Document text
National Center for Emerging and Zoonotic Infectious Diseases
PROPOSED POLICY OPTIONS FOR
CHIKUNGUNYA VACCINE USE AMONG
U.S. 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, February 28, 2024
Chikungunya virus and transmission
Alphavirus
Key vectors are Aedes aegypti
and Aedes albopictus mosquitoes
Mainly feed in daytime with peak
activity early morning and late
afternoon
Other uncommon transmission modes
Intrauterine Intrapartum
Bloodborne Laboratory
exposure
Distribution and disease burden in endemic areas
Typically tropical and
subtropical regions
Periodically causes large outbreaks
–Often high attack rates
Virus transmission usually
highest during wet season
Large numbers of cases reported annuallyCountries and territories with current or past transmission
of chikungunya virus
Clinical features of acute chikungunya virus infection
Febrile illness with typically severe
arthralgia, can be debilitating
Joint symptoms involve multiple joints, most commonly hands and
feet
Other symptoms include
headache, rash, myalgia, anorexia
No anti -viral treatment available
Image above from : https://www.paho.org/en/topics/chikungunya
Complications of chikungunya
Rare serious complications (e.g.,
myocarditis, hepatitis, acute renal disease,
neurologic illness)
Deaths rare and reported mostly in
–Older adults, particularly those with
comorbidities
–Young infants infected perinatally or by mosquito bites
Images from : https://www.paho.org/en/topics/chikungunya
Chronic arthralgia following chikungunya
Acute symptoms usually resolve in 7 –10 days
Some patients have continuation or relapse of symptoms
Studies reported variable proportions of
patients with persistent symptoms and likely
varies with
–Severity of acute illness
–Age
–Preexisting joint problems
Ongoing arthralgia of variable severity possibly
present in up to ~50% at 3 months and up to
~30% at 12 months
Chikungunya among U.S. travelers
Approximately 100 –200 reported cases
annually
Infection most commonly acquired in
locations in Asia and Americas
Greatest risk factor for travelers is traveling to area with outbreak
Example of higher risk during outbreak: Risk for travelers
to Paraguay in 2023
<1%
Percentage of all U.S. persons
traveling to areas with
chikungunya risk visiting Paraguay 25%*
Percentage of all reported U.S. traveler
chikungunya cases who indicated they
had traveled to Paraguay
*20 of 80 travelers with destination data, preliminary ArboNET data, 2023
Chikungunya vaccine
Live attenuated vaccine
Single dose schedule
Administered intramuscularly
Licensure based on data from
–~620 subjects for immunogenicity
–~3,500 subjects for safety (including ~3,100 in pivotal clinical trial)
Short - and long -term protection ( seroresponse rates)
Short -term protection (28 days after vaccination)
–98% (611 of 622) combined seroresponse rate from two studies
Long-term protection (12 months after vaccination)
–99% (356 of 360) seroreponse rate from one study
Work Group summary
–Although data are limited, vaccine highly immunogenic
Vaccine safety (1)
Pivotal Phase 3 clinical trial included 3,082 adults in vaccine arm and
1,033 in placebo arm
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
Any related severe sy stemic AEs *
–1.9% in vaccinees vs 0.1% in placebo recipients
–Commonest were fever (1.3%), arthralgia (0.3%), myalgia (0.3%)
*Prevented daily activity or required medical attention or fever ≥39°C (102.1° F)
Vaccine safety (2)
Serious adverse events within 6 months of vaccination
–1.5% in vaccinees vs 0.8% of placebo recipients
–Two events in vaccinated subjects considered vaccine -related
Arthr algia/arthritis
–Any arthralgia within 10 days in 17% vaccinees vs 5% placebo recipients
–Severe arthralgia, persistent arthralgia, arthritis, and new onset or worsening
osteoarthritis not reported in significantly higher percentage of vaccinees vs placebo recipients
Chikungunya- like adverse reactions: Background
Safety outcome of interest has been chikungunya -like illness after vaccination
Work Group had reviewed data on “adverse events of special interest” defined
by manufacturer
FDA-requested reanalysis based on revised case definition that was less
restrictive in terms of timing of onset of events, clustering of symptoms, and
duration of events
–Revised FDA definition was fever* and ≥1 of arthralgia or arthritis, myalgia,
headache, back pain, rash, lymphadenopathy, or certain neurological, cardiac or
ocular symptoms that occurred within 30 days after vaccination
* Fever ≥100.4 °F
Chikungunya- like adverse reactions: Results per reanalysis
Chikungunya -like adverse reactions
–11.7% (361 of 3,082) vaccine recipients and 0.6% (6 of 1,033) placebo
recipients
–Most symptoms mild or moderate
Severe reactions that prevented daily activity or required medical
intervention, or fever ≥102.1 °F (39° C)
–1.6% (n=48) vaccine recipients vs 0% of placebo recipients
Prolonged reactions with duration ≥30 days
–0.5% (n=14) vaccine recipients vs 0% of placebo recipients
Chikungunya- like adverse reactions:
Work Groups conclusions
Already considered reactogenic nature of vaccine
Looked closely at similar events when conducting GRADE analysis
Noted some other reactogenic vaccines have similar rates of adverse events
In Evidence to Recommendations framework when considering if desirable
effects outweighed undesirable effects of vaccination had noted risk -benefit
assessment
–Will vary substantially depending on chikungunya virus transmission intensity
and other factors
–Was likely favorable if used in line with our proposed recommendations
No change in Work Group assessment
Vaccine safety: Work Group summary
Reactogenic vaccine
Will be important to continue to monitor vaccine safety post -
licensure
Summary of Work Group considerations
Disease that can result in severe arthralgia during the acute illness,
rare serious complications, and sometimes long -term arthralgia
Highest risk for severe outcomes is among older adults, particularly those with comorbidities, and neonates and young infants
Moderate disease burden among US travelers with 100- 200 cases
reported annually
Substantially higher risk for infection if travel during an outbreak
Immunogenic but reactogenic vaccine
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
–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
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 for
persons aged >65 years or traveling for a longer duration
More uncertainty in risk -benefit assessment in these cases
Likely to be circumstances where some individuals might reasonably
choose vaccination or some providers might wish to recommend it
Appropriate to hold conversation between healthcare provider and patient about the risks and benefits including
–likelihood of exposure based on factors including activities, time of year,
duration of travel
–disease and potential severity
–vaccine efficacy
–possibility of vaccine -associated adverse events
Takes into account traveler’s personal perceptions and tolerance of risk
Persons >65 years, particularly those with underlying
medical conditions
Key risk factors for severe disease include older age and underlying
medical conditions (e.g., diabetes, cardiac disease, hypertension)
Key risk factors for chronic arthralgia are older age and pre -existing joint
problems
1. To ra le s M, e t al. MMWR Morb Mortal Wkly R ep 2023
Vaccine not
available for
children Risk for higher morbidity and
mortality in older persons
supported by data from recent
outbreak in Paraguay1
Travel for cumulative period of ≥6 months
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 longer term and likely some seasonal variation in mosquito activity impacting risk
Expatriates in location with risk might not have access to vaccine if risk increased or outbreak began
Providing clarity on 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 -up map to demonstrate transmission of chikungunya virus
among humans during last 5 years
Providing clarity on moderate exposure
Travelers who might have at least 2 weeks (cumulative) of exposure to
mosquitoes in indoor and/or outdoor settings
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)
65
Work Group deliberations when developing
recommendations
Aim to balance desirable and undesirable effects of vaccination
–“Recommended”: for travelers with highest risk
–“May be considered”: some individuals might reasonably choose
vaccination and some providers might wish to recommend it
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
–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
*Moderate exposure could include travelers who might have at least 2 weeks (cumulative) of exposure to mosquitoes
in indoor and/or outdoor settings