Neil S. Silverman, MD

Center for Fetal Medicine & Women’s Ultrasound, LA

Clinical Professor, Dept. of Obstetrics and Gynecology

Division of Maternal-Fetal Medicine

David Geffen School of Medicine at UCLA

Vaccine Importance and Strategies

Children have benefited the most from vaccines in terms of declines in disability and death, primarily because vaccination programs are generally targeted to children

In 1994, reported that 50,000-70,000 adults compared to 500 children died each year from vaccine-preventable illnesses

(Fedson D, JAMA 1994)

More than 50% of cases of significant vaccine-preventable illnesses reported to the CDC in 2004 occurred in individuals > 15 years old

Many of the most vulnerable adults are seen in practices that provide health care to women

Immunization services have not historically been part of obgyn care

Need to address benefit of vaccination both for women and for the long-term health of their children

Vaccination: Key Areas

Influenza (focus on pregnancy

and HCWs)

Tdap (tetanus, diphtheria,

pertussis)

Physician protection/liability

Inadvertent vaccination

Side effects/complications

Influenza

Influenza and Pregnancy

Increased morbidity/hospitalization rates for pregnant women

in every trimester compared to rates in nonpregnant persons

(Dodds L et al, CMAJ 2007)

When no comorbidities: risk ratio 1.7 (1st tri) – 5.1 (3rd tri)

With comorbidities: risk ratio 2.9 (1st tri) – 7.9 (3rd tri)

Increased risks of maternal deaths reported in pan-epidemics

(CDC 2007)

Newer live-attenuated nasal flu vaccine should not be given in

pregnancy, or in those > 65 years old (GYN)

Demonstrated benefit for mothers and newborns

Immunization with the trivalent inactivated flu vaccine

(TIV) is recommended for all pregnant women

(ACOG CO #608, Sept 2014; CDC 2013)

Neonatal Benefits of Maternal Influenza Vaccination

Flu vaccine not recommended for children < 6 months of age

Pregnant women have been shown to have protective levels of anti-influenza antibodies after vaccination

(Munoz FM, AJOG 2005)

Passive transfer of antibodies that might provide protection from vaccinated women to neonates has been reported

(Englund JA et al, J Infect Dis 1993; Reumen PD et al, Ped Infect Dis J 1987)

Retrospective clinic-based study in 1998-2003 showed (nonsignificant) trend toward fewer episodes of newborn respiratory illness among newborns of vaccinated pregnant women (Black SB ,Am J Perinatol 2004)

Neonatal Benefits of Maternal

Influenza Vaccination (2)

Randomized study of flu vaccine during

pregnancy to assess neonatal impact:

NEJM, Sept 2008, Zaman K, et al

340 women received either flu vaccine or

pneumococcal vaccine (Hopkins study group in

Bangladesh)

63% lower risk of lab-confirmed neonatal influenza in

children of vaccinated moms, up to 6 months of age

1st study to definitively show benefit to women and

children

Zaman K et al, NEJM 2008

Influenza Vaccination of Pregnant Women and

Protection of their Infants (2014)

Report on 2 double-blind R-PC trials of trivalent influenza

vaccine in pregnant women with and without HIV infection

Study cohorts: 2116 pregnant women without and 194

pregnant women with HIV infection (South Africa)

At 1 month after vaccination, seroconversion rates and

rates of antibody titers were significantly higher for vaccine

recipients vs placebo in both cohorts (90-97% vs 25-44%)

Vaccine efficacy (placebo vs vaccine)

HIV-uninfected women/infants: 3.6% infection rate vs 1.9%

HIV-infected women: 17% infected vs 7.0%

Madhi SA, et al. NEJM, Sept 2014

Kaplan–Meier Estimates of Percentages of Confirmed Cases of Influenza According to Cohort and Study Group.

Madhi SA et al. N Engl J Med 2014;371:918-931.

So..why aren’t more pregnant women

vaccinated against influenza?

Lack of information

Variability in flu severity year-to-year

Current flu season ending: mildest in CA in

recent years

“Short memory” syndrome

Concerns over risk for pregnancy

Provider interest: concerns over

reimbursement, litigation

Confusion over recommendations

Recommendations of ACIP for Maternal

Influenza Vaccination

1964-1966: Any stage of pregnancy

1966-1969: HR conditions, any gestational age

1969-1974: No mention of maternal immunization

1974-1976: Pregnancy not an indication

1976-1977: No evidence to document influenza a risk

1977-1981: Evaluate pregnant as non-pregnant

1981-1986: Vaccinate HR pregnant women

1987-1995: Vaccinate HR pregnant women in any age

1995-1997: HR at any gestational age; others 3rd trimester

1997-2004: HR at any time, other in 2nd and 3rd trimester

2004-2008: Women pregnant during influenza season at any trimester

Are we barriers to vaccination during pregnancy?

Prospective survey study during 3 months of flu season

• Among responding women, only 22% reported discussing flu

vaccine with doctor, and only 8% were vaccinated

More physicians said they discussed vaccine with patients

than did patients say it was discussed (74% v 22%; p<0.01)

Physicians were more likely to vaccinate if: Aware of CDC guidelines (RR 2.6; 1.1-5.9)

Gave vaccinations in their office (RR 1.2; 1.01-1.4)

Had received flu vaccine themselves (RR 1.9; 1.3-2.8)

Study demonstrated gaps in both groups’ understanding

of benefit of vaccine for both pregnant women &

newborns

Silverman NS, Greif A. J Repro Med, Nov 2001

HCW Vaccinations 2013-14

Overall influenza coverage rate

for 2013-14 season was 75.2%

Coverage was > 90% for;

1. Physicians, regardless of work setting

2. HCW with employer vaccination

requirement, regardless of work setting

Majority of vaccinated HCWs (77.3%)

reported receiving vaccine at work

If vaccines not required at work:

80%: vaccine if free and on-site > 1 day

62%: vaccine if free and on-site only 1 day

49%: vaccine if not available on-site

MMWR: Sept 19, 2014

MMWR, Sept 19, 2014

MMWR, Sept 19, 2014

, Sept 19, 2014

Doctors ARE Covered:

National Childhood Vaccine Injury Act

www.hrsa.gov/vaccinecompensation

Established by Congress in 1986

Began operation 1988

No-fault federal compensation

program

Alternative to tort system

NCVI Act

Table of injury established for each vaccine

Alleged injury must be on the table

Financed by $0.75 tax per antigen and each tax must be passed by congress

Time limits for inquiries

But this is a Childhood Vaccine

Injury Act, right? Yes, but it covers all vaccines that are part of the

childhood vaccination schedule, regardless of who’s getting them e.g.: Influenza, hepatitis B, varicella, tetanus

Requires health-care provider who administers VCIP-covered vaccines to record, either in an office log or the recipient’s permanent medical record: Date of vaccine, manufacturer and lot #, name and title of

person administering the vaccine

Also requires reporting of adverse vaccination reactions to Vaccine Adverse Event Reporting System (VAERS) 800-338-2382 or http://vaers.hhs.gov

Influenza Antivirals and Pregnancy

Issue initially arose with H1N1 (A strain), since it

was susceptible, choice was between oseltamavir

and zanamavir Both OK in pregnancy; rimantidine also OK , only IF susceptible

Neuraminidase inhibitors usually also effective against B strains

Oseltamavir, as a systemic agent, may be

preferable

Treat mother and, possibly, fetus: does cross placenta

Treatment dose: 75 mg BID X 5 days

Ideally, within 2 days after onset of symptoms

Prophylactic dose: 75 mg daily X 10 days

Exposure window: 7 days

BUT:

Vaccination is

ALWAYS

better than

treatment

2014-15 Influenza Vaccine (MMWR, Aug 15, 2014)

In June 2014, the ACIP voted on updated recommendations

for use of trivalent seasonal influenza vaccine for the 2014-

2015 influenza season.

Expanded vaccination recommendations for adults were

established in 2009 to include all adults. Therefore, all

people age 6 months and older are now recommended to

receive annual influenza vaccination.

The 2014–2015 trivalent vaccine is identical to last year’s:

A/California/7/2009 (H1N1)-like, A/Texas/50/2012 (H3N2)-

like, and B/Massachusetts/2/2012-like antigens.

Recombinant trivalent vaccine available for persons with severe egg

allergy (anaphylaxis): FluBlok®. Nasal vaccine NOT an alternative.

Quadrivalent vaccine also available but no CDC recommendation

Influenza Vaccine:

Preparations and Preservatives

Quadrivalent vaccine also available but no

ACIP/CDC or ACOG recommendation or

preference 1,2

Recombinant trivalent vaccine available for

persons with severe egg allergy (anaphylaxis):

FluBlok®. (allergy no longer an “excuse”)

Thimerosal: a mercury-containing preservative

used in multi-dose vials of the vaccine

Thimerosal-free formulations are available, NO

scientific evidence that thimerosal-containing vaccines

result in adverse effects in newborns whose mothers

got them during pregnancy 1

1. CDC/MMWR 2013. 2. ACOG 2014

Pertussis and Tdap

Pertussis Epidemiology

Pertussis is

— an endemic human disease that peaks

every 3 to 5 years

— increasingly being reported in adolescents

and adults; immunity wanes

• In 2005, ~60% of cases ≥11 years of age*

Adolescents and adults serve as vectors of

infection for non-immune infants, in whom disease

is often quite severe

Probably not a disease reservoir

— Prolonged carriage most likely does not occur

*CDC. Pertussis Surveillance Report, Oct 14, 2006. Weeks 1-52 (final data)

Tetanus-Diphtheria-Pertussis Vaccines:

New Considerations

Tetanus booster recommendations have not changed:

every 10 years, with pregnancy no exception (toxoid)

DTP typically a childhood vaccine, with adults receiving Td

boosters

However, rates of pertussis infection have soared in

US despite childhood vaccination

Pertussis is highly contagious and spread easily by inhalation

of respiratory droplets or aerosols

Cases reported to CDC have doubled between 2003 and

2004, and are higher than any year since 1959

Adults and adolescents accounted for 67% of cases in 2006

Why here? Why now?

Pertussis cyclical

— Epidemics occur every 3-5 yrs when enough

susceptible people accumulate in population

to sustain widespread transmission

— Last US epidemic in 2005 (nationwide)

Susceptible people increase in population due to — New birth cohorts of unvaccinated infants

— Waning population immunity from vaccine or disease

(and less chance for boosting opportunities)

— Parental choice not to vaccinate children, etc.

Unclear why California most affected state so far

— Speculation: may have less population immunity than

other states because (until recently) one of only 11 states not

having requirement that all middle school students receive Tdap

Courtesy of Kathleen Harriman, California Dept of Public Health

?

Why the New Pertussis-containing

Vaccines?

Newer vaccine is an acellular pertussis-containing

preparation (Tdap): presumed better and more

durable immunogenicity

Approved in 2005 for individuals 11-64 years of age

Compensates for waning immunity (5-10 yrs) from old vaccine

DTaP is similar vaccine in pediatric formulation, with

3-5 X as much diphtheria component

Higher amount of pertussis component also is pediatric

preparation

Upper case “D” for pediatric formulation, lower case “d” for

adult formulation (same for “P” vs “p”)

Tetanus components equivalent

Pertussis: Common Questions (1)

A child or adult who has had pertussis can

(uncommonly) get the disease again, so vaccination is

recommended

Reinfection may present as persistent cough rather than

typical pertussis

After a tetanus-prone injury, in an adult whose last

booster was > 2 years ago?

Give Tdap, not Td or tetanus toxoid (TT) alone (can give Td

only if prior Tdap can be documented)

Age no excuse: TT became available in 1938, routinely used in

1944

No documentation → assume to be unimmunized

Pertussis: Common Questions (2)

Tdap can be given at same visit as other vaccines

Different site, using a separate syringe (don’t mix)

Mixed clinic setting (peds/adult) and an adult got DtaP

in error instead of Tdap

No harm to adult

Age limitations?

Both current commercially available Tdap formulations are

licensed for ages 11 and up. Recent ACIP/CDC

recommendations (June 2011): approved for ages > 65

New Tdap Urgency: CA Outbreak

Largest pertussis outbreak in 65 years in CA in 2010

9120 cases statewide; 304 cases through same time in 2009

10 infant deaths

Studies have shown that household contacts, most

often mothers, are the most common source of

pertussis in infants (Wendleboe AM, Ped Infect Dis J, 2009)

CA Dept. of Public Health, CDC, and CA-ACOG

endorsed vaccinating women during pregnancy

At least 2 weeks before contact with young infants

Household contacts are also to be vaccinated

Health-care personnel and childcare workers also

need to be vaccinated

2010-2011 ACIP Pertussis Recommendations

October 2010

— No interval necessary between Td and Tdap

(Previously: 2-year interval recommended)

— Tdap for adults ≥65 years of age with infant contact

— One dose Tdap for un-/under-immunized children 7-10

years of age

February 2011

— All healthcare personnel (HCP) who have not

received Tdap should receive ASAP

— Healthcare facilities should take steps to encourage

Tdap, including providing at no cost

http://www.cdc.gov/vaccines/recs/acip/

http://www.cdc.gov/vaccines/recs/acip/slides-jun11.htm#pertussis

How to Best Protect the Infant Tdap during Pregnancy!

Gall SA, AJOG 2011;204;334.e1-5.

Tdap during Pregnancy:

Safety and Immunogenicity

Randomized clinical trial evaluating Tdap during

pregnancy or postpartum

Significantly higher pertussis antibodies if Tdap

given during pregnancy compared to postpartum

in both women and in their infants at birth (p< 0.001)

No increased risk in serious adverse events in

women or infants, other than injection site

reactions in women

Pertussis antibodies in newborns did not alter

infant responses to Dtap vaccine in infancy

Munoz FM, et al. JAMA , May 2014

http://www.msnbc.msn.com/id/43502623/ns/health-

pregnancy

Pertussis Recommendations Current Landscape

All health care personnel

All adults, adolescents

After wound (instead of Td)

7-10 yo, if not completely immunized

Cocooning—including GRANDPARENTS

Antepartum—2nd or 3rd trimester

If not antepartum, give postpartum

Other Vaccines & Issues

Inadvertent vaccinations

Issue arises when a live attenuated vaccine (MMR or varicella)

is administered to a women whose early pregnancy was

undiagnosed

Rubella

Congenital rubella syndrome (CRS) reported with rubella infection in any

trimester

However, no proven vaccine-caused cases of CRS in either the US or

UK registries with current RA27/3 vaccine (MMWR, RR-8, 1998)

Varicella

Nonpregnant women who are vaccinate are counseled to avoid

pregnancy for 1 month (MMWR, RR-11, 1996)

Current Varivax® registry data report no attributable cases of congenital

varicella syndrome

Varicella or rubella vaccination during early pregnancy should not

be regarded as reasons to terminate pregnancy (MMWR, RR-15, 2006)

www.immunizationforwomen.org

Outreach to Ob-Gyns

Visit our Website:

www.immunizationforwomen.org