M t l I i ti T f OMaternal Immunization: Two for One

Laura Hammitt, MDAssistant Professor, Johns Hopkins School of Public HealthDirector of Infectious Disease Programs, Center for American Indian Health

Di lDisclosures

• Laura Hammitt has the following financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity– Grants/Research Support: Pfizer, GSK– Speakers Bureau/Honoraria: None– Stock/Bonds in: None– Consulting Fees: None– Other: None

• Laura Hammitt does intend to discuss an unapproved/investigative use of a commercial product/device in this presentation and will identify it as such.

A dAgenda1. Introduction and overview maternal

immunizationLaura Hammitt, MD, Assistant Professor, Center for American immunization Indian Health, Johns Hopkins Bloomberg School of Public Health

2. Antenatal influenza and pertussis uptake Ab i i l th i A t li

Annette Regan, PhD, MPH, Research Fellow Curtin Universityamong Aboriginal mothers in Australia Research Fellow, Curtin University School of Public Health

3. Validation of an algorithm to measure Cheyenne Jim, MS, Indian Health S i I i ti Pmaternal vaccine uptake Service Immunization Program Analyst

4 Facilitators and barriers to maternal Jessica Atwell, PhD, MPH, Assistant 4. Facilitators and barriers to maternal vaccine uptake among Navajo and White Mountain Apache women

, , ,Scientist, Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health

5 Discussion/Questions All5. Discussion/Questions All

Wh i t tWhy vaccinate pregnant women• Neonates uniquely at risk

f i f ti th tfor infections that cause death and disability

• Immune system of yneonates is immature

• Active immunization of b i l

• High risk for exposure of pregnant women to disease

newborns is rarely successful

• Infection poses a special risk to the mother

• Infection poses a specialInfection poses a special risk to the fetus

V i ti d i “N t ’ Gift”Vaccination during pregnancy – “Nature’s Gift”Period of highest severity of early

Child’s antibody

y ychildhood infections

Maternal antibody

Infant immunization starts Birth

I i ti i Immunization in pregnancy

https://https://www.cdc.govwww.cdc.gov/vaccines/schedules/downloads/adult/adult/vaccines/schedules/downloads/adult/adult--combinedcombined--schedule.pdfschedule.pdf

Clinical presentation and burden of influenzap

• Sudden onset of fever, cough, sore Pneumonia and Influenza Death throat, body aches, headaches, fatigue

• Spread by respiratory droplets C li ti i 30

35 Soutwest AI U.S. White

Rate, 1999-2009

• Complications: pneumonia, myocarditis, encephalitis, death

• Highest risk in young children, adults ≥65 years pregnant women

20

25

30

,000

yea

rs

adults ≥65 years, pregnant women and people with chronic conditions

• 7,000-26,000 pediatric hospitalizations per year 5

10

15

Rat

e/10

0,• Child deaths

– 148 in 2014-2015– 61 so far this season

0<1 1-4 5-19 20-49 50-64

Age group (years)

Groom et al, Am J Pub Health (2014); e1–e10. doi:10.2105/AJPH.2013.301740

CDC d ti f i fl i tiAll persons ≥ 6 months should be vaccinated annually

CDC recommendations for influenza vaccination

When vaccine supply is limited, focus should be on: Children ages 6 months-4 years Adults ≥ 50 years Adults ≥ 50 years Those with chronic heart, lung, kidney or metabolic disease Those who are immunosuppressed or on aspirin therapy Those who are or will be pregnant during flu season Residents or nursing homes or chronic care facilitiesA i I di /Al k N ti l ti American Indian/Alaska Native populations Morbidly obese

HCW and household contacts/caregivers for high risk patientsHCW and household contacts/caregivers for high risk patients

http://www.cdc.gov/flu/professionals/acip/flu_vax1011.htm#box1

P d i flPregnancy and influenza

• Seasonal influenza (non-pH1N1) in pregnancy( p ) p g y– 5-fold increase in perinatal mortality including miscarriages, stillbirths,

early neonatal disease and death

– 3-fold increase in preterm birth

• 2009 pH1N1• 2009 pH1N1– Pregnant women ~1% of the population BUT

6% f i fl i t d h it li ti6% of influenza-associated hospitalizations

6% of ICU admissions (stronger risk factor than cardiac failure, diabetes or obesity)diabetes or obesity)

6% of deaths

M t l i fl i ti t t i f tMaternal influenza vaccination protects infants

From: Effectiveness of Maternal Influenza Immunization in Mothers and Infants. Zaman K et al. N Engl J Med (2008)359(15):1555-1564. Reprinted with permission from Massachusetts Medical Society.

Vaccine Efficacy: 63% (95%CI: 5, 85)

M t l i fl i t d i N j dMaternal influenza vaccine study in Navajo and White Mountain Apache mothers

• Nonrandomized, observational, open label, cohort study

• Three influenza seasons• 2002-2005

• N = 1160 pregnant women • 573 received influenza vaccine• 587 did not receive influenza vaccine

Eick AA et al, Arch Pediatr Adolesc Med. (2010) doi:10.1001/archpediatrics.2010.192

R l ti i k f i fl i th i f t b t lRelative risk of influenza in the infant, by maternal vaccination status

8

n- V i d

6

7

00 p

erso

n VaccinatedUnvaccinated

RR=0.92 (0.73, 1.16)

4

5

te p

er 1

00da

ys

39% reduction

1

2

3

denc

e R

at

41% reductionRR=0.59 (0.37, 0.93)

RR=0.61 (0.45, 0.84)

0

1

Lab-Confirmed Infl en a

ILI Hospitalized ILI

Inci

d

Influenza

Eick AA et al, Arch Pediatr Adolesc Med. (2010) doi:10.1001/archpediatrics.2010.192

https://www.ihs.gov/flu/includes/themes/newihstheme/display_objects/documents/NDAmericanIndianAllPosterdf

https://www.ihs.gov/flu/includes/themes/newihstheme/display_objects/documents/AlaskaNativePoster.pdfhttps://www.cdc.gov/flu/pdf/freeresources/native/protect_circle_life_poster_8.5x

Cli i l t ti d b d f t iClinical presentation and burden of pertussis

• Cough illness lasts 2-10 weeks, with paroxysms, “whooping”, post-tussive vomiting, apneaC li ti ib f t• Complications: rib fractures, malnutrition, pneumonia, seizures, death

• 10 000-50 000 pediatric cases per10,000 50,000 pediatric cases per year

• 10-20 child deaths per year (most in 1st 3 months of life)

M t l Td i ti t t i f tMaternal Tdap vaccination protects infants

• Tdap during each pregnancy– Preferably at 27-36 weeks gestation

• Retrospective analysis of hospitalized infants born to vaccinated and unvaccinated mothers in Californiavaccinated and unvaccinated mothers in California– Infants born to vaccinated mothers had LOWER risk of

• Hospitalization (RR 0.5; 95% CI: 0.4, 0.6)ICU d i i (RR 0 6 95% CI 0 7 0 9)• ICU admission (RR 0.6; 95% CI: 0.7, 0.9)

• And had shorter hospital stays (median 3 vs 6 days)– Adjusted vaccine effectiveness: 58% (95% CI 15, 80)

• Vaccine effectiveness of maternal Tdap vaccination in the United Kingdom– 91% for infants <3 months of age91% for infants <3 months of age

Winter et al, Clin Infect Dis. 2017;64(1):9-14.Amirthalingam et al, Clin Infect Dis. 2016;63(S4):S236–43.

V i f d iVaccines for women during pregnancy

Licensed and Ti i Benefit to Benefit to S f tLicensed and recommended Timing Benefit to

the motherBenefit to the infant Safety

Tetanus 3rd trimester ✔ ✔ ✔

Acellular pertussis 27-36 weeks ✔ ✔ ✔

Inactivated influenza Anytime ✔ ✔ ✔Inactivated influenza Anytime ✔ ✔ ✔

Under development

Group B Strep No data ✔ No data No data

RSV No data No data No data No dataRSV No data No data No data No data

Adapted from Kachikis et al, J Infection; Vol 5 July 2016, Pages S83–S90

St t i f i i t l i tiStrategies for improving maternal vaccination• Understand facilitators and barriers • Promote provider recommendation

– Education– RemindersReminders – Establish who is responsible

• Ensure access • Develop evidence-based interventions

– Emphasize safety – Mention disease severity in infancy– Are culturally congruent

• Identify and use effective channels of communicationcommunication

V i ti f P t W S LiVaccination of Pregnant Women Saves Lives

• Changes in immune function during pregnancy still allow forChanges in immune function during pregnancy still allow for good response to inactivated vaccines

• Maternally-derived IgG can prevent morbidity and mortalityy g p y y– Maternal

– Fetal

– Neonatal

– Young infant

• Inactivated vaccines are safe• Inactivated vaccines are safe

• We should not exclude pregnant women or their offspring from vaccine-derived benefits (equity)vaccine derived benefits (equity)

References on safety of maternal vaccinationReferences on safety of maternal vaccination• Omer et al. Maternal immunization. N Engl J Med 2017;376:1256-67.• Annette K. Regan (2016) The safety of maternal immunization, Human Vaccines &

Immunotherapeutics, 12:12, 3132-3136, DOI:10.1080/21645515.2016.1222341p , , ,• Marshall et al (2016). Vaccines in pregnancy: The dual benefit for pregnant women and infants,

Human Vaccines & Immunotherapeutics, 12:4, 848-856, DOI: 10.1080/21645515.2015.1127485• Nordin et al. Maternal influenza vaccine and risks for preterm or small for gestational age birth. J

Peds 2014;164(5):1051-1057.• Kharbanda et al. Inactivated influenza vaccine during pregnancy and risks for adverse obstetric

events. Obstetrics and Gynecology 2013; 122(3):659-667.• Pasternak et al. Risk of adverse fetal outcomes following administartaion of a pandemic influenza

A (H1N1) vaccine during pregnancy, JAMA 2012 Jul 11;308(2):165-74• McMillan et al. Safety of tetanus, diphtheria, and pertussis vaccination during pregnancy: A

systematic review. Obstet Gynecol. 2017 Feb 6. [Epub ahead of print]• Sukarman et al. Safety of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis and

influenza vaccinations in pregnancy, Obstet Gynecol. 2015 Nov; 126(5): 1069-74M t l P t ft t t t t di hth i d ll l t i• Morgan et al. Pregnancy outcomes after antepartum tetanus, diphtheria, and acellular pertussis vaccination. Obstet Gynecol. 2015;125(6):1433–8.

• Munoz et al. Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: A randomized clinical trial. JAMA. 2014;311(17):1760–92014;311(17):1760 9.

• Donegan et al. Safety of pertussis vaccination in pregnant women in UK: Observational study. BMJ. 2014;349:g4219.

A dAgenda1. Introduction and overview maternal

immunizationLaura Hammitt, MD, Assistant Professor, Center for American immunization Indian Health, Johns Hopkins Bloomberg School of Public Health

2. Antenatal influenza and pertussis uptake Ab i i l th i A t li

Annette Regan, PhD, MPH, Research Fellow Curtin Universityamong Aboriginal mothers in Australia Research Fellow, Curtin University School of Public Health

3. Validation of an algorithm to measure Cheyenne Jim, MS, Indian Health S i I i ti Pmaternal vaccine uptake Service Immunization Program Analyst

4 Facilitators and barriers to maternal Jessica Atwell, PhD, MPH, Assistant 4. Facilitators and barriers to maternal vaccine uptake among Navajo and White Mountain Apache women

, , ,Scientist, Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health

5 Discussion/Questions All5. Discussion/Questions All

https://www.cdc.gov/flu/pdf/freeresources/pregnant/pregnant-women-risk-17x11.pdf

Th t ff ti t l i th ld l k ifThe most effective tool in the world only works if you use it

Smallpox vaccination in Nigeria

Photo courtesy of Stan Foster

R i t f Td d i b t i tReceipt of Tdap during pregnancy by trimester, 2007-2013, Vaccine Safety Datalink Data

Reprinted from Vaccine Vol 34(7), Kharbanda et al., Maternal Tdap vaccination: Coverage and acute safety outcomes in the vaccine safety datalink, 2007–2013, with permission from Elsevier

M t l i ti i id th dMaternal vaccination - easier said than done

• Debate about risk/benefit poor-moderate uptake• Lack of data (until recently) to assure safety and efficacy• Thalidomide profound changes to regulatory p g g y

environment– FDA excluded pregnant women from clinical trials– Pharma concerned about liability– Providers perceive unwillingness of pregnant women to receive

recommended vaccines

• Perceived that potential risk trumped benefit

UNTIL 2009 pandemic H1N1 andUNTIL 2009 pandemic H1N1 and resurgence of infant pertussis cases

M t l i i ti i NOT tMaternal immunization is NOT a new concept

• 1879: Maternal immunization with cowpox virus protected p pmothers and infants from smallpox

• 1938: Maternal immunization with whole cell pertussis vaccine protected infants from complications of pertussis

• 1961: Maternal immunization with tetanus toxoid vaccine in New Guinea protected infants millions of maternal and neonatal deaths prevented worldwide since then

1964 I ti t d i fl i d d• 1964: Inactivated influenza vaccine recommended

Acknowledgements

Ruth Karron Shabir Madhi Carol Baker Kate O’Brien

Reasons for flu immunization during pregnancy

Influenza 5x more likely to cause severe illness in pregnant women Increased risk of preterm labor and birth in pregnant women p p g

with influenza Influenza hospitalization rates in infants <6 mos are 10x greater

than in older children but there are no licensed vaccines forthan in older children but there are no licensed vaccines for children <6 mos Vaccination during pregnancy has been shown to protect both

th th d h i f t f i fl ill i flthe mother and her infant from influenza illness, influenza hospitalization and influenza-related preterm birth Babies whose mother have a flu shot in pregnancy are ~50% less

lik l t b di d ith fl i th i fi t fllikely to be diagnosed with flu in their first flu season

Neonatal tetanus

Clostridium tetaniTetanusWHO 2015 Data

34 019 NT• 34,019 NT deaths

• 96% reduction f 1988from 1988

ubiquitous spores – majority cases birth‐associated 

Image: https://www.cdc.gov/tetanus/about/photos.html

AI/AN vs non-AI/AN rates of death related to 2009 pH1N1, 12 states

AI/AN N AI/AN

8910

AI/AN Non AI/AN

RR 5 0

5678

 100,000

RR 7 2RR 3.7

(2 5 5 6)

RR 5.0 (2.3-10.8)

RR 4 0

2345

Rate per RR 7.2

(2.4-21.8)

RR 2.7 (1 1 6 8)

(2.5-5.6) RR 4.0 (2.9-5.6)

01

0‐4 5‐24 25‐64 ≥65 Total

(1.1-6.8)

Age group (years)

MMWR Dec 11, 2009

M t l i fl i ti t d 2002 2005

1160

Maternal influenza vaccination study, 2002-2005

Mother-infant pairs

573573Given the flu

shot

587 Not given the

flu shot

31Lab-

confirmed flu cases

293 Flu-like

Symptoms

52Lab-

confirmed flu cases

312Flu-like

Symptomscases

76 Hospitalized for

fl lik

cases

117 Hospitalized for

fl likflu like symptoms

flu like symptoms

Main reason for receiving vaccination

https://www.cdc.gov/flu/fluvaxview/pregnant‐women‐nov2016.htm

Main reason for NOT receiving vaccination

https://www.cdc.gov/flu/fluvaxview/pregnant‐women‐nov2016.htm