Infant Meningococcal Vaccine: Why Not?

Haemophilus influenzae type B-Neisseria meningitidis serogroups C (MenC) and Y (MenY)-tetanus toxoid (Hib-MenCY-TT, MenHibrix) vaccine has been approved by the Food and Drug Administration for an infant indication to be administered according to the standard 2-, 4-, 6-, and 12 months vaccine schedule in the United States as endorsed by the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the Centers for Disease Control and Prevention (CDC).

According to the presentation given at the CDC meeting Oct. 14, 2011, by Dr. Ismael Ortega-Sanchez, giving the vaccine could prevent 130 of the projected 377 (34.5%) cases of meningococcal infection in the 4-million-child birth cohort of the United States cumulatively to age 10 years. Also infant vaccination would prevent one death per 642,000 infants (seven deaths/year). The vaccine could be given along with a DTaP/inactivated polio vaccine/hepatitis b vaccine (DTaP/IPV/HepB, Pediarix) and the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar13) without increasing the total number of shots in a visit. The vaccine has been proven safe and effective.

Yet at the October meeting of the CDC Advisory Committee on Immunization Practices (ACIP), Hib-MenCY-TT (MenHibrix) vaccine was not recommended for universal use. Instead, it was recommended for high risk children as previously defined as complement deficient and asplenic. Why the restricted recommendation?*

• It isn’t the right time. When the ACIP/AAP/AAFP endorsed meningococcal vaccination for 11- to 12-year-olds 7 years ago, the annual incidence of meningococcal disease was fivefold higher than it is now. The drop in incidence cannot be fully attributed to the initiation of our national vaccination campaign. It was known before the meningococcal conjugate vaccine was recommended that meningococcal disease had a cyclical pattern with high and low years of incidence. But, had the incidence been as low as it is now, then one might speculate that the vote to recommend universal vaccination might have been different. The passionate pleas of concerned parents and the desire by all of us in health care to protect every single adolescent against the devastation of meningococcal infections carried the day, even though the cost for prevention of those cases and deaths was the highest ever seen up to that time. So, if the incidence of meningococcal infections is now at an all time low, the calculations of cost to prevent cases and deaths would be a multiple of what it was 7 years ago.

• The vaccine doesn’t include all the serotypes. Hib-MenCY-TT has meningococcal serotypes C and Y. The vaccine does not include serotype A or serotype W-135 (because these serotypes are virtually absent and uncommon, respectively, in the United States and other developed countries. So, a concern could be that serotype replacement might occur over time as we have seen with Prevnar7, now replaced in the United States with Prevnar13 because of serotype replacement. But more importantly is the absence of serotype B in the vaccine. Serotype B meningococci cause 60%-65% of meningococcal disease in the United States in infants. That is why the number of cases projected to be prevented with Hib-MenCY-TT is about one-third of all cases among infants.

• The total number of shots goes up per visit unless GlaxoSmithKline vaccines are preferentially used. Hib-MenCY-TT was developed and is licensed by GlaxoSmithKline, a world leader in pediatric vaccines, and they are building a portfolio of vaccines that can fit together well. There is nothing wrong with that – it is good marketing. Sanofi Pasteur Vaccines is doing the same thing and, as more products are forthcoming from Pfizer Vaccines, Novartis Vaccines, and others, we can expect the same strategy. However, the CDC, AAP, and AAFP do not want to endorse products that limit choices and/or provide any single company with a competitive advantage. So, to endorse Hib-MenCY-TT that clearly fits best with only GlaxoSmithKline vaccine products may be an unspoken concern.

• The National Immunization Program cannot afford it. Going back to the presentation to ACIP at the CDC in October 2011, a key aspect was the cost of vaccination calculated against cases prevented and lives saved. The calculation for Quality-Adjusted Life Year (QALY) saved for a two-dose schedule among adolescents came out to $157,000/case. For the infant vaccination, the numbers were pretty staggering at $3.6 million/case, based on the current incidence of meningococcal infections in the United States (see sidebar). Even if the incidence of meningococcal infections were currently as high as they were back in 1997-1999, the cost would be $0.5 million/case. For those thinking about the option of toddler vaccination with the quadrivalent meningococcal conjugate vaccine (Menactra), the calculations for QALYs concluded that such a strategy prevented half as many cases at half the cost.

So where do we go from here? The lack of an endorsement by ACIP/AAP/AAFP for universal use* normally means that the vaccine will not be available within the Vaccines for Children free program, and it will not be covered by commercial health insurance plans except for the specific indications endorsed by the recommending bodies.* So these are huge barriers to use. Nevertheless, it is a licensed vaccine and it is safe and effective, just not perfect and not cost-effective for widespread public use at government expense. How much is a child’s life worth? If it is your child, then the life is priceless. But in public health there are limits to what can be afforded. We will see more of these types of issues in the future. Another unspoken concern of the ACIP/AAP/AAFP is that a two-tiered vaccine access situation develops. In other words, for those who can afford to pay, Hib-MenCY-TT is available and, if they can pay for it out-of-pocket, then they can buy it to protect their child.

The following are cost-effectiveness analysis conclusions that were presented to the CDC:

• 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 – cost per QALY saved is similar for both strategies.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Hospital Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero disclosed that in the past 3 years, he has served as a consultant to Sanofi Pasteur, Pfizer, Novartis, and Crucell for their vaccines currently licensed and in development. Dr. Pichichero also disclosed that in the past 3 years, his academic institution has received research grants to support vaccine work from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Novartis, and Crucell, including studies involving Hib-MenCY-TT produced by GlaxoSmithKline and Quadrivalent meningococcal vaccine by Sanofi Pasteur and Novartis.

* This article was updated on 10/26/12.

Haemophilus influenzae type B-Neisseria meningitidis serogroups C (MenC) and Y (MenY)-tetanus toxoid (Hib-MenCY-TT, MenHibrix) vaccine has been approved by the Food and Drug Administration for an infant indication to be administered according to the standard 2-, 4-, 6-, and 12 months vaccine schedule in the United States as endorsed by the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the Centers for Disease Control and Prevention (CDC).

According to the presentation given at the CDC meeting Oct. 14, 2011, by Dr. Ismael Ortega-Sanchez, giving the vaccine could prevent 130 of the projected 377 (34.5%) cases of meningococcal infection in the 4-million-child birth cohort of the United States cumulatively to age 10 years. Also infant vaccination would prevent one death per 642,000 infants (seven deaths/year). The vaccine could be given along with a DTaP/inactivated polio vaccine/hepatitis b vaccine (DTaP/IPV/HepB, Pediarix) and the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar13) without increasing the total number of shots in a visit. The vaccine has been proven safe and effective.

Yet at the October meeting of the CDC Advisory Committee on Immunization Practices (ACIP), Hib-MenCY-TT (MenHibrix) vaccine was not recommended for universal use. Instead, it was recommended for high risk children as previously defined as complement deficient and asplenic. Why the restricted recommendation?*

• It isn’t the right time. When the ACIP/AAP/AAFP endorsed meningococcal vaccination for 11- to 12-year-olds 7 years ago, the annual incidence of meningococcal disease was fivefold higher than it is now. The drop in incidence cannot be fully attributed to the initiation of our national vaccination campaign. It was known before the meningococcal conjugate vaccine was recommended that meningococcal disease had a cyclical pattern with high and low years of incidence. But, had the incidence been as low as it is now, then one might speculate that the vote to recommend universal vaccination might have been different. The passionate pleas of concerned parents and the desire by all of us in health care to protect every single adolescent against the devastation of meningococcal infections carried the day, even though the cost for prevention of those cases and deaths was the highest ever seen up to that time. So, if the incidence of meningococcal infections is now at an all time low, the calculations of cost to prevent cases and deaths would be a multiple of what it was 7 years ago.

• The vaccine doesn’t include all the serotypes. Hib-MenCY-TT has meningococcal serotypes C and Y. The vaccine does not include serotype A or serotype W-135 (because these serotypes are virtually absent and uncommon, respectively, in the United States and other developed countries. So, a concern could be that serotype replacement might occur over time as we have seen with Prevnar7, now replaced in the United States with Prevnar13 because of serotype replacement. But more importantly is the absence of serotype B in the vaccine. Serotype B meningococci cause 60%-65% of meningococcal disease in the United States in infants. That is why the number of cases projected to be prevented with Hib-MenCY-TT is about one-third of all cases among infants.

• The total number of shots goes up per visit unless GlaxoSmithKline vaccines are preferentially used. Hib-MenCY-TT was developed and is licensed by GlaxoSmithKline, a world leader in pediatric vaccines, and they are building a portfolio of vaccines that can fit together well. There is nothing wrong with that – it is good marketing. Sanofi Pasteur Vaccines is doing the same thing and, as more products are forthcoming from Pfizer Vaccines, Novartis Vaccines, and others, we can expect the same strategy. However, the CDC, AAP, and AAFP do not want to endorse products that limit choices and/or provide any single company with a competitive advantage. So, to endorse Hib-MenCY-TT that clearly fits best with only GlaxoSmithKline vaccine products may be an unspoken concern.

• The National Immunization Program cannot afford it. Going back to the presentation to ACIP at the CDC in October 2011, a key aspect was the cost of vaccination calculated against cases prevented and lives saved. The calculation for Quality-Adjusted Life Year (QALY) saved for a two-dose schedule among adolescents came out to $157,000/case. For the infant vaccination, the numbers were pretty staggering at $3.6 million/case, based on the current incidence of meningococcal infections in the United States (see sidebar). Even if the incidence of meningococcal infections were currently as high as they were back in 1997-1999, the cost would be $0.5 million/case. For those thinking about the option of toddler vaccination with the quadrivalent meningococcal conjugate vaccine (Menactra), the calculations for QALYs concluded that such a strategy prevented half as many cases at half the cost.

So where do we go from here? The lack of an endorsement by ACIP/AAP/AAFP for universal use* normally means that the vaccine will not be available within the Vaccines for Children free program, and it will not be covered by commercial health insurance plans except for the specific indications endorsed by the recommending bodies.* So these are huge barriers to use. Nevertheless, it is a licensed vaccine and it is safe and effective, just not perfect and not cost-effective for widespread public use at government expense. How much is a child’s life worth? If it is your child, then the life is priceless. But in public health there are limits to what can be afforded. We will see more of these types of issues in the future. Another unspoken concern of the ACIP/AAP/AAFP is that a two-tiered vaccine access situation develops. In other words, for those who can afford to pay, Hib-MenCY-TT is available and, if they can pay for it out-of-pocket, then they can buy it to protect their child.

The following are cost-effectiveness analysis conclusions that were presented to the CDC:

• 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 – cost per QALY saved is similar for both strategies.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Hospital Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero disclosed that in the past 3 years, he has served as a consultant to Sanofi Pasteur, Pfizer, Novartis, and Crucell for their vaccines currently licensed and in development. Dr. Pichichero also disclosed that in the past 3 years, his academic institution has received research grants to support vaccine work from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Novartis, and Crucell, including studies involving Hib-MenCY-TT produced by GlaxoSmithKline and Quadrivalent meningococcal vaccine by Sanofi Pasteur and Novartis.

* This article was updated on 10/26/12.

Haemophilus influenzae type B-Neisseria meningitidis serogroups C (MenC) and Y (MenY)-tetanus toxoid (Hib-MenCY-TT, MenHibrix) vaccine has been approved by the Food and Drug Administration for an infant indication to be administered according to the standard 2-, 4-, 6-, and 12 months vaccine schedule in the United States as endorsed by the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the Centers for Disease Control and Prevention (CDC).

According to the presentation given at the CDC meeting Oct. 14, 2011, by Dr. Ismael Ortega-Sanchez, giving the vaccine could prevent 130 of the projected 377 (34.5%) cases of meningococcal infection in the 4-million-child birth cohort of the United States cumulatively to age 10 years. Also infant vaccination would prevent one death per 642,000 infants (seven deaths/year). The vaccine could be given along with a DTaP/inactivated polio vaccine/hepatitis b vaccine (DTaP/IPV/HepB, Pediarix) and the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar13) without increasing the total number of shots in a visit. The vaccine has been proven safe and effective.

Yet at the October meeting of the CDC Advisory Committee on Immunization Practices (ACIP), Hib-MenCY-TT (MenHibrix) vaccine was not recommended for universal use. Instead, it was recommended for high risk children as previously defined as complement deficient and asplenic. Why the restricted recommendation?*

• It isn’t the right time. When the ACIP/AAP/AAFP endorsed meningococcal vaccination for 11- to 12-year-olds 7 years ago, the annual incidence of meningococcal disease was fivefold higher than it is now. The drop in incidence cannot be fully attributed to the initiation of our national vaccination campaign. It was known before the meningococcal conjugate vaccine was recommended that meningococcal disease had a cyclical pattern with high and low years of incidence. But, had the incidence been as low as it is now, then one might speculate that the vote to recommend universal vaccination might have been different. The passionate pleas of concerned parents and the desire by all of us in health care to protect every single adolescent against the devastation of meningococcal infections carried the day, even though the cost for prevention of those cases and deaths was the highest ever seen up to that time. So, if the incidence of meningococcal infections is now at an all time low, the calculations of cost to prevent cases and deaths would be a multiple of what it was 7 years ago.

• The vaccine doesn’t include all the serotypes. Hib-MenCY-TT has meningococcal serotypes C and Y. The vaccine does not include serotype A or serotype W-135 (because these serotypes are virtually absent and uncommon, respectively, in the United States and other developed countries. So, a concern could be that serotype replacement might occur over time as we have seen with Prevnar7, now replaced in the United States with Prevnar13 because of serotype replacement. But more importantly is the absence of serotype B in the vaccine. Serotype B meningococci cause 60%-65% of meningococcal disease in the United States in infants. That is why the number of cases projected to be prevented with Hib-MenCY-TT is about one-third of all cases among infants.

• The total number of shots goes up per visit unless GlaxoSmithKline vaccines are preferentially used. Hib-MenCY-TT was developed and is licensed by GlaxoSmithKline, a world leader in pediatric vaccines, and they are building a portfolio of vaccines that can fit together well. There is nothing wrong with that – it is good marketing. Sanofi Pasteur Vaccines is doing the same thing and, as more products are forthcoming from Pfizer Vaccines, Novartis Vaccines, and others, we can expect the same strategy. However, the CDC, AAP, and AAFP do not want to endorse products that limit choices and/or provide any single company with a competitive advantage. So, to endorse Hib-MenCY-TT that clearly fits best with only GlaxoSmithKline vaccine products may be an unspoken concern.

• The National Immunization Program cannot afford it. Going back to the presentation to ACIP at the CDC in October 2011, a key aspect was the cost of vaccination calculated against cases prevented and lives saved. The calculation for Quality-Adjusted Life Year (QALY) saved for a two-dose schedule among adolescents came out to $157,000/case. For the infant vaccination, the numbers were pretty staggering at $3.6 million/case, based on the current incidence of meningococcal infections in the United States (see sidebar). Even if the incidence of meningococcal infections were currently as high as they were back in 1997-1999, the cost would be $0.5 million/case. For those thinking about the option of toddler vaccination with the quadrivalent meningococcal conjugate vaccine (Menactra), the calculations for QALYs concluded that such a strategy prevented half as many cases at half the cost.

So where do we go from here? The lack of an endorsement by ACIP/AAP/AAFP for universal use* normally means that the vaccine will not be available within the Vaccines for Children free program, and it will not be covered by commercial health insurance plans except for the specific indications endorsed by the recommending bodies.* So these are huge barriers to use. Nevertheless, it is a licensed vaccine and it is safe and effective, just not perfect and not cost-effective for widespread public use at government expense. How much is a child’s life worth? If it is your child, then the life is priceless. But in public health there are limits to what can be afforded. We will see more of these types of issues in the future. Another unspoken concern of the ACIP/AAP/AAFP is that a two-tiered vaccine access situation develops. In other words, for those who can afford to pay, Hib-MenCY-TT is available and, if they can pay for it out-of-pocket, then they can buy it to protect their child.

The following are cost-effectiveness analysis conclusions that were presented to the CDC:

• 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 – cost per QALY saved is similar for both strategies.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Hospital Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero disclosed that in the past 3 years, he has served as a consultant to Sanofi Pasteur, Pfizer, Novartis, and Crucell for their vaccines currently licensed and in development. Dr. Pichichero also disclosed that in the past 3 years, his academic institution has received research grants to support vaccine work from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Novartis, and Crucell, including studies involving Hib-MenCY-TT produced by GlaxoSmithKline and Quadrivalent meningococcal vaccine by Sanofi Pasteur and Novartis.

* This article was updated on 10/26/12.