Immunology

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."

[email protected]

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."

[email protected]

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."

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

A two-dose varicella vaccination program, begun in 2006, has been shown to be more effective in promoting population immunity than the single-dose regimen introduced more than a decade earlier, in addition to further reducing disease severity and incidence.

Although the single-dose regimen, implemented in 1995, was associated with dramatic declines in varicella-related illness and deaths of 90% and 88%, respectively (Pediatrics 2011;128:214-20), a new study, published online Oct. 7 in Pediatrics showed that implementation of the two-dose scheme not only slashed cases further, but conferred protection even among unvaccinated infants and adults (Pediatrics 2013;132:1-7 [doi: 10.1542/peds.2013-0863]).

© Design Pics

For their research, Dr. Stephanie R. Bialek of the National Center for Immunization and Respiratory Diseases, Atlanta, and her colleagues analyzed incidence rates and disease characteristics in two metropolitan centers totaling 650,000 in population between 1995 and 2010; one was a suburb of Los Angeles and the other was an inner-city area of Philadelphia. The study period covered the rollout of the single-dose vaccine and the two-dose scheme.

In 2010, the California surveillance area showed an incidence of 0.3 cases per 1,000 population, a decline of 76% since 2006 and a 97% decline from 1995. The Pennsylvania site, with 0.1 cases per 1,000, saw a 67% decline since 2006 and a 97% decline since 1995. From 2006 to 2010, 61.7% of case patients in both surveillance areas had been vaccinated with a single dose and 7.5% with two doses. Hospitalizations declined by half in both areas between 2006 and 2010.

Approximately 15%-20% of children do not adequately respond to a single dose of vaccine, Dr. Bialek and her colleagues noted, and the two surveillance areas continued to see outbreaks even after the single-dose scheme was in effect. About 65% of outbreak cases after 2007 in California had received one dose, and a larger proportion had milder disease (50 lesions or less) than in outbreaks earlier in the study period. During the two-dose period, the California surveillance area saw a fourfold decrease in outbreaks while the Pennsylvania area reported no outbreaks at all.

"The substantial declines in varicella incidence and outbreaks we report on from these two active surveillance areas during the first 5 years of the two-dose varicella vaccination program provide additional evidence of the program’s sustained impact," Dr. Bialek and her colleagues wrote in their analysis. "With full implementation of the two-dose varicella vaccination program, it may be possible to eliminate the most severe outcomes of varicella."

Dr. Bialek and her colleagues noted as limitations to their study the fact that not all cases reported in the study were laboratory confirmed, allowing for potential overreporting of cases and an underestimation of declines. They also acknowledged that some varicella cases may not have been reported, leading to overestimation of declines, and that their data sources for estimating two-dose coverage levels were limited.

The research was publicly funded, and none of the investigators reported conflicts of interest.

A two-dose varicella vaccination program, begun in 2006, has been shown to be more effective in promoting population immunity than the single-dose regimen introduced more than a decade earlier, in addition to further reducing disease severity and incidence.

Although the single-dose regimen, implemented in 1995, was associated with dramatic declines in varicella-related illness and deaths of 90% and 88%, respectively (Pediatrics 2011;128:214-20), a new study, published online Oct. 7 in Pediatrics showed that implementation of the two-dose scheme not only slashed cases further, but conferred protection even among unvaccinated infants and adults (Pediatrics 2013;132:1-7 [doi: 10.1542/peds.2013-0863]).

© Design Pics

For their research, Dr. Stephanie R. Bialek of the National Center for Immunization and Respiratory Diseases, Atlanta, and her colleagues analyzed incidence rates and disease characteristics in two metropolitan centers totaling 650,000 in population between 1995 and 2010; one was a suburb of Los Angeles and the other was an inner-city area of Philadelphia. The study period covered the rollout of the single-dose vaccine and the two-dose scheme.

In 2010, the California surveillance area showed an incidence of 0.3 cases per 1,000 population, a decline of 76% since 2006 and a 97% decline from 1995. The Pennsylvania site, with 0.1 cases per 1,000, saw a 67% decline since 2006 and a 97% decline since 1995. From 2006 to 2010, 61.7% of case patients in both surveillance areas had been vaccinated with a single dose and 7.5% with two doses. Hospitalizations declined by half in both areas between 2006 and 2010.

Approximately 15%-20% of children do not adequately respond to a single dose of vaccine, Dr. Bialek and her colleagues noted, and the two surveillance areas continued to see outbreaks even after the single-dose scheme was in effect. About 65% of outbreak cases after 2007 in California had received one dose, and a larger proportion had milder disease (50 lesions or less) than in outbreaks earlier in the study period. During the two-dose period, the California surveillance area saw a fourfold decrease in outbreaks while the Pennsylvania area reported no outbreaks at all.

"The substantial declines in varicella incidence and outbreaks we report on from these two active surveillance areas during the first 5 years of the two-dose varicella vaccination program provide additional evidence of the program’s sustained impact," Dr. Bialek and her colleagues wrote in their analysis. "With full implementation of the two-dose varicella vaccination program, it may be possible to eliminate the most severe outcomes of varicella."

Dr. Bialek and her colleagues noted as limitations to their study the fact that not all cases reported in the study were laboratory confirmed, allowing for potential overreporting of cases and an underestimation of declines. They also acknowledged that some varicella cases may not have been reported, leading to overestimation of declines, and that their data sources for estimating two-dose coverage levels were limited.

The research was publicly funded, and none of the investigators reported conflicts of interest.

A two-dose varicella vaccination program, begun in 2006, has been shown to be more effective in promoting population immunity than the single-dose regimen introduced more than a decade earlier, in addition to further reducing disease severity and incidence.

Although the single-dose regimen, implemented in 1995, was associated with dramatic declines in varicella-related illness and deaths of 90% and 88%, respectively (Pediatrics 2011;128:214-20), a new study, published online Oct. 7 in Pediatrics showed that implementation of the two-dose scheme not only slashed cases further, but conferred protection even among unvaccinated infants and adults (Pediatrics 2013;132:1-7 [doi: 10.1542/peds.2013-0863]).

© Design Pics

For their research, Dr. Stephanie R. Bialek of the National Center for Immunization and Respiratory Diseases, Atlanta, and her colleagues analyzed incidence rates and disease characteristics in two metropolitan centers totaling 650,000 in population between 1995 and 2010; one was a suburb of Los Angeles and the other was an inner-city area of Philadelphia. The study period covered the rollout of the single-dose vaccine and the two-dose scheme.

In 2010, the California surveillance area showed an incidence of 0.3 cases per 1,000 population, a decline of 76% since 2006 and a 97% decline from 1995. The Pennsylvania site, with 0.1 cases per 1,000, saw a 67% decline since 2006 and a 97% decline since 1995. From 2006 to 2010, 61.7% of case patients in both surveillance areas had been vaccinated with a single dose and 7.5% with two doses. Hospitalizations declined by half in both areas between 2006 and 2010.

Approximately 15%-20% of children do not adequately respond to a single dose of vaccine, Dr. Bialek and her colleagues noted, and the two surveillance areas continued to see outbreaks even after the single-dose scheme was in effect. About 65% of outbreak cases after 2007 in California had received one dose, and a larger proportion had milder disease (50 lesions or less) than in outbreaks earlier in the study period. During the two-dose period, the California surveillance area saw a fourfold decrease in outbreaks while the Pennsylvania area reported no outbreaks at all.

"The substantial declines in varicella incidence and outbreaks we report on from these two active surveillance areas during the first 5 years of the two-dose varicella vaccination program provide additional evidence of the program’s sustained impact," Dr. Bialek and her colleagues wrote in their analysis. "With full implementation of the two-dose varicella vaccination program, it may be possible to eliminate the most severe outcomes of varicella."

Dr. Bialek and her colleagues noted as limitations to their study the fact that not all cases reported in the study were laboratory confirmed, allowing for potential overreporting of cases and an underestimation of declines. They also acknowledged that some varicella cases may not have been reported, leading to overestimation of declines, and that their data sources for estimating two-dose coverage levels were limited.

The research was publicly funded, and none of the investigators reported conflicts of interest.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

SAN FRANCISCO – An investigational norovirus vaccine safely reduced the vomiting and diarrhea associated with norovirus genotype GII.4, the most common strain of the disease, in a randomized, double-blind, placebo-controlled trial.

Study subjects were randomized to receive either placebo or the bivalent vaccine, which also targets norovirus genotype GI.1 (the Norwalk strain), and they subsequently drank water containing a significant amount of the GII.4 strain of the virus. Infection with the challenge virus occurred in 52% of 56 subjects in the vaccine group and 60.4% of 53 subjects in the placebo group. Significantly fewer patients with infection in the vaccine group, compared with the placebo group, reported severe vomiting and/or diarrhea (0% vs. 8.3%), moderate or severe diarrhea or vomiting (6.0% vs. 18.8%), and vomiting and/or diarrhea of any severity (20.0% vs. 41.7%), Dr. David I. Bernstein reported during a press conference at an annual scientific meeting on infectious diseases.

Also, fewer subjects in the vaccine group shed norovirus at day 10 after the challenge (22.4% vs. 36.2%), according to Dr. Bernstein of Cincinnati Children’s Hospital Medical Center and the University of Cincinnati.

Participants in this multicenter trial were adults aged 18-50 years who were injected twice, 28 days apart, with either placebo or the vaccine – a virus-like particle vaccine adjuvanted with monophosphoryl lipid A (MPL) and alum. The virus challenge included 4,000 real-time polymerase chain reaction genome equivalents of a heterologous GII.4 norovirus. Subjects were isolated for 4 days as inpatients following the challenge, during which time they were monitored for infection.

"We are excited about the results," Dr. Bernstein said, noting that the findings with respect to the effect on severe symptoms are particularly encouraging because it is severe disease that is of the most concern.

Larger trials in a real-world setting are planned, he said.

Norovirus is the leading cause of acute gastroenteritis among both adults and children, and it is highly contagious. Significant outbreaks occur in many settings where people are in close quarters, including health care facilities, child care centers, cruise ships, and in the military, he said.

In fact, 19-21 million Americans are infected each year, and as many as 800 die from the infection. Children and older adults are particularly vulnerable to developing more serious illness.

"Until recently we accepted [norovirus] as a part of life, but this research gives us a glimmer as to a very different future," said Dr. Andrew T. Pavia of the University of Utah, Salt Lake City, the press conference moderator.

Indeed, one could envision a scenario in which this vaccine, if ultimately approved, could be used to help prevent norovirus among nursing home residents, members of the military, cruise ship passengers, and children in school settings, Dr. Bernstein said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

"This [research] is a good start," he said, adding that there is still a long way to go.

If this vaccine proves as safe and effective in the real world as in the challenge setting used in this trial, it would be a minimum of 5 years before a commercial vaccine was available, he estimated.

Dr. Bernstein reporting serving as an investigator for and receiving research support from LigoCyte Inc., the maker of the investigational vaccine. He also receives royalties for a different norovirus vaccine.

 To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

SAN FRANCISCO – An investigational norovirus vaccine safely reduced the vomiting and diarrhea associated with norovirus genotype GII.4, the most common strain of the disease, in a randomized, double-blind, placebo-controlled trial.

Study subjects were randomized to receive either placebo or the bivalent vaccine, which also targets norovirus genotype GI.1 (the Norwalk strain), and they subsequently drank water containing a significant amount of the GII.4 strain of the virus. Infection with the challenge virus occurred in 52% of 56 subjects in the vaccine group and 60.4% of 53 subjects in the placebo group. Significantly fewer patients with infection in the vaccine group, compared with the placebo group, reported severe vomiting and/or diarrhea (0% vs. 8.3%), moderate or severe diarrhea or vomiting (6.0% vs. 18.8%), and vomiting and/or diarrhea of any severity (20.0% vs. 41.7%), Dr. David I. Bernstein reported during a press conference at an annual scientific meeting on infectious diseases.

Also, fewer subjects in the vaccine group shed norovirus at day 10 after the challenge (22.4% vs. 36.2%), according to Dr. Bernstein of Cincinnati Children’s Hospital Medical Center and the University of Cincinnati.

Participants in this multicenter trial were adults aged 18-50 years who were injected twice, 28 days apart, with either placebo or the vaccine – a virus-like particle vaccine adjuvanted with monophosphoryl lipid A (MPL) and alum. The virus challenge included 4,000 real-time polymerase chain reaction genome equivalents of a heterologous GII.4 norovirus. Subjects were isolated for 4 days as inpatients following the challenge, during which time they were monitored for infection.

"We are excited about the results," Dr. Bernstein said, noting that the findings with respect to the effect on severe symptoms are particularly encouraging because it is severe disease that is of the most concern.

Larger trials in a real-world setting are planned, he said.

Norovirus is the leading cause of acute gastroenteritis among both adults and children, and it is highly contagious. Significant outbreaks occur in many settings where people are in close quarters, including health care facilities, child care centers, cruise ships, and in the military, he said.

In fact, 19-21 million Americans are infected each year, and as many as 800 die from the infection. Children and older adults are particularly vulnerable to developing more serious illness.

"Until recently we accepted [norovirus] as a part of life, but this research gives us a glimmer as to a very different future," said Dr. Andrew T. Pavia of the University of Utah, Salt Lake City, the press conference moderator.

Indeed, one could envision a scenario in which this vaccine, if ultimately approved, could be used to help prevent norovirus among nursing home residents, members of the military, cruise ship passengers, and children in school settings, Dr. Bernstein said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

"This [research] is a good start," he said, adding that there is still a long way to go.

If this vaccine proves as safe and effective in the real world as in the challenge setting used in this trial, it would be a minimum of 5 years before a commercial vaccine was available, he estimated.

Dr. Bernstein reporting serving as an investigator for and receiving research support from LigoCyte Inc., the maker of the investigational vaccine. He also receives royalties for a different norovirus vaccine.

 To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

SAN FRANCISCO – An investigational norovirus vaccine safely reduced the vomiting and diarrhea associated with norovirus genotype GII.4, the most common strain of the disease, in a randomized, double-blind, placebo-controlled trial.

Study subjects were randomized to receive either placebo or the bivalent vaccine, which also targets norovirus genotype GI.1 (the Norwalk strain), and they subsequently drank water containing a significant amount of the GII.4 strain of the virus. Infection with the challenge virus occurred in 52% of 56 subjects in the vaccine group and 60.4% of 53 subjects in the placebo group. Significantly fewer patients with infection in the vaccine group, compared with the placebo group, reported severe vomiting and/or diarrhea (0% vs. 8.3%), moderate or severe diarrhea or vomiting (6.0% vs. 18.8%), and vomiting and/or diarrhea of any severity (20.0% vs. 41.7%), Dr. David I. Bernstein reported during a press conference at an annual scientific meeting on infectious diseases.

Also, fewer subjects in the vaccine group shed norovirus at day 10 after the challenge (22.4% vs. 36.2%), according to Dr. Bernstein of Cincinnati Children’s Hospital Medical Center and the University of Cincinnati.

Participants in this multicenter trial were adults aged 18-50 years who were injected twice, 28 days apart, with either placebo or the vaccine – a virus-like particle vaccine adjuvanted with monophosphoryl lipid A (MPL) and alum. The virus challenge included 4,000 real-time polymerase chain reaction genome equivalents of a heterologous GII.4 norovirus. Subjects were isolated for 4 days as inpatients following the challenge, during which time they were monitored for infection.

"We are excited about the results," Dr. Bernstein said, noting that the findings with respect to the effect on severe symptoms are particularly encouraging because it is severe disease that is of the most concern.

Larger trials in a real-world setting are planned, he said.

Norovirus is the leading cause of acute gastroenteritis among both adults and children, and it is highly contagious. Significant outbreaks occur in many settings where people are in close quarters, including health care facilities, child care centers, cruise ships, and in the military, he said.

In fact, 19-21 million Americans are infected each year, and as many as 800 die from the infection. Children and older adults are particularly vulnerable to developing more serious illness.

"Until recently we accepted [norovirus] as a part of life, but this research gives us a glimmer as to a very different future," said Dr. Andrew T. Pavia of the University of Utah, Salt Lake City, the press conference moderator.

Indeed, one could envision a scenario in which this vaccine, if ultimately approved, could be used to help prevent norovirus among nursing home residents, members of the military, cruise ship passengers, and children in school settings, Dr. Bernstein said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

"This [research] is a good start," he said, adding that there is still a long way to go.

If this vaccine proves as safe and effective in the real world as in the challenge setting used in this trial, it would be a minimum of 5 years before a commercial vaccine was available, he estimated.

Dr. Bernstein reporting serving as an investigator for and receiving research support from LigoCyte Inc., the maker of the investigational vaccine. He also receives royalties for a different norovirus vaccine.

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