Immunology

WOODINVILLE, WASH. – Identifying the culprit in allergic contact dermatitis often requires careful sleuthing and tailored patch testing, according to Dr. James G. Marks Jr.

Dr. Marks reviewed the current options for patch testing trays, described several cases of allergic contact dermatitis, and shared pointers for diagnosis and management at the annual Coastal Dermatology Symposium.

Allergen-screening series

Dermatologists can now choose from a variety of standard screening trays for patch testing, said Dr. Marks, professor and chair of the department of dermatology, Pennsylvania State University, Hershey. The TRUE test (the only one approved by the Food and Drug Administration) contains 35 antigens.

However, dermatologists can supplement and customize these screening trays to create a system specific to their practice and geographic area. Dr. Marks said he uses a customized tray with 100 antigens.

"The important point is there is no universal standard screening tray, so pick what works for you," he said.

"Those of you who use the TRUE test, great; as you know in the last year you have had another panel [added], so you get more screening antigens," he said. "It makes sense intuitively, and it’s proven by publications of the North American [Contact Dermatitis] Group and others that the more antigens you test with, the more positives you get and the more relevant reactions you can get," he explained.

"Then create your own," Dr. Marks advised. "So if you use the TRUE test, maybe supplement ... with a few more allergens."

Alpha-methylene-gamma-butyrolactone

Florists may come in contact with alpha-methylene-gamma-butyrolactone through handling Alstroemeria (also known as Peruvian lily), a flower popular because of its long-lasting blooms.

The compound is found in the sap that leaks out from cut stems; thus, the presentation is typically finger dermatitis, Dr. Marks said at the meeting, which was presented by the Caribbean Dermatology Symposium.

"It is the most common cause of allergic contact dermatitis in florists. So if you see florists, this is the allergen until proven otherwise," he said.

The compound is also found in the white epidermis of tulips, in which case it is known as tuliposide A. About half of tulip bulb sorters are allergic to it.

"You either patch test with parts of the Alstroemeria plant or get the allergen alpha-methylene-gamma-butyrolactone" commercially, Dr. Marks said. "I test everyone to alpha-methylene-gamma-butyrolactone, even though it’s a small subset. That’s one of my 100 [antigens]."

Methylisothiazolinone

"Methylisothiazolinone has become a very important and hot allergen," Dr. Marks commented. This allergen is increasingly used in personal care products and requires a special approach to patch testing. It is found in many wet wipes, use of which can produce, for example, perioral dermatitis.

The standard combination test antigen, applied at 100 parts per million, contains 3 parts methylchloroisothiazolinone (MCI) and 1 part methylisothiazolinone (MI), he noted. Thus, "you are really only patch testing to 25 parts per million of MI."

"The recommended concentration of patch test to MI is a bit in flux," said Dr. Marks; the North American group currently uses 2,000 parts per million but is considering halving that number, he noted.

"You can see how you can miss patients who are allergic to MI if you only patch test to MCI/MI," he commented. "So those of you who are using the TRUE test, you are going to miss patients who are allergic to MI."

"The important point is you’ve got to test both – MCI/MI and MI alone. ... You should supplement what you are patch testing with MI, certainly at least at 1,000 parts per million, if not at 2,000," Dr. Marks advised.

"The Cosmetic Ingredient Review, which sets limits for [MI] in the U.S., is going to be reevaluating, and I’m sure will be having lower limits in leave-on and rinse-off products," he noted.

Rubber accelerators

Surgeons may develop particularly problematic allergic contact dermatitis as a reaction to the rubber accelerators used in the manufacturing of many surgical gloves, Dr. Marks noted.

He described the case of a surgeon who developed severe hand dermatitis and eventually a generalized dermatitis. "In this case, if you used the TRUE test, you would make the diagnosis; he was positive to thiuram and carba mix."

Allergen avoidance entailed finding an alternative, rubber-free surgical glove, the Derma Prene Ultra glove (manufactured by Ansell), which is made of neoprene. Also, the surgeon switched to vinyl exam gloves for outpatient care.

"There may be other surgical gloves ...," Dr. Marks acknowledged. "But be sure and keep this some place because some time in the future when you have your surgeon friend with hand dermatitis, you can recommend that glove after you patch test them and prove that they are rubber-accelerator positive."

Cocamidopropyl betaine contaminants

Patients may develop allergic contact dermatitis after using shampoos and bath gels containing cocamidopropyl betaine, a surfactant.

In fact, they are actually reacting to a contaminant or impurity generated in the manufacturing process, either 3-dimethylaminopropylamine or amidoamine, according to Dr. Marks.

"So if you have pure cocamidopropyl betaine, there will be no allergy," he noted. But if you test for "cocamidopropyl betaine, and what you are patch testing with is from, say, Chemotechnique or Allergeaze, it’s going to have presumably the contaminants or the impurities in it, 3-dimethylaminopropylamine and amidoamine."

Treatment entails careful reading of labels on personal care products and avoidance of those containing cocamidopropyl betaine.

Acrylates

Don’t rule out acrylates – either acrylic or methacrylic acid – monomers that are polymerized with heat or light to form solid plastics that can cause reactions.

"The monomers are both irritants and allergens, so you need the right concentration to patch test to," Dr. Marks noted. "They are found in all sorts of things – adhesives, inks, artificial nails, dental resins, bone cement, and plastics."

Presentations may vary widely, including, for example, finger dermatitis in patients who have sculptured nails, and gum stomatitis in patients who have undergone procedures involving dental resin, said Dr. Marks.

"If you have workers or patients who have exposure to acrylates, you need more extensive screening," Dr. Marks advised, noting that his acrylate patch test series contains six compounds.

"No one is a screen for all of them," he commented. "Some [experts] feel that ethyl acrylate is the best screen; certainly, for sculptured nails it’s good." Others in his series include methyl methacrylate (found in bone cement) and ethyl cyanoacrylate (found in Super Glue adhesive).

Glyceryl thioglycolate

Allergy to glyceryl thioglycolate, found in acid permanent waves, can manifest as hand dermatitis in hairdressers and as dermatitis of the face, neck, and ears in their clients.

"If you see hairdressers [in your practice], you should consider strongly having this antigen as part of your [patch test] armamentarium," Dr. Marks recommended.

Alkaline perms, by contrast, do not contain glyceryl thioglycolate and thus provide a simple solution. "You can cure that hairdresser, and she or he can continue to do perms just by switching from an acid to an alkaline perm," he explained.

Dr. Marks said he had no relevant financial disclosures.

sknews@frontlinemedcom.com

WOODINVILLE, WASH. – Identifying the culprit in allergic contact dermatitis often requires careful sleuthing and tailored patch testing, according to Dr. James G. Marks Jr.

Dr. Marks reviewed the current options for patch testing trays, described several cases of allergic contact dermatitis, and shared pointers for diagnosis and management at the annual Coastal Dermatology Symposium.

Allergen-screening series

Dermatologists can now choose from a variety of standard screening trays for patch testing, said Dr. Marks, professor and chair of the department of dermatology, Pennsylvania State University, Hershey. The TRUE test (the only one approved by the Food and Drug Administration) contains 35 antigens.

However, dermatologists can supplement and customize these screening trays to create a system specific to their practice and geographic area. Dr. Marks said he uses a customized tray with 100 antigens.

"The important point is there is no universal standard screening tray, so pick what works for you," he said.

"Those of you who use the TRUE test, great; as you know in the last year you have had another panel [added], so you get more screening antigens," he said. "It makes sense intuitively, and it’s proven by publications of the North American [Contact Dermatitis] Group and others that the more antigens you test with, the more positives you get and the more relevant reactions you can get," he explained.

"Then create your own," Dr. Marks advised. "So if you use the TRUE test, maybe supplement ... with a few more allergens."

Alpha-methylene-gamma-butyrolactone

Florists may come in contact with alpha-methylene-gamma-butyrolactone through handling Alstroemeria (also known as Peruvian lily), a flower popular because of its long-lasting blooms.

The compound is found in the sap that leaks out from cut stems; thus, the presentation is typically finger dermatitis, Dr. Marks said at the meeting, which was presented by the Caribbean Dermatology Symposium.

"It is the most common cause of allergic contact dermatitis in florists. So if you see florists, this is the allergen until proven otherwise," he said.

The compound is also found in the white epidermis of tulips, in which case it is known as tuliposide A. About half of tulip bulb sorters are allergic to it.

"You either patch test with parts of the Alstroemeria plant or get the allergen alpha-methylene-gamma-butyrolactone" commercially, Dr. Marks said. "I test everyone to alpha-methylene-gamma-butyrolactone, even though it’s a small subset. That’s one of my 100 [antigens]."

Methylisothiazolinone

"Methylisothiazolinone has become a very important and hot allergen," Dr. Marks commented. This allergen is increasingly used in personal care products and requires a special approach to patch testing. It is found in many wet wipes, use of which can produce, for example, perioral dermatitis.

The standard combination test antigen, applied at 100 parts per million, contains 3 parts methylchloroisothiazolinone (MCI) and 1 part methylisothiazolinone (MI), he noted. Thus, "you are really only patch testing to 25 parts per million of MI."

"The recommended concentration of patch test to MI is a bit in flux," said Dr. Marks; the North American group currently uses 2,000 parts per million but is considering halving that number, he noted.

"You can see how you can miss patients who are allergic to MI if you only patch test to MCI/MI," he commented. "So those of you who are using the TRUE test, you are going to miss patients who are allergic to MI."

"The important point is you’ve got to test both – MCI/MI and MI alone. ... You should supplement what you are patch testing with MI, certainly at least at 1,000 parts per million, if not at 2,000," Dr. Marks advised.

"The Cosmetic Ingredient Review, which sets limits for [MI] in the U.S., is going to be reevaluating, and I’m sure will be having lower limits in leave-on and rinse-off products," he noted.

Rubber accelerators

Surgeons may develop particularly problematic allergic contact dermatitis as a reaction to the rubber accelerators used in the manufacturing of many surgical gloves, Dr. Marks noted.

He described the case of a surgeon who developed severe hand dermatitis and eventually a generalized dermatitis. "In this case, if you used the TRUE test, you would make the diagnosis; he was positive to thiuram and carba mix."

Allergen avoidance entailed finding an alternative, rubber-free surgical glove, the Derma Prene Ultra glove (manufactured by Ansell), which is made of neoprene. Also, the surgeon switched to vinyl exam gloves for outpatient care.

"There may be other surgical gloves ...," Dr. Marks acknowledged. "But be sure and keep this some place because some time in the future when you have your surgeon friend with hand dermatitis, you can recommend that glove after you patch test them and prove that they are rubber-accelerator positive."

Cocamidopropyl betaine contaminants

Patients may develop allergic contact dermatitis after using shampoos and bath gels containing cocamidopropyl betaine, a surfactant.

In fact, they are actually reacting to a contaminant or impurity generated in the manufacturing process, either 3-dimethylaminopropylamine or amidoamine, according to Dr. Marks.

"So if you have pure cocamidopropyl betaine, there will be no allergy," he noted. But if you test for "cocamidopropyl betaine, and what you are patch testing with is from, say, Chemotechnique or Allergeaze, it’s going to have presumably the contaminants or the impurities in it, 3-dimethylaminopropylamine and amidoamine."

Treatment entails careful reading of labels on personal care products and avoidance of those containing cocamidopropyl betaine.

Acrylates

Don’t rule out acrylates – either acrylic or methacrylic acid – monomers that are polymerized with heat or light to form solid plastics that can cause reactions.

"The monomers are both irritants and allergens, so you need the right concentration to patch test to," Dr. Marks noted. "They are found in all sorts of things – adhesives, inks, artificial nails, dental resins, bone cement, and plastics."

Presentations may vary widely, including, for example, finger dermatitis in patients who have sculptured nails, and gum stomatitis in patients who have undergone procedures involving dental resin, said Dr. Marks.

"If you have workers or patients who have exposure to acrylates, you need more extensive screening," Dr. Marks advised, noting that his acrylate patch test series contains six compounds.

"No one is a screen for all of them," he commented. "Some [experts] feel that ethyl acrylate is the best screen; certainly, for sculptured nails it’s good." Others in his series include methyl methacrylate (found in bone cement) and ethyl cyanoacrylate (found in Super Glue adhesive).

Glyceryl thioglycolate

Allergy to glyceryl thioglycolate, found in acid permanent waves, can manifest as hand dermatitis in hairdressers and as dermatitis of the face, neck, and ears in their clients.

"If you see hairdressers [in your practice], you should consider strongly having this antigen as part of your [patch test] armamentarium," Dr. Marks recommended.

Alkaline perms, by contrast, do not contain glyceryl thioglycolate and thus provide a simple solution. "You can cure that hairdresser, and she or he can continue to do perms just by switching from an acid to an alkaline perm," he explained.

Dr. Marks said he had no relevant financial disclosures.

sknews@frontlinemedcom.com

WOODINVILLE, WASH. – Identifying the culprit in allergic contact dermatitis often requires careful sleuthing and tailored patch testing, according to Dr. James G. Marks Jr.

Dr. Marks reviewed the current options for patch testing trays, described several cases of allergic contact dermatitis, and shared pointers for diagnosis and management at the annual Coastal Dermatology Symposium.

Allergen-screening series

Dermatologists can now choose from a variety of standard screening trays for patch testing, said Dr. Marks, professor and chair of the department of dermatology, Pennsylvania State University, Hershey. The TRUE test (the only one approved by the Food and Drug Administration) contains 35 antigens.

However, dermatologists can supplement and customize these screening trays to create a system specific to their practice and geographic area. Dr. Marks said he uses a customized tray with 100 antigens.

"The important point is there is no universal standard screening tray, so pick what works for you," he said.

"Those of you who use the TRUE test, great; as you know in the last year you have had another panel [added], so you get more screening antigens," he said. "It makes sense intuitively, and it’s proven by publications of the North American [Contact Dermatitis] Group and others that the more antigens you test with, the more positives you get and the more relevant reactions you can get," he explained.

"Then create your own," Dr. Marks advised. "So if you use the TRUE test, maybe supplement ... with a few more allergens."

Alpha-methylene-gamma-butyrolactone

Florists may come in contact with alpha-methylene-gamma-butyrolactone through handling Alstroemeria (also known as Peruvian lily), a flower popular because of its long-lasting blooms.

The compound is found in the sap that leaks out from cut stems; thus, the presentation is typically finger dermatitis, Dr. Marks said at the meeting, which was presented by the Caribbean Dermatology Symposium.

"It is the most common cause of allergic contact dermatitis in florists. So if you see florists, this is the allergen until proven otherwise," he said.

The compound is also found in the white epidermis of tulips, in which case it is known as tuliposide A. About half of tulip bulb sorters are allergic to it.

"You either patch test with parts of the Alstroemeria plant or get the allergen alpha-methylene-gamma-butyrolactone" commercially, Dr. Marks said. "I test everyone to alpha-methylene-gamma-butyrolactone, even though it’s a small subset. That’s one of my 100 [antigens]."

Methylisothiazolinone

"Methylisothiazolinone has become a very important and hot allergen," Dr. Marks commented. This allergen is increasingly used in personal care products and requires a special approach to patch testing. It is found in many wet wipes, use of which can produce, for example, perioral dermatitis.

The standard combination test antigen, applied at 100 parts per million, contains 3 parts methylchloroisothiazolinone (MCI) and 1 part methylisothiazolinone (MI), he noted. Thus, "you are really only patch testing to 25 parts per million of MI."

"The recommended concentration of patch test to MI is a bit in flux," said Dr. Marks; the North American group currently uses 2,000 parts per million but is considering halving that number, he noted.

"You can see how you can miss patients who are allergic to MI if you only patch test to MCI/MI," he commented. "So those of you who are using the TRUE test, you are going to miss patients who are allergic to MI."

"The important point is you’ve got to test both – MCI/MI and MI alone. ... You should supplement what you are patch testing with MI, certainly at least at 1,000 parts per million, if not at 2,000," Dr. Marks advised.

"The Cosmetic Ingredient Review, which sets limits for [MI] in the U.S., is going to be reevaluating, and I’m sure will be having lower limits in leave-on and rinse-off products," he noted.

Rubber accelerators

Surgeons may develop particularly problematic allergic contact dermatitis as a reaction to the rubber accelerators used in the manufacturing of many surgical gloves, Dr. Marks noted.

He described the case of a surgeon who developed severe hand dermatitis and eventually a generalized dermatitis. "In this case, if you used the TRUE test, you would make the diagnosis; he was positive to thiuram and carba mix."

Allergen avoidance entailed finding an alternative, rubber-free surgical glove, the Derma Prene Ultra glove (manufactured by Ansell), which is made of neoprene. Also, the surgeon switched to vinyl exam gloves for outpatient care.

"There may be other surgical gloves ...," Dr. Marks acknowledged. "But be sure and keep this some place because some time in the future when you have your surgeon friend with hand dermatitis, you can recommend that glove after you patch test them and prove that they are rubber-accelerator positive."

Cocamidopropyl betaine contaminants

Patients may develop allergic contact dermatitis after using shampoos and bath gels containing cocamidopropyl betaine, a surfactant.

In fact, they are actually reacting to a contaminant or impurity generated in the manufacturing process, either 3-dimethylaminopropylamine or amidoamine, according to Dr. Marks.

"So if you have pure cocamidopropyl betaine, there will be no allergy," he noted. But if you test for "cocamidopropyl betaine, and what you are patch testing with is from, say, Chemotechnique or Allergeaze, it’s going to have presumably the contaminants or the impurities in it, 3-dimethylaminopropylamine and amidoamine."

Treatment entails careful reading of labels on personal care products and avoidance of those containing cocamidopropyl betaine.

Acrylates

Don’t rule out acrylates – either acrylic or methacrylic acid – monomers that are polymerized with heat or light to form solid plastics that can cause reactions.

"The monomers are both irritants and allergens, so you need the right concentration to patch test to," Dr. Marks noted. "They are found in all sorts of things – adhesives, inks, artificial nails, dental resins, bone cement, and plastics."

Presentations may vary widely, including, for example, finger dermatitis in patients who have sculptured nails, and gum stomatitis in patients who have undergone procedures involving dental resin, said Dr. Marks.

"If you have workers or patients who have exposure to acrylates, you need more extensive screening," Dr. Marks advised, noting that his acrylate patch test series contains six compounds.

"No one is a screen for all of them," he commented. "Some [experts] feel that ethyl acrylate is the best screen; certainly, for sculptured nails it’s good." Others in his series include methyl methacrylate (found in bone cement) and ethyl cyanoacrylate (found in Super Glue adhesive).

Glyceryl thioglycolate

Allergy to glyceryl thioglycolate, found in acid permanent waves, can manifest as hand dermatitis in hairdressers and as dermatitis of the face, neck, and ears in their clients.

"If you see hairdressers [in your practice], you should consider strongly having this antigen as part of your [patch test] armamentarium," Dr. Marks recommended.

Alkaline perms, by contrast, do not contain glyceryl thioglycolate and thus provide a simple solution. "You can cure that hairdresser, and she or he can continue to do perms just by switching from an acid to an alkaline perm," he explained.

Dr. Marks said he had no relevant financial disclosures.

sknews@frontlinemedcom.com

Better vaccine coverage of adolescents against HPV infection hinges on clinicians and other health care professionals both recommending the vaccine and educating patients and parents about its importance, according to a report published online Nov. 25 in JAMA Pediatrics.

In a review of the extensive literature concerning barriers to HPV vaccination among patients aged 11-17 years, health care professionals’ failure to recommend the vaccine was found to be a leading obstacle to more widespread coverage, said Dawn M. Holman of the division of cancer prevention and control, Centers for Disease Control and Prevention, Atlanta, and her associates.

©BVDC/Fotolia.com

The most recent data from the National Immunization Survey indicates that only 53% of adolescent girls in the United States have received at least one dose of the HPV vaccine series, only 35% have completed all three doses in the series, and only 8% of adolescent boys in the United States have initiated the HPV vaccine series. By comparison, coverage for the meningococcal conjugate vaccine is approximately 70% and coverage for the tetanus, diphtheria, and acellular pertussis vaccine is 78% in the same age group.

Ms. Holman and her associates performed a systematic review of the literature and found 55 studies published in 2009-2012 that addressed obstacles to HPV vaccination in this age group.

In ten articles that addressed barriers to HPV vaccination among health care professionals, researchers found that while most physicians support HPV vaccination and offer it to their patients, many tend not to offer it to the youngest adolescents or to boys. Many also offer HPV vaccination only according to their own perception of the patient’s risk of contracting the virus. And many do not appear to understand the importance of giving the HPV vaccine well before adolescents become sexually active.

Health care professionals also tend not to provide detailed information to either patients or their parents regarding the risks and benefits of HPV vaccination, or they emphasize the fact that it is optional – both of which come across to patients and parents as a less-than-ringing endorsement. Some health care professionals reported that HPV vaccination is under the parents’ control rather than theirs, and many cited the cost of the HPV vaccine, and the lack or lateness of insurance reimbursement, as a significant obstacle.

In contrast, concerns about the safety and efficacy of the HPV vaccine were rarely cited as contributing to poor coverage (JAMA Pediatrics 2013 Nov. 25 [doi:10.1001/jamapediatrics.2013.2752]).

A total of 64% of the reviewed articles involved barriers to vaccination among parents. Not having a physician recommendation and not getting enough information about the HPV vaccine from health care providers were the chief obstacles to greater coverage in this group. Certain religious affiliations also were associated with opposition to the HPV vaccine.

In contrast, costs and lack of access were cited infrequently. Few parents reported concerns about vaccine safety or efficacy, and few reported concern that the vaccination might affect their child’s sexual behavior.

"Providing adequate, clear, and accessible information to parents about HPV infection, vaccine safety, adverse effects, and the appropriate age for vaccination may be one way health care professionals can reduce concerns and misconceptions about the vaccine," Ms. Holman and her colleagues noted.

Other strategies to improve HPV vaccination coverage include educating health care professionals and the public in general about the importance of vaccinating adolescent males, and ensuring that underserved populations are informed about and given access to the vaccine, they added.

Better vaccine coverage of adolescents against HPV infection hinges on clinicians and other health care professionals both recommending the vaccine and educating patients and parents about its importance, according to a report published online Nov. 25 in JAMA Pediatrics.

In a review of the extensive literature concerning barriers to HPV vaccination among patients aged 11-17 years, health care professionals’ failure to recommend the vaccine was found to be a leading obstacle to more widespread coverage, said Dawn M. Holman of the division of cancer prevention and control, Centers for Disease Control and Prevention, Atlanta, and her associates.

©BVDC/Fotolia.com

The most recent data from the National Immunization Survey indicates that only 53% of adolescent girls in the United States have received at least one dose of the HPV vaccine series, only 35% have completed all three doses in the series, and only 8% of adolescent boys in the United States have initiated the HPV vaccine series. By comparison, coverage for the meningococcal conjugate vaccine is approximately 70% and coverage for the tetanus, diphtheria, and acellular pertussis vaccine is 78% in the same age group.

Ms. Holman and her associates performed a systematic review of the literature and found 55 studies published in 2009-2012 that addressed obstacles to HPV vaccination in this age group.

In ten articles that addressed barriers to HPV vaccination among health care professionals, researchers found that while most physicians support HPV vaccination and offer it to their patients, many tend not to offer it to the youngest adolescents or to boys. Many also offer HPV vaccination only according to their own perception of the patient’s risk of contracting the virus. And many do not appear to understand the importance of giving the HPV vaccine well before adolescents become sexually active.

Health care professionals also tend not to provide detailed information to either patients or their parents regarding the risks and benefits of HPV vaccination, or they emphasize the fact that it is optional – both of which come across to patients and parents as a less-than-ringing endorsement. Some health care professionals reported that HPV vaccination is under the parents’ control rather than theirs, and many cited the cost of the HPV vaccine, and the lack or lateness of insurance reimbursement, as a significant obstacle.

In contrast, concerns about the safety and efficacy of the HPV vaccine were rarely cited as contributing to poor coverage (JAMA Pediatrics 2013 Nov. 25 [doi:10.1001/jamapediatrics.2013.2752]).

A total of 64% of the reviewed articles involved barriers to vaccination among parents. Not having a physician recommendation and not getting enough information about the HPV vaccine from health care providers were the chief obstacles to greater coverage in this group. Certain religious affiliations also were associated with opposition to the HPV vaccine.

In contrast, costs and lack of access were cited infrequently. Few parents reported concerns about vaccine safety or efficacy, and few reported concern that the vaccination might affect their child’s sexual behavior.

"Providing adequate, clear, and accessible information to parents about HPV infection, vaccine safety, adverse effects, and the appropriate age for vaccination may be one way health care professionals can reduce concerns and misconceptions about the vaccine," Ms. Holman and her colleagues noted.

Other strategies to improve HPV vaccination coverage include educating health care professionals and the public in general about the importance of vaccinating adolescent males, and ensuring that underserved populations are informed about and given access to the vaccine, they added.

Better vaccine coverage of adolescents against HPV infection hinges on clinicians and other health care professionals both recommending the vaccine and educating patients and parents about its importance, according to a report published online Nov. 25 in JAMA Pediatrics.

In a review of the extensive literature concerning barriers to HPV vaccination among patients aged 11-17 years, health care professionals’ failure to recommend the vaccine was found to be a leading obstacle to more widespread coverage, said Dawn M. Holman of the division of cancer prevention and control, Centers for Disease Control and Prevention, Atlanta, and her associates.

©BVDC/Fotolia.com

The most recent data from the National Immunization Survey indicates that only 53% of adolescent girls in the United States have received at least one dose of the HPV vaccine series, only 35% have completed all three doses in the series, and only 8% of adolescent boys in the United States have initiated the HPV vaccine series. By comparison, coverage for the meningococcal conjugate vaccine is approximately 70% and coverage for the tetanus, diphtheria, and acellular pertussis vaccine is 78% in the same age group.

Ms. Holman and her associates performed a systematic review of the literature and found 55 studies published in 2009-2012 that addressed obstacles to HPV vaccination in this age group.

In ten articles that addressed barriers to HPV vaccination among health care professionals, researchers found that while most physicians support HPV vaccination and offer it to their patients, many tend not to offer it to the youngest adolescents or to boys. Many also offer HPV vaccination only according to their own perception of the patient’s risk of contracting the virus. And many do not appear to understand the importance of giving the HPV vaccine well before adolescents become sexually active.

Health care professionals also tend not to provide detailed information to either patients or their parents regarding the risks and benefits of HPV vaccination, or they emphasize the fact that it is optional – both of which come across to patients and parents as a less-than-ringing endorsement. Some health care professionals reported that HPV vaccination is under the parents’ control rather than theirs, and many cited the cost of the HPV vaccine, and the lack or lateness of insurance reimbursement, as a significant obstacle.

In contrast, concerns about the safety and efficacy of the HPV vaccine were rarely cited as contributing to poor coverage (JAMA Pediatrics 2013 Nov. 25 [doi:10.1001/jamapediatrics.2013.2752]).

A total of 64% of the reviewed articles involved barriers to vaccination among parents. Not having a physician recommendation and not getting enough information about the HPV vaccine from health care providers were the chief obstacles to greater coverage in this group. Certain religious affiliations also were associated with opposition to the HPV vaccine.

In contrast, costs and lack of access were cited infrequently. Few parents reported concerns about vaccine safety or efficacy, and few reported concern that the vaccination might affect their child’s sexual behavior.

"Providing adequate, clear, and accessible information to parents about HPV infection, vaccine safety, adverse effects, and the appropriate age for vaccination may be one way health care professionals can reduce concerns and misconceptions about the vaccine," Ms. Holman and her colleagues noted.

Other strategies to improve HPV vaccination coverage include educating health care professionals and the public in general about the importance of vaccinating adolescent males, and ensuring that underserved populations are informed about and given access to the vaccine, they added.

Because efficacy of the shingles vaccine appears to wane over time, it should not routinely be given to people in their 50s, according to information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

"At this time, there is insufficient evidence supporting long-term protection of the vaccine, so if people younger than 60 [years] are vaccinated, they might not be protected when chance of disease is highest," said Dr. Jeff Duchin, chair of the ACIP’s herpes zoster working group. "We will continue to monitor data as they becomes available, but at this point we are reaffirming that vaccination be done in those age 60 [years] and older."

©clsgraphics/iStockphoto.com

The committee made its recommendation after reviewing newly released data from Merck’s Long-Term Persistence Study for shingles. It found that, 10 years after vaccination, the overall incidence rate of shingles had increased from about 4/1,000 person-years to 11/1,000 person-years. The observed incidence rate of shingles in historical controls is about 13 cases/1,000 person-years.

Dr. Janie Parrino, director of vaccine clinical research at Merck Research Laboratories, presented results of the company’s latest study of the vaccine’s extended efficacy. The shingles Long-Term Persistence Study is an 8-year follow-up of the Shingles Prevention Study, in which subjects were randomized to Merck’s Zostavax vaccine or placebo. It showed that the vaccine significantly reduced the incidence of herpes zoster and postherpetic neuralgia (PHN) as well as the shingles burden of illness, in adults older than 60 years.

A short-term follow-up study appeared last year; it added 4 more years of follow-up data on more than 14,000 of the original cohort.

It found a gradual decrease in vaccine efficacy by 6-7 years after vaccination. "Analysis of vaccine efficacy in each year after vaccination for all outcomes showed a decrease after year 1, with a further decline thereafter," the investigators said. "Vaccine efficacy was statistically significant for the incidence of herpes zoster and herpes zoster burden of illness through year 5 after vaccination, but vaccine efficacy is uncertain beyond that point."

The long-term study presented at the Atlanta meeting involved up to 12 years of data on almost 7,000 people in the original cohort. It demonstrated a continuous time-bound waning of efficacy.

In addition to the increasing annual incidence of shingles, the study found an increasing incidence of PHN, from less than 1/1,000 person-years during the year of vaccination to about 1/1,000 person years by year 10. However, the incidence among placebo subjects and historical controls was more than 2/1,000 person years by that time. The shingles burden of illness (a measure of acute pain) also increased as time passed, Dr. Parrino noted.

Taking into account both clinical efficacy and cost, Ismael Ortega-Sanchez, Ph.D., a health economist with the CDC, concluded that the shingles vaccine is most effective when given to people in their 60s and 70s.

Vaccinating from age 50-59 years would prevent about 20,000 shingles cases annually. But vaccinating in the 60s would prevent 26,000 and, in the 70s, 21,000. The trend was similar for cases of PHN: prevention of 1,000 cases for vaccinating in the 50s, 4,000 for vaccinating in the 60s, and 8,000 for vaccinating in the 70s.

Other outcomes – emergency visits, ambulatory visits, hospitalizations, length of hospital stay, and prescriptions – also increased significantly over the 3 decades.

Savings tracked clinical outcomes in a value assessment model of 6 million people: 1 million vaccinated and unvaccinated in each of the three age cohorts.

Compared with not vaccinating, vaccinating those in their 50s would save $16.8 million annually. Vaccinating during the 60s would save about $24.3 million, and during the 70s, $31.9 million.

And, because younger people are likely to have more systemic reactions, they cost more to vaccinate. A model that accounted for the cost of the vaccine, administration, and treating local and systemic reactions, put the total price tag at $193 million for those in their 50s, and $190 million for each of the two older groups.

Finally, the number needed to treat to prevent one case of shingles, PHN, or non-PHN complication case was higher in those in their 50s than in those in their 60s or 70s (one shingles case – 51, 38, and 47 respectively; one PHN case – 988, 247, and 124).

"This isn’t intended to tell people not to get the vaccine early, but to make them aware of the risks and benefits, given that the greatest risk of the disease is later in life," Dr. Duchin said. Since there are no data on booster shingles vaccines, he said "we only have one shot at this and we need to focus our efforts on those at the greatest risk."

msullivan@frontlinemedcom.com

Because efficacy of the shingles vaccine appears to wane over time, it should not routinely be given to people in their 50s, according to information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

"At this time, there is insufficient evidence supporting long-term protection of the vaccine, so if people younger than 60 [years] are vaccinated, they might not be protected when chance of disease is highest," said Dr. Jeff Duchin, chair of the ACIP’s herpes zoster working group. "We will continue to monitor data as they becomes available, but at this point we are reaffirming that vaccination be done in those age 60 [years] and older."

©clsgraphics/iStockphoto.com

The committee made its recommendation after reviewing newly released data from Merck’s Long-Term Persistence Study for shingles. It found that, 10 years after vaccination, the overall incidence rate of shingles had increased from about 4/1,000 person-years to 11/1,000 person-years. The observed incidence rate of shingles in historical controls is about 13 cases/1,000 person-years.

Dr. Janie Parrino, director of vaccine clinical research at Merck Research Laboratories, presented results of the company’s latest study of the vaccine’s extended efficacy. The shingles Long-Term Persistence Study is an 8-year follow-up of the Shingles Prevention Study, in which subjects were randomized to Merck’s Zostavax vaccine or placebo. It showed that the vaccine significantly reduced the incidence of herpes zoster and postherpetic neuralgia (PHN) as well as the shingles burden of illness, in adults older than 60 years.

A short-term follow-up study appeared last year; it added 4 more years of follow-up data on more than 14,000 of the original cohort.

It found a gradual decrease in vaccine efficacy by 6-7 years after vaccination. "Analysis of vaccine efficacy in each year after vaccination for all outcomes showed a decrease after year 1, with a further decline thereafter," the investigators said. "Vaccine efficacy was statistically significant for the incidence of herpes zoster and herpes zoster burden of illness through year 5 after vaccination, but vaccine efficacy is uncertain beyond that point."

The long-term study presented at the Atlanta meeting involved up to 12 years of data on almost 7,000 people in the original cohort. It demonstrated a continuous time-bound waning of efficacy.

In addition to the increasing annual incidence of shingles, the study found an increasing incidence of PHN, from less than 1/1,000 person-years during the year of vaccination to about 1/1,000 person years by year 10. However, the incidence among placebo subjects and historical controls was more than 2/1,000 person years by that time. The shingles burden of illness (a measure of acute pain) also increased as time passed, Dr. Parrino noted.

Taking into account both clinical efficacy and cost, Ismael Ortega-Sanchez, Ph.D., a health economist with the CDC, concluded that the shingles vaccine is most effective when given to people in their 60s and 70s.

Vaccinating from age 50-59 years would prevent about 20,000 shingles cases annually. But vaccinating in the 60s would prevent 26,000 and, in the 70s, 21,000. The trend was similar for cases of PHN: prevention of 1,000 cases for vaccinating in the 50s, 4,000 for vaccinating in the 60s, and 8,000 for vaccinating in the 70s.

Other outcomes – emergency visits, ambulatory visits, hospitalizations, length of hospital stay, and prescriptions – also increased significantly over the 3 decades.

Savings tracked clinical outcomes in a value assessment model of 6 million people: 1 million vaccinated and unvaccinated in each of the three age cohorts.

Compared with not vaccinating, vaccinating those in their 50s would save $16.8 million annually. Vaccinating during the 60s would save about $24.3 million, and during the 70s, $31.9 million.

And, because younger people are likely to have more systemic reactions, they cost more to vaccinate. A model that accounted for the cost of the vaccine, administration, and treating local and systemic reactions, put the total price tag at $193 million for those in their 50s, and $190 million for each of the two older groups.

Finally, the number needed to treat to prevent one case of shingles, PHN, or non-PHN complication case was higher in those in their 50s than in those in their 60s or 70s (one shingles case – 51, 38, and 47 respectively; one PHN case – 988, 247, and 124).

"This isn’t intended to tell people not to get the vaccine early, but to make them aware of the risks and benefits, given that the greatest risk of the disease is later in life," Dr. Duchin said. Since there are no data on booster shingles vaccines, he said "we only have one shot at this and we need to focus our efforts on those at the greatest risk."

msullivan@frontlinemedcom.com

Because efficacy of the shingles vaccine appears to wane over time, it should not routinely be given to people in their 50s, according to information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

"At this time, there is insufficient evidence supporting long-term protection of the vaccine, so if people younger than 60 [years] are vaccinated, they might not be protected when chance of disease is highest," said Dr. Jeff Duchin, chair of the ACIP’s herpes zoster working group. "We will continue to monitor data as they becomes available, but at this point we are reaffirming that vaccination be done in those age 60 [years] and older."

©clsgraphics/iStockphoto.com

The committee made its recommendation after reviewing newly released data from Merck’s Long-Term Persistence Study for shingles. It found that, 10 years after vaccination, the overall incidence rate of shingles had increased from about 4/1,000 person-years to 11/1,000 person-years. The observed incidence rate of shingles in historical controls is about 13 cases/1,000 person-years.

Dr. Janie Parrino, director of vaccine clinical research at Merck Research Laboratories, presented results of the company’s latest study of the vaccine’s extended efficacy. The shingles Long-Term Persistence Study is an 8-year follow-up of the Shingles Prevention Study, in which subjects were randomized to Merck’s Zostavax vaccine or placebo. It showed that the vaccine significantly reduced the incidence of herpes zoster and postherpetic neuralgia (PHN) as well as the shingles burden of illness, in adults older than 60 years.

A short-term follow-up study appeared last year; it added 4 more years of follow-up data on more than 14,000 of the original cohort.

It found a gradual decrease in vaccine efficacy by 6-7 years after vaccination. "Analysis of vaccine efficacy in each year after vaccination for all outcomes showed a decrease after year 1, with a further decline thereafter," the investigators said. "Vaccine efficacy was statistically significant for the incidence of herpes zoster and herpes zoster burden of illness through year 5 after vaccination, but vaccine efficacy is uncertain beyond that point."

The long-term study presented at the Atlanta meeting involved up to 12 years of data on almost 7,000 people in the original cohort. It demonstrated a continuous time-bound waning of efficacy.

In addition to the increasing annual incidence of shingles, the study found an increasing incidence of PHN, from less than 1/1,000 person-years during the year of vaccination to about 1/1,000 person years by year 10. However, the incidence among placebo subjects and historical controls was more than 2/1,000 person years by that time. The shingles burden of illness (a measure of acute pain) also increased as time passed, Dr. Parrino noted.

Taking into account both clinical efficacy and cost, Ismael Ortega-Sanchez, Ph.D., a health economist with the CDC, concluded that the shingles vaccine is most effective when given to people in their 60s and 70s.

Vaccinating from age 50-59 years would prevent about 20,000 shingles cases annually. But vaccinating in the 60s would prevent 26,000 and, in the 70s, 21,000. The trend was similar for cases of PHN: prevention of 1,000 cases for vaccinating in the 50s, 4,000 for vaccinating in the 60s, and 8,000 for vaccinating in the 70s.

Other outcomes – emergency visits, ambulatory visits, hospitalizations, length of hospital stay, and prescriptions – also increased significantly over the 3 decades.

Savings tracked clinical outcomes in a value assessment model of 6 million people: 1 million vaccinated and unvaccinated in each of the three age cohorts.

Compared with not vaccinating, vaccinating those in their 50s would save $16.8 million annually. Vaccinating during the 60s would save about $24.3 million, and during the 70s, $31.9 million.

And, because younger people are likely to have more systemic reactions, they cost more to vaccinate. A model that accounted for the cost of the vaccine, administration, and treating local and systemic reactions, put the total price tag at $193 million for those in their 50s, and $190 million for each of the two older groups.

Finally, the number needed to treat to prevent one case of shingles, PHN, or non-PHN complication case was higher in those in their 50s than in those in their 60s or 70s (one shingles case – 51, 38, and 47 respectively; one PHN case – 988, 247, and 124).

"This isn’t intended to tell people not to get the vaccine early, but to make them aware of the risks and benefits, given that the greatest risk of the disease is later in life," Dr. Duchin said. Since there are no data on booster shingles vaccines, he said "we only have one shot at this and we need to focus our efforts on those at the greatest risk."

msullivan@frontlinemedcom.com

Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.

Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.

These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.

Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.

For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.

Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).

Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.

Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.

"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.

HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.

This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.

Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.

Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.

These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.

Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.

For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.

Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).

Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.

Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.

"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.

HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.

This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.

Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.

Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.

These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.

Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.

For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.

Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).

Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.

Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.

"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.

HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.

This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.

The results of a randomized, open-label study suggest that reducing the ribavirin dose should be the "primary approach" for managing anemia associated with peginterferon, ribavirin, and boceprevir therapy in patients with chronic hepatitis C, the authors of the study concluded.

In the study, the effects of two anemia-management strategies, ribavirin (RBV) dose reduction and erythropoietin (EPO) treatment, on the sustained virologic response (SVR) were similar – there was less than 1% difference between the two groups, according to the investigators, Dr. Fred F. Poordad of the Texas Liver Institute, at the University of Texas Health Science Center, San Antonio, and his associates. They also found that SVR rates were significantly lower among those who received less than half of the total ribavirin dose during the entire treatment period, compared with those who received a greater proportion of the total dosage.

"There appears to be no apparent benefit of using EPO as a first-line anemia-management strategy to enhance SVR rate or minimize relapse," the authors concluded. "EPO can be used as a secondary management strategy to prevent treatment interruption if RBV dosage reduction alone is inadequate, but the safety of EPO use in this setting has not been clearly established," they added. The study was published in the November issue of Gastroenterology (2013 [doi:10.1053/j.gastro.2013.07.051]).

The study includes an algorithm for managing boceprevir-related anemia, based on the results of this and other clinical studies, and the authors’ expertise.
See the full algorithm here. 

The study, conducted between December 2009 and October 2011, compared the two regimens in 500 of 687 previously untreated patients with chronic HCV genotype-1 infections, who became anemic (hemoglobin levels dropping to 10 g/dL or lower) during treatment with the three drugs: peginterferon alfa-2b (PegIntron) at a dose of 1.5 mcg/kg per week; ribavirin at a dose of 600-1400 mg per day depending on weight; and boceprevir (Victrelis) at a dose of 800 mg three times a day. (After 4 weeks of treatment with peginterferon and RBV, boceprevir was added for 24 or 44 weeks). Their mean age was about 50 years, 33% were men, 77% were white, and 18% were black; 91% had a baseline viral load of more than 400,000 IU/mL. Almost 90% were in the United States, the rest were in Canada and Europe.

The 500 patients were randomized to treatment with EPO (a subcutaneous infusion of 40,000 IU a week) or a reduction in the ribavirin dose (200 mg/day or, for those on the 1,400 mg daily dose, a 400-mg reduction). If hemoglobin levels dropped to 7.5 g/dL or lower, the patients were dropped from the study.

The SVR rate (undetectable HCV RNA 24 weeks after the end of treatment) was 71.5% among those whose ribavirin dosage was reduced and 70.9% among those treated with EPO. Among the 187 patients who did not develop anemia, the SVR rate was 40.1%; this group included a large number of patients who discontinued treatment because of adverse events. But of the 64 who completed treatment, the SVR rate was 89%. The overall SVR rate – among all 687 patients, those randomized and not randomized – was 63%.

Common adverse events were similar in the two randomized treatment groups, with anemia, fatigue, nausea, and headache being the most commonly reported. The rates of serious adverse events were 16% among those in the RBV dose-reduction arm and 13% of those on EPO. There were more thromboembolic events among the patients treated with EPO. There was one death in a patient in the RBV arm, a sudden cardiac death 3 weeks after stopping treatment.

The algorithm proposed by the authors, which has different hemoglobin monitoring recommendations for those with and without advanced fibrosis and cirrhosis, recommends that the primary intervention for managing anemia should be to reduce the RBV dosage. But if hemoglobin levels remain below 10 g/dL, "secondary interventions, such as administration of EPO, red cell transfusions, and reducing the dosage of peginterferon can be considered," the authors wrote. In addition, "it is important that the patient receives at least 50% of the total milligrams of RBV calculated from the initial RBV dosage (mg/d) and the assigned duration" defined by the response-guided therapy algorithm, they added.

The open-label design was one of the study’s limitations, and whether these results apply to other HCV treatment regimens is unclear, the authors noted. However, the results "would most likely be applicable to all RBV- and peginterferon/RBV-based regimens" for hepatitis C, they added.

The study was funded by Schering-Plough, the manufacturer of PegIntron and combination packs of PegIntron with ribavirin, which is now part of Merck. The investigator disclosures included having served as consultants and speakers, and/or having received grants from multiple pharmaceutical companies; the investigators include several current and former employees of Merck Sharp & Dohme Corp. (a subsidiary of Merck & Co.), the manufacturer of Victrelis.

emechcatie@frontlinemedcom.com

The results of a randomized, open-label study suggest that reducing the ribavirin dose should be the "primary approach" for managing anemia associated with peginterferon, ribavirin, and boceprevir therapy in patients with chronic hepatitis C, the authors of the study concluded.

In the study, the effects of two anemia-management strategies, ribavirin (RBV) dose reduction and erythropoietin (EPO) treatment, on the sustained virologic response (SVR) were similar – there was less than 1% difference between the two groups, according to the investigators, Dr. Fred F. Poordad of the Texas Liver Institute, at the University of Texas Health Science Center, San Antonio, and his associates. They also found that SVR rates were significantly lower among those who received less than half of the total ribavirin dose during the entire treatment period, compared with those who received a greater proportion of the total dosage.

"There appears to be no apparent benefit of using EPO as a first-line anemia-management strategy to enhance SVR rate or minimize relapse," the authors concluded. "EPO can be used as a secondary management strategy to prevent treatment interruption if RBV dosage reduction alone is inadequate, but the safety of EPO use in this setting has not been clearly established," they added. The study was published in the November issue of Gastroenterology (2013 [doi:10.1053/j.gastro.2013.07.051]).

The study includes an algorithm for managing boceprevir-related anemia, based on the results of this and other clinical studies, and the authors’ expertise.
See the full algorithm here. 

The study, conducted between December 2009 and October 2011, compared the two regimens in 500 of 687 previously untreated patients with chronic HCV genotype-1 infections, who became anemic (hemoglobin levels dropping to 10 g/dL or lower) during treatment with the three drugs: peginterferon alfa-2b (PegIntron) at a dose of 1.5 mcg/kg per week; ribavirin at a dose of 600-1400 mg per day depending on weight; and boceprevir (Victrelis) at a dose of 800 mg three times a day. (After 4 weeks of treatment with peginterferon and RBV, boceprevir was added for 24 or 44 weeks). Their mean age was about 50 years, 33% were men, 77% were white, and 18% were black; 91% had a baseline viral load of more than 400,000 IU/mL. Almost 90% were in the United States, the rest were in Canada and Europe.

The 500 patients were randomized to treatment with EPO (a subcutaneous infusion of 40,000 IU a week) or a reduction in the ribavirin dose (200 mg/day or, for those on the 1,400 mg daily dose, a 400-mg reduction). If hemoglobin levels dropped to 7.5 g/dL or lower, the patients were dropped from the study.

The SVR rate (undetectable HCV RNA 24 weeks after the end of treatment) was 71.5% among those whose ribavirin dosage was reduced and 70.9% among those treated with EPO. Among the 187 patients who did not develop anemia, the SVR rate was 40.1%; this group included a large number of patients who discontinued treatment because of adverse events. But of the 64 who completed treatment, the SVR rate was 89%. The overall SVR rate – among all 687 patients, those randomized and not randomized – was 63%.

Common adverse events were similar in the two randomized treatment groups, with anemia, fatigue, nausea, and headache being the most commonly reported. The rates of serious adverse events were 16% among those in the RBV dose-reduction arm and 13% of those on EPO. There were more thromboembolic events among the patients treated with EPO. There was one death in a patient in the RBV arm, a sudden cardiac death 3 weeks after stopping treatment.

The algorithm proposed by the authors, which has different hemoglobin monitoring recommendations for those with and without advanced fibrosis and cirrhosis, recommends that the primary intervention for managing anemia should be to reduce the RBV dosage. But if hemoglobin levels remain below 10 g/dL, "secondary interventions, such as administration of EPO, red cell transfusions, and reducing the dosage of peginterferon can be considered," the authors wrote. In addition, "it is important that the patient receives at least 50% of the total milligrams of RBV calculated from the initial RBV dosage (mg/d) and the assigned duration" defined by the response-guided therapy algorithm, they added.

The open-label design was one of the study’s limitations, and whether these results apply to other HCV treatment regimens is unclear, the authors noted. However, the results "would most likely be applicable to all RBV- and peginterferon/RBV-based regimens" for hepatitis C, they added.

The study was funded by Schering-Plough, the manufacturer of PegIntron and combination packs of PegIntron with ribavirin, which is now part of Merck. The investigator disclosures included having served as consultants and speakers, and/or having received grants from multiple pharmaceutical companies; the investigators include several current and former employees of Merck Sharp & Dohme Corp. (a subsidiary of Merck & Co.), the manufacturer of Victrelis.

emechcatie@frontlinemedcom.com

The results of a randomized, open-label study suggest that reducing the ribavirin dose should be the "primary approach" for managing anemia associated with peginterferon, ribavirin, and boceprevir therapy in patients with chronic hepatitis C, the authors of the study concluded.

In the study, the effects of two anemia-management strategies, ribavirin (RBV) dose reduction and erythropoietin (EPO) treatment, on the sustained virologic response (SVR) were similar – there was less than 1% difference between the two groups, according to the investigators, Dr. Fred F. Poordad of the Texas Liver Institute, at the University of Texas Health Science Center, San Antonio, and his associates. They also found that SVR rates were significantly lower among those who received less than half of the total ribavirin dose during the entire treatment period, compared with those who received a greater proportion of the total dosage.

"There appears to be no apparent benefit of using EPO as a first-line anemia-management strategy to enhance SVR rate or minimize relapse," the authors concluded. "EPO can be used as a secondary management strategy to prevent treatment interruption if RBV dosage reduction alone is inadequate, but the safety of EPO use in this setting has not been clearly established," they added. The study was published in the November issue of Gastroenterology (2013 [doi:10.1053/j.gastro.2013.07.051]).

The study includes an algorithm for managing boceprevir-related anemia, based on the results of this and other clinical studies, and the authors’ expertise.
See the full algorithm here. 

The study, conducted between December 2009 and October 2011, compared the two regimens in 500 of 687 previously untreated patients with chronic HCV genotype-1 infections, who became anemic (hemoglobin levels dropping to 10 g/dL or lower) during treatment with the three drugs: peginterferon alfa-2b (PegIntron) at a dose of 1.5 mcg/kg per week; ribavirin at a dose of 600-1400 mg per day depending on weight; and boceprevir (Victrelis) at a dose of 800 mg three times a day. (After 4 weeks of treatment with peginterferon and RBV, boceprevir was added for 24 or 44 weeks). Their mean age was about 50 years, 33% were men, 77% were white, and 18% were black; 91% had a baseline viral load of more than 400,000 IU/mL. Almost 90% were in the United States, the rest were in Canada and Europe.

The 500 patients were randomized to treatment with EPO (a subcutaneous infusion of 40,000 IU a week) or a reduction in the ribavirin dose (200 mg/day or, for those on the 1,400 mg daily dose, a 400-mg reduction). If hemoglobin levels dropped to 7.5 g/dL or lower, the patients were dropped from the study.

The SVR rate (undetectable HCV RNA 24 weeks after the end of treatment) was 71.5% among those whose ribavirin dosage was reduced and 70.9% among those treated with EPO. Among the 187 patients who did not develop anemia, the SVR rate was 40.1%; this group included a large number of patients who discontinued treatment because of adverse events. But of the 64 who completed treatment, the SVR rate was 89%. The overall SVR rate – among all 687 patients, those randomized and not randomized – was 63%.

Common adverse events were similar in the two randomized treatment groups, with anemia, fatigue, nausea, and headache being the most commonly reported. The rates of serious adverse events were 16% among those in the RBV dose-reduction arm and 13% of those on EPO. There were more thromboembolic events among the patients treated with EPO. There was one death in a patient in the RBV arm, a sudden cardiac death 3 weeks after stopping treatment.

The algorithm proposed by the authors, which has different hemoglobin monitoring recommendations for those with and without advanced fibrosis and cirrhosis, recommends that the primary intervention for managing anemia should be to reduce the RBV dosage. But if hemoglobin levels remain below 10 g/dL, "secondary interventions, such as administration of EPO, red cell transfusions, and reducing the dosage of peginterferon can be considered," the authors wrote. In addition, "it is important that the patient receives at least 50% of the total milligrams of RBV calculated from the initial RBV dosage (mg/d) and the assigned duration" defined by the response-guided therapy algorithm, they added.

The open-label design was one of the study’s limitations, and whether these results apply to other HCV treatment regimens is unclear, the authors noted. However, the results "would most likely be applicable to all RBV- and peginterferon/RBV-based regimens" for hepatitis C, they added.

The study was funded by Schering-Plough, the manufacturer of PegIntron and combination packs of PegIntron with ribavirin, which is now part of Merck. The investigator disclosures included having served as consultants and speakers, and/or having received grants from multiple pharmaceutical companies; the investigators include several current and former employees of Merck Sharp & Dohme Corp. (a subsidiary of Merck & Co.), the manufacturer of Victrelis.

emechcatie@frontlinemedcom.com

SAN DIEGO – Only 8.5% of children and young adults with autoimmune diseases and 9.1% of those without such diseases received one or more doses of the human papillomavirus vaccine, a large analysis of national claims data showed.

"Despite the high efficacy of HPV vaccine in preventing cervical cancer and clinically acceptable safety profile in the general population, the vast majority of patients aged 9-26 in our study cohort with and without autoimmune diseases did not receive the HPV vaccine," Dr. Seoyoung C. Kim said in an interview prior to the annual meeting of the American College of Rheumatology, where the study was presented.

"Patients at high risk of persistent HPV infection should be encouraged to receive the vaccine, although future study is needed to determine the effectiveness of HPV vaccine in patients with autoimmune diseases, particularly those on immunosuppressive drugs," she added.

In 2006 and 2009, two three-dose series HPV vaccines were approved for use in males and females aged 9-26 years. Prior research has suggested that patients with lupus or inflammatory bowel disease or those who take immunosuppressive agents have a higher risk of persistent HPV infection or cervical dysplasia, said Dr. Kim of the division of pharmacoepidemiology and pharmacoeconomics in the department of medicine at Brigham and Women’s Hospital, Boston.

"HPV vaccine has been available for the past several years in the U.S. and in other countries," she said. "As far as we know, there has not been any study looking at the uptake of HPV vaccine in the autoimmune disease population."

Using United HealthCare national claims data for 2005-2012, Dr. Kim and her associates identified patients aged 9-26 years with at least 1 year of continuous enrollment who had at least two autoimmune disease diagnosis codes 7 or more days apart. Vaccination was defined as one or more vaccine codes after 2006, and the researchers accounted for coexisting diseases, use of health care treatments, and geographic regions when assessing vaccine uptake.

Dr. Kim, the study’s senior investigator, reported data for 29,255 children and young adults with autoimmune diseases and 117,020 without. The mean age was 19 years, and 59% were female. Patients in the autoimmune diseases group had a higher number of physician visits, abnormal pap smears, and sexually transmitted diseases, compared with their counterparts without autoimmune disease (all P values less than .01).

Overall, autoimmune disease patients and their counterparts had similarly low uptake of at least one vaccine dose (8.5% vs. 9.1%, respectively; P = .34). The uptake was higher among females in both groups (13.1% vs. 14.1%, respectively; P less than .01), yet fewer than 5% of female patients in both groups completed a three-dose vaccine series (4.7% vs. 4.6%; P = .57). A higher percentage of patients in the Northeast received one or more HPV vaccine doses (16.3% vs. 11.8%; P = .02); otherwise vaccinations were equally distributed from a geographic standpoint.

In a subgroup of female patients who had at least 2 years of follow-up, 20.6% with autoimmune disease and 23.1% without autoimmune disease received at least one vaccine dose. Of those, 53.1% and 51.4%, respectively, completed the series.

"We were generally surprised to see how low the uptake has been in both autoimmune and nonautoimmune populations," Dr. Kim said. She acknowledged certain limitations of the study, including the fact that it was conducting using the claims data from United HealthCare, "so it only captures patients who used the insurance card to pay for the vaccine," she said. "However, given the high cost of the HPV vaccine, this limitation is probably not substantial. We [also] did not have information on race/ethnicity."

Dr. Kim disclosed that she is supported by a grant from the National Institutes of Health. She received a research grant from Pfizer and tuition support for the pharmacoepidemiology program at the Harvard School of Public Health, which is funded by Pfizer, Millennium Pharma, and Asisa.

dbrunk@frontlinemedcom.com

SAN DIEGO – Only 8.5% of children and young adults with autoimmune diseases and 9.1% of those without such diseases received one or more doses of the human papillomavirus vaccine, a large analysis of national claims data showed.

"Despite the high efficacy of HPV vaccine in preventing cervical cancer and clinically acceptable safety profile in the general population, the vast majority of patients aged 9-26 in our study cohort with and without autoimmune diseases did not receive the HPV vaccine," Dr. Seoyoung C. Kim said in an interview prior to the annual meeting of the American College of Rheumatology, where the study was presented.

"Patients at high risk of persistent HPV infection should be encouraged to receive the vaccine, although future study is needed to determine the effectiveness of HPV vaccine in patients with autoimmune diseases, particularly those on immunosuppressive drugs," she added.

In 2006 and 2009, two three-dose series HPV vaccines were approved for use in males and females aged 9-26 years. Prior research has suggested that patients with lupus or inflammatory bowel disease or those who take immunosuppressive agents have a higher risk of persistent HPV infection or cervical dysplasia, said Dr. Kim of the division of pharmacoepidemiology and pharmacoeconomics in the department of medicine at Brigham and Women’s Hospital, Boston.

"HPV vaccine has been available for the past several years in the U.S. and in other countries," she said. "As far as we know, there has not been any study looking at the uptake of HPV vaccine in the autoimmune disease population."

Using United HealthCare national claims data for 2005-2012, Dr. Kim and her associates identified patients aged 9-26 years with at least 1 year of continuous enrollment who had at least two autoimmune disease diagnosis codes 7 or more days apart. Vaccination was defined as one or more vaccine codes after 2006, and the researchers accounted for coexisting diseases, use of health care treatments, and geographic regions when assessing vaccine uptake.

Dr. Kim, the study’s senior investigator, reported data for 29,255 children and young adults with autoimmune diseases and 117,020 without. The mean age was 19 years, and 59% were female. Patients in the autoimmune diseases group had a higher number of physician visits, abnormal pap smears, and sexually transmitted diseases, compared with their counterparts without autoimmune disease (all P values less than .01).

Overall, autoimmune disease patients and their counterparts had similarly low uptake of at least one vaccine dose (8.5% vs. 9.1%, respectively; P = .34). The uptake was higher among females in both groups (13.1% vs. 14.1%, respectively; P less than .01), yet fewer than 5% of female patients in both groups completed a three-dose vaccine series (4.7% vs. 4.6%; P = .57). A higher percentage of patients in the Northeast received one or more HPV vaccine doses (16.3% vs. 11.8%; P = .02); otherwise vaccinations were equally distributed from a geographic standpoint.

In a subgroup of female patients who had at least 2 years of follow-up, 20.6% with autoimmune disease and 23.1% without autoimmune disease received at least one vaccine dose. Of those, 53.1% and 51.4%, respectively, completed the series.

"We were generally surprised to see how low the uptake has been in both autoimmune and nonautoimmune populations," Dr. Kim said. She acknowledged certain limitations of the study, including the fact that it was conducting using the claims data from United HealthCare, "so it only captures patients who used the insurance card to pay for the vaccine," she said. "However, given the high cost of the HPV vaccine, this limitation is probably not substantial. We [also] did not have information on race/ethnicity."

Dr. Kim disclosed that she is supported by a grant from the National Institutes of Health. She received a research grant from Pfizer and tuition support for the pharmacoepidemiology program at the Harvard School of Public Health, which is funded by Pfizer, Millennium Pharma, and Asisa.

dbrunk@frontlinemedcom.com

SAN DIEGO – Only 8.5% of children and young adults with autoimmune diseases and 9.1% of those without such diseases received one or more doses of the human papillomavirus vaccine, a large analysis of national claims data showed.

"Despite the high efficacy of HPV vaccine in preventing cervical cancer and clinically acceptable safety profile in the general population, the vast majority of patients aged 9-26 in our study cohort with and without autoimmune diseases did not receive the HPV vaccine," Dr. Seoyoung C. Kim said in an interview prior to the annual meeting of the American College of Rheumatology, where the study was presented.

"Patients at high risk of persistent HPV infection should be encouraged to receive the vaccine, although future study is needed to determine the effectiveness of HPV vaccine in patients with autoimmune diseases, particularly those on immunosuppressive drugs," she added.

In 2006 and 2009, two three-dose series HPV vaccines were approved for use in males and females aged 9-26 years. Prior research has suggested that patients with lupus or inflammatory bowel disease or those who take immunosuppressive agents have a higher risk of persistent HPV infection or cervical dysplasia, said Dr. Kim of the division of pharmacoepidemiology and pharmacoeconomics in the department of medicine at Brigham and Women’s Hospital, Boston.

"HPV vaccine has been available for the past several years in the U.S. and in other countries," she said. "As far as we know, there has not been any study looking at the uptake of HPV vaccine in the autoimmune disease population."

Using United HealthCare national claims data for 2005-2012, Dr. Kim and her associates identified patients aged 9-26 years with at least 1 year of continuous enrollment who had at least two autoimmune disease diagnosis codes 7 or more days apart. Vaccination was defined as one or more vaccine codes after 2006, and the researchers accounted for coexisting diseases, use of health care treatments, and geographic regions when assessing vaccine uptake.

Dr. Kim, the study’s senior investigator, reported data for 29,255 children and young adults with autoimmune diseases and 117,020 without. The mean age was 19 years, and 59% were female. Patients in the autoimmune diseases group had a higher number of physician visits, abnormal pap smears, and sexually transmitted diseases, compared with their counterparts without autoimmune disease (all P values less than .01).

Overall, autoimmune disease patients and their counterparts had similarly low uptake of at least one vaccine dose (8.5% vs. 9.1%, respectively; P = .34). The uptake was higher among females in both groups (13.1% vs. 14.1%, respectively; P less than .01), yet fewer than 5% of female patients in both groups completed a three-dose vaccine series (4.7% vs. 4.6%; P = .57). A higher percentage of patients in the Northeast received one or more HPV vaccine doses (16.3% vs. 11.8%; P = .02); otherwise vaccinations were equally distributed from a geographic standpoint.

In a subgroup of female patients who had at least 2 years of follow-up, 20.6% with autoimmune disease and 23.1% without autoimmune disease received at least one vaccine dose. Of those, 53.1% and 51.4%, respectively, completed the series.

"We were generally surprised to see how low the uptake has been in both autoimmune and nonautoimmune populations," Dr. Kim said. She acknowledged certain limitations of the study, including the fact that it was conducting using the claims data from United HealthCare, "so it only captures patients who used the insurance card to pay for the vaccine," she said. "However, given the high cost of the HPV vaccine, this limitation is probably not substantial. We [also] did not have information on race/ethnicity."

Dr. Kim disclosed that she is supported by a grant from the National Institutes of Health. She received a research grant from Pfizer and tuition support for the pharmacoepidemiology program at the Harvard School of Public Health, which is funded by Pfizer, Millennium Pharma, and Asisa.

dbrunk@frontlinemedcom.com

The quadrivalent meningococcal vaccine MenACWY-CRM, or Menveo, may now be given to infants aged 2-23 months who are considered at high risk for meningococcal disease or who travel to areas where it is hyperendemic or epidemic, according to the recommendations of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

High-risk children are those with component complement deficiency, HIV infection, or anatomic or functional asplenia. Children in an outbreak of a vaccine-preventable meningitis serogroup also should receive the series. About 5,000 infants per year fit into these categories.

The Advisory Committee on Immunization Practices (ACIP) approved the decision by a vote of 13-1, with one abstention. The decision aligns ACIP’s recommendation with the recently expanded indication for the vaccine, which protects against serotypes A, C, W-135, and Y. In August, the Food and Drug Administration approved the vaccine for infants and toddlers older than 2 months.

However, because of the extremely low incidence of meningococcal disease in children in the United States, the committee did not recommend it for all healthy children. "Very few children are considered at increased risk, so a routine recommendation would prevent just a very low number of cases," said Jessica MacNeil, an epidemiologist with the CDC.

The FDA licensing of MenACWY-CRM and ACIP’s recommendation give pediatricians a third option for infant meningococcal vaccination. HibMenCY-TT (MenHibrix) and MenACWY-D (Menactra) are also approved for some of these same indications. However, Ms. MacNeil noted, Menactra cannot be used in children with asplenia, and MenHibrix can’t be used for travel or as a booster dose.

The committee based its decision on three phase III safety and efficacy trials. These studies comprised nearly 11,000 infants – 9,000 of whom had the four-dose series and 2,000 of whom had a two-dose series, said Dr. Peter Dull of Novartis Vaccines.

The studies confirmed an average 90% efficacy against all four serotypes after the 12-month dose. By 40 months of age, efficacy had waned somewhat: 10% of infants had a seroresponse to type A; 34%, to type C; 76%, to type W-135; and 67%, to type Y. Of the strains included in the vaccine, types C, Y, and W-135 cause 75% of meningococcal disease in those aged 11 years and older.

Dr. Dull said that Novartis is following a cohort that received the vaccine as infants; next year, 60-month immunogenicity data will be available.

After adjustment for some confounders, the vaccine did not significantly interact with the immunogenic potential of other recommended childhood vaccines. Novartis studies also found it safe. Up to 60% of children had mild to moderate injection site reactions. The incidence of systemic reactions was no different from that for routine vaccines alone.

There were 11 serious adverse events possibly related to the vaccine among the 5,000 children included in the safety analyses. These included acute encephalomyelitis, cellulitis, complex partial seizure, epilepsy, febrile seizure, and Kawasaki disease. Ten deaths occurred, but were not considered vaccine related.

The recommended dosing schedule will be:

• Aged 2-6 months: Four doses at 2, 4, 6, and 12 months.

• Aged 7-23 months: Two doses with the second dose given in the second year of life.

• Aged 2-11 years: One or two doses.

Boosters should be given to those who remain at risk, beginning at 3 years after the primary series and then every 5 years thereafter.

The committee also agreed, by a vote of 14 with one abstention, to include MenACWY-CRM in the Vaccines for Children program.

One member who voted disclosed that her institution receives research funding from drug companies. None of the other voting members had any relevant financial disclosures.

msullivan@frontlinemedcom.com

The quadrivalent meningococcal vaccine MenACWY-CRM, or Menveo, may now be given to infants aged 2-23 months who are considered at high risk for meningococcal disease or who travel to areas where it is hyperendemic or epidemic, according to the recommendations of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

High-risk children are those with component complement deficiency, HIV infection, or anatomic or functional asplenia. Children in an outbreak of a vaccine-preventable meningitis serogroup also should receive the series. About 5,000 infants per year fit into these categories.

The Advisory Committee on Immunization Practices (ACIP) approved the decision by a vote of 13-1, with one abstention. The decision aligns ACIP’s recommendation with the recently expanded indication for the vaccine, which protects against serotypes A, C, W-135, and Y. In August, the Food and Drug Administration approved the vaccine for infants and toddlers older than 2 months.

However, because of the extremely low incidence of meningococcal disease in children in the United States, the committee did not recommend it for all healthy children. "Very few children are considered at increased risk, so a routine recommendation would prevent just a very low number of cases," said Jessica MacNeil, an epidemiologist with the CDC.

The FDA licensing of MenACWY-CRM and ACIP’s recommendation give pediatricians a third option for infant meningococcal vaccination. HibMenCY-TT (MenHibrix) and MenACWY-D (Menactra) are also approved for some of these same indications. However, Ms. MacNeil noted, Menactra cannot be used in children with asplenia, and MenHibrix can’t be used for travel or as a booster dose.

The committee based its decision on three phase III safety and efficacy trials. These studies comprised nearly 11,000 infants – 9,000 of whom had the four-dose series and 2,000 of whom had a two-dose series, said Dr. Peter Dull of Novartis Vaccines.

The studies confirmed an average 90% efficacy against all four serotypes after the 12-month dose. By 40 months of age, efficacy had waned somewhat: 10% of infants had a seroresponse to type A; 34%, to type C; 76%, to type W-135; and 67%, to type Y. Of the strains included in the vaccine, types C, Y, and W-135 cause 75% of meningococcal disease in those aged 11 years and older.

Dr. Dull said that Novartis is following a cohort that received the vaccine as infants; next year, 60-month immunogenicity data will be available.

After adjustment for some confounders, the vaccine did not significantly interact with the immunogenic potential of other recommended childhood vaccines. Novartis studies also found it safe. Up to 60% of children had mild to moderate injection site reactions. The incidence of systemic reactions was no different from that for routine vaccines alone.

There were 11 serious adverse events possibly related to the vaccine among the 5,000 children included in the safety analyses. These included acute encephalomyelitis, cellulitis, complex partial seizure, epilepsy, febrile seizure, and Kawasaki disease. Ten deaths occurred, but were not considered vaccine related.

The recommended dosing schedule will be:

• Aged 2-6 months: Four doses at 2, 4, 6, and 12 months.

• Aged 7-23 months: Two doses with the second dose given in the second year of life.

• Aged 2-11 years: One or two doses.

Boosters should be given to those who remain at risk, beginning at 3 years after the primary series and then every 5 years thereafter.

The committee also agreed, by a vote of 14 with one abstention, to include MenACWY-CRM in the Vaccines for Children program.

One member who voted disclosed that her institution receives research funding from drug companies. None of the other voting members had any relevant financial disclosures.

msullivan@frontlinemedcom.com

The quadrivalent meningococcal vaccine MenACWY-CRM, or Menveo, may now be given to infants aged 2-23 months who are considered at high risk for meningococcal disease or who travel to areas where it is hyperendemic or epidemic, according to the recommendations of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

High-risk children are those with component complement deficiency, HIV infection, or anatomic or functional asplenia. Children in an outbreak of a vaccine-preventable meningitis serogroup also should receive the series. About 5,000 infants per year fit into these categories.

The Advisory Committee on Immunization Practices (ACIP) approved the decision by a vote of 13-1, with one abstention. The decision aligns ACIP’s recommendation with the recently expanded indication for the vaccine, which protects against serotypes A, C, W-135, and Y. In August, the Food and Drug Administration approved the vaccine for infants and toddlers older than 2 months.

However, because of the extremely low incidence of meningococcal disease in children in the United States, the committee did not recommend it for all healthy children. "Very few children are considered at increased risk, so a routine recommendation would prevent just a very low number of cases," said Jessica MacNeil, an epidemiologist with the CDC.

The FDA licensing of MenACWY-CRM and ACIP’s recommendation give pediatricians a third option for infant meningococcal vaccination. HibMenCY-TT (MenHibrix) and MenACWY-D (Menactra) are also approved for some of these same indications. However, Ms. MacNeil noted, Menactra cannot be used in children with asplenia, and MenHibrix can’t be used for travel or as a booster dose.

The committee based its decision on three phase III safety and efficacy trials. These studies comprised nearly 11,000 infants – 9,000 of whom had the four-dose series and 2,000 of whom had a two-dose series, said Dr. Peter Dull of Novartis Vaccines.

The studies confirmed an average 90% efficacy against all four serotypes after the 12-month dose. By 40 months of age, efficacy had waned somewhat: 10% of infants had a seroresponse to type A; 34%, to type C; 76%, to type W-135; and 67%, to type Y. Of the strains included in the vaccine, types C, Y, and W-135 cause 75% of meningococcal disease in those aged 11 years and older.

Dr. Dull said that Novartis is following a cohort that received the vaccine as infants; next year, 60-month immunogenicity data will be available.

After adjustment for some confounders, the vaccine did not significantly interact with the immunogenic potential of other recommended childhood vaccines. Novartis studies also found it safe. Up to 60% of children had mild to moderate injection site reactions. The incidence of systemic reactions was no different from that for routine vaccines alone.

There were 11 serious adverse events possibly related to the vaccine among the 5,000 children included in the safety analyses. These included acute encephalomyelitis, cellulitis, complex partial seizure, epilepsy, febrile seizure, and Kawasaki disease. Ten deaths occurred, but were not considered vaccine related.

The recommended dosing schedule will be:

• Aged 2-6 months: Four doses at 2, 4, 6, and 12 months.

• Aged 7-23 months: Two doses with the second dose given in the second year of life.

• Aged 2-11 years: One or two doses.

Boosters should be given to those who remain at risk, beginning at 3 years after the primary series and then every 5 years thereafter.

The committee also agreed, by a vote of 14 with one abstention, to include MenACWY-CRM in the Vaccines for Children program.

One member who voted disclosed that her institution receives research funding from drug companies. None of the other voting members had any relevant financial disclosures.

msullivan@frontlinemedcom.com

WASHINGTON – Community-acquired methicillin-resistant Staphylococcus aureus should be considered in the differential diagnosis of skin and soft tissue infections, as well as neonatal eye infections, Dr. Morven Edwards said at a practical pediatrics meeting sponsored by the American Academy of Pediatrics.

Dr. Edwards, an infectious disease specialist at Texas Children’s Hospital, Houston, said that unlike a decade ago, she now considers community-acquired MRSA as a possible cause "in almost any manifestation of a problem with the skin or soft tissue, even including those entities that we used to think were caused by other microorganisms."

For example, in the past, perianal dermatitis in a young infant "was essentially a pathognomonic presentation for group A strep infection," which did not even require a culture for an accurate diagnosis and appropriate treatment, said Dr. Edwards, who is a professor of pediatrics at Baylor College of Medicine, Houston.

She referred to a small retrospective study of children between the ages of 5 months and 12 years with perianal erythema, which found that the dominant culture results were MRSA and methicillin-sensitive S. aureus (MSSA), some streptococci, and some mixed infections. In the past, staphylococcal skin and soft tissue infections were considered uncommon among healthy term newborns discharged home, "unless it was just a very mild diaper dermatitis," she noted.

In a 2006 study of healthy term babies who returned to the hospital within a month of discharge to Texas Children’s Hospital’s emergency department, cases of MRSA peaked at 8-12 days after discharge. Almost all were skin and soft tissue infections (SSTIs), and some of the babies had mild, pustular skin disease and were treated as outpatients with topical therapy and/or oral antistaphylococcal medications. But almost 40% required admission for incision and drainage and parenteral antibiotic therapy.

Dr. Edwards referred to a case of an SSTI that started with a stubbed toe and progressed to a disseminated staphylococcal infection and endocarditis – illustrating that "even with an apparently limited minor staph infection, it always should go through our minds that this could be one that’s more serious."

The healthy teenage boy had stubbed his toe during a wrestling match, then developed fever, fatigue, and buttock and back pain, along with swelling and pain in the toe 4 days later. A fracture was diagnosed at an urgent care clinic, and he was sent home, but 9 days after the initial injury, symptoms persisted and he was admitted to the hospital for treatment with broad-spectrum antimicrobials, including clindamycin.

On the fourth day in the hospital, he had a fever of 104° F, "massive" facial swelling, bibasilar crackles, a systolic murmur, left lower quadrant pain, and a large parietal abscess seen on MRI. He had vegetations on the anterior leaflet of the mitral valve and multiple microemboli to the brain. The abscess was drained, and he had a vegetectomy, where vegetation was "peeled" off the leaflet, leaving the valve intact. After 6 weeks of intravenous antimicrobial treatment, he did well and was discharged.

"The lesson is that a seemingly innocuous SSTI always has the potential to disseminate," Dr. Edwards said, adding that while this is very uncommon, especially in a healthy child, "it’s always something to keep in mind."

Transmitted by direct contact, risk factors for community-acquired MRSA include chronic skin conditions, participation in sports teams that involve close contact with other players, and a history of such infections in family members, she noted.

In infants, MRSA infection also should be included in the differential diagnosis of ophthalmia neonatorum, Dr. Edwards said. She described the case of a healthy term 4-day-old baby who presented with eye swelling and purulent discharge, but no other systemic findings. The mother’s pregnancy had been uncomplicated; maternal tests were negative for group B streptococcus, chlamydia, and Neisseria gonorrhoea; and the baby had been discharged home by the second day after a normal vaginal birth.

The cause turned out to be community-acquired MRSA infection. "We need to consider this diagnosis with a higher index of suspicion in young infants now," she said, noting that the peak onset is at age 4-6 days, and it is characterized by a purulent discharge not likely to be a gonococcal infection. The baby was admitted to the hospital and treated with parenteral antimicrobial therapy.

Dr. Edwards disclosed that she is a consultant for and has received research funds from Novartis related to the development of a group B streptococcus vaccine.

emechcatie@frontlinemedcom.com

WASHINGTON – Community-acquired methicillin-resistant Staphylococcus aureus should be considered in the differential diagnosis of skin and soft tissue infections, as well as neonatal eye infections, Dr. Morven Edwards said at a practical pediatrics meeting sponsored by the American Academy of Pediatrics.

Dr. Edwards, an infectious disease specialist at Texas Children’s Hospital, Houston, said that unlike a decade ago, she now considers community-acquired MRSA as a possible cause "in almost any manifestation of a problem with the skin or soft tissue, even including those entities that we used to think were caused by other microorganisms."

For example, in the past, perianal dermatitis in a young infant "was essentially a pathognomonic presentation for group A strep infection," which did not even require a culture for an accurate diagnosis and appropriate treatment, said Dr. Edwards, who is a professor of pediatrics at Baylor College of Medicine, Houston.

She referred to a small retrospective study of children between the ages of 5 months and 12 years with perianal erythema, which found that the dominant culture results were MRSA and methicillin-sensitive S. aureus (MSSA), some streptococci, and some mixed infections. In the past, staphylococcal skin and soft tissue infections were considered uncommon among healthy term newborns discharged home, "unless it was just a very mild diaper dermatitis," she noted.

In a 2006 study of healthy term babies who returned to the hospital within a month of discharge to Texas Children’s Hospital’s emergency department, cases of MRSA peaked at 8-12 days after discharge. Almost all were skin and soft tissue infections (SSTIs), and some of the babies had mild, pustular skin disease and were treated as outpatients with topical therapy and/or oral antistaphylococcal medications. But almost 40% required admission for incision and drainage and parenteral antibiotic therapy.

Dr. Edwards referred to a case of an SSTI that started with a stubbed toe and progressed to a disseminated staphylococcal infection and endocarditis – illustrating that "even with an apparently limited minor staph infection, it always should go through our minds that this could be one that’s more serious."

The healthy teenage boy had stubbed his toe during a wrestling match, then developed fever, fatigue, and buttock and back pain, along with swelling and pain in the toe 4 days later. A fracture was diagnosed at an urgent care clinic, and he was sent home, but 9 days after the initial injury, symptoms persisted and he was admitted to the hospital for treatment with broad-spectrum antimicrobials, including clindamycin.

On the fourth day in the hospital, he had a fever of 104° F, "massive" facial swelling, bibasilar crackles, a systolic murmur, left lower quadrant pain, and a large parietal abscess seen on MRI. He had vegetations on the anterior leaflet of the mitral valve and multiple microemboli to the brain. The abscess was drained, and he had a vegetectomy, where vegetation was "peeled" off the leaflet, leaving the valve intact. After 6 weeks of intravenous antimicrobial treatment, he did well and was discharged.

"The lesson is that a seemingly innocuous SSTI always has the potential to disseminate," Dr. Edwards said, adding that while this is very uncommon, especially in a healthy child, "it’s always something to keep in mind."

Transmitted by direct contact, risk factors for community-acquired MRSA include chronic skin conditions, participation in sports teams that involve close contact with other players, and a history of such infections in family members, she noted.

In infants, MRSA infection also should be included in the differential diagnosis of ophthalmia neonatorum, Dr. Edwards said. She described the case of a healthy term 4-day-old baby who presented with eye swelling and purulent discharge, but no other systemic findings. The mother’s pregnancy had been uncomplicated; maternal tests were negative for group B streptococcus, chlamydia, and Neisseria gonorrhoea; and the baby had been discharged home by the second day after a normal vaginal birth.

The cause turned out to be community-acquired MRSA infection. "We need to consider this diagnosis with a higher index of suspicion in young infants now," she said, noting that the peak onset is at age 4-6 days, and it is characterized by a purulent discharge not likely to be a gonococcal infection. The baby was admitted to the hospital and treated with parenteral antimicrobial therapy.

Dr. Edwards disclosed that she is a consultant for and has received research funds from Novartis related to the development of a group B streptococcus vaccine.

emechcatie@frontlinemedcom.com

WASHINGTON – Community-acquired methicillin-resistant Staphylococcus aureus should be considered in the differential diagnosis of skin and soft tissue infections, as well as neonatal eye infections, Dr. Morven Edwards said at a practical pediatrics meeting sponsored by the American Academy of Pediatrics.

Dr. Edwards, an infectious disease specialist at Texas Children’s Hospital, Houston, said that unlike a decade ago, she now considers community-acquired MRSA as a possible cause "in almost any manifestation of a problem with the skin or soft tissue, even including those entities that we used to think were caused by other microorganisms."

For example, in the past, perianal dermatitis in a young infant "was essentially a pathognomonic presentation for group A strep infection," which did not even require a culture for an accurate diagnosis and appropriate treatment, said Dr. Edwards, who is a professor of pediatrics at Baylor College of Medicine, Houston.

She referred to a small retrospective study of children between the ages of 5 months and 12 years with perianal erythema, which found that the dominant culture results were MRSA and methicillin-sensitive S. aureus (MSSA), some streptococci, and some mixed infections. In the past, staphylococcal skin and soft tissue infections were considered uncommon among healthy term newborns discharged home, "unless it was just a very mild diaper dermatitis," she noted.

In a 2006 study of healthy term babies who returned to the hospital within a month of discharge to Texas Children’s Hospital’s emergency department, cases of MRSA peaked at 8-12 days after discharge. Almost all were skin and soft tissue infections (SSTIs), and some of the babies had mild, pustular skin disease and were treated as outpatients with topical therapy and/or oral antistaphylococcal medications. But almost 40% required admission for incision and drainage and parenteral antibiotic therapy.

Dr. Edwards referred to a case of an SSTI that started with a stubbed toe and progressed to a disseminated staphylococcal infection and endocarditis – illustrating that "even with an apparently limited minor staph infection, it always should go through our minds that this could be one that’s more serious."

The healthy teenage boy had stubbed his toe during a wrestling match, then developed fever, fatigue, and buttock and back pain, along with swelling and pain in the toe 4 days later. A fracture was diagnosed at an urgent care clinic, and he was sent home, but 9 days after the initial injury, symptoms persisted and he was admitted to the hospital for treatment with broad-spectrum antimicrobials, including clindamycin.

On the fourth day in the hospital, he had a fever of 104° F, "massive" facial swelling, bibasilar crackles, a systolic murmur, left lower quadrant pain, and a large parietal abscess seen on MRI. He had vegetations on the anterior leaflet of the mitral valve and multiple microemboli to the brain. The abscess was drained, and he had a vegetectomy, where vegetation was "peeled" off the leaflet, leaving the valve intact. After 6 weeks of intravenous antimicrobial treatment, he did well and was discharged.

"The lesson is that a seemingly innocuous SSTI always has the potential to disseminate," Dr. Edwards said, adding that while this is very uncommon, especially in a healthy child, "it’s always something to keep in mind."

Transmitted by direct contact, risk factors for community-acquired MRSA include chronic skin conditions, participation in sports teams that involve close contact with other players, and a history of such infections in family members, she noted.

In infants, MRSA infection also should be included in the differential diagnosis of ophthalmia neonatorum, Dr. Edwards said. She described the case of a healthy term 4-day-old baby who presented with eye swelling and purulent discharge, but no other systemic findings. The mother’s pregnancy had been uncomplicated; maternal tests were negative for group B streptococcus, chlamydia, and Neisseria gonorrhoea; and the baby had been discharged home by the second day after a normal vaginal birth.

The cause turned out to be community-acquired MRSA infection. "We need to consider this diagnosis with a higher index of suspicion in young infants now," she said, noting that the peak onset is at age 4-6 days, and it is characterized by a purulent discharge not likely to be a gonococcal infection. The baby was admitted to the hospital and treated with parenteral antimicrobial therapy.

Dr. Edwards disclosed that she is a consultant for and has received research funds from Novartis related to the development of a group B streptococcus vaccine.

emechcatie@frontlinemedcom.com

Inducing hypothermia in patients with severe bacterial meningitis offers no clinical benefit and might, in fact, be harmful, according to a clinical trial conducted in France.

Investigators had planned to enroll up to 318 patients in a randomized trial comparing hypothermia treatment to standard care, conducted at 49 intensive care units in France between February 2009 and November 2011. They halted the trial, however, after enrolling the first 98 patients because of concerns by the data and safety monitoring board about excess mortality among those randomized to receive hypothermia treatment, which consisted of a loading dose of 4°C/39°F cold saline and cooling the patient to 32°C/90°F to 34°C/93°F for 48 hours, then passive warming. The trial was led by Dr. Bruno Mourvillier of the Groupe Hospitalier Bichat-Claude Bernard in Paris.

Twenty-five of 49 patients (51%) in the hypothermia group died, compared with 15 of 49 patients (31%) receiving standard care (relative risk, 1.99). Pneumococcal meningitis was diagnosed in 77% of patients. At 3 months, 42 of 49 patients (86%) in the hypothermia group and 36 of 49 patients (74%) in the control group had an unfavorable outcome (RR, 2.17), as gauged by the Glasgow Outcome Scale.

After adjustment for age, scores on the Glasgow Coma Scale at the point of study inclusion, and the presence of septic shock at study inclusion, mortality remained higher in the hypothermia group, but not significantly (hazard ratio, 1.76). However, a post hoc analysis showed a low probability to reach statistical significance in favor of hypothermia by the end of the three original planned stages of the trial.

The study, published online (JAMA 2013 Oct. 8 [doi:10.1001/jama.2013.280506]), was released at the European Society of Intensive Care Medicine’s annual congress in Paris.

Potential mechanisms behind the mortality difference "remain unclear," the authors wrote, noting that they found no difference in nosocomial infections, hemorrhage, cardiovascular effects, or hyperglycemia between the treatment groups. In addition, no significant differences were found in baseline characteristics. All patients received mechanical ventilation and were severely ill, with an average Glasgow Coma Scale rating of 7.

In animal model studies of meningitis, moderate hypothermia has shown favorable effects, such as lowering intracranial pressure and reducing cerebral injury, Dr. Mourvillier and associates noted. They hypothesized that hypothermia would improve functional outcome at 3 months.

"Our trial does not support the use of hypothermia in adults with severe meningitis," they concluded. "Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Our results may have important implications for future trials on hypothermia in patients presenting with septic shock or stroke."

Careful evaluation of safety issues in ongoing trials is needed, they said.

The study was supported by the French Ministry of Health, IST Cardiology, and Covidien. The authors reported no conflicts of interest.

Inducing hypothermia in patients with severe bacterial meningitis offers no clinical benefit and might, in fact, be harmful, according to a clinical trial conducted in France.

Investigators had planned to enroll up to 318 patients in a randomized trial comparing hypothermia treatment to standard care, conducted at 49 intensive care units in France between February 2009 and November 2011. They halted the trial, however, after enrolling the first 98 patients because of concerns by the data and safety monitoring board about excess mortality among those randomized to receive hypothermia treatment, which consisted of a loading dose of 4°C/39°F cold saline and cooling the patient to 32°C/90°F to 34°C/93°F for 48 hours, then passive warming. The trial was led by Dr. Bruno Mourvillier of the Groupe Hospitalier Bichat-Claude Bernard in Paris.

Twenty-five of 49 patients (51%) in the hypothermia group died, compared with 15 of 49 patients (31%) receiving standard care (relative risk, 1.99). Pneumococcal meningitis was diagnosed in 77% of patients. At 3 months, 42 of 49 patients (86%) in the hypothermia group and 36 of 49 patients (74%) in the control group had an unfavorable outcome (RR, 2.17), as gauged by the Glasgow Outcome Scale.

After adjustment for age, scores on the Glasgow Coma Scale at the point of study inclusion, and the presence of septic shock at study inclusion, mortality remained higher in the hypothermia group, but not significantly (hazard ratio, 1.76). However, a post hoc analysis showed a low probability to reach statistical significance in favor of hypothermia by the end of the three original planned stages of the trial.

The study, published online (JAMA 2013 Oct. 8 [doi:10.1001/jama.2013.280506]), was released at the European Society of Intensive Care Medicine’s annual congress in Paris.

Potential mechanisms behind the mortality difference "remain unclear," the authors wrote, noting that they found no difference in nosocomial infections, hemorrhage, cardiovascular effects, or hyperglycemia between the treatment groups. In addition, no significant differences were found in baseline characteristics. All patients received mechanical ventilation and were severely ill, with an average Glasgow Coma Scale rating of 7.

In animal model studies of meningitis, moderate hypothermia has shown favorable effects, such as lowering intracranial pressure and reducing cerebral injury, Dr. Mourvillier and associates noted. They hypothesized that hypothermia would improve functional outcome at 3 months.

"Our trial does not support the use of hypothermia in adults with severe meningitis," they concluded. "Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Our results may have important implications for future trials on hypothermia in patients presenting with septic shock or stroke."

Careful evaluation of safety issues in ongoing trials is needed, they said.

The study was supported by the French Ministry of Health, IST Cardiology, and Covidien. The authors reported no conflicts of interest.

Inducing hypothermia in patients with severe bacterial meningitis offers no clinical benefit and might, in fact, be harmful, according to a clinical trial conducted in France.

Investigators had planned to enroll up to 318 patients in a randomized trial comparing hypothermia treatment to standard care, conducted at 49 intensive care units in France between February 2009 and November 2011. They halted the trial, however, after enrolling the first 98 patients because of concerns by the data and safety monitoring board about excess mortality among those randomized to receive hypothermia treatment, which consisted of a loading dose of 4°C/39°F cold saline and cooling the patient to 32°C/90°F to 34°C/93°F for 48 hours, then passive warming. The trial was led by Dr. Bruno Mourvillier of the Groupe Hospitalier Bichat-Claude Bernard in Paris.

Twenty-five of 49 patients (51%) in the hypothermia group died, compared with 15 of 49 patients (31%) receiving standard care (relative risk, 1.99). Pneumococcal meningitis was diagnosed in 77% of patients. At 3 months, 42 of 49 patients (86%) in the hypothermia group and 36 of 49 patients (74%) in the control group had an unfavorable outcome (RR, 2.17), as gauged by the Glasgow Outcome Scale.

After adjustment for age, scores on the Glasgow Coma Scale at the point of study inclusion, and the presence of septic shock at study inclusion, mortality remained higher in the hypothermia group, but not significantly (hazard ratio, 1.76). However, a post hoc analysis showed a low probability to reach statistical significance in favor of hypothermia by the end of the three original planned stages of the trial.

The study, published online (JAMA 2013 Oct. 8 [doi:10.1001/jama.2013.280506]), was released at the European Society of Intensive Care Medicine’s annual congress in Paris.

Potential mechanisms behind the mortality difference "remain unclear," the authors wrote, noting that they found no difference in nosocomial infections, hemorrhage, cardiovascular effects, or hyperglycemia between the treatment groups. In addition, no significant differences were found in baseline characteristics. All patients received mechanical ventilation and were severely ill, with an average Glasgow Coma Scale rating of 7.

In animal model studies of meningitis, moderate hypothermia has shown favorable effects, such as lowering intracranial pressure and reducing cerebral injury, Dr. Mourvillier and associates noted. They hypothesized that hypothermia would improve functional outcome at 3 months.

"Our trial does not support the use of hypothermia in adults with severe meningitis," they concluded. "Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Our results may have important implications for future trials on hypothermia in patients presenting with septic shock or stroke."

Careful evaluation of safety issues in ongoing trials is needed, they said.

The study was supported by the French Ministry of Health, IST Cardiology, and Covidien. The authors reported no conflicts of interest.