Meningococcal Vaccine Not Cost Effective in Infants, Toddlers

ATLANTA – Routine infant or toddler immunization against meningococcal disease does not appear to be a cost-effective measure, according to an assessment from a working group of the Advisory Committee on Immunization Practices.

That conclusion was presented to the full committee at its October meeting. If a conjugate meningococcal vaccine is licensed for use in infants before the next Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) meeting Feb. 22-23, the committee will vote on it then, said Dr. Amanda Cohn of the CDC’s National Center for Immunization and Respiratory Disease (NCIRD).

The working group’s assessment was based primarily on the low proportion of preventable disease cases and the high cost of vaccinating infants or toddlers with meningococcal vaccine per case prevented. Moreover, although current meningococcal conjugate vaccines are safe and immunogenic, they show evidence of declining antibodies after about 3 years, suggesting that a booster dose at age 6 years would likely be needed to protect children until the routine 11-to 12-year-old (adolescent) immunization, Dr. Cohn noted.

Jessica MacNeil, MPH, also with NCIRD, presented epidemiologic data showing that meningococcal disease has been declining in all age groups. The data do not suggest this is due to the adolescent immunization program.** The first evidence of an impact of the adolescent immunization program was detected in 2008-2009, when the incidence was 0.14 per 100,000 population among those aged 11-19 years and 0.82 among children less than 1 year of age. In contrast, those rates in 2006-2007 were 0.27 and 1.07, respectively. Moreover, the largest proportion of cases in children aged less than 5 years is due to meningococcal serotype B, which is not included in the any of the vaccines, she noted.

Surveillance data from 1993-2009 show that while 86% of children under 5 years of age who contract meningococcal disease are hospitalized, the case-fatality ratio is low, ranging from 1% for serogroup Y to 10% for serogroup C. A large majority – 75%-80% of children under 5 years with meningococcal disease – survives and recover. Major complications – including skin necrosis, amputation, hearing loss, and death – are less frequent in infants than in adolescents, Ms. MacNeil noted.

In a cost-effectiveness analysis presented by Ismael Ortega-Sanchez, Ph.D., the cost per quality-adjusted life year (QALY) saved for either giving four doses of the vaccine to infants at 2, 4, 6, and 12 months or two doses to toddlers at 9 and 12 months varied with different assumptions of what the vaccine will cost and whether it was given during a season of high or low disease incidence. Assuming a cost of $60 per vaccine dose and an average incidence rate, the costs would be approximately $1,015,000* per QALY saved for infants and $1,036,000* per QALY saved for toddlers.

"Vaccinating infants or toddlers with meningococcal vaccine has a high cost per case prevented, even at a low vaccine price. Cost estimates are much higher than prior analyses because of declining incidence and shorter duration of protection. Infant vaccination prevents twice as many cases as toddler vaccination but at twice the cost," said Dr. Ortega-Sanchez, also with NCIRD.

No conjugate meningococcal vaccine is yet licensed for use in young infants. MenACWY-D (Sanofi Pasteur’s Menactra) is licensed for persons aged 2-55 years as a single dose. In April 2011, it was also licensed as a two-dose series for ages 9-23 months (on a 9- and 12-month schedule). MenACWY-CRM (Novartis’ Menveo), is also licensed as a single dose for ages 2-55 years, and an indication for a 4-dose infant series at 2, 4, 6, and 12 months is under review by the Food and Drug Administration. A combination product, HibMenCY-T (GlaxoSmithKline’s MenHibrix) is under FDA review for a 4 dose infant series, also at 2, 4, 6, and 12 months.

Sanofi Pasteur said in a statement, "With the current incidence of meningococcal disease at an all time low in the United States, a recommendation for children at highest risk is a prudent course of action. CDC has indicated that ACIP would consider making a routine infant recommendation in the future, should U.S. meningococcal disease incidence rates return to the historically higher levels observed prior to the introduction of meningococcal conjugate vaccines in adolescents.

"Sanofi Pasteur supports the ACIP’s recommendation calling for a 2-dose series of meningococcal vaccine for infants and children 9 through 23 months of age who are at high risk for getting meningococcal disease, including those traveling to countries where meningococcal infection is endemic, and those with human immunodeficiency virus (HIV) infection or certain complement component deficiencies. Given the rapid and potentially devastating nature of meningococcal disease and the incidence of infection in children under 1 year of age, we believe this recommendation will make significant strides in helping to protect those at greatest risk for the disease.

And, in a statement from Novartis, "When looking at the incidence of meningococcal disease, it is important to not only look at the number of cases but also the substantial life-long effects of the disease, which include significant psychosocial, economic, and emotional burden for victims’ families and their communities. Novartis believes that health care professionals and parents should have the choice to immunize infants against the potentially devastating consequences of this disease. We will continue our dialogue with the CDC and with ACIP prior to their vote on this matter in February, 2012.

"Infants are at highest risk for meningococcal disease due to the relative immaturity of their immune systems. Approximately 1 in 10 infants under 1 year of age die after contracting meningococcal disease, even with appropriate medical care, and as many as 1 in 5 will suffer serious life-long complications such as limb amputations, seizures, paralysis, hearing loss, and learning disabilities. The health care costs associated with meningococcal disease and the long-term management of its complications are substantial and present a significant public health burden.

"At Novartis, we are committed to eliminating meningococcal disease and we have made a significant effort to develop a safe and effective vaccine to help protect infants."

And, from GSK: "GlaxoSmithKline is committed to making MenHibrix available in the United States. We believe there is a clear public health benefit in recommending meningococcal vaccines for use in infants and toddlers in the United States. Rates of meningococcal disease are highest in infants and toddlers younger than 2 years of age. Approximately 300 cases of meningococcal disease from all serogroups were reported annually in the United States in this age group between 1998 and 2007."

As a CDC employee, Dr. Cohn has no conflicts of interest.

*Correction, 11/8/2011: An earlier version of this story gave the incorrect cost savings per QALY for infants and toddlers with certain doses of the vaccine.

**Correction, 11/9/2011: An earlier version of this story misstated the impact of the adolescent immunization program.

ATLANTA – Routine infant or toddler immunization against meningococcal disease does not appear to be a cost-effective measure, according to an assessment from a working group of the Advisory Committee on Immunization Practices.

That conclusion was presented to the full committee at its October meeting. If a conjugate meningococcal vaccine is licensed for use in infants before the next Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) meeting Feb. 22-23, the committee will vote on it then, said Dr. Amanda Cohn of the CDC’s National Center for Immunization and Respiratory Disease (NCIRD).

The working group’s assessment was based primarily on the low proportion of preventable disease cases and the high cost of vaccinating infants or toddlers with meningococcal vaccine per case prevented. Moreover, although current meningococcal conjugate vaccines are safe and immunogenic, they show evidence of declining antibodies after about 3 years, suggesting that a booster dose at age 6 years would likely be needed to protect children until the routine 11-to 12-year-old (adolescent) immunization, Dr. Cohn noted.

Jessica MacNeil, MPH, also with NCIRD, presented epidemiologic data showing that meningococcal disease has been declining in all age groups. The data do not suggest this is due to the adolescent immunization program.** The first evidence of an impact of the adolescent immunization program was detected in 2008-2009, when the incidence was 0.14 per 100,000 population among those aged 11-19 years and 0.82 among children less than 1 year of age. In contrast, those rates in 2006-2007 were 0.27 and 1.07, respectively. Moreover, the largest proportion of cases in children aged less than 5 years is due to meningococcal serotype B, which is not included in the any of the vaccines, she noted.

Surveillance data from 1993-2009 show that while 86% of children under 5 years of age who contract meningococcal disease are hospitalized, the case-fatality ratio is low, ranging from 1% for serogroup Y to 10% for serogroup C. A large majority – 75%-80% of children under 5 years with meningococcal disease – survives and recover. Major complications – including skin necrosis, amputation, hearing loss, and death – are less frequent in infants than in adolescents, Ms. MacNeil noted.

In a cost-effectiveness analysis presented by Ismael Ortega-Sanchez, Ph.D., the cost per quality-adjusted life year (QALY) saved for either giving four doses of the vaccine to infants at 2, 4, 6, and 12 months or two doses to toddlers at 9 and 12 months varied with different assumptions of what the vaccine will cost and whether it was given during a season of high or low disease incidence. Assuming a cost of $60 per vaccine dose and an average incidence rate, the costs would be approximately $1,015,000* per QALY saved for infants and $1,036,000* per QALY saved for toddlers.

"Vaccinating infants or toddlers with meningococcal vaccine has a high cost per case prevented, even at a low vaccine price. Cost estimates are much higher than prior analyses because of declining incidence and shorter duration of protection. Infant vaccination prevents twice as many cases as toddler vaccination but at twice the cost," said Dr. Ortega-Sanchez, also with NCIRD.

No conjugate meningococcal vaccine is yet licensed for use in young infants. MenACWY-D (Sanofi Pasteur’s Menactra) is licensed for persons aged 2-55 years as a single dose. In April 2011, it was also licensed as a two-dose series for ages 9-23 months (on a 9- and 12-month schedule). MenACWY-CRM (Novartis’ Menveo), is also licensed as a single dose for ages 2-55 years, and an indication for a 4-dose infant series at 2, 4, 6, and 12 months is under review by the Food and Drug Administration. A combination product, HibMenCY-T (GlaxoSmithKline’s MenHibrix) is under FDA review for a 4 dose infant series, also at 2, 4, 6, and 12 months.

Sanofi Pasteur said in a statement, "With the current incidence of meningococcal disease at an all time low in the United States, a recommendation for children at highest risk is a prudent course of action. CDC has indicated that ACIP would consider making a routine infant recommendation in the future, should U.S. meningococcal disease incidence rates return to the historically higher levels observed prior to the introduction of meningococcal conjugate vaccines in adolescents.

"Sanofi Pasteur supports the ACIP’s recommendation calling for a 2-dose series of meningococcal vaccine for infants and children 9 through 23 months of age who are at high risk for getting meningococcal disease, including those traveling to countries where meningococcal infection is endemic, and those with human immunodeficiency virus (HIV) infection or certain complement component deficiencies. Given the rapid and potentially devastating nature of meningococcal disease and the incidence of infection in children under 1 year of age, we believe this recommendation will make significant strides in helping to protect those at greatest risk for the disease.

And, in a statement from Novartis, "When looking at the incidence of meningococcal disease, it is important to not only look at the number of cases but also the substantial life-long effects of the disease, which include significant psychosocial, economic, and emotional burden for victims’ families and their communities. Novartis believes that health care professionals and parents should have the choice to immunize infants against the potentially devastating consequences of this disease. We will continue our dialogue with the CDC and with ACIP prior to their vote on this matter in February, 2012.

"Infants are at highest risk for meningococcal disease due to the relative immaturity of their immune systems. Approximately 1 in 10 infants under 1 year of age die after contracting meningococcal disease, even with appropriate medical care, and as many as 1 in 5 will suffer serious life-long complications such as limb amputations, seizures, paralysis, hearing loss, and learning disabilities. The health care costs associated with meningococcal disease and the long-term management of its complications are substantial and present a significant public health burden.

"At Novartis, we are committed to eliminating meningococcal disease and we have made a significant effort to develop a safe and effective vaccine to help protect infants."

And, from GSK: "GlaxoSmithKline is committed to making MenHibrix available in the United States. We believe there is a clear public health benefit in recommending meningococcal vaccines for use in infants and toddlers in the United States. Rates of meningococcal disease are highest in infants and toddlers younger than 2 years of age. Approximately 300 cases of meningococcal disease from all serogroups were reported annually in the United States in this age group between 1998 and 2007."

As a CDC employee, Dr. Cohn has no conflicts of interest.

*Correction, 11/8/2011: An earlier version of this story gave the incorrect cost savings per QALY for infants and toddlers with certain doses of the vaccine.

**Correction, 11/9/2011: An earlier version of this story misstated the impact of the adolescent immunization program.

ATLANTA – Routine infant or toddler immunization against meningococcal disease does not appear to be a cost-effective measure, according to an assessment from a working group of the Advisory Committee on Immunization Practices.

That conclusion was presented to the full committee at its October meeting. If a conjugate meningococcal vaccine is licensed for use in infants before the next Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) meeting Feb. 22-23, the committee will vote on it then, said Dr. Amanda Cohn of the CDC’s National Center for Immunization and Respiratory Disease (NCIRD).

The working group’s assessment was based primarily on the low proportion of preventable disease cases and the high cost of vaccinating infants or toddlers with meningococcal vaccine per case prevented. Moreover, although current meningococcal conjugate vaccines are safe and immunogenic, they show evidence of declining antibodies after about 3 years, suggesting that a booster dose at age 6 years would likely be needed to protect children until the routine 11-to 12-year-old (adolescent) immunization, Dr. Cohn noted.

Jessica MacNeil, MPH, also with NCIRD, presented epidemiologic data showing that meningococcal disease has been declining in all age groups. The data do not suggest this is due to the adolescent immunization program.** The first evidence of an impact of the adolescent immunization program was detected in 2008-2009, when the incidence was 0.14 per 100,000 population among those aged 11-19 years and 0.82 among children less than 1 year of age. In contrast, those rates in 2006-2007 were 0.27 and 1.07, respectively. Moreover, the largest proportion of cases in children aged less than 5 years is due to meningococcal serotype B, which is not included in the any of the vaccines, she noted.

Surveillance data from 1993-2009 show that while 86% of children under 5 years of age who contract meningococcal disease are hospitalized, the case-fatality ratio is low, ranging from 1% for serogroup Y to 10% for serogroup C. A large majority – 75%-80% of children under 5 years with meningococcal disease – survives and recover. Major complications – including skin necrosis, amputation, hearing loss, and death – are less frequent in infants than in adolescents, Ms. MacNeil noted.

In a cost-effectiveness analysis presented by Ismael Ortega-Sanchez, Ph.D., the cost per quality-adjusted life year (QALY) saved for either giving four doses of the vaccine to infants at 2, 4, 6, and 12 months or two doses to toddlers at 9 and 12 months varied with different assumptions of what the vaccine will cost and whether it was given during a season of high or low disease incidence. Assuming a cost of $60 per vaccine dose and an average incidence rate, the costs would be approximately $1,015,000* per QALY saved for infants and $1,036,000* per QALY saved for toddlers.

"Vaccinating infants or toddlers with meningococcal vaccine has a high cost per case prevented, even at a low vaccine price. Cost estimates are much higher than prior analyses because of declining incidence and shorter duration of protection. Infant vaccination prevents twice as many cases as toddler vaccination but at twice the cost," said Dr. Ortega-Sanchez, also with NCIRD.

No conjugate meningococcal vaccine is yet licensed for use in young infants. MenACWY-D (Sanofi Pasteur’s Menactra) is licensed for persons aged 2-55 years as a single dose. In April 2011, it was also licensed as a two-dose series for ages 9-23 months (on a 9- and 12-month schedule). MenACWY-CRM (Novartis’ Menveo), is also licensed as a single dose for ages 2-55 years, and an indication for a 4-dose infant series at 2, 4, 6, and 12 months is under review by the Food and Drug Administration. A combination product, HibMenCY-T (GlaxoSmithKline’s MenHibrix) is under FDA review for a 4 dose infant series, also at 2, 4, 6, and 12 months.

Sanofi Pasteur said in a statement, "With the current incidence of meningococcal disease at an all time low in the United States, a recommendation for children at highest risk is a prudent course of action. CDC has indicated that ACIP would consider making a routine infant recommendation in the future, should U.S. meningococcal disease incidence rates return to the historically higher levels observed prior to the introduction of meningococcal conjugate vaccines in adolescents.

"Sanofi Pasteur supports the ACIP’s recommendation calling for a 2-dose series of meningococcal vaccine for infants and children 9 through 23 months of age who are at high risk for getting meningococcal disease, including those traveling to countries where meningococcal infection is endemic, and those with human immunodeficiency virus (HIV) infection or certain complement component deficiencies. Given the rapid and potentially devastating nature of meningococcal disease and the incidence of infection in children under 1 year of age, we believe this recommendation will make significant strides in helping to protect those at greatest risk for the disease.

And, in a statement from Novartis, "When looking at the incidence of meningococcal disease, it is important to not only look at the number of cases but also the substantial life-long effects of the disease, which include significant psychosocial, economic, and emotional burden for victims’ families and their communities. Novartis believes that health care professionals and parents should have the choice to immunize infants against the potentially devastating consequences of this disease. We will continue our dialogue with the CDC and with ACIP prior to their vote on this matter in February, 2012.

"Infants are at highest risk for meningococcal disease due to the relative immaturity of their immune systems. Approximately 1 in 10 infants under 1 year of age die after contracting meningococcal disease, even with appropriate medical care, and as many as 1 in 5 will suffer serious life-long complications such as limb amputations, seizures, paralysis, hearing loss, and learning disabilities. The health care costs associated with meningococcal disease and the long-term management of its complications are substantial and present a significant public health burden.

"At Novartis, we are committed to eliminating meningococcal disease and we have made a significant effort to develop a safe and effective vaccine to help protect infants."

And, from GSK: "GlaxoSmithKline is committed to making MenHibrix available in the United States. We believe there is a clear public health benefit in recommending meningococcal vaccines for use in infants and toddlers in the United States. Rates of meningococcal disease are highest in infants and toddlers younger than 2 years of age. Approximately 300 cases of meningococcal disease from all serogroups were reported annually in the United States in this age group between 1998 and 2007."

As a CDC employee, Dr. Cohn has no conflicts of interest.

*Correction, 11/8/2011: An earlier version of this story gave the incorrect cost savings per QALY for infants and toddlers with certain doses of the vaccine.

**Correction, 11/9/2011: An earlier version of this story misstated the impact of the adolescent immunization program.