors with us, but we can’t guarantee that.”

Dr. Kovacs disclosed that he is a consultant for BARDA within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health & Human Services, and that he was speaking at the meeting on behalf of the organization.

dchitnis@frontlinemedcom.com

 

Progress continues to be made on creating a Zika vaccine, but taking any of the current candidates all the way through clinical trials and into production could take another few years, according to the latest information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

“As we all know, there is no vaccine for Zika, but there are a number of vaccines that have been developed over the last century or so for other flaviviruses, [such as] dengue, yellow fever, Japanese encephalitis, [West Nile], and we know a great deal about flaviviruses in general and the pathology that they have,” explained Gerald R. Kovacs, PhD, of the Biomedical Advanced Research and Development Authority (BARDA). “What we’re doing is using our lessons learned and working with the epidemiologists, with the clinicians, with the nonclinical development people, and using those lessons to develop new vaccines for Zika.”

Aunt_Spray/Thinkstock

Currently, Zika vaccine development is in the first of three “aims,” according to Dr. Kovacs. The first aim, which began last year and is expected to continue into 2018, is to evaluate available vaccine candidates to assess safety, efficacy, and immunogenicity, while also identifying protective immune correlates during the period of most frequent disease incidence.

By next year, the second aim should begin to take shape, which will be the deployment of available vaccines under an appropriate regulatory mechanism to U.S. populations at high risk of exposure.

Finally, by 2020, Dr. Kovacs explained that the government hopes to be partnering with industry to commercialize a Zika vaccine and make it available for broad distribution.

The vaccines being looked at include an inactivated whole-virus vaccine, a live attenuated vaccine that utilizes flavichimeras, a recombinant vaccine, and nucleic acid vaccines, including DNA and mRNA varieties. While each have their pros and cons, only the inactivated whole-virus and live attenuated virus vaccines have licensed human flavivirus vaccines already available for protection against Japanese encephalitis, tick-borne encephalitis, yellow fever, and dengue.

The Zika Purified Inactivated Vaccine (ZPIV) has two candidates in “advanced development,” one by Sanofi Pasteur and the other by Takeda. Currently, the Walter Reed Army Institute of Research and the National Institute of Allergy and Infectious Diseases are conducting phase I clinical trials on both ZPIV candidates to determine their safety and immunogenicity profiles and gathering information on regimen, dosing, and prior flavi immunity. ZPIV has already proven to be fully protective in mice and nonhuman primates. Both the Sanofi and Takeda ZPIVs are expected to enter phase II testing by the middle of next year, and phase III testing at some point in 2019 or 2020.

“Human challenge was discussed at a consultation that the [National Institutes of Health] held a couple of months ago [and] in a nutshell, what the committee found was that there isn’t sufficient information right now on Zika relative to its pathology and how it’s transmitted from humans to humans to support a human clinical study at this time,” said Dr. Kovacs. “But they will, as we accrue more information about this disease, revisit the potential of doing this type of study.”

Dr. Kovacs also highlighted the need for manufacturers to stay in the game as long as possible, urging them not to be discouraged by dwindling interest and funding regarding the Zika vaccine initiative.

“We can develop as many vaccines as possible, but what’s necessary is for these manufacturers to stay in for the long haul,” he explained. “With cuts in funding and less and less enthusiasm for Zika, it becomes challenging for the U.S. government to continue to engage with manufacturers on these types of products [but] we hope that all of our partners will continue on their endeavors with us, but we can’t guarantee that.”

Dr. Kovacs disclosed that he is a consultant for BARDA within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health & Human Services, and that he was speaking at the meeting on behalf of the organization.

dchitnis@frontlinemedcom.com

 

Progress continues to be made on creating a Zika vaccine, but taking any of the current candidates all the way through clinical trials and into production could take another few years, according to the latest information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

“As we all know, there is no vaccine for Zika, but there are a number of vaccines that have been developed over the last century or so for other flaviviruses, [such as] dengue, yellow fever, Japanese encephalitis, [West Nile], and we know a great deal about flaviviruses in general and the pathology that they have,” explained Gerald R. Kovacs, PhD, of the Biomedical Advanced Research and Development Authority (BARDA). “What we’re doing is using our lessons learned and working with the epidemiologists, with the clinicians, with the nonclinical development people, and using those lessons to develop new vaccines for Zika.”

Aunt_Spray/Thinkstock

Currently, Zika vaccine development is in the first of three “aims,” according to Dr. Kovacs. The first aim, which began last year and is expected to continue into 2018, is to evaluate available vaccine candidates to assess safety, efficacy, and immunogenicity, while also identifying protective immune correlates during the period of most frequent disease incidence.

By next year, the second aim should begin to take shape, which will be the deployment of available vaccines under an appropriate regulatory mechanism to U.S. populations at high risk of exposure.

Finally, by 2020, Dr. Kovacs explained that the government hopes to be partnering with industry to commercialize a Zika vaccine and make it available for broad distribution.

The vaccines being looked at include an inactivated whole-virus vaccine, a live attenuated vaccine that utilizes flavichimeras, a recombinant vaccine, and nucleic acid vaccines, including DNA and mRNA varieties. While each have their pros and cons, only the inactivated whole-virus and live attenuated virus vaccines have licensed human flavivirus vaccines already available for protection against Japanese encephalitis, tick-borne encephalitis, yellow fever, and dengue.

The Zika Purified Inactivated Vaccine (ZPIV) has two candidates in “advanced development,” one by Sanofi Pasteur and the other by Takeda. Currently, the Walter Reed Army Institute of Research and the National Institute of Allergy and Infectious Diseases are conducting phase I clinical trials on both ZPIV candidates to determine their safety and immunogenicity profiles and gathering information on regimen, dosing, and prior flavi immunity. ZPIV has already proven to be fully protective in mice and nonhuman primates. Both the Sanofi and Takeda ZPIVs are expected to enter phase II testing by the middle of next year, and phase III testing at some point in 2019 or 2020.

“Human challenge was discussed at a consultation that the [National Institutes of Health] held a couple of months ago [and] in a nutshell, what the committee found was that there isn’t sufficient information right now on Zika relative to its pathology and how it’s transmitted from humans to humans to support a human clinical study at this time,” said Dr. Kovacs. “But they will, as we accrue more information about this disease, revisit the potential of doing this type of study.”

Dr. Kovacs also highlighted the need for manufacturers to stay in the game as long as possible, urging them not to be discouraged by dwindling interest and funding regarding the Zika vaccine initiative.

“We can develop as many vaccines as possible, but what’s necessary is for these manufacturers to stay in for the long haul,” he explained. “With cuts in funding and less and less enthusiasm for Zika, it becomes challenging for the U.S. government to continue to engage with manufacturers on these types of products [but] we hope that all of our partners will continue on their endeavors with us, but we can’t guarantee that.”

Dr. Kovacs disclosed that he is a consultant for BARDA within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health & Human Services, and that he was speaking at the meeting on behalf of the organization.

dchitnis@frontlinemedcom.com

 

The prevailing notion that concussions should be managed solely or primarily with prescribed cognitive and physical rest is shifting.

 

Experts in concussion management are increasingly in agreement that concussion is a much more heterogeneous injury than previously believed, and that “active” approaches targeting specific symptoms and impairments can be initiated early and may improve recovery for patients who have concussions from sports as well as from falls, motor vehicle accidents, or other accidents.

Evidence for such active approaches to rehabilitation – including vestibular, vision, and behavioral therapies, and submaximal aerobic training – is deemed “preliminary” by experts and comes from small, mostly single-center studies.

But “the literature is way, way behind what people are understanding clinically,” said Brian Hainline, MD, clinical professor of neurology at New York University, and Indiana University, Indianapolis, and chief medical officer of the National Collegiate Athletic Association, Indianapolis.

“There’s emerging evidence that strict or prolonged rest is not good, and there’s emerging consensus that we need to start looking at concussion subtypes” and then target treatments to those clinical profiles, he said. “We’re at the cusp of dramatic changes [in management].”

An article published recently in Neurosurgery and coauthored by several dozen concussion experts details 16 “statements of agreement” on targeted evaluation and active management. The experts – from neuropsychology, sports medicine, neurology and neurosurgery, athletic training, and other fields – convened in Pittsburgh in late 2015 at the invitation of Michael W. Collins, PhD, and his colleagues at the University of Pittsburgh Medical Center (UPMC), where the Sports Medicine Concussion Program was established in 2000 (Neurosurgery. 2016 Dec;79[6]:912-29).

The NCAA Sport Science Institute also just published a “best practices” document that similarly encourages consideration of active treatment approaches for some patients. And a consensus statement to be published soon from the 5th International Conference on Concussion in Sport, held in October 2016, is expected to more substantively address active management than did the 4th statement issued in 2013.

Thus far, guidelines and statements on concussion in sport have advised a rest-based approach to management that’s dependent on the spontaneous resolution of symptoms. In some documents, rest is recommended until patients are asymptomatic. Other statements mention the possibility of symptom-based approaches after initial rest, but offer little if any guidance.

The theory of prescribed rest has been twofold, driven both by concern about re-injury in sport and by the belief that cognitive and physical activity can exacerbate symptoms and concussion-associated impairments, thus prolonging recovery, the Pittsburgh paper says.

However, “avoiding contact during the vulnerable period after concussion and prescribed rest represent two separate strategies,” the experts wrote. Avoiding contact “is always recommended to avoid further head impacts,” they say, but monitored activity does not appear to worsen injury.

Recent research suggests, moreover, that prolonged physical and cognitive rest – not activity – is associated with increased symptoms and delayed recovery. And strict rest – avoidance of nearly all brain stimulation – is “not empirically supported ... and may have unintended adverse effects,” the experts wrote.

Courtesy Washington University

Mark Halstead, MD, a member of the American Academy of Pediatrics’ Council on Sports Medicine and Fitness, said a revision of the AAP’s 2010 clinical report on sport-related concussion in children and adolescents is expected out later this year and will advocate against “the extremes of rest for kids.”

Physicians and others “have to avoid treating concussion as a punishment,” said Dr. Halstead of St. Louis Children’s Hospital in Chesterfield, Mo., who coauthored a recent editorial entitled “Rethinking Cognitive Rest” (Br J Sports Med. 2017;51:147).

“It’s been taken to the extreme. When we talk about not texting or not going out or not doing anything physically active until you’re without symptoms ... students can develop symptoms of depression and anxiety that then just complicate the injury altogether,” he said.

Physicians also need to dig beneath symptom checklists and perform multidomain assessments to better understand root contributors of symptoms that, without active treatment, can persist for weeks upon weeks in some patients. “There could be neck injuries, sleep issues, vestibular issues, oculomotor issues” and different types of headache, Dr. Halstead said. “If we can identify these things, we can actually be doing rehabilitation to fix these injuries.”

At UPMC’s Sports Medicine Concussion Program, concussions are generally categorized into six clinical profiles – vestibular, ocular-motor, cognitive/fatigue, posttraumatic migraine, cervical, and anxiety/mood. The profiles are not mutually exclusive, but each drives particular rehabilitation recommendations. Clinicians at other concussion programs and centers are similarly attempting to classify concussions.

“We still need to come to agreement as to what exactly the clinical profiles are,” said UPMC’s Dr. Collins, who directs the concussion program and is the lead author of the Neurosurgery paper. “But I think the big concept to come out of our meeting is that we now agree there are different profiles and that we have to match treatment.”

Additional research is needed to determine and validate concussion clinical profiles, to identify biomarkers to assess recovery and determine the effectiveness of treatments, and to determine the best timing of specific active treatments, he and his coauthors said.

Applying individualized and active treatments after concussion is consistent with approaches taken for other injuries and conditions, noted Dr. Hainline, who attended both the UPMC conference and the 5th International Conference on Concussion in Sport.

“It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged,” he said.

“If you keep [concussion] patients with predominantly vestibular symptoms at rest [for example], the vestibular symptoms can become more centralized, and that then becomes the behavior of the nervous system,” he said. “Another example is convergence insufficiencies – if you keep resting [the vision system] and don’t rehabilitate it,” symptoms perpetuate.

Prolonged rest also may lead to deconditioning that lowers tolerance for physical activity. Randomized clinical trials are needed to compare the benefits of physical rest with those of more physically active treatments, but “emerging clinical research” suggests that exposing patients to supervised low-level physical activity (for example, submaximal aerobic training) after an initial period of rest is “not only safe but effective,” the Pittsburgh conference paper says.

Robert L. Wergin, MD, a family physician in Milford, Neb., and former president of the American Academy of Family Physicians, said he has been individualizing his approach in recent years, bringing most adolescents back to school part-time on the third day after injury and monitoring symptoms with help of parents, coaches, and teachers. For younger children, the “return to learn” process may start a bit later, he said.

The Pittsburgh conference paper “rang a bell with me,” Dr. Wergin said. “Rest is still important, but prolonged rest may not be best for all patients, and maybe it’s possible to do some interventions. We need to stay tuned as we get more of an evidence base.”

The conference – coined the TEAM (for targeted evaluation and active management) Approaches to Treating Concussion Meeting – was attended by staff from the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Defense, and the National Football League (NFL) and other sporting organizations, Dr. Collins said. It was sponsored by UPMC and the NFL. Coauthors reported numerous disclosures, including various advising and consulting roles with the NFL.

 

The prevailing notion that concussions should be managed solely or primarily with prescribed cognitive and physical rest is shifting.

 

Experts in concussion management are increasingly in agreement that concussion is a much more heterogeneous injury than previously believed, and that “active” approaches targeting specific symptoms and impairments can be initiated early and may improve recovery for patients who have concussions from sports as well as from falls, motor vehicle accidents, or other accidents.

Evidence for such active approaches to rehabilitation – including vestibular, vision, and behavioral therapies, and submaximal aerobic training – is deemed “preliminary” by experts and comes from small, mostly single-center studies.

But “the literature is way, way behind what people are understanding clinically,” said Brian Hainline, MD, clinical professor of neurology at New York University, and Indiana University, Indianapolis, and chief medical officer of the National Collegiate Athletic Association, Indianapolis.

“There’s emerging evidence that strict or prolonged rest is not good, and there’s emerging consensus that we need to start looking at concussion subtypes” and then target treatments to those clinical profiles, he said. “We’re at the cusp of dramatic changes [in management].”

An article published recently in Neurosurgery and coauthored by several dozen concussion experts details 16 “statements of agreement” on targeted evaluation and active management. The experts – from neuropsychology, sports medicine, neurology and neurosurgery, athletic training, and other fields – convened in Pittsburgh in late 2015 at the invitation of Michael W. Collins, PhD, and his colleagues at the University of Pittsburgh Medical Center (UPMC), where the Sports Medicine Concussion Program was established in 2000 (Neurosurgery. 2016 Dec;79[6]:912-29).

The NCAA Sport Science Institute also just published a “best practices” document that similarly encourages consideration of active treatment approaches for some patients. And a consensus statement to be published soon from the 5th International Conference on Concussion in Sport, held in October 2016, is expected to more substantively address active management than did the 4th statement issued in 2013.

Thus far, guidelines and statements on concussion in sport have advised a rest-based approach to management that’s dependent on the spontaneous resolution of symptoms. In some documents, rest is recommended until patients are asymptomatic. Other statements mention the possibility of symptom-based approaches after initial rest, but offer little if any guidance.

The theory of prescribed rest has been twofold, driven both by concern about re-injury in sport and by the belief that cognitive and physical activity can exacerbate symptoms and concussion-associated impairments, thus prolonging recovery, the Pittsburgh paper says.

However, “avoiding contact during the vulnerable period after concussion and prescribed rest represent two separate strategies,” the experts wrote. Avoiding contact “is always recommended to avoid further head impacts,” they say, but monitored activity does not appear to worsen injury.

Recent research suggests, moreover, that prolonged physical and cognitive rest – not activity – is associated with increased symptoms and delayed recovery. And strict rest – avoidance of nearly all brain stimulation – is “not empirically supported ... and may have unintended adverse effects,” the experts wrote.

Courtesy Washington University

Mark Halstead, MD, a member of the American Academy of Pediatrics’ Council on Sports Medicine and Fitness, said a revision of the AAP’s 2010 clinical report on sport-related concussion in children and adolescents is expected out later this year and will advocate against “the extremes of rest for kids.”

Physicians and others “have to avoid treating concussion as a punishment,” said Dr. Halstead of St. Louis Children’s Hospital in Chesterfield, Mo., who coauthored a recent editorial entitled “Rethinking Cognitive Rest” (Br J Sports Med. 2017;51:147).

“It’s been taken to the extreme. When we talk about not texting or not going out or not doing anything physically active until you’re without symptoms ... students can develop symptoms of depression and anxiety that then just complicate the injury altogether,” he said.

Physicians also need to dig beneath symptom checklists and perform multidomain assessments to better understand root contributors of symptoms that, without active treatment, can persist for weeks upon weeks in some patients. “There could be neck injuries, sleep issues, vestibular issues, oculomotor issues” and different types of headache, Dr. Halstead said. “If we can identify these things, we can actually be doing rehabilitation to fix these injuries.”

At UPMC’s Sports Medicine Concussion Program, concussions are generally categorized into six clinical profiles – vestibular, ocular-motor, cognitive/fatigue, posttraumatic migraine, cervical, and anxiety/mood. The profiles are not mutually exclusive, but each drives particular rehabilitation recommendations. Clinicians at other concussion programs and centers are similarly attempting to classify concussions.

“We still need to come to agreement as to what exactly the clinical profiles are,” said UPMC’s Dr. Collins, who directs the concussion program and is the lead author of the Neurosurgery paper. “But I think the big concept to come out of our meeting is that we now agree there are different profiles and that we have to match treatment.”

Additional research is needed to determine and validate concussion clinical profiles, to identify biomarkers to assess recovery and determine the effectiveness of treatments, and to determine the best timing of specific active treatments, he and his coauthors said.

Applying individualized and active treatments after concussion is consistent with approaches taken for other injuries and conditions, noted Dr. Hainline, who attended both the UPMC conference and the 5th International Conference on Concussion in Sport.

“It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged,” he said.

“If you keep [concussion] patients with predominantly vestibular symptoms at rest [for example], the vestibular symptoms can become more centralized, and that then becomes the behavior of the nervous system,” he said. “Another example is convergence insufficiencies – if you keep resting [the vision system] and don’t rehabilitate it,” symptoms perpetuate.

Prolonged rest also may lead to deconditioning that lowers tolerance for physical activity. Randomized clinical trials are needed to compare the benefits of physical rest with those of more physically active treatments, but “emerging clinical research” suggests that exposing patients to supervised low-level physical activity (for example, submaximal aerobic training) after an initial period of rest is “not only safe but effective,” the Pittsburgh conference paper says.

Robert L. Wergin, MD, a family physician in Milford, Neb., and former president of the American Academy of Family Physicians, said he has been individualizing his approach in recent years, bringing most adolescents back to school part-time on the third day after injury and monitoring symptoms with help of parents, coaches, and teachers. For younger children, the “return to learn” process may start a bit later, he said.

The Pittsburgh conference paper “rang a bell with me,” Dr. Wergin said. “Rest is still important, but prolonged rest may not be best for all patients, and maybe it’s possible to do some interventions. We need to stay tuned as we get more of an evidence base.”

The conference – coined the TEAM (for targeted evaluation and active management) Approaches to Treating Concussion Meeting – was attended by staff from the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Defense, and the National Football League (NFL) and other sporting organizations, Dr. Collins said. It was sponsored by UPMC and the NFL. Coauthors reported numerous disclosures, including various advising and consulting roles with the NFL.

 

The prevailing notion that concussions should be managed solely or primarily with prescribed cognitive and physical rest is shifting.

 

Experts in concussion management are increasingly in agreement that concussion is a much more heterogeneous injury than previously believed, and that “active” approaches targeting specific symptoms and impairments can be initiated early and may improve recovery for patients who have concussions from sports as well as from falls, motor vehicle accidents, or other accidents.

Evidence for such active approaches to rehabilitation – including vestibular, vision, and behavioral therapies, and submaximal aerobic training – is deemed “preliminary” by experts and comes from small, mostly single-center studies.

But “the literature is way, way behind what people are understanding clinically,” said Brian Hainline, MD, clinical professor of neurology at New York University, and Indiana University, Indianapolis, and chief medical officer of the National Collegiate Athletic Association, Indianapolis.

“There’s emerging evidence that strict or prolonged rest is not good, and there’s emerging consensus that we need to start looking at concussion subtypes” and then target treatments to those clinical profiles, he said. “We’re at the cusp of dramatic changes [in management].”

An article published recently in Neurosurgery and coauthored by several dozen concussion experts details 16 “statements of agreement” on targeted evaluation and active management. The experts – from neuropsychology, sports medicine, neurology and neurosurgery, athletic training, and other fields – convened in Pittsburgh in late 2015 at the invitation of Michael W. Collins, PhD, and his colleagues at the University of Pittsburgh Medical Center (UPMC), where the Sports Medicine Concussion Program was established in 2000 (Neurosurgery. 2016 Dec;79[6]:912-29).

The NCAA Sport Science Institute also just published a “best practices” document that similarly encourages consideration of active treatment approaches for some patients. And a consensus statement to be published soon from the 5th International Conference on Concussion in Sport, held in October 2016, is expected to more substantively address active management than did the 4th statement issued in 2013.

Thus far, guidelines and statements on concussion in sport have advised a rest-based approach to management that’s dependent on the spontaneous resolution of symptoms. In some documents, rest is recommended until patients are asymptomatic. Other statements mention the possibility of symptom-based approaches after initial rest, but offer little if any guidance.

The theory of prescribed rest has been twofold, driven both by concern about re-injury in sport and by the belief that cognitive and physical activity can exacerbate symptoms and concussion-associated impairments, thus prolonging recovery, the Pittsburgh paper says.

However, “avoiding contact during the vulnerable period after concussion and prescribed rest represent two separate strategies,” the experts wrote. Avoiding contact “is always recommended to avoid further head impacts,” they say, but monitored activity does not appear to worsen injury.

Recent research suggests, moreover, that prolonged physical and cognitive rest – not activity – is associated with increased symptoms and delayed recovery. And strict rest – avoidance of nearly all brain stimulation – is “not empirically supported ... and may have unintended adverse effects,” the experts wrote.

Courtesy Washington University

Mark Halstead, MD, a member of the American Academy of Pediatrics’ Council on Sports Medicine and Fitness, said a revision of the AAP’s 2010 clinical report on sport-related concussion in children and adolescents is expected out later this year and will advocate against “the extremes of rest for kids.”

Physicians and others “have to avoid treating concussion as a punishment,” said Dr. Halstead of St. Louis Children’s Hospital in Chesterfield, Mo., who coauthored a recent editorial entitled “Rethinking Cognitive Rest” (Br J Sports Med. 2017;51:147).

“It’s been taken to the extreme. When we talk about not texting or not going out or not doing anything physically active until you’re without symptoms ... students can develop symptoms of depression and anxiety that then just complicate the injury altogether,” he said.

Physicians also need to dig beneath symptom checklists and perform multidomain assessments to better understand root contributors of symptoms that, without active treatment, can persist for weeks upon weeks in some patients. “There could be neck injuries, sleep issues, vestibular issues, oculomotor issues” and different types of headache, Dr. Halstead said. “If we can identify these things, we can actually be doing rehabilitation to fix these injuries.”

At UPMC’s Sports Medicine Concussion Program, concussions are generally categorized into six clinical profiles – vestibular, ocular-motor, cognitive/fatigue, posttraumatic migraine, cervical, and anxiety/mood. The profiles are not mutually exclusive, but each drives particular rehabilitation recommendations. Clinicians at other concussion programs and centers are similarly attempting to classify concussions.

“We still need to come to agreement as to what exactly the clinical profiles are,” said UPMC’s Dr. Collins, who directs the concussion program and is the lead author of the Neurosurgery paper. “But I think the big concept to come out of our meeting is that we now agree there are different profiles and that we have to match treatment.”

Additional research is needed to determine and validate concussion clinical profiles, to identify biomarkers to assess recovery and determine the effectiveness of treatments, and to determine the best timing of specific active treatments, he and his coauthors said.

Applying individualized and active treatments after concussion is consistent with approaches taken for other injuries and conditions, noted Dr. Hainline, who attended both the UPMC conference and the 5th International Conference on Concussion in Sport.

“It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged,” he said.

“If you keep [concussion] patients with predominantly vestibular symptoms at rest [for example], the vestibular symptoms can become more centralized, and that then becomes the behavior of the nervous system,” he said. “Another example is convergence insufficiencies – if you keep resting [the vision system] and don’t rehabilitate it,” symptoms perpetuate.

Prolonged rest also may lead to deconditioning that lowers tolerance for physical activity. Randomized clinical trials are needed to compare the benefits of physical rest with those of more physically active treatments, but “emerging clinical research” suggests that exposing patients to supervised low-level physical activity (for example, submaximal aerobic training) after an initial period of rest is “not only safe but effective,” the Pittsburgh conference paper says.

Robert L. Wergin, MD, a family physician in Milford, Neb., and former president of the American Academy of Family Physicians, said he has been individualizing his approach in recent years, bringing most adolescents back to school part-time on the third day after injury and monitoring symptoms with help of parents, coaches, and teachers. For younger children, the “return to learn” process may start a bit later, he said.

The Pittsburgh conference paper “rang a bell with me,” Dr. Wergin said. “Rest is still important, but prolonged rest may not be best for all patients, and maybe it’s possible to do some interventions. We need to stay tuned as we get more of an evidence base.”

The conference – coined the TEAM (for targeted evaluation and active management) Approaches to Treating Concussion Meeting – was attended by staff from the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Defense, and the National Football League (NFL) and other sporting organizations, Dr. Collins said. It was sponsored by UPMC and the NFL. Coauthors reported numerous disclosures, including various advising and consulting roles with the NFL.

 

A single dose of an inactivated hepatitis A virus (HAV) vaccine resulted in high seropositive rates and antibody concentrations, persisting for at least 5 years in children, a study has shown.

In October 2008, a team of investigators in China led by Zhilun Zhang of the Tianjin Center for Disease Control and Prevention, randomly assigned 332 children aged 18-60 months with prevaccination anti-HAV antibody titers of less than 20 mIU/mL to receive either one dose of inactivated hepatitis A vaccine or one dose of live, attenuated hepatitis A vaccine. Both groups were followed through December 2013, with assessments of anti-HAV antibody concentrations at years 1, 2, and 5 post vaccination. In all, 182 successfully completed the study, meeting all requirements, including providing serum samples at each time point.

©Choreograph/Thinkstock

At year 1, the rate was 95.3% in the group receiving the inactivated hepatitis A vaccine and 91.8% in the other group (P greater than .05). At year 2, the seropositive rate of the group receiving the inactivated vaccines was 90.6% and the rate for the group receiving the live, attenuated vaccine (P greater than .05) was 90.7%. At year 5, the seropositive rate was 85.9% for the group receiving the inactivated vaccine and 90.7% for the group receiving the live attenuated vaccine (P greater than .05).

Titer levels were 76.3% mIU/mL and 66.8mIU/mL for the inactivated and live vaccines at 5 years, respectively. No clinical hepatitis A case was reported.

The study appears online in Human Vaccines & Immunotherapeutics (doi: 10.1080/21645515.2016.1278329).
 

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

 

A single dose of an inactivated hepatitis A virus (HAV) vaccine resulted in high seropositive rates and antibody concentrations, persisting for at least 5 years in children, a study has shown.

In October 2008, a team of investigators in China led by Zhilun Zhang of the Tianjin Center for Disease Control and Prevention, randomly assigned 332 children aged 18-60 months with prevaccination anti-HAV antibody titers of less than 20 mIU/mL to receive either one dose of inactivated hepatitis A vaccine or one dose of live, attenuated hepatitis A vaccine. Both groups were followed through December 2013, with assessments of anti-HAV antibody concentrations at years 1, 2, and 5 post vaccination. In all, 182 successfully completed the study, meeting all requirements, including providing serum samples at each time point.

©Choreograph/Thinkstock

At year 1, the rate was 95.3% in the group receiving the inactivated hepatitis A vaccine and 91.8% in the other group (P greater than .05). At year 2, the seropositive rate of the group receiving the inactivated vaccines was 90.6% and the rate for the group receiving the live, attenuated vaccine (P greater than .05) was 90.7%. At year 5, the seropositive rate was 85.9% for the group receiving the inactivated vaccine and 90.7% for the group receiving the live attenuated vaccine (P greater than .05).

Titer levels were 76.3% mIU/mL and 66.8mIU/mL for the inactivated and live vaccines at 5 years, respectively. No clinical hepatitis A case was reported.

The study appears online in Human Vaccines & Immunotherapeutics (doi: 10.1080/21645515.2016.1278329).
 

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

 

A single dose of an inactivated hepatitis A virus (HAV) vaccine resulted in high seropositive rates and antibody concentrations, persisting for at least 5 years in children, a study has shown.

In October 2008, a team of investigators in China led by Zhilun Zhang of the Tianjin Center for Disease Control and Prevention, randomly assigned 332 children aged 18-60 months with prevaccination anti-HAV antibody titers of less than 20 mIU/mL to receive either one dose of inactivated hepatitis A vaccine or one dose of live, attenuated hepatitis A vaccine. Both groups were followed through December 2013, with assessments of anti-HAV antibody concentrations at years 1, 2, and 5 post vaccination. In all, 182 successfully completed the study, meeting all requirements, including providing serum samples at each time point.

©Choreograph/Thinkstock

At year 1, the rate was 95.3% in the group receiving the inactivated hepatitis A vaccine and 91.8% in the other group (P greater than .05). At year 2, the seropositive rate of the group receiving the inactivated vaccines was 90.6% and the rate for the group receiving the live, attenuated vaccine (P greater than .05) was 90.7%. At year 5, the seropositive rate was 85.9% for the group receiving the inactivated vaccine and 90.7% for the group receiving the live attenuated vaccine (P greater than .05).

Titer levels were 76.3% mIU/mL and 66.8mIU/mL for the inactivated and live vaccines at 5 years, respectively. No clinical hepatitis A case was reported.

The study appears online in Human Vaccines & Immunotherapeutics (doi: 10.1080/21645515.2016.1278329).
 

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

 

Approval to changes of current recommendations for hepatitis B vaccinations for children were voted on by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The 14-member panel voted to approve changes to existing language, which states that infants who are HBsAg negative with anti-HBs levels of less than 10 mIU/mL should be revaccinated with a second three-dose series and retested within 2 months of the series’ final dose. The approved proposal will change that language to state that these infants should receive only one dose, not the entire series of three. However, if anti-HBs levels remain lower than 10 mIU/mL after the one dose, the remaining two vaccinations should be administered, along with testing within 2 months of the final dose.

CDC/Dr. Erskine Palmer

“Available data do not suggest a benefit from administering additional HepB vaccine doses to infants who have not attained anti-HBs [of at least] 10 [mIU/mL] following receipt of two complete [three-dose] HepB vaccine series,” explained Noele P. Nelson, MD, of Georgetown University in Washington and the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.

The other change, a relatively minor one, affects the wording of the recommendations regarding the Vaccines for Children program. In addition to incorporating a language change similar to the aforementioned one – the only difference being that now, the recommendations will explicitly mention postvaccination serologic testing within 2 months of series completion – under the minimum dosing intervals for interrupted vaccination schedules, the second bullet has been modified to say “final dose” instead of “third dose,” as it currently does.

“[This is] to address potential confusion related to different schedules when single-antigen or combination vaccines are used,” explained Jeanne Santoli, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, adding that “the eligible groups are unchanged, schedule and intervals are unchanged, [so] the purpose is to clarify related to dosing intervals and revaccination.”

Both votes were approved of nearly unanimously, with 13 committee members voting to approve while 1 – José R. Romero, MD, who holds the Horace C. Cabe Endowed Chair in Pediatric Infectious Diseases at the University of Arkansas in Little Rock – abstained because of potential conflicts of interest.

Approval by ACIP does not automatically mean that these changes will go into effect; they must first be approved by CDC director Tom Frieden, MD. However, the CDC generally follows ACIP guidance.
 

dchitnis@frontlinemedcom.com

 

Approval to changes of current recommendations for hepatitis B vaccinations for children were voted on by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The 14-member panel voted to approve changes to existing language, which states that infants who are HBsAg negative with anti-HBs levels of less than 10 mIU/mL should be revaccinated with a second three-dose series and retested within 2 months of the series’ final dose. The approved proposal will change that language to state that these infants should receive only one dose, not the entire series of three. However, if anti-HBs levels remain lower than 10 mIU/mL after the one dose, the remaining two vaccinations should be administered, along with testing within 2 months of the final dose.

CDC/Dr. Erskine Palmer

“Available data do not suggest a benefit from administering additional HepB vaccine doses to infants who have not attained anti-HBs [of at least] 10 [mIU/mL] following receipt of two complete [three-dose] HepB vaccine series,” explained Noele P. Nelson, MD, of Georgetown University in Washington and the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.

The other change, a relatively minor one, affects the wording of the recommendations regarding the Vaccines for Children program. In addition to incorporating a language change similar to the aforementioned one – the only difference being that now, the recommendations will explicitly mention postvaccination serologic testing within 2 months of series completion – under the minimum dosing intervals for interrupted vaccination schedules, the second bullet has been modified to say “final dose” instead of “third dose,” as it currently does.

“[This is] to address potential confusion related to different schedules when single-antigen or combination vaccines are used,” explained Jeanne Santoli, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, adding that “the eligible groups are unchanged, schedule and intervals are unchanged, [so] the purpose is to clarify related to dosing intervals and revaccination.”

Both votes were approved of nearly unanimously, with 13 committee members voting to approve while 1 – José R. Romero, MD, who holds the Horace C. Cabe Endowed Chair in Pediatric Infectious Diseases at the University of Arkansas in Little Rock – abstained because of potential conflicts of interest.

Approval by ACIP does not automatically mean that these changes will go into effect; they must first be approved by CDC director Tom Frieden, MD. However, the CDC generally follows ACIP guidance.
 

dchitnis@frontlinemedcom.com

 

Approval to changes of current recommendations for hepatitis B vaccinations for children were voted on by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The 14-member panel voted to approve changes to existing language, which states that infants who are HBsAg negative with anti-HBs levels of less than 10 mIU/mL should be revaccinated with a second three-dose series and retested within 2 months of the series’ final dose. The approved proposal will change that language to state that these infants should receive only one dose, not the entire series of three. However, if anti-HBs levels remain lower than 10 mIU/mL after the one dose, the remaining two vaccinations should be administered, along with testing within 2 months of the final dose.

CDC/Dr. Erskine Palmer

“Available data do not suggest a benefit from administering additional HepB vaccine doses to infants who have not attained anti-HBs [of at least] 10 [mIU/mL] following receipt of two complete [three-dose] HepB vaccine series,” explained Noele P. Nelson, MD, of Georgetown University in Washington and the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.

The other change, a relatively minor one, affects the wording of the recommendations regarding the Vaccines for Children program. In addition to incorporating a language change similar to the aforementioned one – the only difference being that now, the recommendations will explicitly mention postvaccination serologic testing within 2 months of series completion – under the minimum dosing intervals for interrupted vaccination schedules, the second bullet has been modified to say “final dose” instead of “third dose,” as it currently does.

“[This is] to address potential confusion related to different schedules when single-antigen or combination vaccines are used,” explained Jeanne Santoli, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, adding that “the eligible groups are unchanged, schedule and intervals are unchanged, [so] the purpose is to clarify related to dosing intervals and revaccination.”

Both votes were approved of nearly unanimously, with 13 committee members voting to approve while 1 – José R. Romero, MD, who holds the Horace C. Cabe Endowed Chair in Pediatric Infectious Diseases at the University of Arkansas in Little Rock – abstained because of potential conflicts of interest.

Approval by ACIP does not automatically mean that these changes will go into effect; they must first be approved by CDC director Tom Frieden, MD. However, the CDC generally follows ACIP guidance.
 

dchitnis@frontlinemedcom.com

 

The identification of risk factors associated with recurrent Clostridium difficile infection (rCDI) might allow early recognition of those children at highest risk, said Dr. Maribeth Nicholson of Vanderbilt University, Nashville, Tenn., and her associates.

In a small study, results showed that fecal lactoferrin, calprotectin, and interleukin-8 (IL-8) should be further studied to determine their value in predicting the risk of rCDI in children.

CDC/Jennifer Hulsey

From May 2013 through May 2014, pediatric patients with C. difficile infection (CDI) were identified through clinical laboratory records at two tertiary care children’s hospitals and those aged 12 months to 18 years were eligible for enrollment. Blood samples were collected at baseline and 30 days later. Stool was collected at enrollment and at the time of a subsequent episode of CDI (Pediatr Infect Dis J. 2016. doi: 10.1097/INF.0000000000001450).

Of the 28 pediatric patients enrolled, 27 completed follow-up and 8 (30%) experienced rCDI. There were higher initial median fecal lactoferrin, calprotectin, and IL-8 values in those with recurrent disease, although there was a notably wide range of results in these patients. These values were lower in children with malignancy, the investigators said.

This study was partially supported by the Thrasher Early Career Award and two National Institutes of Health grants. The investigators had no relevant financial disclosures.

acruz@frontlinemedcom.com

 

The identification of risk factors associated with recurrent Clostridium difficile infection (rCDI) might allow early recognition of those children at highest risk, said Dr. Maribeth Nicholson of Vanderbilt University, Nashville, Tenn., and her associates.

In a small study, results showed that fecal lactoferrin, calprotectin, and interleukin-8 (IL-8) should be further studied to determine their value in predicting the risk of rCDI in children.

CDC/Jennifer Hulsey

From May 2013 through May 2014, pediatric patients with C. difficile infection (CDI) were identified through clinical laboratory records at two tertiary care children’s hospitals and those aged 12 months to 18 years were eligible for enrollment. Blood samples were collected at baseline and 30 days later. Stool was collected at enrollment and at the time of a subsequent episode of CDI (Pediatr Infect Dis J. 2016. doi: 10.1097/INF.0000000000001450).

Of the 28 pediatric patients enrolled, 27 completed follow-up and 8 (30%) experienced rCDI. There were higher initial median fecal lactoferrin, calprotectin, and IL-8 values in those with recurrent disease, although there was a notably wide range of results in these patients. These values were lower in children with malignancy, the investigators said.

This study was partially supported by the Thrasher Early Career Award and two National Institutes of Health grants. The investigators had no relevant financial disclosures.

acruz@frontlinemedcom.com

 

The identification of risk factors associated with recurrent Clostridium difficile infection (rCDI) might allow early recognition of those children at highest risk, said Dr. Maribeth Nicholson of Vanderbilt University, Nashville, Tenn., and her associates.

In a small study, results showed that fecal lactoferrin, calprotectin, and interleukin-8 (IL-8) should be further studied to determine their value in predicting the risk of rCDI in children.

CDC/Jennifer Hulsey

From May 2013 through May 2014, pediatric patients with C. difficile infection (CDI) were identified through clinical laboratory records at two tertiary care children’s hospitals and those aged 12 months to 18 years were eligible for enrollment. Blood samples were collected at baseline and 30 days later. Stool was collected at enrollment and at the time of a subsequent episode of CDI (Pediatr Infect Dis J. 2016. doi: 10.1097/INF.0000000000001450).

Of the 28 pediatric patients enrolled, 27 completed follow-up and 8 (30%) experienced rCDI. There were higher initial median fecal lactoferrin, calprotectin, and IL-8 values in those with recurrent disease, although there was a notably wide range of results in these patients. These values were lower in children with malignancy, the investigators said.

This study was partially supported by the Thrasher Early Career Award and two National Institutes of Health grants. The investigators had no relevant financial disclosures.

acruz@frontlinemedcom.com