Document text
Background on invasive Hib disease and
vaccination among American Indian and
Alaska Native populations
Jennifer Collins MD, MSc
Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group
February 29, 2024National Center for Immunization & Respiratory Diseases
Background
3▪Gram -negative bacilli
▪Originally thought to be the cause of influenza
▪Abbreviated “ H. flu ” or Hi
▪Infections range from mild to severe invasive disease
Haemophilus influenzae
NTUnencapsulated
(Non -typeable)
b a c d e fEncapsulated
(6 serotypes based on polysaccharide antigens)Classification of H. influenzae
4
H. influenzae serotype b (Hib) is most virulent and
is the only type preventable through vaccination
NTUnencapsulated
(Non -typeable)
b a c d e fEncapsulated
(6 serotypes based on polysaccharide antigens)
•Before the introduction of effective vaccines, Hib was the leading cause of
bacterial meningitis and other invasive bacterial disease in the United
States, primarily among children aged <5 years
5
6Risk factors for invasive Hib disease in the pre -
vaccine era
Immunocompromising conditions
•HIV infection
•Asplenia / Sickle cell disease
•IgG deficiency
•Early component complement
deficiency
•Hematopoietic stem cell
transplantation
•ChemotherapyDemographic factors
•Male sex
•Race/Ethnicity
•American Indian
•Alaska Native
•Black
•Social factors
•Household c rowding
•Large household size
•Low SES
•School -aged siblings
•Daycare attendance
6
Bacteremic
pneumoniaMost common clinical syndromes of invasive Hib
disease in the post -vaccine era
Meningitis Bacteremia
without a focus
7
Estimated incidence of invasive Hib disease in children
aged <5 years decreased dramatically after
introduction of Hib vaccines
051015202530
1980 1985 1990 1995 2000 2005 2010Estimated
incidence per
100,000
populationConjugate vaccine licensed for use
in children aged ≥18 months
Conjugate vaccine licensed for use
in infants aged ≥2 monthsPolysaccharide vaccine licensed for
use in children aged ≥18 months
8
9▪Capsular polysaccharide (PRP) conjugated to carrier proteins
–Tetanus toxoid (PRP -T)
–Outer membrane protein of meningococcal serogroup B (PRP -OMP)
▪Highly immunogenic via activation of T -cell dependent immunity
–95% of infants develop protective antibody levels after a primary series
–No cross protection against non -b serotypes/ NTHi
▪Estimated clinical efficacy 95% ─100%
▪Invasive Hib disease is uncommon in children who are fully vaccinated Hib polysaccharide conjugate vaccines
remain the primary prevention strategy for Hib
9
10Current Hib vaccines in the United States
Vaccine Product Trade Name Primary series Booster dose
Monovalent vaccines
PRP-OMP PedvaxHIB * 2, 4 months 12–15 months
PRP-T ActHIB 2, 4, 6 months 12–15 months
PRP-T Hiberix 2, 4, 6 months 12–15 months
Combination vaccines**
DTaP -IPV/Hib Pentacel 2, 4, 6 months 12–15 months
DTaP -IPV-Hib-HepB Vaxelis 2, 4, 6 months ***
*Recommended vaccine for American Indian/Alaska Native children
**Hib component of Pentacel is PRP -T. Hib component of Vaxelis is PRP -OMP .
***Vaxelis is not recommended for the booster dose. A different Hib -containing vaccine should be administered as a booster at 12 –15 months.
10
Invasive Hib disease disproportionately
affects American Indian and Alaska
Native populations
12051015202530
1980 1985 1990 1995 2000 2005 2010Incidence declined >99%Incidence of invasive Hib disease among children aged
<5 years declined >99% with introduction of Hib vaccines
12Estimated
incidence per
100,000 of
invasive Hib
disease among
children aged
<5 years
13050100150200250300
1980 1985 1990 1995 2000 2005 2010U.S. childrenExpanding the y -axis…
13Estimated
incidence per
100,000 of
invasive Hib
disease among
children aged
<5 years
14050100150200250300
1980 1985 1990 1995 2000 2005 2010280
American Indian and
Alaska Native
children
U.S. childrenIncidence among AI/AN children aged <5 years was >10x
the incidence among U.S. children aged <5 years overall
14Estimated
incidence per
100,000 of
invasive Hib
disease among
children aged
<5 years
15Incidence of Hib disease among AI/AN children
aged <5 years declined >98% with Hib vaccination
050100150200250300
Pre-vaccine era Post-vaccine era
15Estimated i ncidence
per 100,000 of
invasive Hib disease
among AI/AN
children aged
<5 years
Incidence per
100,000 of invasive
H. influenzae
disease by type
among children
aged <5 years,
2011 –2020
012345
Hia Hib Hif NTHiAI/AN Non-AI/ANIncidence of invasive H. influenzae disease remains
substantially higher among American Indian and
Alaska Native children compared with non-Native
children
5.1
2.5
0.92.1
0.6 0.080.31.3
16
Incidence per
100,000 of invasive
H. influenzae
disease by type
among children
aged <5 years,
2011 –2020
012345
Hia Hib Hif NTHiAI/AN Non-AI/AN
17AI/AN children have 31 -fold higher incidence of
invasive Hib disease than non -Native children
31x
In the pre -vaccine era, the incidence of Hib meningitis
peaked at a younger age among AI/AN populations
than the general U.S. population
18 Data from Ward JI, et al. Lancet . 1981. 1(8233); 1281 –5. Graph credit: Laura Hammitt’s February 2019 ACIP Meeting presentation
Cases per 100,000
(1971–1977)
19Invasive Hib disease among AI/AN children
aged <5 years―Active Bacterial Core
surveillance, 2003 –2023*
Characteristic N=28
Patient age, months
Median
IQR
Range 12
5–31
0–56
Unvaccinated , n (%) 9 (31)
Syndrome
Meningitis
Pneumonia
Cellulitis
Bacteremia without a focus 13 (45)
12 (41)
3 (10)
1 (3)
19*2022 and 2023 data are preliminary
Hib vaccination among American Indian
and Alaska Native infants
Briere EC, et al. Prevention and Control of Haemophilus influenzae Type b Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and Reports . 63(RR01);1 -14PedvaxHIB (PRP-OMP) is preferentially recommended
for AI/AN infants
•Vaccination with a 2 dose primary series of a Hib vaccine that contains
PRP-OMP ( PedvaxHIB ) is preferred for AI/AN infants to provide early
protection because this vaccine produce a protective antibody response
after the first dose
•A booster dose (dose 3) of Hib vaccine is recommended at age 12
through 15 months; for the booster dose, there is no preferred vaccine
formulation
21
22
PRP-OMP provides earlier protection
*PRP ≥0.15 ug/ml and ≥1.0 ug/ml are correlates of short -term, and long -term protection, respectively.
Watt JP , et al. Global reduction of Hib disease: what are the next steps? The Journal of Pediatrics 2003. 22PRP-OMP produces a
protective antibody
response after the
first dose
Anti-PRP GMT
µg/mL*
After dose 1
(age 2 months)Before After dose 2
(age 4 months)After dose 3
(age 6 months)Final titers
are higher
with PRP -T
23The incidence of invasive Hib disease in Alaska
Native populations increased in late 1990s amid
vaccine policy changes
Singleton R et al. The Alaska Haemophilus influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9Invasive Hib disease
rates per 100 000 in
Alaska Native and
non-Native children
aged 5 years, 1980 –
2004
23
24
Singleton R et al. The Alaska Haemophilus influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9
Universal Hib
vaccination:
HbOC in January
PRP-OMP in JulyCombination vaccine
DTP-HbOC replaced
PRP-OMP
Change to PRP -OMP for
dose 1 followed by HbOC
for doses 2 –4
HbOC = Hib oligosaccharide CRM 197 vaccine
DTP = Diphtheria, tetanus toxoids, pertussis Timeline of Hib vaccine policy changes in Alaska
.Change to PRP -OMP for
all Hib doses
24
25Vaccine status among children aged <10 years
with invasive Hib disease in Alaska, 1991 –2004
Singleton R et al. The Alaska Haemophilus influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9
▪During 1996–2000 , a greater
proportion of cases
–Occurred among Alaska
Native children
–Occurred among partially
immunized children
–Were considered true vaccine
failures
25
26Vaccine administration errors may have
contributed to some cases when both PRP -OMP
and HbOC were used
Singleton R et al. The Alaska Haemophilus influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9▪October 1997 –December 2000
–14 cases occurred in Alaska Native children aged <5
years
–3 children (21%) had inadvertently received HbOC for
their first and only dose
26
27Increases in Hib disease in Alaska during
1996–2000 were attributed to
▪Use of HbOC , which did not achieve short -term
protective antibody concentrations (0.15 µg/mL) until the
third dose
▪Low rates of on -time immunization
Singleton R et al. The Alaska Haemophilus influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9 27
28National Immunization Survey –Child
Estimated vaccination coverage with Hib full series* by age 24
months among American Indian or Alaska Native children by
birth year
Birth yearⴕ% 95% CI
2016 77.0 64.8 –87.4
2017 69.6 55.1 –83.0
2018 76.3 66.0 –85.4
2019 69.9 59.5 –79.7
2020 67.5 54.6 –79.7
* Hib Full Series: primary series and booster dose, which includes receipt of ≥3 or ≥4 doses, depending on product type recei ved.
† Data for the 2016 birth year are from survey years 2017, 2018, and 2019; data for the 2017 birth year are from survey years 2018, 2019, and 2020; data for the
2018 birth year are from survey years 2019, 2020, and 2021; data for the 2019 birth year are from survey years 2020, 2021, an d 2022; data for the 2020 birth year
are considered preliminary and are from survey years 2021 and 2022 (2023 data are not yet available).
Hill HA et al. Vaccination Coverage by Age 24 Months Among Children Born in 2019 and 2020 — National Immunization Survey -Child, United States, 2020 –2022 . MMWR Weekly / November 3, 2023 / 72(44);1190 –1196. 28
29National Immunization Survey –Child:
In 2019–2020, American Indian/Alaska Native children were
less likely than White children to have received the Hib full
series* by age 24 months
Race, Ethnicity 2019–2020 (prelim)ⴕ
%, 95% CIDifference (White –AI/AN)
2019–2020 (prelim)ⴕ
% 95% CI p-value
White, non -Hispanic 80.8 (79.4 –82.1) REF REF REF
American Indian or Alaska
Native, non -Hispanic68.7 (60.3 –76.8) 12.1 (3.6–20.5) 0.01
*Hib full series: primary series and booster dose, which includes receipt of ≥3 or ≥4 doses, depending on product type receiv ed.
ⴕData for the 2019 birth year are from survey years 2020, 2021, and 2022; data for the 2020 birth year are considered prelimin ary and are
from survey years 2021 and 2022 (2023 data are not yet available).
Hill HA et al. Vaccination Coverage by Age 24 Months Among Children Born in 2019 and 2020 — National Immunization Survey -Child, United States, 2020 –2022. MMWR Weekly / November 3, 2023 / 72(44);1190 –1196. 29
Vaxelis (DTaP -IPV-Hib-HepB )
31Vaxelis (DTaP -IPV-Hib-HepB ) is newer
▪Licensed in December 2018
▪ACIP voted to include in VFC in June 2019
▪More than 6.2 million doses distributed in the United
States as of Q4 2023
*Data provided by the manufacturer.31 The use of trade names is for identification purposes only and does not imply endorsement by CDC.
32Vaxelis (DTaP -IPV-Hib-HepB ) does not
currently have a preferential recommendation
for AI/AN infants
Vaccine Product Trade Name PRP OMP
PRP-OMP PedvaxHIB 7.5 mcg 125 mcg
DTaP -IPV-Hib-HepB Vaxelis 3 mcg 50 mcg
32▪Post -dose 1 immunogenicity data not previously available
▪Lower dose of PRP -OMP than PedvaxHIB
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
33In Phase III clinical
trials, Hib antibody
responses after the
3-dose primary
series were non -
inferior to licensed
comparator
vaccines
21
Vaxelis group
Control group
Marshall GS, et al. Immunogenicity, safety and tolerability of a hexavalent vaccine in infants. Pediatrics 2015;136:e323 –32.33- Vaxelis group received DTaP5 -IPV-Hib-HepB, PCV13, and RV5 at 2, 4, and 6 months of age followed by DTaP5, Hib -OMP, and PCV13 at 15 months of a ge.
- Control group received DTaP5 -IPV/Hib,PCV13, and RV5 at 2, 4, and 6 months of age, with HepB at 2 and 6 months of age, followed by DTaP5, Hib -TT, and PCV13 at 15 months of age.
- PRP ≥0.15 ug/ml and ≥1.0 ug/ml are correlates of short -term, and long -term protection, respectively.
- The use of trade names is for identification purposes only and does not imply endorsement by CDC.
.
34Safety of Vaxelis (DTaP -IPV-Hib-HepB )
34▪In clinical trials, the safety profile was consistent with that of licensed
comparator vaccines except higher rate of fever than with DTaP -IPV/Hib
(47.1% –47.4% vs. 33.2% –34.4%)1,2; rates of fever -related medical events
were similar between groups
▪Post -licensure analysis of VAERS data from June 26, 2019 – June 16, 2023
did not identify new or unexpected safety issues
1Marshall GS, et al. Immunogenicity, safety and tolerability of a hexavalent vaccine in infants. Pediatrics 2015;136:e323 –32.
2Block SL, et al. Lot -to-lot consistency, safety, tolerability and immunogenicity of an investigational hexavalent vaccine in U.S . infants. Pediatr Infect Dis J 2017;36:202 –8.
35Vaxelis protects against 6 infections with fewer
injections
Pediarix is a combination vaccine that protects against diphtheria, tetanus, pertussis, polio, and hepatitis B.
DTaP is a vaccine that protects against diphtheria, tetanus, and pertussis. The 4th dose of DTaP is recommended at age 15 –18 months.
IPV is inactivated polio vaccine.Vaxelis Vaxelis VaxelisOption 2 months 4 months 6 months 12–15
monthsTotal shots
1 Vaxelis Vaxelis Vaxelis PedvaxHIB
DTaP5
2 PedvaxHIB
PediarixPedvaxHIB
Pediarix PediarixPedvaxHIB
DTaP7
3 PedvaxHIB
DTaP
IPV
HepBPedvaxHIB
DTaP
IPVDTaP
IPV
HepBPedvaxHIB
DTaP12
The use of trade names is for identification purposes only and does not imply endorsement by CDC. 35
Policy question
▪Should Vaxelis (DTaP -IPV-Hib-HepB ) be included with
PedvaxHIB in the preferential recommendation for
American Indian and Alaska Native infants?
The use of trade names is for identification purposes only and does not imply endorsement by CDC. 36
Acknowledgments
▪ ACIP Members on the WG
– Jamie Loehr (Interim Chair)
– Wilbur Chen
▪ Ex Officio WG Members
– Margaret Bash (FDA)
– Matthew Clark (IHS)
– Mark Connelly (FDA)
– Francisco Leyva (NIH)
▪ WG Liaisons and Consultants
– Amra Resic (AAFP)
– Samir Shah (AAP)
– Barb Fluty (ACHA)
– Karyn Lyons (AIM)
– Paul Cieslak (CSTE)
– Kathy Hsu (IDSA)
– Joseline Zafack (NACI)
– Jeff Goad (NFID)
– Jessica Cataldi (PIDS)
– Amy Middleman (SAHM)
– Kathy Poehling (Wake Forest)
– Lynn Bahta (Minnesota Department of Health)
– David Stephens (Emory)▪ CDC Contributors
– Lucy McNamara (DBD/NCIRD)
– Sarah Schillie (DBD/NCIRD)
– LeAnne Fox (DBD/NCIRD)
– Susan Hariri (DBD/NCIRD)
– Amy Rubis (DBD/NCIRD)
– Noele Nelson (DBD/NCIRD)
– Alison Albert (DBD/NCIRD)
– Angela Jiles (DBD/NCIRD)
– Marc Fischer (DIDRI/NCEZID)
– Jonathan Duffy (DHQP/NCEZID)
– Pedro Moro (DHQP/NCEZID)
– Tanya Myers (DHQP/NCEZID)
– Liz Velazquez (ISD/NCIRD)
– Jessica MacNeil (ACIP Secretariat)
– Hannah Rosenblum (ACIP Secretariat)
– Melinda Wharton (ACIP Secretariat)
▪ GRADE/ EtR Support
– Doug Campos -Outcalt (Arizona)
– Rebecca Morgan (Case Western Reserve)
Thank you!
Questions?