National Center for Emerging and Zoonotic Infectious Diseases

EVIDENCE TO RECOMMENDATIONS FOR 

CHIKUNGUNYA VACCINE USE AMONG 

ADULT TRAVELERS

Susan Hills, MBBS, MTH

CDC Lead, Chikungunya Vaccines Work Group

Arboviral Diseases Branch

Division of Vector-Borne Diseases

Fort Collins, Colorado

ACIP meeting, October 26, 2023
Chikungunya virus and transmission

 Alphavirus 

 Primarily transmitted by Aedes 

aegypti and Aedes albopictus

 Uncommon modes of 

transmission

– Laboratory exposure

– Intrauterine and intrapartum

– Bloodborne transmission 

through needlestick
Distribution

 Tropical and subtropical 

regions

 Large outbreaks have 

occurred in most parts of 

the world

– Often high attack rates

Countries and territories with current or past transmission 

of chikungunya virus

https://www.cdc.gov/chikungunya/geo/index.html
Clinical features of acute chikungunya virus infection

 Febrile illness with arthralgia which is often severe and debilitating 

 Rare serious complications (e.g., neurologic illness, myocarditis, hepatic or 

renal disease)

 No anti-viral treatment
Risk factors for severe disease 

 Age >65 years 

 Age <1 year

 Underlying medical conditions 

(e.g., diabetes, heart disease, 

hypertension)

 Intrapartum transmission 
Chikungunya vaccine

 Live attenuated vaccine manufactured by Valneva

 Single dose primary schedule

 Initial licensure for adults aged ≥18 years

 Currently under consideration by US Food & Drug Administration

 Not yet licensed anywhere in world

 No existing vaccine recommendations from ACIP or other vaccine 

advisory groups 
Evidence to Recommendations for 

chikungunya vaccination for travelers 
Policy question

Should chikungunya vaccine be recommended for use in 

persons aged ≥18 years traveling to areas with risk of 

chikungunya virus transmission? 
Domain 1. Public health problem

Is chikungunya of public health importance?
Hundreds of thousands of cases 

reported annually 
Risk highly variable for US travelers

100–200 reported cases annually 

Hundreds of thousands of cases 

reported annually 
Risk highly variable for US travelers

100–200 reported cases annually 

Hundreds of thousands of cases 

reported annually 
Risk highly variable for US travelers

100–200 reported cases annually 

Hundreds of thousands of cases 

reported annually 

Mortality <1%
Public health problem

Is chikungunya of public health importance?

o No o Probably no o Probably yes o Yes o Varies o Don’t know
Domain 2: Benefits and harms of chikungunya 

vaccine

How substantial are the desirable anticipated effects?
Short-term and long-term protection from disease

 No efficacy data so immunogenicity data reviewed

– No correlate of protection

 Licensure through Accelerated Approval pathway

– Effectiveness demonstrated by clinical trials showing vaccine has effect on 

surrogate endpoint reasonably likely to predict clinical benefit

– Vaccine effectiveness will need to be confirmed in post-licensure field studies

 Marker of protection based on neutralizing antibody titer estimated from 

validated non-human primate model
Seroresponse at 28 days after vaccination

 Two studies 

– One randomized controlled trial

– One lot-to-lot consistency study with no placebo group 

 Total of 622 subjects

 Seroresponse at 28 days: ≥98% 

 None of 96 subjects in placebo arm of randomized controlled trial 

had seroresponse
Seroresponse at 12 months after vaccination

 One study with 360 subjects

 Seroresponse at 12 months: 99% 
How substantial are the desirable anticipated effects?

o Minimal o Small o Moderate o Large o Varies o Don’t know
How substantial are the undesirable anticipated effects?
Serious adverse events (SAE) within 6 months

 SAE

– 51 (1.5%) of 3,490 vaccinated subjects in 2 trials reported SAE

– 8 (0.8%) of 1,033 placebo recipients in randomized controlled trial reported SAE*

 Related SAEs 

– 2 events (0.1%) considered vaccine-related by study investigators

• Hospitalization for severe myalgia

• Hospitalization for myalgia, high fever, syndrome of inappropriate antidiuretic 

hormone excretion, and atrial fibrillation

*No significant difference from vaccine group; 46 (1.5%) of 3,082 vaccinated subjects in randomized, controlled trial
Arthralgia and arthritis in randomized controlled trial*

Vaccinated group 

(N=3082)

Placebo group

(N=1033)

n (%) n (%) Risk ratio (95% CI)

Any arthralgia within 10 days# 520 (17%) 50 (5%) 3.5 (2.6, 4.6) ¥

Severe arthralgia within 10 days#,€ 9 (0.3%) 0 (0%) 6.0 (0.4, 104.2)

Persistent arthralgia≠ 9 (0.3%) 4 (0.4%) 0.8 (0.2, 2.4)

Arthritis within 6 months£ 5 (0.2%) 2 (0.2%) 0.8 (0.2, 4.3)

New onset or worsening osteoarthritis 

within 6 months£

12 (0.4%) 2 (0.2%) 2 (0.5, 9.0)

#Solicited adverse event; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; ≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event

*Similar percentage of events in vaccinated subjects in lot-to-lot consistency study (N=408) without placebo control group
Arthralgia and arthritis in randomized controlled trial

Vaccinated group 

(N=3082)

Placebo group

(N=1033)

n (%) n (%) Risk ratio (95% CI)

Any arthralgia within 10 days# 520 (17%) 50 (5%) 3.5 (2.6, 4.6) ¥

Severe arthralgia within 10 days#,€ 9 (0.3%) 0 (0%) 6.0 (0.4, 104.2)

Persistent arthralgia≠ 9 (0.3%) 4 (0.4%) 0.8 (0.2, 2.4)

Arthritis within 6 months£ 5 (0.2%) 2 (0.2%) 0.8 (0.2, 4.3)

New onset or worsening osteoarthritis 

within 6 months£

12 (0.4%) 2 (0.2%) 2 (0.5, 9.0)

#Solicited adverse event; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; ≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event
Arthralgia and arthritis in randomized controlled trial

Vaccinated group 

(N=3082)

Placebo group

(N=1033)

n (%) n (%) Risk ratio (95% CI)

Any arthralgia within 10 days# 520 (17%) 50 (5%) 3.5 (2.6, 4.6) ¥

Severe arthralgia within 10 days#,€ 9 (0.3%) 0 (0%) 6.0 (0.4, 104.2)

Persistent arthralgia≠ 9 (0.3%) 4 (0.4%) 0.8 (0.2, 2.4)

Arthritis within 6 months£ 5 (0.2%) 2 (0.2%) 0.8 (0.2, 4.3)

New onset or worsening osteoarthritis 

within 6 months£

12 (0.4%) 2 (0.2%) 2 (0.5, 9.0)

#Solicited adverse event; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; ≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event
Arthralgia and arthritis in randomized controlled trial

Vaccinated group 

(N=3082)

Placebo group

(N=1033)

n (%) n (%) Risk ratio (95% CI)

Any arthralgia within 10 days# 520 (17%) 50 (5%) 3.5 (2.6, 4.6) ¥

Severe arthralgia within 10 days#,€ 9 (0.3%) 0 (0%) 6.0 (0.4, 104.2)

Persistent arthralgia≠ 9 (0.3%) 4 (0.4%) 0.8 (0.2, 2.4)

Arthritis within 6 months£ 5 (0.2%) 2 (0.2%) 0.8 (0.2, 4.3)

New onset or worsening osteoarthritis 

within 6 months£

12 (0.4%) 2 (0.2%) 2 (0.5, 9.0)

#Solicited adverse event; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; ≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event
Arthralgia and arthritis in randomized controlled trial

Vaccinated group 

(N=3082)

Placebo group

(N=1033)

n (%) n (%) Risk ratio (95% CI)

Any arthralgia within 10 days# 520 (17%) 50 (5%) 3.5 (2.6, 4.6) ¥

Severe arthralgia within 10 days#,€ 9 (0.3%) 0 (0%) 6.0 (0.4, 104.2)

Persistent arthralgia≠ 9 (0.3%) 4 (0.4%) 0.8 (0.2, 2.4)

Arthritis within 6 months£ 5 (0.2%) 2 (0.2%) 0.8 (0.2, 4.3)

New onset or worsening osteoarthritis 

within 6 months£

12 (0.4%) 2 (0.2%) 2 (0.5, 9.0)

#Solicited adverse event; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; ≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event
Arthralgia and arthritis in randomized controlled trial

Vaccinated group 

(N=3082)

Placebo group

(N=1033)

n (%) n (%) Risk ratio (95% CI)

Any arthralgia within 10 days# 520 (17%) 50 (5%) 3.5 (2.6, 4.6) ¥

Severe arthralgia within 10 days#,€ 9 (0.3%) 0 (0%) 6.0 (0.4, 104.2)

Persistent arthralgia≠ 9 (0.3%) 4 (0.4%) 0.8 (0.2, 2.4)

Arthritis within 6 months£ 5 (0.2%) 2 (0.2%) 0.8 (0.2, 4.3)

New onset or worsening osteoarthritis 

within 6 months£

12 (0.4%) 2 (0.2%) 2 (0.5, 9.0)

#Solicited adverse event; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; ≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event
How substantial are the undesirable anticipated effects?

o Minimal o Small o Moderate o Large o Varies o Don’t know
Do the desirable effects outweigh the undesirable effects?
Balance of desirable and undesirable effects

 High seroresponse rates through at least 1 year after vaccination

 No serious safety concerns identified in trials performed to date

 Prevents disease that can result in severe arthralgia during acute illness, 

rare serious complications, and sometimes long-term arthralgia 

 Healthcare provider should discuss desirable and undesirable effects of 

vaccination and individual risk based on disease risk at destination, 

activities, and personal factors 

– For some travelers, even low probability of SAE might be higher than disease risk 

– Target vaccine to travelers at higher risk for disease
Do the desirable effects outweigh the undesirable effects?

o Favors 

intervention 

o Favors 

comparison

o Favors 

both

o Favors 

neither o Varies o Don’t know
What is the overall certainty of the evidence for the 

critical outcomes?
What is the overall certainty of the evidence for 

protection from chikungunya?

o No studies found o Very low o Low o Moderate o High

 No vaccine efficacy data, no immunologic correlate of protection, 

protection based on surrogate endpoint reasonably likely to predict 

clinical benefit and requiring confirmation by post-licensure vaccine 

effectiveness studies
What is the overall certainty of the evidence for 

safety of chikungunya vaccination?

o No studies found o Very low o Low o Moderate o High

 Number of subjects in trials insufficient to detect rare adverse events, 

confidence intervals indicated potential for benefit or harm, and/or 

suboptimal method for collection of specific outcome information 
Domain 3. Values

Does the target population feel that the desirable 

effects are large relative to undesirable effects?

Is there important uncertainty about or variability 

in how much people value the main outcomes?
Perceptions among US adults aged ≥18 years of the 

value of a chikungunya vaccine (CDC study) 

 Online survey conducted in 2022 

 Participants provided information on 

– Risk for disease with travel during outbreak or non-outbreak 

periods

– Rates of chronic arthralgia after chikungunya

– Vaccine cost 
Results 

42%

26%

32%

Likely* Unsure Unlikely**

*Includes very and somewhat likely responses

**Includes very and somewhat unlikely responses

Outbreak period (risk of 1 in 150) Non-outbreak period (risk of 1 in 15,000)

27%

24%

49%

Likely* Unsure Unlikely**

N=4,146 N=4,138
Variability in responses 

 Lower likelihood of vaccination

– Persons aged 18–29 years

– Lower education

– Lower household income

– Black race
Important factors in decision-making

Risk of disease

Vaccine side effects Avoid risk of long-term joint pain Vaccine cost
Perceptions among US adults aged ≥18 years of value of 

chikungunya vaccine (Valneva study) 

 Online survey conducted in 2021 

 2,002 US residents who had traveled internationally during last 3 

years or planned to do so within next 3 years

 Limited information about participants provided but anyone who 

self-identified as ‘anti-vaccination’ excluded 
Results

 After being provided basic information on chikungunya 

and its sequelae

– 72% were very or somewhat likely to ask healthcare provider 

about a vaccine

– 81% were very or somewhat likely to be vaccinated if 

recommended by healthcare provider
Values

Does the target population feel that the desirable 

effects are large relative to undesirable effects?

o No o Probably no o Probably yes o Yes o Varies o Don’t know
Values

Is there important uncertainty about or variability 

in how much people value the main outcomes?

o Important 

uncertainty 

or variability

o Probably 

important 

uncertainty 

or variability

o Probably not 

important 

uncertainty or 

variability

o No important 

uncertainty or 

variability

o No known 

undesirable 

outcomes
Domain 4. Acceptability

Is chikungunya vaccine acceptable to key stakeholders?
Acceptability to key stakeholders

 Travel medicine and other healthcare providers

– Online survey in 2021 (Valneva) among 158 US healthcare 

providers who routinely provide travel health services 

indicated 87% were very or somewhat likely to 

recommend vaccine if recommended by ACIP

 Travelers

– Option for protection from a disease that can cause 

severe arthralgia and potentially long-term joint pain
Acceptability

Is the intervention acceptable to key stakeholders?

o No o Probably no o Probably yes o Yes o Varies o Don’t know
Domain 5. Resource use

Is chikungunya vaccination a reasonable and efficient 

allocation of resources?
Cost-effectiveness considerations

 No cost-effectiveness analysis (CEA)

– Most travel vaccines are not cost-effective

– Chikungunya vaccine for travelers is not likely to be cost-effective 

 CEA less relevant for travel vaccine

– Decision is for individual traveler and not for population

– Vaccine paid for by traveler and generally not covered by insurance 

 Vaccine recommendations targeting higher risk travelers probably reasonable 

allocation of resources

– Financial implications borne by travelers most at risk and who benefit most
Resource use

Is chikungunya vaccination a reasonable and 

efficient allocation of resources?

o No o Probably no o Probably yes o Yes o Varies o Don’t know
Domain 6. Equity

What would be the impact on health equity?
Health equity considerations

 Vaccine primarily paid for out of pocket

– Some travelers not have resources to pay for vaccine

 Travel medicine providers likely have better awareness of disease and 

vaccine availability than non-specialist providers

– People with fewer resources less likely to attend travel medicine 

provider

 Chikungunya vaccine recommendations cannot address these issues
Equity

What would be the impact on health equity?

o Reduced o Probably 

reduced

o Probably 

no impact

o Probably 

increased o Increased o Varies o Don’t 

know
Domain 7. Feasibility

Is the intervention feasible to implement?
Feasibility considerations

 Single dose primary series allows administration in pre-travel 

consultation

 Disease risk highest, and vaccination most of benefit, during 

outbreaks

– Challenge with delay in awareness of outbreaks

– CDC will post information on website once aware of outbreaks
Feasibility

Is the intervention feasible to implement?

o No o Probably no o Probably yes o Yes o Varies o Don’t know
Balance of consequences

o Undesirable 

consequenc

e clearly 

outweigh

desirable 

consequenc

es in most 

settings

o Undesirable 

consequences 

probably 

outweigh 

desirable 

consequences in 

most settings

o The balance 

between 

desirable and 

undesirable 

consequences is 

closely balanced 

or uncertain

o Desirable 

consequences 

probably 

outweigh 

undesirable 

consequences 

in most settings

o Desirable 

consequences 

clearly 

outweigh 

undesirable 

consequences 

in most settings

o There is 

insufficient 

evidence to 

determine the 

balance of 

consequences
Draft recommendations for 

ACIP’s consideration
Draft recommendations

 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

– Older persons (e.g., >65 years), particularly those with underlying 

medical conditions, who are likely to have at least moderate exposure 

to mosquitoes 

– Persons staying for a cumulative period of 6 months or more during a 

2-year period
Example of data supporting recommendation: Substantially higher 

risk for travelers during outbreak, Paraguay 2023

<1%

Percentage of all US persons 

traveling to areas with 

chikungunya risk visiting Paraguay 

26%*

Percentage of all reported US traveler 

chikungunya cases whose travel 

destination was Paraguay

*18 of 69 travelers with destination data, preliminary ArboNET data, 2023
Providing clarity on chikungunya outbreaks

 For the purposes of the recommendation, an outbreak 

will be defined as occurring when CDC posts information 

on an outbreak on CDC website 
Shared clinical decision-making recommendation

 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

– Older persons (e.g., >65 years), particularly those with underlying 

medical conditions, who are likely to have at least moderate exposure 

to mosquitoes 

– Persons staying for a cumulative period of 6 months or more during a 

2-year period
Older persons, particularly those with underlying medical 

conditions?

 Key risk factors for severe disease 

– Older age 

– Underlying medical conditions

 Key risk factors for chronic arthralgia 

– Older age 

– Presence of pre-existing joint problems

 Risk for higher morbidity and mortality 

in older persons supported by data 

from recent outbreak in Paraguay1

1. Torales M, et al. Notes from the Field: Chikungunya Outbreak - Paraguay, 2022-2023. MMWR Morb Mortal Wkly Rep 2023; 72:636-638

Vaccine not 

available for 

children 
Cumulative period of ≥6 months during 2-year period*

 Key risk factor for chikungunya virus infection is intensity of 

transmission 

– If equivalent transmission, cumulative duration of exposure important

 Transmission patterns can be unpredictable over the longer term and 

likely to be some seasonal variation in mosquito activity that might 

impact risk

*2-year period based on immunogenicity data showing high seroresponse rate (99%) at one year after vaccination 

suggesting good protection at least through second year but no longer-term data
Evidence of chikungunya virus transmission among humans 

within the last 5 years

 Rationale: 5-year time frame provides interval that allows reasonable 

confidence there is transmission or insufficient transmission to be concern 

for travelers 

 Tool: Map that shows countries 

with chikungunya virus 

transmission among humans 

reported during last 5 years, 

posted on CDC website 

Mock map to demonstrate transmission of chikungunya virus among 

humans during last 5 years
Moderate exposure

 Moderate exposure could include travelers who might have at least 2 

weeks (cumulative) of exposure to mosquitoes in indoor and/or 

outdoor settings. It does not include travelers who might have limited 

exposure to mosquitoes (e.g., those traveling for business and likely to 

be mainly in mosquito-protected indoor settings)
General considerations*

 All persons who travel to areas with possible chikungunya virus transmission should be advised to 

take precautions to avoid mosquito bites

 The risk for chikungunya for most US travelers to countries or territories with evidence of 

transmission is low. However, some travelers are at increased risk for infection or more severe 

disease. In the discussion between the healthcare provider and traveler on the need for vaccination, 

consideration should be given to 

1) whether there is a recognized outbreak or ongoing disease activity 

2) the duration of travel or residence, including likelihood of future travel to an area with 

chikungunya virus transmission

3) the likelihood of exposure to Aedes mosquitoes

4) older age (e.g., >65 years)

5) underlying medical conditions that increase the risk for severe disease (e.g., diabetes, cardiac 

disease, hypertension)

6) underlying conditions that increase the risk for chronic arthralgia after infection (e.g., existing 

joint disease)

7) an individual’s personal perception and tolerance of risk 

*Provided in background materials
Draft recommendations

 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

– Older persons (e.g., >65 years), particularly those with underlying 

medical conditions, who are likely to have at least moderate exposure* 

to mosquitoes 

– Persons staying for a cumulative period of 6 months or more during a 

2-year period

*Moderate exposure could include travelers who might have at least 2 weeks (cumulative) of exposure to mosquitoes in 

indoor and/or outdoor settings