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National Center for Emerging and Zoonotic Infectious Diseases
CLINICAL GUIDANCE FOR USE OF LIVE ATTENUATED
CHIKUNGUNYA VACCINE AMONG PREGNANT AND
BREASTFEEDING INDIVIDUALS
Susan Hills, MBBS, MTH
CDC Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector -Borne Diseases
Fort Collins, Colorado
ACIP meeting, February 28, 2024
Clinical guidance for use of live attenuated
chikungunya vaccine in pregnant individuals
Presentation of chikungunya among pregnant persons
Clinical disease similar to non-pregnant persons
Outcomes of chikungunya virus infection during pregnancy
Adverse outcomes such as fetal loss, stillbirth, or preterm birth
documented but rare
–Mouse studies and examination of placentas from infected women suggest
placenta is refractory to chikungunya virus infection1,2
Infection commonly results in adverse neonatal outcomes if pregnant
individual infected around time of delivery
–In these cases, intrapartum transmission occurs in ~30% –50% cases3–6
–Mechanism considered to be transplacental transmission with hypothesis that maternal blood enters fetal circulation by placental barrier breaches
from uterine contractions during labor
1. Fritel X et al, Emerg Infect Dis 2010; 2. Couderc T et al, PLoS Pathog 2008; 3. Gerardin P et al, PLoS Medicine 2008; 4. Ramful D et al, Ped Infect Dis J 2007; 5.
Torres JR et al, Int J Infect Dis 2016; 6. Senanayake MP et al, Ceylon Med J 2009.
Disease in neonates infected via intrapartum transmission
Severe and sometime fatal illness
–In one prospective study 53% (10 of 19 neonates) had severe disease1
Presentations include encephalopathy, sepsis -like illness, cardiac,
dermatologic, and hemorrhagic manifestations
Neurocognitive outcomes often poor, particularly if initial clinical
presentation with encephalopathy
Bin S et al, Clin Case Rep 2023
Jebain J et al, ID Cases 2020
Villamil -Gomez W et al, J Trop Ped 2015
1. Gerardin P et al, PLoS Medicine 2008
Chikungunya and young infants
Young infants infected via
mosquito -borne transmission
also at risk for severe disease, particularly during the first few months of life
Clinical presentations similar to those with neonatal infections
Valamparampil JJ et al, Ind J Ped 2009
Gupta D et al, Ind J Ped 2015
Vaccination during pregnancy: Immunogenicity
No data available on immunologic response to chikungunya vaccine
administered to pregnant individual
General principles and experience with other vaccines
–Transplacental transfer of antibodies after maternal immunization demonstrated
to confer protection with most vaccines
–Examples of benefits include decreased rates of hospitalization in infants born to
vaccinated women (e.g., influenza, COVID -19, RSV vaccines) and decreased risk
for preterm birth (e.g., COVID -19 vaccine)
Vaccination during pregnancy: Safety
Data are insufficient to determine whether any safety risks from vaccination
during pregnancy
–Pregnancy was an exclusion criteria in clinical trials
–Only two pregnant persons inadvertently vaccinated during pregnancy
Two pregnant persons vaccinated during 1st trimester
–36-year -old: spontaneous abortion 59 days after vaccination at gestational age
~10– 14 weeks
–23-year -old: anembryonic pregnancy noted at 53 days, spontaneous abortion at 55
days after vaccination at ~8 weeks gestation
General notes on cases
–Anembryonic pregnancies generally result from chromosomal problem at conception
–Estimated 20%– 25% of all pregnancies lead to pregnancy loss, with highest rates in
1st trimester and increasing rates with increasing maternal age
Key language related to pregnancy in package insert1
Noted under “Warnings and Precautions”
–Vertical transmission of wild-type chikungunya virus from pregnant individuals with
viremia at delivery is common and can cause potentially fatal chikungunya virus
disease in neonates. Vaccine viremia occurs in the first week following administration
of chikungunya vaccine….it is not known if the vaccine virus can be vertically transmitted and cause fetal or neonatal adverse reactions
Noted under “Use in Specific Populations”
–A decision to administer chikungunya vaccine during pregnancy should take into consideration the individual’s risk of wild -type chikungunya virus infection,
gestational age, and risks to the fetus or neonate from vertical transmission of wild -
type chikungunya virus....If neonates are born within 14 days of their mother receiving chikungunya vaccine, closely monitor them after birth for potential disease due to vaccine virus
1. FDA. Package Insert – IXCHIQ. Available at: https://www.fda.gov/vaccines -blood -biologics/ixchiq
Viremia after vaccination
In Phase 1 clinical trial
–Viremia after vaccination assessed by quantitative reverse transcription-
polymerase chain reaction ( qRT-PCR)
–Plasma tested on days 3, 7, and 14 after vaccination
Among 30 subjects vaccinated with vaccine dose with equivalent amount
of attenuated chikungunya virus as in licensed vaccine, viremia detected in
–90% on day 3
–17% on day 7
–0% on day 14
For many live vaccines, pregnancy is contraindication
–Theoretical risk to fetus from maternal viremia and viral transmission to fetus
–MMR and varicella vaccines contraindicated during pregnancy, although no
cases of congenital rubella or varicella syndrome or abnormalities attributable to fetal infection observed among infants born to women inadvertently vaccinated during pregnancy
For some live vaccines, pregnancy is precaution
–Vaccines can be used after considering the risks of disease and risks and benefits of vaccination
–Yellow fever, dengue vaccines
Kroger A et al. General Best Practice Guidance for Immunization (https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.h tml) Live, attenuated vaccines and pregnancy:
ACIP General Best Practice Guidelines for Immunization
Groups for whom clinical guidance will be relevant
Travelers and laboratory workers
Persons in U.S. territories and states with risk of chikungunya virus
transmission
Objectives of vaccinating pregnant individuals
Protect pregnant person from chikungunya virus infection
Avoid maternal infection around time of delivery to prevent
intrapartum virus transmission and severe disease in newborn
Transplacental transfer of antibodies might also protect young infant from mosquito -borne transmission and severe disease
Proposed clinical guidance for use of chikungunya
vaccine in pregnant individuals (1)
Pregnant individuals should avoid the risk for chikungunya virus infection, if possible
(e.g., by avoiding travel to an area with virus transmission particularly during an outbreak).
Proposed clinical guidance for use of chikungunya
vaccine in pregnant individuals (2)
Pregnancy is a precaution for vaccination with the live attenuated chikungunya
vaccine. In general, vaccination should be deferred until after delivery. However, when the risk of infection is high and exposure cannot be avoided, a health care provider should discuss with a pregnant person the potential risks of chikungunya virus infection and the potential benefits and risks of vaccination so that vaccination can be considered.
Proposed clinical guidance for use of chikungunya
vaccine in pregnant individuals (3)
If pregnant persons choose to be vaccinated, out of caution vaccination should
generally be avoided during the 1st trimester (until 14 weeks gestation) and after the
36th week of gestation.
oAvoiding vaccination during the 1st trimester is preferred for two reasons. Firstly,
pregnancy loss has been reported in two individuals vaccinated during the 1st
trimester, although one was an anembryonic pregnancy. In addition, the vaccine is
reactogenic and can cause fever, and fever has been linked to birth defects in the
1st trimester.
oAvoidance of vaccination after the 36th week of gestation is to limit the risk of
vaccine -induced viremia occurring in the intrapartum period and thus to reduce
the theoretical risk for perinatal transmission and potential adverse outcomes.*
*Vaccine viremia is considered to occur in most individuals in the first few days after vaccination and to decrease thereafte r;
viremia was no longer detectable in any clinical trial subjects at 14 days after vaccination.
Proposed clinical guidance for use of chikungunya
vaccine in pregnant individuals (4)
In line with common practice following vaccination with live vaccines, non -pregnant
vaccine recipients should generally wait 4 weeks before becoming pregnant. If a
pregnant person is inadvertently vaccinated outside of the preferred period or becomes pregnant within 4 weeks after chikungunya vaccination, this should not be considered a reason to terminate the pregnancy.
This guidance is intended to maximize the benefits of vaccination while minimizing
risks associated with vaccination during pregnancy.
Guidance that maximizes benefits of vaccination while
minimizing risks associated with vaccination during pregnancy
1. Avoid risk if possible
2. In general, defer vaccination until after delivery
3. If exposure risk high, consider vaccination given risk for severe adverse
outcomes of infection particularly if intrapartum transmission occurs
4. If consider vaccination, where possible avoid 1st trimester and after 36th
week of gestation
Clinical guidance for use of live attenuated
chikungunya vaccine in breastfeeding individuals
Chikungunya and breastfeeding
Chikunguny a viral ribonucleic acid (RNA) detected in breast milk on
very rare occasions1,2
–No studies have reported detection of replicating virus
Case report describing mother with chikungunya and chikungunya
virus RNA detected in her breast milk was breastfeeding her 3 -
month -old infant1
–No symptoms or laboratory evidence of infection in infant
1. Campos GS et al, Pediatr Infect Dis J 2017; 2. De Paula Souza et al, Transl Res 2023.
Chikungunya vaccine and breastfeeding
No human data on whether chikungunya vaccine virus or antibodies are
present in breast milk after vaccination
Neonates and other infants aged <1 year are at risk for severe disease if infected with wild -type chikungunya virus
–Vaccine virus is attenuated, but outcome if chikungunya vaccine virus was
transmitted by breastfeeding unknown
Key language related to lactation in package insert1
Breastfeeding is neither contraindication nor precaution for vaccination
Developmental and health benefits of breastfeeding should be
considered along with the mother's clinical need for the vaccine and any
potential adverse effects on the breastfed child from the vaccine or from
the mother’s susceptibility to chikungunya
Vaccine viremia occurs after vaccination…the potential for transmission of vaccine virus from mother to infant through breastmilk is unknown
1. FDA. Package Insert – IXCHIQ. Available at: https://www.fda.gov/vaccines -blood -biologics/ixchiq
Live attenuated vaccines and breastfeeding:
ACIP General Best Practice Guidelines for Immunization
Although live viruses in vaccines can replicate in mother, majority of live
viruses in vaccines have been shown not to be excreted in milk
–Varicella vaccine virus has not been detected in human milk
–Rubella vaccine virus has been detected in human milk, but virus usually does
not infect infant, and if infection occurs, the attenuated virus is well tolerated
Live vaccines considered to be safe for administration to breastfeeding
individuals with two exceptions:
–Yellow fever vaccine: three breastfed infants developed encephalitis after mother
vaccinated
–Smallpox vaccine (ACAM2000): theoretical risk for contact transmission from mother to infant
Kroger A et al. General Best Practice Guidance for Immunization (https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.h tml)
ACIP breastfeeding guidance for other live vaccines
MMR: Not a precaution or contraindication
Varicella: Not a precaution or contraindication
Yellow fever: Precaution
Smallpox (ACAM2000): Contraindication
Groups for whom clinical guidance will be relevant
Travelers and laboratory workers
Persons in U.S. territories and states with risk of chikungunya virus
transmission
Objectives of vaccinating breastfeeding individuals
Protect breastfeeding individual
Added benefit might be reduction in risk for infant through transfer
of protective antibodies in breast milk
Proposed clinical guidance for use of chikungunya
vaccine in breastfeeding individuals
Breastfeeding individuals and their infants should avoid the risk for chikungunya virus
infection, if possible (e.g., by avoiding travel to an area with transmission particularly during an outbreak).
In the absence of data, breastfeeding is a precaution for vaccination. When the risk
of infection is high (e.g., during an outbreak) and exposure cannot be avoided, a health care provider should discuss with a breastfeeding individual the developmental and health benefits of breastfeeding for the infant, the risks of chikungunya virus infection, and the potential benefits and risks of vaccination, and offer the vaccine to the breastfeeding person. At the current time, the data are insufficient to make a recommendation to defer breastfeeding for any period after
vaccination.
Acknowledgements
Dana Meaney -Delman
Nicole Lindsey
Erin Staples
ACOG and AAP members for their review of draft clinical guidance
Chikungunya Vaccines Work Group members