Document text
Surveillance for adverse events following use of
live attenuated chikungunya vaccine and its use
among travelersNational Center for Emerging and Zoonotic Infectious Diseases
Dr. Susan Hills
CDC Lead, Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector -Borne Diseases
Fort Collins, Colorado
Advisory Committee on Immunization Practices meeting
April 16 , 2025
Background on live attenuated
chikungunya vaccine
Live attenuated chikungunya vaccine (CHIK -LA)
•Manufactured by Valneva and called IXCHIQ
•Licensed in United States in November 2023 for individuals aged ≥18 years
•Single dose primary schedule
•Licensed based on immunogenicity and safety data in ~3,500 adults
Local and systemic adverse events in pivotal Phase 3 trial
•Safety data from 3,082 subjects
•Solicited local reactions within 10 days after vaccination
-15% in vaccinees vs 11% in placebo recipients
•Solicited systemic adverse events (AE) within 10 days after vaccination
-50% in vaccinees vs 27% in placebo recipients
-Most common were headache, fatigue and myalgia in ~25% –30% of vaccinees
Schneider M et al. Safety and immunogenicity of a single -shot live -attenuated chikungunya vaccine: a double -blind, multicentre , randomised , placebo- controlled, phase 3 trial. Lancet 2023; 401: 2138 –2147.
Comparison of adverse events in 18 –64 years and ≥65 years*
18–64 years ≥65 years
Vaccine
(n=2,736)(95% CI) Placebo
(n=916)(95% CI) Vaccine
(n=346)(95% CI) Placebo
(n=117)(95% CI)
Any related AE 52% (50%– 54%) 32% (29% –35%) 46% (41%– 52%) 26% (18% –35%)
Any related
severe AE2% (2%– 3%) 0.1% (0%–0.6%) 1% (0.3%– 3%) 0 (0%–3%)
*Data from pivotal Phase 3 trial
Comparison of adverse events in 18 –64 years and ≥65 years*
18–64 years ≥65 years
Vaccine
(n=2,736)(95% CI) Placebo
(n=916)(95% CI) Vaccine
(n=346)(95% CI) Placebo
(n=117)(95% CI)
Any related AE 52% (50%– 54%) 32% (29% –35%) 46% (41%– 52%) 26% (18% –35%)
Any related
severe AE2% (2%– 3%) 0.1% (0%–0.6%) 1% (0.3%– 3%) 0 (0%–3%)
*Data from pivotal Phase 3 trial
•Fever ≥100.4° F (38° C) and ≥1 of:
•Symptom onset within 30 days of vaccination Chikungunya- like adverse reactions (1)
- Arthralgia or arthritis
- Myalgia
- Headache
- Back pain
- Rash
- Lymphadenopathy
- Certain neurologic, cardiac, or ocular symptoms
Package insert – IXCHIQ (https://www.fda.gov/vaccines -blood -biologics/ixchiq)
•Chikungunya -like adverse reactions
-11.7% of vaccine recipients and 0.6% of placebo recipients
•Severe reactions preventing daily activity or requiring medical
intervention
-1.6% vaccine recipients vs 0% of placebo recipients
•Prolonged reactions with duration ≥30 days
-0.5% vaccine recipients vs 0% of placebo recipients
Chikungunya- like adverse reactions (2)
Two serious adverse events considered related to vaccination
•58-year -old female, history of
fibromyalgia and hypertension
•Severe myalgia
•Hospitalized for 6 days for pain
management and diagnostic procedures•66-year -old male, history of
hypertension
•Myalgia, high fever, atrial fibrillation,
and hypovolemic hyponatremia
•Hospitalized for 4 days
FDA Clinical Review Memo (https://www.fda.gov/vaccines -blood -biologics/ixchiq)
ACIP Work Group summary of CHIK -LA safety in Evidence
to Recommendations, February 2024
•Reactogenic vaccine but similar adverse event rates to some other
vaccines
•Important to monitor for rare adverse events post- licensure as sample
size of ~3,500 vaccinated subjects too small to detect rare events
Post -marketing studies
•FDA-required post -marketing studies
-Vaccine effectiveness study in persons aged ≥12 years with safety component (Brazil)
-Pragmatic randomized controlled trial in ≥10,000 individuals to assess effectiveness
and safety
Post -marketing studies
•FDA-required post -marketing studies
-Vaccine effectiveness study in persons aged ≥12 years with safety component (Brazil)
-Pragmatic randomized controlled trial in ≥10,000 individuals to assess effectiveness
and safety
•Additional safety data collection
-Valneva conducting safety study of 5,000 U.S. travelers for medically attended
adverse events of special interest
-Observational registry study of pregnant women in Brazil
Post -licensure surveillance for adverse
events following use of CHIK- LA
•National reporting system for adverse events (AE) following vaccination co- managed by CDC
and FDA
•Designed to detect rare or previously unreported AE or changes in reporting patterns that
might signal a potential safety concern that warrants further investigation
•Anyone (e.g., healthcare providers, patients, vaccine manufacturers) can submit reports
•Effective in intended role as early warning system but limitations includeVaccine Adverse Event Reporting System (VAERS)
-Under -and over -reporting, variable report quality and
accuracy, lack of data on vaccine doses administered,
and lack of unvaccinated comparator group
•Generally cannot determine if AEs caused by
vaccine
Timeline
Licensure
November 2023ACIP
recommendations
February 2024Exact timing of
distribution
unknown*
*First report (non -serious event ) to VAERS received May 6, 2024
28 AEs reported to VAERS after CHIK -LA vaccine
administered in May -Dec 2024*
*Excludes 1 foreign report (non- serious)28 AEs reported
22 non- serious 6 serious
22 n on-serious AEs
22 non- serious AE
10 chikungunya -like
adverse reactions4 arthralgia or
arthritis without
fever8 other*
*Syncope (n=1), flushing (n=1), rash/headache (n=1), musculoskeletal pain (n=1), low grade
fever/headache (n=2), respiratory tract symptoms (n=2)
Serious adverse events (SAEs)
Any adverse event associated with use of biological
product, whether or not considered product -related,
that results in:
•Death
•Life-threatening adverse experience
•Inpatient hospitalization or prolongation of existing
hospitalization
•Persistent or significant disability/incapacity
•Congenital anomaly/birth defect
•Other medically important event that may jeopardize
patient and may require intervention to prevent one of the
outcomes listedFDA definition of SAE per federal law
Code of Federal Regulations Title 21 (https://www.ecfr.gov/current/title -21/chapter -I/subchapter -F/part -600/subpart -D/section -600.80)6 SAEs
5 hospitalizations1 other medically
important event
Any adverse event associated with use of biological
product, whether or not considered product -related,
that results in:
•Death
•Life-threatening adverse experience
•Inpatient hospitalization or prolongation of existing
hospitalization
•Persistent or significant disability/incapacity
•Congenital anomaly/birth defect
•Other medically important event that may jeopardize
patient and may require intervention to prevent one of the
outcomes listedFDA definition of SAE per federal law
Code of Federal Regulations Title 21 (https://www.ecfr.gov/current/title -21/chapter -I/subchapter -F/part -600/subpart -D/section -600.80)6 SAEs
5 hospitalizations1 other medically
important event
When SAEs reported to VAERS,
attempts made to collect additional
information (e.g., medical records)
Case 1: 83 -year -old male
Case 1: 83 -year -old male
Coronary artery disease Hypertension
Hyperlipidemia
Chronic
thrombocytopeniaChronic heart failure
Chronic kidney disease
Multiple medications to treat comorbidities
Active at baseline
•Received CHIK -LA vaccine
for travel to South America
and AfricaCase 1: 83 -year -old male
Coronary artery disease Hypertension
Hyperlipidemia
Chronic
thrombocytopeniaChronic heart failure
Chronic kidney disease
Multiple medications to treat comorbidities
Active at baseline
Case 1. 83 -year -old male
Day 0:
Received
CHIK -LA
(only)
Case 1. 83 -year -old male
Day 0:
Received
CHIK -LA
(only)Day 3:
Initial
symptoms
Case 1. 83 -year -old male
Day 0:
Received
CHIK -LA
(only)Day 3:
Initial
symptoms
Myalgia, arthralgia,
mild fever, chills, headache, generalized weakness, brain fog,
anorexia, severe
fatigue, unsteady gait
Case 1. 83 -year -old male
Day 0:
Received
CHIK -LA
(only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weakness
Case 1. 83 -year -old male
Day 0:
Received
CHIK -LA
(only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weakness
Determined to have
acute kidney injury likely from dehydration; brain MRI and head CT - no acute changes;
discharged home
Case 1. 83 -year -old male
Day 0:
Received
CHIK -LA
(only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weaknessDay 11: Returned to
hospital with persistent
weakness; admitted
Left lower extremity (hip flexor) weakness, myalgia,
fatigue
Case 1. 83 -year -old male
Day 0:
Received
CHIK -LA
(only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weaknessDay 11: Returned to
hospital with persistent
weakness; admitted
Left lower extremity (hip flexor) weakness, myalgia,
fatigue
Leukopenia, acute on chronic thrombocytopenia,
elevated liver function tests; declined lumbar puncture
Case 1. 83 -year -old male
Day 0:
Received
CHIK -LA
(only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weaknessDay 11: Returned to
hospital with persistent
weakness; admitted
Left lower extremity (hip flexor) weakness, myalgia,
fatigue
Leukopenia, acute on chronic thrombocytopenia,
elevated liver function tests; declined lumbar puncture
COVID, influenza A/B, RSV PCR: negative
Blood cultures: no growth
Case 1. 83 -year -old male
Day 0:
Received
CHIK -LA
(only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weaknessDay 11: Returned to
hospital with persistent
weakness; admitted
Case 1. Encephalopathy in 83-year -old male
•Discharge diagnosis: Encephalopathy and generalized weakness -
suspected association with chikungunya vaccination
•Completely resolved after 3.5 weeks
Case 1. Encephalopathy in 83 -year -old male
Day 0:
Received
CHIK -LA
(only)Day 3:
Initial
symptoms
Myalgia, arthralgia,
mild fever, chills, headache, generalized weakness, brain fog,
anorexia, severe
fatigue, unsteady gaitDay 7: Presents to ED
with ongoing
generalized weakness
Determined to have acute kidney injury likely from dehydration
Brain MRI and head CT
- no acute changes
Discharged homeDay 11: Returned to
hospital with persistent
weakness; admitted
Left lower extremity (hip flexor) weakness, myalgia, fatigue
Leukopenia, acute on chronic thrombocytopenia,
elevated liver function tests; declined lumbar puncture
COVID –19, influenza A/B, RSV PCR: negative
Blood cultures: no growth
Case 2. 77 -year -old male
Coronary artery disease
Hypothyroidism
Selective IgA deficiencyHypertension
Benign prostatic
hyperplasia
Several medications to treat comorbidities
Active at baselineHyperlipidemia
Case 2. 77 -year -old male
Coronary artery disease
Hypothyroidism
Selective IgA deficiencyHypertension
Benign prostatic
hyperplasia
Several medications to treat comorbidities
Active at baseline•Received CHIK -LA vaccine
for travel to Southeast AsiaHyperlipidemia
Case 2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VC*
*JE-VC: Inactivated Vero cell culture -derived JE vaccine
Case 2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptoms
Case 2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptoms
Severe fatigue,
fever, diarrhea, myalgia, urinary urgency
Case 2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent Care
Diagnosed
with viral illness
Case 2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Profound weakness with inability
to stand and intermittent confusion; no dysuria or macroscopic hematuria
Admission diagnosis of fever of
unknown origin, diarrhea, dehydration, hyponatremia,
hypochloremia, and suspected
urinary tract infection
Case 2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Urinalysis: Negative
Case 2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Urinalysis: Negative
COVID PCR, influenza A/B
antigen: negative
Blood cultures: no growth
Case 2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Urinalysis: Negative
COVID PCR, influenza A/B
antigen: negative
Blood cultures: no growth
Brain MRI: no acute intracranial
abnormalities
Case 2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VC*Day 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Urinalysis: Negative
COVID PCR, influenza A/B
antigen: negative
Blood cultures: no growth
Brain MRI: no acute intracranial
abnormalities
•Discharge diagnosis: Acute metabolic encephalopathy – possible
association with vaccination – and fever of unknown origin (resolved)Case 2. Encephalopathy in 77 -year -old male
Case 2. Encephalopathy in 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Day 19:
Readmitted with
urinary retention
for ~24 hours
•At ~4 months after onset: Still recovering with ongoing weaknessCase 2. Encephalopathy in 77 -year -old male: outcome
Day 0:
Received
CHIK -LA &
JE-VC*Day 4:
Initial
symptoms
Severe fatigue,
fever, diarrhea, myalgia, urinary urgencyDay 6:
Presented to
Urgent Care
Diagnosed with viral illnessDay 8: Presented to
hospital with
worsening
symptoms; admitted
Profound weakness with inability to stand and intermittent confusion; no dysuria or macroscopic hematuria
Admission diagnosis of fever of
unknown origin, diarrhea, dehydration, hyponatremia,
hypochloremia, and suspected
urinary tract infection
*JE-VC: Inactivated Vero cell culture -derived JE vaccine
Urinalysis: Negative
COVID PCR, influenza A/B
antigen: negative
Blood cultures: no growth
Brain MRI: no acute intracranial
abnormalitiesDay 19:
Readmitted for
~24 hours with
urinary retentionCase 2. Encephalopathy in 77 -year -old male
Case 3. 86-year -old male
Diabetes mellitus
Medications to manage comorbiditiesHypertension
Heart failure
Hyperlipidemia AnemiaHypothyroidism
Case 3. 86-year -old male
Diabetes mellitus
Medications to manage comorbiditiesHypertension
Heart failure
Hyperlipidemia AnemiaHypothyroidism•Received CHIK -LA vaccine
for travel to South Asia
Case 3. 86 -year -old male
Day 0:
Received
CHIK -LA
Case 3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptoms
Lethargy,
drowsiness,
fever
Case 3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptoms
Lethargy,
drowsiness,
feverDeterioration
in mental
status,
shortness of
breath
Case 3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Altered mental
status, acute
encephalopathy
secondary to
hyponatremia
(118 mmol/L),
shortness of
breath
Case 3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Hypokalemia, hypochloremia,
hypocalcemia, hypomagnesemiaElevated liver function tests
Case 3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Hypokalemia, hypochloremia,
hypocalcemia, hypomagnesemiaElevated liver function tests
CT head: No acute abnormalities
Chest X -ray: bilateral infiltrates
Echocardiogram: Small pericardial effusion
Case 3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Hypokalemia, hypochloremia,
hypocalcemia, hypomagnesemiaElevated liver function tests
CT head: No acute abnormalities
Chest X -ray: bilateral infiltrates
Echocardiogram: Small pericardial effusion
Day 13 post -vaccination serum
sample: chikungunya virus RNA
Case 3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Day 31:
Discharged
after 23 -day
hospitalization
Case 3. Metabolic encephalopathy in 83-year -old male
•Discharge diagnosis:
-Toxic metabolic encephalopathy
-Fever possibly related to a post- vaccination inflammatory response
with possible superadded bacterial pneumonia
•Mostly recovered at 1 month after discharge from hospital
Case 4. 68-year -old male
Prostate cancer*
Medications to manage comorbiditiesHypertension
Hypothyroidism Dyslipidemia
*Radiation therapy pending
Case 4. 68-year -old male
Prostate cancer*
Medications to manage comorbiditiesHypertension
Hypothyroidism Dyslipidemia
*Radiation therapy pending•Received CHIK -LA vaccine
for trip to Southeast Asia
Case 4. 68 -year -old male
Day 0:
Received
CHIK -LA*
*At intervals 8– 15 days earlier, received six inactivated vaccines: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A
Case 4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptoms
Fever,
headache,
fatigue, body
achesPhotophobia and neck
stiffness
Case 4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
Case 4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Case 4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Meningoencephalitis and respiratory PCR
panels negative, CSF culture no growth
Case 4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Meningoencephalitis and respiratory PCR
panels negative, CSF culture no growth
Brain MRI, CT: no acute abnormalities
Case 4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Meningoencephalitis and respiratory PCR
panels negative, CSF culture no growth
Brain MRI, CT: no acute abnormalities
CSF chikungunya testing: IgM and
neutralizing antibodies detected
Case 4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
•Discharge diagnoses: Meningismus /aseptic meningitis likely
secondary to recent vaccination
•Status : Headache and fatigue initially persisted but fully recovered by
~1 monthCase 4. Meningitis in 68- year -old male
Case 4. Meningitis in 68- year -old male
Day 0:
Received
CHIK -LA*
*At intervals 8– 15 days earlier, received six inactivated vaccines: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis ADay 5:
Initial symptoms
Fever,
headache,
fatigue, body
achesPhotophobia and neck
stiffnessDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Meningoencephalitis and respiratory PCR
panels negative, CSF culture no growth
Brain MRI, CT: no acute abnormalities
CSF chikungunya testing: IgM and
neutralizing antibodies detected
Case 5. 67-year -old male
Hyperlipidemia
Medication to manage condition
Case 5. 67-year -old male
Hyperlipidemia
Medication to manage condition•Received CHIK -LA vaccine
for trip to central America
Case 5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccine*
*19 days prior: COVID -19 and inactivated influenza vaccines
Case 5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptoms
Myalgia, fever
Case 5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 6:
Palpitations
Case 5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
Case 5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
Elevated troponin, proBNP
Nuclear stress test: suspicious for small infarct
Case 5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
Elevated troponin, proBNP
Nuclear stress test: suspicious for small infarct
No evidence of pulmonary embolism, normal
thyroid -stimulating hormone
Case 5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
Elevated troponin, proBNP
Nuclear stress test: suspicious for small infarct
No evidence of pulmonary embolism, normal
thyroid -stimulating hormone
COVID, influenza, RSV PCR: negative
Case 5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
•Discharge diagnoses: atrial flutter with rapid ventricular response,
suspected small non- ST segment elevation myocardial infarction
•Status : Fully recovered on discharge, medication ongoing 3 months laterCase 5. Atrial flutter and non -ST segment elevation
myocardial infarction in 67- year -old male
Case 5. Atrial flutter and non -ST segment elevation
myocardial infarction in 67- year -old male with
Day 0:
Received
CHIK -LA & oral
typhoid vaccine*Day 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular response
*19 days prior: COVID -19 and inactivated influenza vaccinesMyalgia, fever
1 day laterDay 6:
Palpitations
Elevated troponin, proBNP
Nuclear stress test: suspicious for small infarct
No evidence of pulmonary embolism, normal
thyroid -stimulating hormone
COVID, influenza, RSV PCR: negative
Case 6. 74 -year -old male
Ischemic
cardiomyopathy
Medications to manage comorbiditiesCoronary artery diseaseHypotensionChronic leukopenia
Chronic thrombocytopenia
Case 6. 74 -year -old male
Ischemic
cardiomyopathy
Medications to manage comorbiditiesCoronary artery diseaseHypotensionChronic leukopenia•Received CHIK -LA vaccine
for planned travel to
Southeast Asia
Chronic
thrombocytopenia
Case 6. 74 -year -old male
Day 0:
Received
CHIK -LA
& JE -VC*
*JE-VC: Inactivated Vero cell culture -derived JE vaccine
Case 6. 74 -year -old male
Day 3:
Initial
symptomsDay 0:
Received
CHIK -LA
& JE -VC
Fatigue, weakness,
lightheadedness,
mild shortness of
breath, noted
hypotension
Case 6. 74 -year -old male
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
& JE -VC
Severe
hypotension
No evidence
of heart
failure
Case 6. 74 -year -old male
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
& JE -VCDay 10:
Blood
collection
Leukopenia,
thrombocytopenia
Case 6. 74 -year -old male
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
& JE -VCDay 15:
Follow -up visit
to internist
Some
improvement in
blood pressureDay 10:
Blood
collection
Case 6. 74 -year -old male#
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
& JE -VCDay 15:
Follow -up visit
to internist
#SAE as “Other medically important event”Day 10:
Blood
collection
Case 6. Worsened and prolonged hypotension in 74 -
year -old male
•Final diagnosis: Episode of worsened and prolonged hypotension on the
background of pre -existing cardiomyopathy and hypotension - likely
related to CHIK -LA vaccination
•Resolved within ~2 weeks
Case 6. 74 -year -old male#
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
& JE -VC*
*JE-VC: Inactivated Vero cell culture -derived JE vaccineFatigue, weakness,
lightheadedness,
mild shortness of
breath, noted
hypotension Day 15:
Follow -up visit
to internist
Severe
hypotension
No evidence
of heart
failure Some
improvement in
blood pressure
#SAE as “Other medically important event”Day 10:
Blood
collection
Leukopenia,
thrombocytopenia
Summary of case characteristics (N=6)
Age
(yrs) Sex Key comorbiditiesCo-administered
vaccinesSymptom
onset (days) Discharge diagnosis(es) Chikungunya testing
83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3
Encephalopathy
Generalized weaknessN/A
77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia,
hyperlipidemia, hypertension, IgA
deficiencyJapanese encephalitis (inactivated)4
Acute metabolic encephalopathy
Fever of unknown originN/A
86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy
Fever possibly related to post -
vaccination inflammatory responseRT-PCR on serum on
day 13: positive
68 MaleProstate cancer, hypothyroidism,
hypertension, dyslipidemia_†
5 Aseptic meningitisIgM & neutralizing
antibodies in CSF
67 Male HyperlipidemiaTyphoid
(oral, live)*4Atrial flutter
Non -ST segment elevation myocardial
infarction (NSTEMI)N/A
74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese
encephalitis
(inactivated)3
Worsened and prolonged hypotension
on background of pre -existing
cardiomyopathy and hypotensionN/A
*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not available
Age
(yrs) Sex Key comorbiditiesCo-administered
vaccinesSymptom
onset (days) Discharge diagnosis(es) Chikungunya testing
83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3
Encephalopathy
Generalized weaknessN/A
77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia,
hyperlipidemia, hypertension, IgA
deficiencyJapanese encephalitis (inactivated)4
Acute metabolic encephalopathy
Fever of unknown originN/A
86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy
Fever possibly related to post -
vaccination inflammatory responseRT-PCR on serum on
day 13: positive
68 MaleProstate cancer, hypothyroidism,
hypertension, dyslipidemia_†
5 Aseptic meningitisIgM & neutralizing
antibodies in CSF
67 Male HyperlipidemiaTyphoid
(oral, live)*4Atrial flutter
Non -ST segment elevation myocardial
infarction (NSTEMI)N/A
74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese
encephalitis
(inactivated)3
Worsened and prolonged hypotension
on background of pre -existing
cardiomyopathy and hypotensionN/A
*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not availableSummary of case characteristics (N=6)
Age
(yrs) Sex Key comorbiditiesCo-administered
vaccinesSymptom
onset (days) Discharge diagnosis(es) Chikungunya testing
83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3
Encephalopathy
Generalized weaknessN/A
77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia,
hyperlipidemia, hypertension, IgA
deficiencyJapanese encephalitis (inactivated)4
Acute metabolic encephalopathy
Fever of unknown originN/A
86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy
Fever possibly related to post -
vaccination inflammatory responseRT-PCR on serum on
day 13: positive
68 MaleProstate cancer, hypothyroidism,
hypertension, dyslipidemia_†
5 Aseptic meningitisIgM & neutralizing
antibodies in CSF
67 Male HyperlipidemiaTyphoid
(oral, live)*4Atrial flutter
Non -ST segment elevation myocardial
infarction (NSTEMI)N/A
74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese encephalitis (inactivated)3
Worsened and prolonged hypotension
on background of pre -existing
cardiomyopathy and hypotensionN/A
*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not availableSummary of case characteristics (N=6)
Age
(yrs) Sex Key comorbiditiesCo-administered
vaccinesSymptom
onset (days) Discharge diagnosis(es) Chikungunya testing
83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3
Encephalopathy
Generalized weaknessN/A
77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia,
hyperlipidemia, hypertension, IgA
deficiencyJapanese encephalitis (inactivated)4
Acute metabolic encephalopathy
Fever of unknown originN/A
86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy
Fever possibly related to post -
vaccination inflammatory responseRT-PCR on serum on
day 13: positive
68 MaleProstate cancer, hypothyroidism,
hypertension, dyslipidemia_†
5 Aseptic meningitisIgM & neutralizing
antibodies in CSF
67 Male HyperlipidemiaTyphoid
(oral, live)*4Atrial flutter
Non -ST segment elevation myocardial
infarction (NSTEMI)N/A
74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese
encephalitis
(inactivated)3
Worsened and prolonged hypotension
on background of pre -existing
cardiomyopathy and hypotensionN/A
*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not availableSummary of case characteristics (N=6)
clinical consult services†
support enhanced surveillance
clinical research
†More information about clinical consults available at :
https://www.cdc.gov/vaccine -safety -systems/hcp/cisa/index.html8 participating medical
research centers with
vaccine safety expertsClinical
Immunization
Safety
Assessment
(CISA) Project C IS A
•Available medical records for each of neurologic (n=4) and cardiac (n=2)
reports reviewed with experts in vaccine safety, infectious diseases, cardiology and neurology
•For each report, at least one CISA expert considered association of CHIK -LA
with SAE plausible
•However, experts noted difficulty differentiating between general reactogenicity in older patients with comorbidities leading to SAE versus chikungunya vaccine causing SAESummary of CISA review of SAEs following CHIK -LA
reported to VAERS
•Temporal association ≠ causal association
•Sometimes concomitant or recent administration of other vaccines
•Comprehensive investigations of possible etiologies not always
conducted or available
•Unlike in controlled clinical trials, no unvaccinated comparator groupGenerally cannot determine causality from VAERS data
Shimabukuro TT, et al. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine 2015;33:4398 -4405.
All events began within 3 –5 days of vaccination
For 3 patients with co -administration of other vaccines (i.e., JE,
typhoid), association with other vaccines less likely1-3
Investigations did not indicate clear alternate etiologies for any
patient and most (n=5) discharge summaries noted potential
association with vaccination
For 2 cases with chikungunya laboratory testing, results
suggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs
1. Rabe IB et al, Vaccine 2015; 2. Walker WL et al, Vaccine 2018; 3. Begier EM et al. Clin Infect Dis 2004.
All events began within 3 –5 days of vaccination
For 3 patients with co -administration of other vaccines (i.e., JE,
typhoid), association with other vaccines less likely1-3
Investigations did not indicate clear alternate etiologies for any
patient and most (n=5) discharge summaries noted potential
association with vaccination
For 2 cases with chikungunya laboratory testing, results
suggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs
1. Rabe IB et al, Vaccine 2015; 2. Walker WL et al, Vaccine 2018; 3. Begier EM et al. Clin Infect Dis 2004.
All events began within 3 –5 days of vaccination
For 3 patients with co -administration of other vaccines (i.e., JE,
typhoid), association with other vaccines less likely1-3
Investigations did not indicate clear alternate etiologies for any
patient and most (n=5) discharge summaries noted potential
association with vaccination
For 2 cases with chikungunya laboratory testing, results
suggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs
1. Rabe IB et al, Vaccine 2015; 2. Walker WL et al, Vaccine 2018; 3. Begier EM et al. Clin Infect Dis 2004.
All events began within 3 –5 days of vaccination
For 3 patients with co -administration of other vaccines (i.e., JE,
typhoid), association with other vaccines less likely1-3
Investigations did not indicate clear alternate etiologies for any
patient and most (n=5) discharge summaries noted potential
association with vaccination
For 2 cases with chikungunya laboratory testing, results
suggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs
1. Rabe IB et al, Vaccine 2015; 2. Walker WL et al, Vaccine 2018; 3. Begier EM et al. Clin Infect Dis 2004.
CHIK -LA and SAEs in persons ≥65 years
•Immunosenescence affects older person’s ability to adequately control
replication of live attenuated vaccine virus
-Example: With live attenuated yellow fever vaccine, SAEs more frequent in older
persons, and age ≥ 60 years is precaution for use
•Wild -type chikungunya virus infections more likely to result in severe
disease in older adults
Estimating incidence of SAEs after CHIK -LA
•Difficult as limited data on vaccine doses distributed and very limited data
on doses administered
•Obtained data from commercial source (IQVIA; private -sector company that
provides healthcare data)
-Sales data : Weekly Sales Perspectives (WSP) data are unprojected (i.e., actual)
sales for prescription products (vaccinations) sold to retail, non -retail, and mail
channels and capture about ~90% of total sales*
-Administration data : National Prescription Audit (NPA) data represent projected
estimates of vaccinations administered in retail and long -term care pharmacies
*Information from IQVIA
Confidential and pre -decisional – for official use onlyCHIK -LA (IXCHIQ) weekly and cumulative sales as of week ending December 27, 2024
IQVIA SMART Weekly Sales Perspective (WSP)
13,891 total
doses
distributed
Pharmacy total = 1,275 (9%) Medical office total = 12,616 (91%)
Confidential and pre -decisional – for official use onlyCHIK -LA (IXCHIQ) weekly and cumulative vaccinations administered in pharmacies ,
as of week ending December 27, 2024. IQVIA SMART NPA Weekly Extended Insights
Estimated
928 doses
administered
in pharmacies
Confidential and pre -decisional – for official use onlyCHIK -LA (IXCHIQ) pharmacy administrations by age, March 3– December 27, 2024
IQVIA SMART NPA Weekly Extended Insights
53% doses
administered
to individuals
aged ≥65 years
N=928
No.
eventsEstimated rate of events
per 100,000 doses administered
(95% CI)Estimated rate of doses administered
resulting in 1 event
(95% CI)
SAEs 682 per 100,000
(30–180) 1 SAE per 1,220 doses
(1 per 3,333 doses to 1 per 556 doses)
*Based on VAERS reports, IQVIA data on doses distributed (N=13,891 doses), and IQVIA data that 52.7% (n=7,320) administered to p ersons aged ≥65 yrsRisk estimates for SAEs and hospitalizations among persons aged
≥65 years*
No.
eventsEstimated rate of events
per 100,000 doses administered
(95% CI)Estimated rate of doses administered
resulting in 1 event
(95% CI)
SAEs 682 per 100,000
(30–180) 1 SAE per 1,220 doses
(1 per 3,333 doses to 1 per 556 doses)
Hospitalizations 568 per 100,000
(20–160) 1 hospitalization per 1,471 doses
(1 per 5,000 doses to 1 per 625 doses)
*Based on VAERS reports, IQVIA data on doses distributed (N=13,891 doses), and IQVIA data that 52.7% (n=7,320) administered to p ersons aged ≥65 yrsRisk estimates for SAEs and hospitalizations among persons aged
≥65 years*
Limitations of risk estimates
•Calculations limited by potential imprecision in numerator and
denominator data
-Unknown completeness of reporting of events to VAERS
-Potential inaccuracies in vaccine administration data overall and by age group
•All VAERS SAE reports included in calculations but cannot confirm causal link between vaccination and all reported events
•Overall low certainty in estimates
•Updated data as of March 21, 2025
-0 SAEs and 9 non- serious AEs reported to VAERS in United States*
-Additional ~4,250 CHIK -LA doses sold#
•Risk estimates not updated for this presentation
-Delays in CHIK -LA reports to VAERS (median 13 days)
-~2,375 doses sold in last ~2 weeks of 2024 and likely not
administered in 2024
-Unknown impact of CDC alert in February 2025 about
hospitalizations after CHIK -LA in ages ≥65 years
-With updated data, risk estimates lower but within 95% confidence limits of previous estimates
Update: 2025 VAERS data
*Excludes 6 (non -serious) reports from other countries; #IQVIA data
https://www.cdc.gov/chikungunya/prevention/chikungunya -vaccine.html
Work Group considerations regarding SAEs
following CHIK -LA
All SAEs in persons aged ≥65 years
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
All SAEs in persons aged ≥65 years
Association of CHIK -LA with SAEs is plausible, but causal association for each event not determined
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
All SAEs in persons aged ≥65 years
Association of CHIK -LA with SAEs is plausible, but causal association for each event not determined
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
All SAEs in persons aged ≥65 years
Association of CHIK -LA with SAEs is plausible, but causal association for each event not determined
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
All SAEs in persons aged ≥65 years
Association of CHIK -LA with SAEs is plausible, but causal association for each event not determined
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
Age ≥65 years should be a precaution * for use of CHIK -LA
•In general, vaccination should be deferred
•Vaccination might be indicated if benefit from protection from vaccination
outweighs risk for adverse reaction
*https://www.cdc.gov/vaccines/hcp/imz -best -practices/contraindications -precautions.html
Work Group proposes revising recommendations for
use of CHIK -LA among travelers
•In accordance with updated Evidence to Recommendations for travelers
presented in earlier presentation for CHIK -VLP
•In consideration of safety signal following use of vaccine in persons aged ≥65 years
Existing CHIK -LA recommendations for travelers*
Chikungunya vaccine is recommended for persons aged ≥18 years traveling
to a country or territory where there is a chikungunya outbreak.
In addition, chikungunya vaccine may be considered for the following
persons traveling to a country or territory without an outbreak but with
evidence of chikungunya virus transmission among humans within the last 5 years
-Persons aged >65 years, particularly those with underlying medical conditions,
who are likely to have at least moderate exposure to mosquitoes, OR
-Persons staying for a cumulative period of 6 months or more
*Approved in February 2024
Existing CHIK -LA recommendations for travelers*
Chikungunya vaccine is recommended for persons aged ≥18 years traveling
to a country or territory where there is a chikungunya outbreak.
In addition, chikungunya vaccine may be considered for the following
persons traveling to a country or territory without an outbreak but with
evidence of chikungunya virus transmission among humans within the last 5 years
-Persons aged >65 years, particularly those with underlying medical conditions,
who are likely to have at least moderate exposure to mosquitoes, OR
-Persons staying for a cumulative period of 6 months or more
*Approved in February 2024
ACIP recommends live attenuated chikungunya vaccine or persons aged ≥18
years traveling to a country or territory where there is a chikungunya
outbreak.
In addition, live attenuated chikungunya vaccine may be considered for
persons aged ≥18 years# traveling or taking up residence in a country or
territory without an outbreak but with elevated risk for US travelers if
planning travel for an extended period of time e.g., 6 months or more.Revised draft recommendations for CHIK -LA among
travelers#
#Age ≥65 years is a precaution for use of CHIK -LA
Arboviral Diseases Branch, CDC
•Rebekah Sutter
•Erin Staples
Immunization Safety Office, CDC
•Sarah Meyer
•Michael McNeil
•Elaine MillerAcknowledgements
Immunization Services Division, CDC
•Seth Meador
•Suchita Patel
Clinical Immunization Safety
Assessment (CISA) vaccine safety
experts
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY: 1 -888- 232- 6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.