HomeMy WebLinkAboutinfluenza-and-pertussis-prenatal-aziz-01242018-archiveInfluenza and Pertussis
in Pregnancy
Natali Aziz, MD, MS
Department of Obstetrics and Gynecology
Stanford University School of Medicine
Bay Area Infectious Disease Conference for Prenatal and Pediatric Providers
California Department of Public Health
January 24, 2018
Disclosures
I have no industry affiliations.
Overview
Influenza and Pertussis
Background/Epidemiology
Clinical features in pregnancy
Fetal and neonatal consequences
Treatment
Vaccination Recommendations
Opportunity for Immunization
~ 4 million live births each year in US
>98% of women have at least 1 prenatal visit
–Health care opportunity for vaccination!
–Immunization effective in pregnant women
Protection for
–Pregnant woman
–Fetus
–Neonate
–Young infant
Zaman 2008, Sumaya 1979, Englund 1993, Puck 1980, Reuman 1987
Opportunity for Immunization
Recommendation from provider is single most
important factor for vaccination uptake in
pregnancy
–Sweden: recommendation from Ob/Gyn
107-fold increase in the likelihood that a pregnant woman
will agree to an influenza vaccination
–Australia: recommendation from provider
20-fold more likely to accept influenza vaccine
–Australia: recommendation from provider
7 times more likely to accept pertussis vaccine
Vilca ML 2017, Blanchard-Rohner G 2012, Wiley KE 2013, Wiley KE 2013
INFLUENZA
Background and
Epidemiology
Influenza Activity
Influenza Activity
Immune Considerations
Pregnant women
–Altered immune response
–Increased risk of some
infections
–Increased risk of severe
outcomes of some
infections
Fetus, newborn, infant
–Immature immune
response
–Increased risk of some
infections
–Increased risk of severe
outcomes of some
infections
–Infection sequelae can
result in lifelong disability
1.7 2.1
5.1
0
2
4
6
8
1st trimester 2nd trimester 3rd trimester
Ra
t
e
R
a
t
i
o
s
Risk of Hospital Admission for Respiratory Illness
during Influenza Season by Pregnancy Status*
among Women with No Comorbidity,
Nova Scotia, 1990-2002
Dodds 2007
*Compared to year before pregnancy
2009 H1N1 Influenza
Obstetric Epidemiology
Prevalence of H1N1 per Trimester
Total Hospitalized or Severe Acute Resp Infection
Cullen 2009, Jain 2009, Oliveira 2009, Siston 2010
0
10
20
30
40
50
60
70
Cullen/Ireland Oliveira/Brazil Siston/US
1st Tri
2nd Tri
3rd Tri
2009 H1N1 Influenza and
Pregnancy
April-August 2009 US Statistics
Siston 2010
0
10
20
30
40
50
60
Total Hosp ICU Deaths
1st Tri
2nd Tri
3rd Tri
Clinical Manifestations
Fever
Cough
Rhinorrhea
Sore throat
Headache
Shortness of breath
Myalgia
Jamieson DJ 2009
Presenting manifestations N (%)
Fever 33 (97%)
Cough 32 (94%)
Rhinorrhea 20 (59%)
Sore throat 17 (50%)
Headache 16 (47%)
Shortness of breath 14 (41%)
Vomiting 6 (18%)
Diarrhea 4 (12%)
Presenting Manifestations in Pregnant
Women with 2009 H1N1 Influenza
United States, April 15 to May 18, 2009
Jamieson DJ 2009
Fetal Effects
Effects of influenza on the fetus
–Unknown and difficult to predict
Viremia in seasonal influenza
–Believed to occur infrequently
–Placental transmission appears to be rare
Case of fatal avian influenza (H5N1)
–2009 H1N1 novel influenza was similar
Hyperthermia
Risk factor for some types of birth defects
and other adverse outcomes
CDC April 2010; ANZIC Influenza Investigators 2009 and 2010
Adverse Obstetric Outcomes
Systematic Review: congenital anomalies
–Influenza/influenza-like illness in 1st trimester
–Increased risk of congenital abnormalities [AOR]
for any anomaly 2.00 (95% CI 1.62-2.48)
Cleft lip (OR 3.2)
Neural tube defects (OR 3.3)
Hydrocephaly (OR 5.7)
Congenital heart defects (OR 1.6)
–Risk attenuated by use of antipyretics
Other reported adverse events
–Increased risk SAB, PTD, LBW, fetal death
Luteijn JM 2014
Clinical Diagnosis
During influenza outbreak
–Acute febrile respiratory illnesses can be
diagnosed as influenza with a high likelihood by
clinical criteria
–Influenza testing is not needed in peak season
–Testing is recommended in complex cases, cases where
management will be affected, etc.
Laboratory Diagnosis
Molecular assays (RT-PCR)
–Highest sensitivity but longer processing time
Rapid diagnostic tests
–Sensitivities ~ 50-70% and specificities ~90-95
–Compared with viral culture or reverse
transcription polymerase chain reaction
–Limited sensitivity of the rapid antigen tests
Negative result should be interpreted with caution
given potential of false negative
Follow-up testing with conventional RT-
PCR and/or viral culture should be considered in
certain situations
Influenza Vaccination
All pregnant women (ACIP 2004)
Indication: Influenza season (October-May)
Timing: Pregnancy (any trimester!)
Dosing: Single-dose series
Use inactivated vaccine for pregnant women
No adverse fetal effects or pregnancy outcomes!
Intranasal vaccine (LAIV, FluMist): live-attenuated
–NOT recommended for use in pregnant women!!!
California mandate of thimerosal-free vaccine for
pregnant women
Harper 2004; Munoz 2005; Pool 2006
Influenza Vaccine Benefits
Maternal illness reduction
–Cochrane Database 2014 systematic review
H1N1 vaccines reduced risk influenza-like illness in
pregnant women by 89% (95% CI 79-94)
Seasonal vaccine reduced risk influenza-like illness in
pregnant women by 24% (95% CI 11-35)
–Randomized trial
36% (95% CI 4-57) reduction in febrile respiratory
illness in pregnant women who received vaccination
–Large case control
44% (95% CI 5%-67%)reduction in lab-confirmed
influenza in cohort who received vaccination
Demicheli V 2014, Zaman K 2008, Thompson MG
Influenza Vaccine Benefits
Improved pregnancy outcomes
–2016 Systematic Review
Reduced risk of stillbirth (RR 0.73, 95% CI 0.55-0.96)
–Others
Reduced risk for small for gestational age infants and
preterm delivery
Increase in birth weight
Bratton KN 2015, Zaman K 2008, Steinhoff MC 2012
Influenza Vaccine Benefits
Infant protection: Passive Immunization
–Anti-influenza-specific IgG actively transferred
across the placenta to the fetus and anti-
influenza-specific IgA in breast milk transferred
to the infant during lactation
Wutzler P 2009, Schlaudecker EP 2013
Influenza Vaccine Benefits
Passive immunity declines over several
months in infants born to vaccinated mothers
–Maternal vaccine efficacy against PCR confirmed
influenza illness was 86% in infants ≤8 weeks of
age and 25-30% in infants 8-24 weeks of age
–Maternally vaccinated infants
Overall cohort: 25% less likely to be hospitalized for an
acute respiratory illness (AHR 0.75, 95% CI 0.56-0.99)
3rd trimester maternal vaccinated infants: 33% less
likely to be hospitalized (AHR: 0.67, 95% CI 0.47-0.95)
Nunes MC 2016, Regan AK 2016
Influenza Vaccine Benefits
Infant protection
–Cochrane Database Sys Rev 2004
Infants born to vaccinated mothers had 41% (95% CI
6-63) reduction in laboratory-confirmed influenza
–Randomized Trial
Lab confirmed influenza reduced by 63% (95% CI 5-
85)in infants of vaccinated mothers
–RCT secondary analysis
Reduced hospitalizations for acute lower respiratory
tract infection < 3 months of age
3.0% (95% CI 1.6-5.7) vs. 7.0% (95% CI 4.6-10.8)
Demicheli V 2014, Zaman K 2008, Nunes MC 2017
2017-2018 Influenza Vaccine
Trivalent
–A/Michigan/45/2015 (H1N1)pdm09-like virus
(updated)
–A/Hong Kong/4801/2014 (H3N2)-like virus
–B/Brisbane/60/2008-like (B/Victoria lineage) virus
Quadrivalent (four-component) protect
against a second lineage of B viruses
–B/Phuket/3073/2013-like (B/Yamagata lineage)
virus
https://www.cdc.gov/flu/about/season/flu-season-2017-2018.htm
Influenza Vaccination Coverage among
Recommended Adult Populations
National Health Interview Survey, 1989-2005
Lu 2008
Vaccination in Pregnancy
Coverage rates low for many years
Following 2009 H1N1 pandemic and broad
educational efforts rates have increased
2016-2017 Season
–53.6% reported having received vaccination
Before (16.2%) pregnancy
During (37.4%) pregnancy
–Providers influence on vaccination in pregnancy
67.3% received a provider offer for vaccination70.5%
11.9% received a recommendation but no offer43.7%
20.7% received no recommendation14.8%
Deng H 2017
Stanford OB Clinic
Vaccination Rates
2008-09 2009-10
(H1N1)
2010-11 2011-12
N=610 N=659 N=650 N=678 p*
Pregnant
Women who
Received
Influenza
Vaccination,
n (%)
206
(33.8%)
465
(70.6%)
382
(58.8%)
430
(63.4%)
<0.001
Singh A 2017 (IDSOG)
Stanford OB Clinic
Vaccination Rates
0
10
20
30
40
50
60
70
80
2008-09 2009-10 2010-11 2011-12
33.8%
70.6%
58.8%
63.4%
Va
c
c
i
n
a
t
i
o
n
Ra
t
e
(
%
)
Year
Singh A 2017 (IDSOG)
Treatment
Prompt treatment
–Pregnant women and postpartum women who are
within 2 weeks of delivery or pregnancy loss
–Suspected or confirmed influenza infection
–Treatment, when indicated, should not be delayed
for diagnostic testing results
–Early treatment
Within 2 days of symptom onset
Associated with a lower risk for admission to an
intensive care unit and death
Treatment >2 days after symptom onset has benefits
Treatment
Neuraminidase inhibitors
–Oseltamivir preferred for treatment
Pending resistance among circulating virus
Greater systemic absorption
Greater clinical experience using this drug in pregnancy
–Zanamivir possibly preferred for chemoprophylaxis
Limited systemic absorption
Respiratory complications due to inhaled route of
administration (asthmatics)
–Peramivir-IV
Antipyretics and symptomatic therapy
Antibiotics for superimposed bacterial infection
Antiviral Summary
Agent Treatment Chemoprophylaxis
Oseltamivir 75 mg PO BID
x 5 days
75 mg PO QD x 7-10
days
Oseltamivir
(Acutely ill)
75-150 mg PO BID
x 10 days
Zanamivir Two 5-mg inhalations
(10 mg total) BID
x 5 days
Two 5-mg inhalations
(10 mg total) QD
x 7-10 days
Peramivir
(FDA approved
2014)
600 mg IV
SINGLE DOSE
CDC 2009, CDC 2017
Other Management
Inpatient management
–Private rooms (confirmed or suspected cases)
–Infection control precautions
Standard precautions for patients
–Hand hygiene
–Respiratory hygiene/cough etiquette
–Mask patient during transport
Contact and droplet: health care workers
–Gloves, gowns, masks, eye protection, as appropriate
Outpatient management
–Screen and triage ASAP (scheduling/check-in)
Masked
Seated in special area
Designated exam room CDC 20017
Infant Care/Feeding
CDC guidelines developed during the 2009
H1N1 pandemic
–Separate mother with 2009 H1N1 from infant
until three criteria met
Mother received antiviral medications for 48 hours
Mother was afebrile without antipyretics for >24 hours
Mother was able to control cough/respiratory secretions
During temporary separation, all feedings provided by a
healthy caregiver
Mothers who intended to breastfeed should be
encouraged to express their milk
CDC November 2009
Infant Care/Feeding
Once mother and infant able to initiate close contact,
immediately prior to feeding and caring for the infant
(including direct breastfeeding) in order to protect
the newborn from droplet exposure mother
recommended
–Wash her hands with soap and water
–Should put on a face mask
–Observe all respiratory hygiene/ cough etiquette guidelines
Precautions should be followed for 7 days after symptom onset or 24 hours after resolution of symptoms, whichever is longer
CDC November 2009
Infant Care/Feeding
CDC guidance 2017-2018
–CONSIDER temporary separation of a mother
with suspected or confirmed influenza from her
newborn
Length of temporary separation needs to be made on a
case-by-case basis
During temporary separation, all feedings should be
provided by healthy caregiver
Mothers who intend to breastfeed should be
encouraged to express their milk
–If temporary separation is not feasible/acceptable
Environmental controls should be considered, such as
physical barriers and keeping the newborn >6 feet
away from the ill mother
CDC 2017
Pertussis
Background and
Epidemiology
Pertussis
Bacterial infection
–Bordetella pertussis
Highly contagious
Acute respiratory illness
Severe cough (whooping cough) x months
Infants < 3 months of age at greatest risk
for life-threatening cases of pertussis
–Hence vaccination in pregnancy recommended
–Infants may start DTaP vaccine series as early
as 6 weeks of age
Forsyth K 2015
Pertussis
Peak in incidence every 3-5 years
Widespread throughout US and the world
Prevalence of pertussis US increasing
–Pertussis immunity after vaccination or disease
wanes over time
Specific outbreaks in California
Child care facilities and schools with low
vaccination rates
–Increased risk for outbreaks
Pertussis
California
–2010: >9,000 cases
Most cases in over 60 years
10 infant deaths
–2014: 10,831 cases
2 infant deaths (<3 months of age)
Hundreds hospitalizations
–2015: 4,707 cases
1 infant death (<3 weeks of age)
–2016: 1,830 cases
2 infant deaths (< 3 months of age)
–2017: 495 cases https://www.cdph.ca.gov May 2017
Clinical Manifestations
Coughing paroxysm
Inspiratory whoops
Nocturnal cough
Post-tussive vomiting
Low-grade fever
Coryza
Pharyngitis
NO EVIDECNE that disease is more severe during pregnancy.
Clinical Manifestations:
Phases
Catarrhal phase
–Earliest phase of illness, lasting one to two weeks
–Generalized malaise, rhinorrhea, mild cough
Paroxysmal phase
–Begins second week of illness, last 2-3 months
–Paroxysmal cough (severe, vigorous)
Convalescent phase
–Lasts 1-2 weeks, reduction of symptoms
Total course: 3 months
Infant Considerations
Infants < 3 months
–Highest risk of morbidity and mortality
>50% of infants with pertussis contract the
disease from family members, mostly mothers
Forsyth K 2015, Bisgard KM 2004, Wendelboe AM 2007
Diagnosis
Outbreak setting/close contact
–Presence of cough lasting ≥2 weeks
Laboratory diagnosis
–<2 weeks of cough: culture and PCR
Culture sensitivity highest in first 2 weeks
–2-4 weeks of cough: culture and PCR
Culture sensitivity decreases after 2 weeks
Accuracy of PCR not fully known
–>4 weeks: serology
Diagnosis
CDC August 2017
Treatment
Most individuals clear pertussis infection
without antibiotic treatment within 6 weeks
Antibiotic treatment in early (catarrhal) phase
–May decrease duration and severity of cough
Antibiotic treatment later in disease course
–Likely does not affect the course of symptoms
–May reduce the spread of the infection to others
https://www.cdph.ca.gov May 2017
Treatment
Antibiotic therapy recommended for patients
within 3 weeks of cough onset
Persistent cough for 3-6weeks
–Antibiotic treatment may not reduce cough
duration or severity but could reduce likelihood
of pertussis transmission to others
Pregnant women, healthcare workers, and
individuals working with infants
–Antibiotic therapy is appropriate for those with
persistent cough for up to 6 weeks
Tiwari T 2005, CDC March 2016
Pertussis Vaccination
Birth to 6 years
–DTaP at 2, 4, and 6 months, at 15 through 18 months,
and at 4 through 6 years
7-10 years
–Tdap for children who are not fully vaccinated against
pertussis
11-18 years
–Tdap as a single dose for those 11 -18 years of age
(preferred 11 -12 years of age)
19 years and older
–Tdap ASAP for any adult 19 years of age or older who
has never received a dose of Tdap
ACIP 2012
Tetanus, Diphtheria, Pertussis
(Tdap) Vaccine in Pregnancy
Indication:
–All pregnant women during each pregnancy
–Regardless of previous immunization history
Timing:
–Ideally 27-36 weeks
Preferably during the earlier part of this period
Do not repeat if administered earlier in pregnancy
–Postpartum if not administered during pregnancy
Dosing: Single-dose series
Tetanus and diphtheria toxoids
Acellular pertussis inactivated vaccine ACIP 2012
Tdap Vaccine for Infant
Caregivers
Tdap vaccine
–Recommended for individuals (such as family
members and childcare providers) who are
expected to have close contact with a newborn
or infant younger than 12 months and have not
received Tdap previously
–Pregnant women are the only population in
whom repeated Tdap immunization is
recommended
–Repeated immunization is not recommended for
household contacts ACIP 2012
Tdap Vaccine Benefits
Infant protection: Passive Immunization
–IgG actively transferred across placenta
Highly effective in providing passive protection against
pertussis in infants in the first few months of life
Infant is not eligible for active immunization until six
weeks of age
–IgA possibly secreted in breastmilk
Tdap Vaccine Benefits
Retrospective 2010-2015
–148 981 newborns
–Vaccine effectiveness of maternal Tdap
91.4% (95% CI 19.5 to 99.1) during first 2 months of life
69.0% (95% CI, 43.6 to 82.9) during first year of life.
–Vaccine effectiveness in relation to Dtap
87.9% (95% CI, 41.4 to 97.5) before infants had any
81.4% (95% CI, 42.5 to 94.0) between doses 1 and 2
6.4% (95% CI, -165.1 to 66.9) between doses 2 and 3
65.9% (95% CI,4.5 to 87.8) after had 3 DTaP doses
Baxter R 2017
Tdap Vaccine Benefits
Women vaccinated ≤6 days before birth
–Vaccine effectiveness in infants lower
Women vaccinated remote from delivery
–Before conception and within two years of delivery or in
early pregnancy
–Cord blood pertussis-specific antibody levels were often
insufficient to protect the infant against infection in the first
two to three months of life
Women vaccinated between 27 and 31 weeks of gestation
had higher cord blood pertussis IgG levels than those
vaccinated at ≥31 weeks
Amirthalingam G 2014, Healy CM 2013, Abu Raya B 2014
ACIP: Administer at 27 and 36 weeks of gestation (and preferably during the earlier
part of this period), intending to maximize both maternal antibody response and
passive antibody transfer to the infant
Tdap Vaccine Safety
Tdap is safe to use during pregnancy
2017 systematic review
–Tdap administered to pregnant women
–There was no increase in significant adverse
maternal, infant, or pregnancy outcomes, even
among women who had received Tdap or other
tetanus-containing vaccine within the previous five
years
McMillan M 2017
Opportunity for Immunization
~ 4 million live births each year in US
>98% of women have at least 1 prenatal visit
–Health care opportunity for vaccination!
–Immunization effective in pregnant women
Protection for
–Pregnant woman
–Fetus
–Neonate
–Young infant
Zaman 2008, Sumaya 1979, Englund 1993, Puck 1980, Reuman 1987
Opportunity for Immunization
Opportunity for Provider Impact
Recommendation from and vaccination
offer by YOU the provider is SINLE MOST
IMPORTANT FACTOR for vaccination
uptake in pregnancy!
Vilca ML 2017, Blanchard-Rohner G 2012, Wiley KE 2013, Wiley KE 2013
Acknowledgements
Amy Pine, MPH
Alameda County Public Health Department
California Department of Public Health
Deborah Cohan, MD, MPH
Thank You!
Pager: 650-723-8222
Pager ID 23344
Resources
Centers for Disease Control and Prevention
–https://www.cdc.gov/flu
–https://www.cdc.gov/flu/professionals
–https://www.cdc.gov/pertussis
–https://www.cdc.gov/pertussis/clinical
California Department of Public Health
–https://www.cdph.ca.gov/Programs/CID/DCDC/Pa
ges/Immunization/Influenza.aspx
–https://www.cdph.ca.gov/Programs/CID/DCDC/Pa
ges/Immunization/pertussis.aspx
Local DPH Resources
Santa Clara County
–Phone: 408-792-5040
San Mateo County
–SMC Communicable Disease Control Program
–Phone: 650-573-2346
Santa Cruz County
–Phone: 831-454-4882 (fax: 831-454-549)
Monterey County
–Phone: 831-755-4521 (fax: 831-754-6682)
California Immunization Registry
CAIR = Statewide Immunization Information System
CA statewide immunization registry network
10 multi-county regional immunization registries
Computerized registry system for provider entered info
–Assist providers to track patient records
–Reduce missed opportunities
–Fully immunize all children in California
Schools, childcare centers, and WIC can link into
regional registries
Ultimate goal to integrate 9 regional district
http://www.ca-siis.org
Antiviral Pregnancy Registry
1-800-258-4263
http://www.apregistry.com
Now on-line patient enrollment
Vaccine Registries
Immunizations During Pregnancy
All vaccinations (general)
–VAERS: Vaccine Adverse Event Reporting System
–800-822-7967; www.vaers.org
HPV Quadrivalent Vaccine
–Gardasil/Merck
–1-800-986-8999
Rubella Vaccine in Pregnancy Registry-discontinued in 1989
Varicella
–VARIVAX Pregnancy Registry
–800-986-8999
Tdap
–BOOSTRIX/GlaxoSmithKline Biologicals (1-888-825-5249)
–ADACEL/Sanofi Pasteur at (1-800-822-2463 or 1-800-VACCINE)
Smallpox
–Centers for Disease Control and Prevention
–Smallpox Vaccine in Pregnancy Registry
–404-639-8253
EXTRA SLIDES
Vaccine Controversy
Autism prevalence has increased
–Changes in case definition and increased awareness
–?Actual increase in incidence of autism
Multiple large, well-designed studies and
systematic reviews have not demonstrated link
between vaccines/MMR and autism
Studies do not demonstrate association between
vaccines and multiple sclerosis or type 1 DM
Immunization Safety Review 2004
Vaccine Controversy
Multiple large, well-designed epidemiologic
studies and systematic reviews have not
demonstrated association between thimerosal
and autism or other developmental disorders
No association b/w thimerosal and CV disease
Mercury poisoning and autism DIFFER
WHO advisory committee concluded it is safe to
continue using thimerosal in vaccines
Yoshizawa 2002; WHO 2002; Hviid 2003; Thompson 2007
Obstetric Immunization Challenges
Limited well-controlled studies in pregnant cohorts
Theoretical concerns about efficacy
Theoretical concerns about safety in pregnancy/BF
–Vaccine type (e.g., live vaccines)
–Additives/adjuvants/preservatives (e.g., thimerosal)
–Timing of vaccination
Interruption of breastfeeding
Impaired newborn/infant immune response to childhood series concerns
Lack of harmonization with FDA labels and indications
Public perception/risks and legal liability
Logistic issues for office-based practice
ACIP April 2008
Infant Care/Feeding
Breast milk is not thought to be a potential
source of influenza virus infections
Expressed milk from mothers with influenza
can be safely fed to their newborn infants
Feedings (expressed milk) during temporary
separation should be provided by a healthy
caregiver (family members or hospital
personnel) until criteria are met for close
contact
Antiviral medication treatment or prophylaxis
is not a contraindication for breastfeeding
CDC November 2009