Recommendations for the use of chikungunya live attenuated vaccine (IXCHIQ)

Published: December 24, 2025

On this page

• Preamble
• Key points for the healthcare provider
• Recommendations
  • Table 1. Examples of individualized assessment
  • Unavoidable travel for persons 65 years or older, or individuals for whom CHIK-LAV is contraindicated
• Background
  • Clinical features
• Methods
  • General
  • Policy question
  • Outcomes and thresholds of importance
  • Literature search
• Evidence assessment and recommendations for chikungunya live attenuated vaccine
  • Summary of evidence
  • Benefits and harms of vaccination with CHIK-LAV
  • Resources (cost), acceptability and feasibility
  • Judgement
  • Recommendations for CHIK-LAV
• Conclusions and research needs
• List of abbreviations
• Acknowledgements
• Conflicts of interest
• Appendices
  • Appendix 1. Literature search strategy
  • Appendix 2. Summary of findings tables
  • Appendix 3. Evidence to decision tables
  • Appendix 4. Assessment for applicability of good practice statement (GPS)
• References

Preamble

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada (PHAC) with ongoing and timely medical, scientific, and public health advice relating to tropical infectious disease and health risks associated with international travel. PHAC acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices and is disseminating this document for information purposes to the medical community caring for travellers.

Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.

Key points for the healthcare provider

• Chikungunya is caused by a mosquito-transmitted alphavirus. It occurs in many tropical and sub-tropical areas, often in locations where other arboviruses, such as dengue and Zika, are also present.
• The risk of acquiring chikungunya during travel is aligned with local levels of transmission. This means a relatively elevated risk if travel is to an area experiencing a significant outbreak/epidemic. Otherwise, the risk of chikungunya infection/disease among travellers is low.
• Most people infected with chikungunya virus develop symptoms, usually manifesting as abrupt onset of fever and joint pain. For a significant proportion of patients (up to 50%) acute illness progresses to longer-term symptoms that can include debilitating polyarthralgia/arthritis. Rarely, chikungunya disease can include potentially life-threatening neurologic, cardiovascular and other effects.
• A single-dose chikungunya live attenuated vaccine (CHIK-LAV), IXCHIQ^® , is authorized for use in Canada. There is currently no direct evidence demonstrating efficacy of this vaccine. However, the vaccine was immunogenic in the pivotal phase 3 clinical trial with 99% of vaccinees meeting the target seroresponse level at 29 days after vaccination^{Footnote 1}.
• In the same phase 3 clinical trial, receipt of CHIK-LAV was associated with several types of adverse effects including:
  • Chikungunya-like adverse reactions (CLARs), defined as a cluster of symptoms consistent with wild-type chikungunya infection^{Footnote 2} and,
  • Two serious adverse events requiring hospitalization that were considered likely to be related to vaccination with CHIK-LAV.
• Global post marketing surveillance detected serious adverse events (SAEs), including cardiac and neurologic events, mostly among CHIK-LAV recipients aged 65 years and older with underlying medical conditions.
• CHIK-LAV is contraindicated during pregnancy and for persons with immunodeficiency^{Footnote 2}.

Recommendations

1. CATMAT recommends against use of the chikungunya live attenuated vaccine (IXCHIQ^®) in persons aged 65 years or older.

   (Strong recommendation, very low certainty of the evidence)

   Rationale:

   • Post-marketing surveillance data identified 28 SAEs in IXCHIQ^® recipients (as of July 11, 2025^{Footnote 3}), most of these events, including three deaths, occurred among persons 65 years of age and older^{Footnote 4}. The chikungunya virus strain used in the vaccine was detected among some of these patients, and the timing of SAE onset was generally consistent with the expectation for a vaccine-related outcome^{Footnote 5}. Hence, CATMAT believes it is likely that at least some of the reported SAEs were caused by vaccination.
   • CATMAT believes travellers would place a very high value on averting vaccine-associated SAE. Therefore, the committee decided to recommend against use of CHIK-LAV in persons 65 years or older even though the certainty of the evidence is very low.
   • SAEs have clustered in older persons with pre-existing health conditions. However, the absolute impact of these health conditions independent of age as a risk factor(s) for SAE is unclear. Therefore, this recommendation is centred on age.

   And

   CATMAT suggests persons aged 65 years or older avoid travel to an area identified as experiencing a chikungunya outbreak.

   (Discretionary recommendation, moderate certainty of evidence)

   Remarks:

   • This recommendation ONLY APPLIES to areas identified as undergoing a chikungunya outbreak.
   • Consult the Government of Canada's Travel Advice and Advisories pages to determine if a location has been identified as experiencing a chikungunya outbreak. Look under the "Health" section of each destination page, specifically for a "Level 2 Travel Health Notice".
   • When discussing avoidance of travel, inform patients that chikungunya outbreaks are relatively short-lived, often lasting a few months to a year, making it possible to avoid travel.

   Rationale:

   • The risk of infection can be high during a chikungunya outbreak (e.g., 1% to 40% per annum) and the risk of severe disease and death resulting from chikungunya infection is higher among older persons.
2. For Canadians aged 18 to 64 years who are at high risk of infection (see Remarks), CATMAT suggests considering the chikungunya live attenuated vaccine (CHIK-LAV). Individualized assessment (see Remarks) and discussion between the traveller and their healthcare provider are necessary to assess the suitability of CHIK-LAV vaccination.

   (Discretionary recommendation, very low certainty of the evidence)

   And

   CATMAT suggests against offering chikungunya live attenuated vaccine (CHIK-LAV) for all other Canadians aged 18 to 64 years of age.

   (Discretionary recommendation, very low certainty of evidence)

   Remarks:

   • CHIK-LAV may result in a large absolute increase in serious adverse events possibly related to vaccination. CATMAT believes travellers would place a very high value on avoiding the potential for vaccine-related SAE and therefore would prefer to receive CHIK-LAV in situations when the estimated infection risk and benefit are highest.
   • An individualized assessment (see Table 1 for examples) includes a discussion about the benefits and harms of CHIK-LAV (Appendix 2) in the context of:
     • Traveller's exposure to chikungunya including the destination, the length of travel and possibility of repeat travel to affected areas.
       • Outbreaks are associated with high infection risk and travellers would be more likely to choose to receive CHIK-LAV when the estimated risk is the highest. To determine if a destination is identified as experiencing an outbreak, consult the Government of Canada's Travel Advice and Advisories pages. Look under the "Health" section of each destination page specifically for a "Level 2 Travel Health Notice".
       • Travellers who are travelling to an outbreak area (Appendix 2-Table 7), as well as those who are planning longer trips and those who might undertake repeated travel to areas of risk, and/or those who might be more likely to suffer complicated or severe chikungunya disease may derive greater benefit from vaccination with CHIK-LAV.
     • Patient information for risk factors related to severe and/or persistent chikungunya disease and vaccine-associated serious adverse events.
       • Some medical conditions are thought to increase the likelihood of developing serious chikungunya disease. These conditions include diabetes, hypertension, cardiac disease and/or persistent symptoms (e.g. pre-existing joint disease).
       • It is not known if pre-existing health conditions (e.g., diabetes, hypertension, heart disease) impact the likelihood of vaccine-associated SAE in persons 18 to 64 years old. However, these conditions are associated with increased likelihood of severe disease in wild-type infections and one or more of these conditions were generally present in older patients who experienced vaccine-associated SAE. Thus, it is reasonable to consider the potential for negative impacts of pre-existing health conditions across all ages in the context of decision-making for use of CHIK-LAV.
     • Travellers' values and preferences
       • Travellers likely have different values and preferences related to chikungunya and its prevention. This includes risk tolerance for the possibility of an adverse event after vaccination and for chikungunya-related symptoms/disease. These differences are expected to result in different travellers making different decisions on whether to receive or not CHIK-LAV.

   Rationale:

   • Estimated absolute benefit of chikungunya vaccination increases with duration of travel and outbreak transmission level (Appendix 2-Table 6 and Table 7).
     • Estimated absolute vaccine-associated reduction in long-term arthralgia varies from moderate for two weeks of travel (0.10 fewer per 1,000, 95% CI 0.07 to 0.21, low certainty of the evidence) to large (Appendix 2- Table 6 and Table 7) depending on these factors. Similar patterns apply to prevention of clinical chikungunya disease.
     • For hospitalization and death, estimated absolute vaccine-associated benefits are trivial except for longer travel to a high transmission outbreak area (Appendix 2- Table 7).
   • Vaccination with CHIK-LAV may result in a large absolute increase in SAE possibly related to vaccination (0.4 per 1,000 in vaccinee group, 0 in placebo group, very low certainty of the evidence) (Appendix 2- Table 8).
   • Vaccination with CHIK-LAV may result in a moderate absolute increase in severe systemic adverse events like fever (22 more per 1,000, 95% CI 6 to 28 more, moderate certainty of the evidence) and chikungunya-like adverse reactions (112 more per 1,000, 95% CI 97 to 125 more, very low certainty of the evidence) (Appendix 2- Table 8).
3. Healthcare providers should advise all travellers to chikungunya-affected areas to use personal protective measures against insect bites.

   (Good Practice Statement)

   • Use an approved and age-appropriate insect repellent.
   • If mosquitoes cannot be excluded from living areas, consider using repellent inside during the day as this is often where/when the chikungunya vectors bite.
   • Protect resting areas against mosquito entry/activity, regardless of time of day e.g., by staying in places that have screening in good repair, air conditioning, no gaps in building that would allow mosquito entry.
   • Consider wearing insecticide-treated clothing.
   • Protection against bites provided by each measure is presumed to be additive.

   For additional details on recommendations related to the prevention of arthropod bites, see the CATMAT statement on measures to prevent arthropod bites (PDF).

Table 1. Examples of individualized assessment

Patient information	ExposureFootnote *	Assessment
A healthy 70-year old male, with no pre-existing medical conditions, is planning to travel to Cuba for 3 weeks.	Cuba is a country identified to be experiencing an outbreak by a Level 2 Travel Health Notice from the Public Health Agency of Canada on its destination page.	This patient is at increased risk of infection based on presence of an outbreak at their destination, however the risk of serious adverse events from vaccination is also a concern for this patient given their age group (65 years or older). Given this, CHIK-LAV is not advised for this patient (Recommendation 1-part 1) and healthcare providers should suggest postponing travel to the patient (Recommendation 1-part 2) to avoid the possibility of serious chikungunya-related outcomes including death. The risk of these events is higher in older people, especially if they have predisposing health conditions such as cardiovascular disease and/or diabetes. Because chikungunya outbreaks are often of short duration (e.g., a few months), it is likely that travel need not be deferred for an extended period.
An 81-year old female, with osteoarthritis, is travelling to India for 3 months.	India is not experiencing an outbreak, as there is no Level 2 Travel Health Notice from the Public Health Agency of Canada on its destination page.	While chikungunya is a risk in India, this country has not been identified as experiencing an outbreak. In the absence of an identified outbreak, CATMAT does not suggest travel be deferred (Recommendation 1-part 2). While this traveller, by virtue of their age, may be more susceptible to serious chikungunya disease if infected, they also are at increased risk for vaccine-associated SAE. Based on the balance of benefits and harms, CATMAT recommends against vaccination (strong) for this traveller (Recommendation 1-part 1). A discussion about the risk of exposure to mosquitoes and serious chikungunya-related symptoms/disease is essential. Advising the patient to adhere to mosquito bite prevention measures is strongly recommended (Recommendation 3).
A 27-year old female, who is healthy with no pre-existing medical conditions is travelling to Sri Lanka for 1 month to visit their family in a rural region of the country.	Sri Lanka is a country identified to be experiencing an outbreak by a Level 2 Travel Health Notice from the Public Health Agency of Canada, on its destination page.	This patient is at increased risk of infection based on the presence of an outbreak at their destination and may be staying in settings that are not well protected from mosquitoes. CHIK-LAV could be considered following a discussion of the possible benefits and harms of vaccination, chikungunya-related symptoms/disease, and the patient's values and preferences (Recommendation 2-part 1). If the patient chooses to receive CHIK-LAV after this discussion, as a person of child-bearing potential they should be advised to avoid pregnancy for one month following vaccinationFootnote 2. Advising the patient to adhere to mosquito bite prevention measures is strongly recommended (Recommendation 3).
A 35-year old male, who is healthy without pre-existing medical conditions, is travelling to Brazil for 2 weeks.	Brazil is not experiencing an outbreak, as there is no Level 2 Travel Health Notice from the Public Health Agency of Canada on its destination page.	The patient is not travelling to a country identified to be experiencing an outbreak, even though chikungunya is a risk in this country. CHIK-LAV is not suggested for this traveller (Recommendation 2-part 2). Advising the patient to adhere to mosquito bite prevention measures is strongly recommended (Recommendation 3).
A 50-year old male, with diabetes, is planning travels to Bolivia for 8 months.	Bolivia is not experiencing an outbreak, as there is no Level 2 Travel Health Notice from the Public Health Agency of Canada on its destination page.	In this example, the patient is not travelling to a country identified to be experiencing an outbreak, even though chikungunya is a risk in this country. Given the patient's medical condition and planned prolonged travel to an area where there is a risk of chikungunya, they are at higher risk of infection and of serious chikungunya disease if infected. The healthcare provider and the patient should discuss the importance of strict adherence to mosquito bite prevention measures for the entirety of their stay (Recommendation 3). The healthcare provider and patient may also discuss the possibility for an outbreak in the area during the prolonged trip and prevention of chikungunya disease if an outbreak occurs, increasing the risk of infection. Having a pre-existing medical condition such as diabetes could increase the risk of serious outcomes from chikungunya infection. Importantly, it is not known if and how pre-existing health conditions impact the risk of vaccine-related SAEs in persons 18 to 64 years of age. Discussion should consider patient's values and preferences including risk tolerance for vaccine harms and for chikungunya-related outcomes such as long-term arthralgia and hospitalization. Based on this discussion, some patients may choose to receive CHIK-LAV and some may choose not to receive CHIK-LAV (Recommendation 2, Remarks).
Footnote * In these examples, the exposure reflects a hypothetical scenario and does not reflect current countries identified by the Public Health Agency of Canada to be experiencing an outbreak (i.e. by a Level 2 Travel Health Notice on its destination page). Return to footnote * referrer

Unavoidable travel for persons 65 years or older, or individuals for whom CHIK-LAV is contraindicated

In populations for whom CHIK-LAV is not advised (e.g. persons 65 years or older) or contraindicated (e.g. pregnant or immunodeficient individuals) there could be complex scenarios where it may not be possible to delay travel. An in-depth discussion about the potential risks of infection, the risk for serious complications from vaccination including SAE and/or the lack of safety evidence for use during pregnancy is necessary to support shared decision making related to receipt of CHIK-LAV. The importance of alternative approaches, especially methods to prevent mosquito bites, should be emphasized.

Background

Chikungunya is an acute viral disease that is endemic in most of the tropical and sub-tropical regions globally, including Asia, Africa and the Americas^{Footnote 6}. The chikungunya virus is transmitted through the bite of an infected mosquito, primarily by Aedes aegypti and Aedes albopictus mosquitoes.

It is presumed many tropical areas experience persistent but relatively low levels of chikungunya transmission. Periodically, large and explosive outbreaks can also occur. During these events, a significant proportion of the resident population is often infected^{Footnote 7} and risk to travellers is accordingly elevated^{Footnote 8 Footnote 9}. Outbreaks are usually short-lived, for example between three to six months, after which there is usually a steep decline in infections and cases. Factors impacting chikungunya transmission levels include environmental conditions, weather, population density, population immunity level, and local vector dynamics.

Prevention of chikungunya virus infection relies on reducing exposure to mosquitoes through the use of repellents, staying in mosquito protected accommodations and other individual level interventions (see CATMAT statement measures to prevent arthropod bites [PDF]). Additionally, mosquito control measures undertaken by local authorities to minimize vectors and reduce breeding sites can reduce the risk of infection.

There are two vaccines approved for use in some countries for the prevention of chikungunya virus infection, a chikungunya live attenuated vaccine (IXCHIQ^®) and a vaccine that uses virus-like particle technology (VIMKUNYA). At the time of this writing, only IXCHIQ^® is authorized in Canada.

Clinical features

Chikungunya infection is characterized by abrupt onset of fever and severe joint pain that usually affects multiple joints^{Footnote 10}. Most people will recover from acute chikungunya infection within a few days, however a high proportion of those infected (approximately 50%^{Footnote 11}) will experience debilitating joint pain, that can last for months or years. Other common symptoms are joint swelling, muscle pain, headache, nausea, fatigue and rash. Severe chikungunya disease could present as cardiac, renal, ocular, or neurologic complications requiring hospitalization due to the risk of organ damage and death. While serious outcomes and death from chikungunya infection are rare, older persons, young infants and those with underlying medical conditions are at higher risk.

There is no specific treatment for chikungunya virus infection. Clinical management is aimed at symptomatic relief of fever and joint pain. Until dengue infections are ruled out, non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided as these can increase the risk of bleeding.

Methods

General

This statement was developed by the CATMAT Chikungunya working group (WG), a sub-group of members of the Committee to Advise on Tropical Medicine and Travel (CATMAT). With support from the CATMAT secretariat, the WG met regularly to review and assess relevant data in detail, and to draft recommendations for CHIK-LAV. Key decisions supporting the recommendation development process were discussed with and approved by the full CATMAT committee. The final version of the statement and its recommendations were reviewed and endorsed by CATMAT.

CATMAT developed recommendations for CHIK-LAV in accordance with our Evidence Based Process for developing travel and tropical medicine related guidelines and recommendations, which includes the use of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology to assess the certainty of the evidence and weigh benefits and harms, while considering other factors, such as patient values and preferences, resources, acceptability, and feasibility. The perspective taken for developing CHIK-LAV guidance was the individual traveller. Our assessment and judgements are summarized in an Evidence to Decision framework (Appendix 3).

A GRADE methodologist from McMaster University supported the development of this guidance.

In accordance with GRADE guidance, good practice statements were developed where CATMAT judged there was unequivocal net benefit from the intervention with negligible harms and costs (Appendix 4)^{Footnote 12}.

Policy question

The policy question was:

Should Canadians travelling to chikungunya affected areas be recommended to receive vaccination (the live attenuated chikungunya vaccine)? If so, who should receive it and under what circumstances?

The key research questions were:

1. Is chikungunya an important hazard to Canadian travellers?
   1. What is the risk of infection in Canadians travelling to chikungunya affected areas?
      1. Does the risk differ during outbreaks versus non-outbreak periods?
   2. What is the morbidity associated with chikungunya infection in Canadian travellers?
   3. What is the mortality associated with chikungunya infection in Canadian travellers?
2. How effective is the CHIK-LAV in preventing chikungunya infection and associated outcomes?
3. What are the harms of the CHIK-LAV?
4. What are the values and preferences of key stakeholders and is the CHIK-LAV acceptable to Canadian travellers?

Outcomes and thresholds of importance

Potential patient-important outcomes related to chikungunya disease and its prevention were identified by reviewing the literature and applying clinical judgement. These were then rated for importance on a scale of 1-10 (low to high) by each WG member, with the final value reflecting the summary estimate across all ratings. Based on a standardized scale of importance, each outcome was designated as critical, important or not important^{Footnote 13}.

Only critical outcomes were further considered in the development of recommendations. They were:

• Benefits: Prevention of clinical chikungunya disease, long-term arthralgia from chikungunya infection, hospitalization, and death.
• Harms: Severe systemic adverse events of short duration, chikungunya-like adverse reactions (CLARs), new or worsening arthritis or osteoarthritis symptoms, and serious adverse events.

A key component for assessing certainty of the evidence is defining a range of absolute effects that constitute an important benefit or harm^{Footnote 14}. This supports assessment of imprecision in the GRADE framework. Importantly, it also provides a rubric for integrating information across different outcomes, in essence supporting the comparison of the benefits and harms of an intervention.

To guide this work for CHIK-LAV, CATMAT defined an absolute effect value, for each critical outcome, that represented a moderately important level of benefit or harm from CHIK-LAV that would be seen as clinically meaningful by a patient. These thresholds for a moderate level of importance were established based on clinical experience and judgement due to limited evidence on patient values for CHIK-LAV.

The level of importance for each outcome was further divided into trivial, small, and large effects (Table 2). The implication being that a patient would value a moderate absolute effect more than a small effect, while trivial effects would not be considered as influential in their decision-making. For comparison across outcomes, for example a large important harm would generally outweigh a moderate important benefit. This framework enables the comparison of benefits and harms of CHIK-LAV, wherein the totality of the evidence for the outcomes and the respective magnitude of their effect size are integrated to support our development of recommendations.

Table 2. Thresholds for an absolute effect size for each critical outcome related to CHIK-LAV

Critical outcome		Thresholds of absolute effectFootnote * (benefits and harms) Number of events per 1,000 person-trips				Key WG Judgements
		Trivial	Small	Moderate	Large
Benefits	Chikungunya disease	< 1	1	2	10	Most travellers would value avoiding chikungunya disease, but would view a risk of <1/1,000 as trivial (relatively unimportant)
	Long-term arthralgia	< 0.05	0.05	0.1	0.5	Most travellers would place a higher value on avoiding debilitating long term arthralgia than acute disease
	Hospitalization	< 0.05	0.05	0.1	0.5	Most travellers would value avoiding long term arthralgia or hospitalization about equally
	Death	< 0.005	0.005	0.01	0.05	Most travellers would place a very high value on avoiding death, but would judge an estimated risk of <1/200,000 as trivial (relatively unimportant)
Harms	Severe systemic adverse events (AE) of short duration	<5	5	10	50	Most travellers would value avoiding vaccine AE, but would view a risk for temporary but severe AE of <1/200 as trivial (relatively unimportant)
	Chikungunya-like adverse reactions (CLARs)	<50	50	100	500	Most travellers would value avoiding vaccine AE, but would view a risk of non-severe CLAR of <1/20 as trivial (relatively unimportant)
	New or worsening arthritis or osteoarthritis symptoms	< 0.1	0.1	0.2	1	Most travellers would value avoiding vaccine AE, but would view a risk of new or worsening arthritic symptoms of <1/10,000 as trivial (relatively unimportant)
	Serious adverse events (SAEs)	< 0.01	0.01	0.02	0.1	Most travellers would place a high value on avoiding vaccine-associated SAE even at a low likelihood (small effect is 1/100,000)
Footnote * All thresholds (benefits and harms) are expressed against the estimated likelihood of an event in the absence of immunization. Return to footnote * referrer

Literature search

With the support of a research librarian, search strategies were developed to answer the key research questions 1 and 4. Searches were conducted in the following electronic databases: Ovid MEDLINE, Embase, Global Health, Scopus for relevant literature in English or French.

Evidence for benefits and harms associated with CHIK-LAV (questions 2 and 3) was identified through a manual search for published clinical trial data and government clinical review reports, and unpublished data shared by the manufacturer.

Evidence assessment and recommendations for CHIK-LAV

Summary of evidence

Chikungunya infection in Canadian travellers

We did not identify robust evidence that well characterizes the incidence of chikungunya infection in Canadian travellers. However, reported cases in travellers has tracked closely to burden of disease in affected countries. For example, reports of chikungunya in returning United States (US) travellers were highest during spread of chikungunya to the Americas in 2014^{Footnote 9}. More recently in 2023, during chikungunya outbreak in Paraguay, an analysis of US traveller data showed that while less than 1% of all US persons travelling to areas with chikungunya risk visited Paraguay, 25% of all reported chikungunya cases among US travellers indicated they had travelled to this country^{Footnote 15}.

Acknowledging that chikungunya activity ebbs and flows, often with long periods of relative inactivity interspersed with temporally intense but somewhat unpredictable outbreaks, we decided to develop models to estimate infection probability for Canadian travellers. These estimates were then used to estimate associated critical outcomes with and without vaccination (see below).

To do this, we relied on two published studies that modelled spatial and temporal infection and outcome probabilities in residents of endemic areas^{Footnote 16 Footnote 17}. This approach makes the conservative assumption that the risk of infection over a given time period for residents of affected areas and exposed travellers is the same.

These modelling studies^{Footnote 16 Footnote 17} considered areas experiencing chikungunya transmission from across the globe where the evidence permitted it, i.e. seroprevalence estimates over time. Given that future outbreaks and their intensity at the spatial scale of country or region are not easily predicted, we relied on global estimates of infection risk rather than location specific estimates. However, we differentiated between endemic and outbreak periods. Further, recognizing outbreaks can vary in intensity, we considered two outbreak scenarios: a lower risk scenario consistent with the estimates of Kang et al^{Footnote 16} and a higher risk scenario consistent with the estimates of Perez et al^{Footnote 17}. This yielded the following annual estimates of risk of infection:

• Endemic transmission of 1 infection per 1000 (95% CI: 0.8 to 1.4)^{Footnote 16}.
• Lower transmission outbreak (LTO) of 9 infections per 1,000 (95% CI 5 to 14 per 1,000)^{Footnote 16}.
• Higher transmission outbreak (HTO) of 330 infections per 1,000 (95% CI 301 to 360 per 1,000)^{Footnote 17}.

We assumed these risks were constant in our estimations, i.e. risk of infection in a traveller is directly proportional to this estimate multiplied by the duration of travel.

Likelihood of chikungunya-related critical outcomes in Canadian travellers

Using the above estimates of risk of infection and adjusted for specific durations of exposure (2 weeks to one year), we calculated the probability of chikungunya infection-associated outcomes (if unimmunized) using the following parameter estimates:

• Likelihood of clinical disease if infected: 80%^{Footnote 11}.
• Likelihood of long-term arthralgia following clinical disease: 50%^{Footnote 11}.
• Likelihood of hospitalization if infected: 0.25% for 18 to 64 years old, and 1.70% for persons 65 years and older^{Footnote 17 Footnote 18}.
• Likelihood of death if infected: 0.004% for 18 to 64 years old, and 0.091% for persons 65 years and older^{Footnote 17}.

Data on hospitalization and death were stratified across additional age bands^{Footnote 17 Footnote 18}. Our estimates for likelihood of hospitalization and death reflect the overall estimate integrated across age bands included in each group.

Efficacy of CHIK-LAV

Direct evidence for CHIK-LAV efficacy is not currently available. We therefore used immunogenicity data from the pivotal phase 3 randomized control trial (RCT)^{Footnote 1} for CHIK-LAV to develop estimates of vaccine performance. The study included 4,115 participants of which 3,082 received CHIK-LAV and 1,033 received placebo group. Approximately 11% of participants were 65 years and older.

Seroconversion predictive of clinical benefit was defined as a 50% micro-plaque reduction neutralization test titer of ≥150 (µPRNT50 ≥150). This level was derived from a trial where human sera post-CHIK-LAV vaccination was transferred to and afforded protection to non-human primates (NHP)^{Footnote 19}.

Seroresponse was high in the CHIK-LAV population (98.9%, 95% CI: 96.7 to 99.8%) at 29 days after vaccination^{Footnote 1} and in follow-up assessments (in a subset of participants) out to 4 years^{Footnote 20}. Seroresponse was similar across ages: 98.6% (95%CI: 95.8 to 99.7%) for 18 to 64 year-olds, and 100% (95% CI: 93.9 to 100.0%) for those 65 years and older.

Given the high seroconversion and evidence of protection in NHP, we assumed that vaccine efficacy was 95% for the purpose of developing estimates of benefit.

Absolute estimates of immunization benefit were calculated as 0.95 multiplied by the absolute estimated likelihood of an outcome in the absence of immunization. This presumes vaccine efficacy of 95%. Thus, for a 65-year-old travelling to a higher transmission outbreak area for a year and who received the vaccine, we calculated absolute benefit for prevention against death as:

0.95 * (330/1,000 (risk of infection) * 0.00091 (likelihood of death if infected) = 0.00029 or 0.029%

Benefits and harms of vaccination with CHIK-LAV

Estimated benefits of CHIK-LAV

The estimated benefits of CHIK-LAV varied depending on the age group, chikungunya transmission level and trip length (Appendix 2). The overall certainty of the evidence for these benefits was low.

For the endemic transmission setting, estimated benefits for CHIK-LAV for prevention of clinical disease, hospitalization and death were trivial across all travel durations and age groups (Appendix 2- Table 5 and Table 9). For long-term arthralgia following clinical disease, we estimated a moderate benefit for longer trip durations, e.g., for a 3-month trip the estimate was 0.1 fewer events per 1,000 travellers (95% CI 0.08 to 0.14 fewer, low certainty of the evidence).

For estimates based on outbreak conditions, there was greater nuance to estimated benefits, especially based on age.

Persons 18 to 64 years old

The estimated benefit of CHIK-LAV for prevention of clinical disease was moderate to large for longer trips (six months to one year) to a lower transmission outbreak (LTO) area (Appendix 2- Table 6). In a higher transmission outbreak (HTO) area, the benefit was large for a two-week trip, i.e. 9.7 fewer events per 1,000 travellers (95% CI: 8.8 to 10.6 fewer, moderate certainty of the evidence), with effect size increasing for longer trips (Appendix 2- Table 7).

The estimated effect for preventing long-term arthralgia associated with chikungunya infection for two weeks of travel in a LTO setting was moderate (0.13 fewer events per 1,000 travellers [95% CI: 0.07 to 0.21 fewer, low certainty of the evidence]). The benefit increased if travel was to a HTO area and for a longer duration, e.g., for a year of travel the effect size was large at 125.4 fewer events per 1,000 travellers (95% CI: 113.8 to 137.4 fewer, moderate certainty of the evidence) (Appendix 2- Table 7).

In this age group, the estimated benefits for prevention of hospitalization and of death were trivial for all trip durations up to one year for a LTO area, and for shorter trips to a HTO setting (Appendix 2- Table 6 and Table 7).

Persons 65 years and older

Estimated benefits for preventing disease and long-term arthralgia were the same as for persons aged 18 to 64 years old.

The benefits at preventing hospitalization and death were more substantial for older persons. For example, for travel to a HTO area the benefit for hospitalization or death were estimated to be moderate for a 2-weeks trip: 0.16 fewer events per 1,000 travellers (95% CI: 0.19 to 0.23 fewer, moderate certainty of the evidence) and 0.011 fewer events per 1,000 travellers (95% CI: 0.010 to 0.012 fewer, moderate certainty of the evidence), respectively. The estimated benefit size increased with duration of travel, and was large for both outcomes if travel was for 3 months or longer (Appendix 2- Table 11).

Adverse events associated with CHIK-LAV (clinical trials)

Likelihoods for adverse events (AEs) were developed using evidence from the phase 3 RCT^{Footnote 1} with interpretative considerations added through review of the Unites States Food and Drugs Administration clinical review memo for CHIK-LAV^{Footnote 21} and data shared by the manufacturer.

For critical outcomes, estimates of burden of harms with CHIK-LAV compared to placebo are summarized in Table 3 below and Appendix 2.

Table 3. Summary of estimates of harm and respective effect sizes with CHIK-LAV, compared to placebo

Critical outcome	Estimate absolute risk difference Number of events per 1,000	Absolute likelihood of event for CHIK-LAV vs. placebo	Importance and size of effect (if important)	Age effect
Severe systemic AE of short durationFootnote *	20 more (13 to 26 more)	2.1% vs 0.1%	Important, moderate size	Indication of decreased likelihood in older persons
Chikungunya-like adverse reactions (CLARs)Footnote †	111 more (47 more to 256 more)	11.7% vs 0.6%	Important, moderate size	No age effect detected
New/worsening arthritis/osteoarthritis	2 more (5 fewer to 6 more)	0.6% vs 0.4%	Important, large size	Indication of increased likelihood in older persons. Sample size too small to reliably detect rare events.
Serious adverse events (SAEs)	1 more (from 3 fewer to 3 more)	0.1% vs 0.0%	Important, large size	Indication of increased likelihood in older persons. Sample size too small to reliably detect rare events.
Footnote * Severe systemic AE were solicited events occurring within 10 days of vaccination that were considered as significant, i.e. prevented normal daily activities. Return to footnote * referrer Footnote † CLARs were defined as fever (≥38 °C / 100.4 °F) AND one or more of any of the following: arthralgia or arthritis, myalgia, headache, back pain, rash, lymphadenopathy, or certain neurological, cardiac or ocular symptoms, occurring within 30 days after vaccination, regardless of order of their onset and durationFootnote 21. Return to footnote † referrer

SAE associated with CHIK-LAV (post-marketing surveillance)

There have been post-marketing reports of SAE associated with CHIK-LAV in Europe and the United States, most are among persons 65 years or older and those with pre-existing health conditions. As of July 2025, the cumulative reports are 28 SAEs including 3 deaths from among approximately 36,000 doses distributed globally^{Footnote 3}. For the United States specifically, and between May to December 2024, there were six reported SAEs to their Vaccine AE Reporting System (VAERS). All were in persons 65 years or older with comorbidities^{Footnote 22}. Based on this data, the US Advisory Committee on Immunization Practices Chikungunya Vaccines Work Group estimated a rate of 82 SAEs per 100,000 doses administered (95% CI: 30 to 180) and a hospitalization rate of 0.68 per 1000 doses administered (from 0.20 to 1.60) in this population.

Resources (cost), acceptability and feasibility

CHIK-LAV is available in Canada through private sale, at an estimated cost of $225^{Footnote 23}. This vaccine may not be covered by private insurance and the traveller may also bear the cost of services from a health care provider for a travel-health consultation and administration of the vaccine. Overall, the cost for an individual is at least moderate while for families, the total cost for all persons eligible who choose to receive the vaccine could be higher.

The schedule for CHIK-LAV consists of one dose prior to travel, CATMAT believes this is likely to be acceptable to the traveller.

Travellers interested in CHIK-LAV would seek a clinic or health care provider with experience in travel medicine, capable of providing an individualized assessment and if required, the vaccine. The process may require one visit for the consultation and another for vaccination, if the vaccine is not readily available. These services may not be readily available in underserviced areas.

Judgement

The evidence on harms from CHIK-LAV exceeded thresholds for a moderate effect size for all critical outcomes identified and ranged from moderate to large effect sizes, across both age groups.

Post-marketing surveillance identified 28 SAEs including three deaths (as of July 11, 2025^{Footnote 3}), mainly in older persons (65 years old or above) with comorbidities who received CHIK-LAV. The chikungunya virus strain used in the vaccine was detected in bodily fluids in some individuals, and the timing of onset of symptoms was generally consistent with the expectation for a vaccine-induced outcome^{Footnote 5}. CATMAT believes it is likely that at least some of the reported SAEs were caused by vaccination. In the balance of benefits against harms of CHIK-LAV for persons 65 years or older, CATMAT believes that most people would place more value on avoiding serious harms associated with vaccination and as a result placed significant weight on the signal of SAEs in persons 65 years or older in our development of recommendations for this age group. We decided to recommend against use of CHIK-LAV in persons 65 years or older, with very low certainty of the evidence. To complement this recommendation, CATMAT also suggests travellers in this population not travel to outbreak areas as the risk of infection can be high and chikungunya infection is more likely to result in severe disease and death in older persons who are not protected. We believe this latter recommendation will be acceptable and feasible for many travellers given that outbreaks are generally short in duration.

Among persons 18 to 64 years old, the benefit of prevention of long-term arthralgia from chikungunya infection exceeded the moderate effect threshold, at all travel durations, for both outbreak transmission levels. The threshold for moderate protection against clinical disease was met for longer trips to a LTO area, and across all trip durations to HTO. Anticipated benefits from vaccination for the prevention of hospitalization and death were notable for HTO setting, where thresholds were met for these outcomes at longer travel duration. When balanced against moderate to large effect size in harms from vaccination, estimated benefit increases with longer trips, travel to an HTO area and/or for persons who could be more likely to suffer from severe chikungunya disease based on their health status. CATMAT recognizes that there are significant uncertainty and variability related to the values and preferences of travellers, as such we chose to make a discretionary recommendation for the use of CHIK-LAV in person aged 18 to 64 years.

In an endemic transmission scenario, estimated benefits from vaccination were trivial for most of the identified critical outcomes across all trip durations, ranging from two weeks up to one year. A moderate level of benefit was estimated only for the prevention of long-term arthralgia associated with chikungunya infection when embarking on long trips. The Committee believes that estimated harms from vaccination, ranging from moderate to large, outweighed the benefits at this transmission level, resulting in a discretionary recommendation against the use of CHIK-LAV in person aged 18 to 64 years who are travelling to endemic areas not known to be experiencing an outbreak.

Estimating benefits and harms in the individual case is affected by knowledge of the risk of chikungunya infection at the destination at the time of travel, which may be difficult to assess or predict. Information about the risk of chikungunya infection will be available through travel health advice posted by the Public Health Agency of Canada on travel.gc.ca for each destination . If there is a "Level 2 Travel Health Notice" specified under the "Health" section of a destination page, this information identifies an area as experiencing an outbreak of chikungunya.

Recommendations for CHIK-LAV

1. CATMAT recommends against use of the chikungunya live attenuated vaccine (IXCHIQ^®) in persons aged 65 years or older.

(Strong recommendation, very low certainty of the evidence)

And

CATMAT suggests persons aged 65 years or older avoid travel to an area identified as experiencing a chikungunya outbreak.

(Discretionary recommendation, moderate certainty of the evidence)

2. For Canadians aged 18 to 64 years who are at high risk of infection (see Remarks), CATMAT suggests considering the chikungunya live attenuated vaccine (CHIK-LAV). Individualized assessment (see Remarks) and discussion between the traveller and their healthcare provider is necessary to assess the suitability of CHIK-LAV vaccination.

(Discretionary recommendation, very low certainty of the evidence)

And

CATMAT suggests against offering chikungunya live attenuated vaccine (CHIK-LAV) for all other Canadians aged 18 to 64 years of age.

(Discretionary recommendation, very low certainty of evidence)

Conclusion and research needs

CHIK-LAV is a reactogenic vaccine that demonstrated high and persistent neutralizing antibody titer (µPRNT₅₀ ≥150) after a single dose in study participants. This surrogate of protection was maintained for up to 4 years after vaccination. The endpoint used was estimated based on the vaccine's ability to prevent viremia in a non-human primate model. Due to the unpredictability of chikungunya outbreaks, vaccine efficacy studies were not conducted. Post-marketing studies are required by international regulators to determine vaccine effectiveness in context of the severity of transmission during outbreaks, and the effect of CHIK-LAV on the prevention of undesirable outcomes of chikungunya infection including severe and long-lasting symptoms of arthralgia, as well as serious outcomes that could result in hospitalization or death.

Among post-marketing reports of SAEs following vaccination with CHIK-LAV to date, many of the SAEs clustered in older persons with a pre-existing health condition. The independent contribution of age and comorbidity to the risk of SAE is unclear as there is a lack of understanding about the biological basis for this problem. Further studies are needed to better understand the occurrence of and biological mechanism for undesirable effects from CHIK-LAV, particular for rare events and the risk in older persons and those with underlying medical conditions.

Additional research is also necessary to investigate the benefits and harms of CHIK-LAV in specific risk groups including immunosuppressed population, pregnant persons and impact on infant health, and in those with underlying conditions including rheumatologic disorders. Results from these studies will be critical for a comprehensive understanding of the benefit and risk of CHIK-LAV.

List of abbreviations

AE

Adverse event

CATMAT

Committee to Advise on Tropical Medicine and Travel

CHIK-LAV

Chikungunya live attenuated vaccine

CI

Confidence interval

CLARs

Chikungunya-like adverse reactions

GPS

Good practice statement

GRADE

Grading of Recommendations, Assessment, Development and Evaluation

HTO

Higher transmission outbreak

LTO

Lower transmission outbreak

NHP

Non-human primates

NSAIDs

Non-steroidal anti-inflammatory drugs

PHAC

Public Health Agency of Canada

RCT

Randomized control trial

SAEs

Serious adverse events

US

United States

VAERS

Vaccine Adverse Effects Reporting System

VE

Vaccine efficacy

WG

Working group

Acknowledgements

This statement was prepared by the CATMAT Chikungunya Working Group: P Lagacé-Wiens (lead), S Schofield (co-lead), I Bogoch, YG Bui, A Khatib, M Libman, T Nguyen, K Plewes, and was approved by CATMAT.

CATMAT gratefully acknowledges the contribution of: M Laplante, S Mehta, N Santesso (GRADE methodologist, McMaster University), and the Public Health Agency of Canada Library.

CATMAT Members: M Libman (Chair), YG Bui (Vice-Chair), K Plewes (Malaria Sub-Committee Chair), I Bogoch, A Khatib, P Lagacé-Wiens, J Lee, and C Yansouni.

Former member: C Greenaway

Liaison representatives: J Pernica (Association of Medical Microbiology and Infectious Disease Canada), K O'Laughlin (US Centers for Disease Control and Prevention), and I Viel-Thériault (Canadian Paediatric Society).

Ex-officio representatives: D Marion (National Defence and the Canadian Armed Forces), S Schofield (National Defence and the Canadian Armed Forces), M Tunis (National Advisory Committee on Immunization [NACI] Secretariat, PHAC) and R Zimmer (Biologic and Radiopharmaceutical Drugs Directorate, Health Canada).

Former ex-officio representative: E Ebert (National Defence and the Canadian Armed Forces)

Conflicts of interest

None declared.

Appendices

Appendix 1. Literature search strategy

Table 4. Sample search strategy and results for research question 1 from Ovid MEDLINE^® 1946 to March 25, 2024

Search number	Search strategy	Results
1	Chikungunya virus/ or Chikungunya Fever/	4594
2	(Chikungunya or chikv).ti,kf.	4578
3	(Chikungunya or chikv).ab. /freq=2	3860
4	or/1-3	5918
5	(english or french).lg.	32949073
6	4 and 5	5746
7	exp animals/	27065891
8	exp animal experimentation/ or exp animal experiment/	10448
9	exp models animal/	647852
10	nonhuman/	0
11	exp vertebrate/ or exp vertebrates/	26305688
12	or/7-11	27067869
13	exp humans/	21859077
14	exp human experimentation/ or exp human experiment/	12687
15	or/13-14	21859736
16	12 not 15	5208761
17	(human* or person* or people* or patient* or worker* or child* or adult* or communit* or travel?er* or tourist*).mp.	24849796
18	(6 not 16) or (6 and 17)	5164
19	exp Disease Outbreaks/ or exp Disease Transmission, Infectious/	307409
20	(pathogenicity or incidence* or outbreak* or infection* or transmission* or prevalen* or spread* or epidem*).tw,kf.	4390695
21	(transmission or epidemiology or pathogenicity).fs.	2454728
22	or/19-21	5635752
23	18 and 22	4501
24	case reports.pt.	2392666
25	23 not 24	4233
26	exp Morbidity/ or exp Mortality/ or exp Hospitalization/	1290560
27	(burden* or morbidit* or hospitaliz* or contact with healthcare or complication* or mortalit* or death* or fatal*).tw,kf.	3584025
28	(mortality or complications).fs.	2820631
29	or/26-28	6167835
30	18 and 29	1564
31	exp risk factors/ or Disease Susceptibility/	1013640
32	(risk* adj5 [increas* or high* or factor*].tw,kf.)	1738841
33	([factor* or risk* or determinant*] adj5 [individual* or community* or household* or environment* or soci* or associat* or transmission* or infection*]).tw,kf.	1257447
34	or/31-33	2846230
35	18 and 34	675
36	25 or 30 or 35	4522
37	(review or meta-analysis).ti,pt.	3685336
38	36 and 37	725
39	travel/ or air travel/ or expeditions/ or tourism/ or exp travel-related illness/ or Travel Medicine/	32266
40	(travel* or touris*).tw,kf.	93635
41	or/39-40	107093
42	36 and 41	427

Appendix 2. Summary of findings tables

Certainty of the evidence assessment

The overall certainty of the evidence for estimated benefits from CHIK-LAV was low (Tables 5 to 7, and 9 to 11). As CHIK-LAV efficacy was not measured directly in clinical trials, seroresponse data was used as a surrogate of protection; the estimated benefits from CHIK-LAV were downgraded by one level for indirectness. Where the 95% confidence interval around the absolute risk reduction suggested a potential for an effect smaller than the threshold for a moderate effect size, the certainty of evidence was downgraded another level for imprecision.

The effect size for adverse events from CHIK-LAV ranged from moderate to large and the overall certainty of the evidence for adverse events was very low (Table 8 and Table 12). There was a general downgrade for indirectness as the phase 3 clinical trial was conducted in healthy individuals who do not fully represent all Canadians travelling to chikungunya-affected areas. The evidence for persons 65 years or older, representing 11% of study participants, was also downgraded. Where applicable, the certainty of evidence was downgraded for imprecision because the sample size was too small to reliably detect rare events and/or because the 95% confidence interval around the estimate suggested a potential for both benefits and harms.

For persons aged 18 to 64 years

Table 5. Estimated benefits of chikungunya live attenuated vaccine in adults aged 18 to 64 years in an endemic transmission area (annual risk of infection 1 per 1,000, 95% CI: 0.8 to 1.4 per 1,000), by travel duration

Benefits of vaccination	Travel duration	Anticipated absolute risk reduction, per 1,000	95% confidence interval for absolute risk reduction	Effect size	Certainty of the evidence (GRADE)	Number needed to immunize
Prevention of clinical chikungunya disease	12 months	0.76	0.60 - 1.08	Trivial	Moderate	1316
	6 months	0.38	0.30 - 0.54	Trivial	Moderate	2632
	3 months	0.19	0.15 - 0.27	Trivial	Moderate	5263
	1 month	0.06	0.05 - 0.09	Trivial	Moderate	15789
	2 weeks	0.03	0.02 - 0.04	Trivial	Moderate	34211
Prevention of long-term (30 or more days) chikungunya associated arthralgia	12 months	0.38	0.30 - 0.54	Large	Moderate	2632
	6 months	0.19	0.15 - 0.27	Moderate	Moderate	5263
	3 months	0.10	0.08 - 0.14	Moderate	Low	10526
	1 month	0.03	0.03 - 0.05	Trivial	Moderate	31579
	2 weeks	0.01	0.01 - 0.02	Trivial	Moderate	68421
Prevention of chikungunya associated hospitalization	12 months	0.002	0.002 - 0.003	Trivial	Moderate	416060
	6 months	0.001	0.001 - 0.002	Trivial	Moderate	832120
	3 months	0.001	0.000 - 0.001	Trivial	Moderate	1664240
	1 month	0.000	0.000 - 0.000	Trivial	Moderate	4992719
	2 weeks	0.000	0.000 - 0.000	Trivial	Moderate	10817558
Prevention of death	12 months	0.0000	0.0000 - 0.0001	Trivial	Moderate	27412281
	6 months	0.0000	0.0000 - 0.0000	Trivial	Moderate	54824561
	3 months	0.0000	0.0000 - 0.0000	Trivial	Moderate	109649123
	1 month	0.0000	0.0000 - 0.0000	Trivial	Moderate	328947368
	2 weeks	0.0000	0.0000 - 0.0000	Trivial	Moderate	712719298
Explanation: Bolded values indicate outcomes which met or exceeded the threshold for a moderate benefit.

Table 6. Estimated benefits of chikungunya live attenuated vaccine in adults aged 18 to 64 years in a low transmission outbreak (annual risk of infection 9 per 1,000, 95% CI: 5 to 14 per 1,000), by travel duration

Benefits of vaccination	Travel duration	Anticipated absolute risk reduction, per 1,000	95% confidence interval for absolute risk reduction	Effect size	Certainty of the evidence (GRADE)	Number needed to immunize
Prevention of clinical chikungunya disease	Annual	6.84	3.64 - 10.84	Large	Moderate	146
	6 months	3.42	1.82 - 5.42	Moderate	Low	292
	3 months	1.71	0.91 - 2.71	Small	Low	585
	1 month	0.57	0.30 - 0.90	Small	Moderate	1754
	2 weeks	0.26	0.14 - 0.42	Trivial	Moderate	3801
Prevention of long-term (30 or more days) chikungunya associated arthralgia	Annual	3.42	1.82 - 5.42	Large	Moderate	292
	6 months	1.71	0.91 - 2.71	Large	Moderate	585
	3 months	0.86	0.46 - 1.36	Large	Moderate	1170
	1 month	0.29	0.15 - 0.45	Large	Moderate	3509
	2 weeks	0.13	0.07 - 0.21	Moderate	Low	7602
Prevention of chikungunya associated hospitalization	Annual	0.02	0.01 - 0.03	Trivial	Moderate	46229
	6 months	0.01	0.01 - 0.02	Trivial	Moderate	92458
	3 months	0.01	0.00 - 0.01	Trivial	Moderate	184916
	1 month	0.00	0.00 - 0.00	Trivial	Moderate	554747
	2 weeks	0.00	0.00 - 0.00	Trivial	Moderate	1201951
Prevention of death	Annual	0.0003	0.0002 - 0.0005	Trivial	Moderate	3045809
	6 months	0.0002	0.0001 - 0.0003	Trivial	Moderate	6091618
	3 months	0.0001	0.0000 - 0.0001	Trivial	Moderate	12183236
	1 month	0.0000	0.0000 - 0.0000	Trivial	Moderate	36549708
	2 weeks	0.0000	0.0000 - 0.0000	Trivial	Moderate	79191033
Explanation : Bolded values indicate outcomes which met or exceeded the threshold for a moderate benefit.

Table 7. Estimated benefits of chikungunya live attenuated vaccine in adults aged 18 to 64 years in a high transmission outbreak (annual risk of infection 330 per 1,000, 95% CI: 301 to 360 per 1,000), by travel duration

Benefits of vaccination	Travel duration	Anticipated absolute risk reduction, per 1,000	95% confidence interval for absolute risk reduction	Effect size	Certainty of the evidence (GRADE)	Number needed to immunize
Prevention of clinical chikungunya disease	Annual	250.80	227.60 - 274.80	Large	Moderate	4
	6 months	125.40	113.80 - 137.40	Large	Moderate	8
	3 months	62.70	56.90 - 68.70	Large	Moderate	16
	1 month	20.90	18.97 - 22.90	Large	Moderate	48
	2 weeks	9.65	8.75 - 10.57	Large	Moderate	104
Prevention of long-term (30 or more days) chikungunya associated arthralgia	Annual	125.40	113.80 - 137.40	Large	Moderate	8
	6 months	62.70	56.90 - 68.70	Large	Moderate	16
	3 months	31.35	28.45 - 34.35	Large	Moderate	32
	1 month	10.45	9.48 - 11.45	Large	Moderate	96
	2 weeks	4.82	4.38 - 5.28	Large	Moderate	207
Prevention of chikungunya associated hospitalization	Annual	0.79	0.72 - 0.87	Large	Moderate	1261
	6 months	0.40	0.36 - 0.43	Large	Moderate	2522
	3 months	0.20	0.18 - 0.22	Moderate	Moderate	5043
	1 month	0.07	0.06 - 0.07	Small	Moderate	15129
	2 weeks	0.03	0.03 - 0.03	Trivial	Moderate	32780
Prevention of death	Annual	0.0120	0.011 - 0.013	Moderate	Moderate	83068
	6 months	0.0060	0.005 - 0.007	Small	Moderate	166135
	3 months	0.0030	0.003 - 0.003	Trivial	Moderate	332270
	1 month	0.0010	0.001 - 0.001	Trivial	Moderate	996810
	2 weeks	0.0005	0.000 - 0.001	Trivial	Moderate	2159755
Explanation: Bolded values indicate outcomes which met or exceeded the threshold for a moderate benefit.

Table 8. Estimated harms of chikungunya live attenuated vaccine in adults aged 18 to 64 years, compared to no vaccination

Harms from vaccination	Anticipated absolute risk difference, per 1,000	95% confidence interval for absolute risk difference	Effect size	Certainty of the evidence (GRADE)
Severe systemic AE of short duration	22 more	16 more to 28 more	Moderate	Moderate
Chikungunya-like adverse reactions (CLARs)	112 more	97 more to 125 more	Moderate	Very low
New/worsening arthritis/osteoarthritis	1 more	6 fewer to 5 more	Large	Very low
Serious adverse events (SAEs)	0.4 more	4 fewer to 2 more	Large	Very low
Explanation: Bolded values indicate outcomes which met or exceeded the threshold for a moderate harm.

For persons aged 65 years or older

Table 9. Estimated benefits of chikungunya live attenuated vaccine in adults 65 years or older in an endemic transmission area (annual risk of infection 1 per 1,000, 95% CI: 0.8 to 1.4 per 1,000), by travel duration

Benefits of vaccination	Travel duration	Anticipated absolute risk reduction, per 1,000	95% confidence interval for absolute risk reduction	Effect size	Certainty of the evidence (GRADE)	Number needed to immunize
Clinical chikungunya disease	Annual	0.76	0.60 - 1.08	Trivial	Moderate	1316
	6 months	0.38	0.30 - 0.54	Trivial	Moderate	2632
	3 months	0.19	0.15 - 0.27	Trivial	Moderate	5263
	1 month	0.06	0.05 - 0.09	Trivial	Moderate	15789
	2 weeks	0.03	0.02 - 0.04	Trivial	Moderate	34211
Long-term (30 or more days) chikungunya associated arthralgia	Annual	0.38	0.30 - 0.54	Large	Moderate	2632
	6 months	0.19	0.15 - 0.27	Moderate	Moderate	5263
	3 months	0.10	0.08 - 0.14	Moderate	Low	10526
	1 month	0.03	0.03 - 0.05	Trivial	Moderate	31579
	2 weeks	0.01	0.01 - 0.02	Trivial	Moderate	68421
Chikungunya associated hospitalization	Annual	0.016	0.013 - 0.023	Trivial	Moderate	61920
	6 months	0.008	0.006 - 0.011	Trivial	Moderate	123839
	3 months	0.004	0.003 - 0.006	Trivial	Moderate	247678
	1 month	0.001	0.001 - 0.002	Trivial	Moderate	743034
	2 weeks	0.001	0.000 - 0.001	Trivial	Moderate	1609907
Death	Annual	0.0009	0.0007 - 0.0012	Trivial	Moderate	1156738
	6 months	0.0004	0.0003 - 0.0006	Trivial	Moderate	2313476
	3 months	0.0002	0.0002 - 0.0003	Trivial	Moderate	4626952
	1 month	0.0001	0.0001 - 0.0001	Trivial	Moderate	13880856
	2 weeks	0.0000	0.0000 - 0.0000	Trivial	Moderate	30075188
Explanation: Bolded values indicate outcomes which met or exceeded the threshold for a moderate benefit.

Table 10. Estimated benefits of chikungunya live attenuated vaccine in adults 65 years or older in a low transmission outbreak (annual risk of infection 9 per 1,000, 95% CI: 5 to 14 per 1,000), by travel duration

Benefits of vaccination	Travel duration	Anticipated absolute risk reduction, per 1,000	95% confidence interval for absolute risk reduction	Effect size	Certainty of the evidence (GRADE)	Number needed to immunize
Clinical chikungunya disease	12 months	6.84	3.64 - 10.84	Large	Moderate	146
	6 months	3.42	1.82 - 5.42	Moderate	Low	292
	3 months	1.71	0.91 - 2.71	Small	Low	585
	1 month	0.57	0.30 - 0.90	Small	Moderate	1754
	2 weeks	0.26	0.14 - 0.42	Trivial	Moderate	3801
Long-term (30 or more days) chikungunya associated arthralgia	12 months	3.42	1.82 - 5.42	Large	Moderate	292
	6 months	1.71	0.91 - 2.71	Large	Moderate	585
	3 months	0.86	0.46 - 1.36	Large	Moderate	1170
	1 month	0.29	0.15 - 0.45	Large	Moderate	3509
	2 weeks	0.13	0.07 - 0.21	Moderate	Low	7602
Chikungunya associated hospitalization	12 months	0.15	0.08 - 0.23	Moderate	Low	6880
	6 months	0.07	0.04 - 0.12	Small	Low	13760
	3 months	0.04	0.02 - 0.06	Trivial	Moderate	27520
	1 month	0.01	0.01 - 0.02	Trivial	Moderate	82559
	2 weeks	0.01	0.00 - 0.01	Trivial	Moderate	178879
Death	12 months	0.0078	0.004 - 0.012	Small	Low	128526
	6 months	0.0039	0.002 - 0.006	Trivial	Moderate	257053
	3 months	0.0019	0.001 - 0.003	Trivial	Moderate	514106
	1 month	0.0006	0.000 - 0.001	Trivial	Moderate	1542317
	2 weeks	0.0003	0.000 - 0.000	Trivial	Moderate	3341688
Explanation: Bolded values indicate outcomes which met or exceeded the threshold for a moderate benefit.

Table 11. Estimated benefits of chikungunya live attenuated vaccine in adults 65 years or older in a high transmission outbreak (annual risk of infection 330 per 1,000, 95% CI: 301 to 360 per 1,000), by travel duration

Benefits of vaccination	Travel duration	Anticipated absolute risk reduction, per 1,000	95% confidence interval for absolute risk reduction	Effect size	Certainty of the evidence (GRADE)	Number needed to immunize
Clinical chikungunya disease	12 months	250.8	227.6 - 274.8	Large	Moderate	4
	6 months	125.4	113.8 - 137.4	Large	Moderate	8
	3 months	62.7	56.9 - 68.7	Large	Moderate	16
	1 month	20.9	19.0 - 22.9	Large	Moderate	48
	2 weeks	9.6	8.8 - 10.6	Large	Moderate	104
Long-term (30 or more days) chikungunya associated arthralgia	12 months	125.4	113.8 - 137.4	Large	Moderate	8
	6 months	62.7	56.9 - 68.7	Large	Moderate	16
	3 months	31.4	28.5 - 34.4	Large	Moderate	32
	1 month	10.5	9.5 - 11.5	Large	Moderate	96
	2 weeks	4.8	4.4 - 5.3	Large	Moderate	207
Chikungunya associated hospitalization	12 months	5.33	4.84 - 5.84	Large	Moderate	188
	6 months	2.13	2.45 - 2.95	Large	Moderate	469
	3 months	1.07	1.22 - 1.47	Large	Moderate	938
	1 month	0.36	0.41 - 0.49	Large	Moderate	2815
	2 weeks	0.16	0.19 - 0.23	Moderate	Moderate	6098
Death	12 months	0.285	0.259 - 0.313	Large	Moderate	3505
	6 months	0.143	0.129 - 0.156	Large	Moderate	7011
	3 months	0.071	0.065 - 0.078	Large	Moderate	14021
	1 month	0.024	0.022 - 0.026	Moderate	Moderate	42063
	2 weeks	0.011	0.010 - 0.012	Moderate	Moderate	91137
Explanation: Bolded values indicate outcomes which met or exceeded the threshold for a moderate benefit.

Table 12. Estimated harms of chikungunya live attenuated vaccine in adults 65 years or older, compared to no vaccination

Harms from vaccination	Anticipated absolute risk difference, per 1,000	95% confidence interval for absolute risk difference	Effect size	Certainty of the evidence (GRADE)
Severe systemic AE of short duration	9 more	24 fewer to 25 more	Moderate	Low
Chikungunya-like adverse reactions (CLARs)	107 more	64 more to 144 more	Moderate	Very low
New/worsening arthritis/osteoarthritis	9 more	24 fewer to 25 more	Large	Very low
Serious adverse events (SAEs)	6 more	29 fewer to 16 more	Large	Very low
Explanation: Bolded values indicate outcomes which met or exceeded the threshold for a moderate harm.

Appendix 3. Evidence to decision table

Question: Should Canadians travelling to chikungunya affected areas be recommended to receive vaccination against this disease? If so, who should receive it and under what circumstances?

Population: Canadians aged 18 years and older travelling to chikungunya affected areas.

Intervention: Vaccination with the chikungunya live attenuated vaccine (CHIK-LAV), IXCHIQ^® , according to recommended dose.

Comparison: No vaccination

Main outcomes:

• Benefits: Prevention of clinical chikungunya disease, long-term arthralgia from chikungunya infection, hospitalization, and death.
• Harms: Severe systemic adverse events of short duration, new or worsening arthritis or osteoarthritis symptoms, serious adverse events, chikungunya-like adverse reactions (CLARs).

Setting: International travel

Perspective: Individual

Background: Chikungunya disease is endemic in tropical and subtropical regions worldwide. The chikungunya virus is transmitted through a bite of certain mosquitoes, generally Aedes aegypti or Aedes albopictus^{Footnote 6}. Symptoms include sudden onset of fever accompanied by severe and often persistent (months to years) joint pain. Outbreaks of chikungunya are often sporadic and short-lived, with high attack rates. Travellers are at greatest risk of infection and disease when travelling to an area(s) suffering a high transmission outbreak^{Footnote 7}.

The chikungunya live attenuated vaccine (CHIK-LAV), IXCHIQ^®, is licensed for use in Canada for the prevention of chikungunya in persons 18 years or older.

Conflict of interests: None

Table 13. Assessment of evidence on CHIK-LAV

Domain	Judgement	Research evidence and additional considerations
Problem: Is the problem a priority?	No Probably no Probably yes Yes Varies Don't know	CHIK-LAV is authorized for use in Canada and recommendations are needed to guide healthcare providers in advising their patients. The risk of chikungunya infection is low for the large majority of Canadian travellers, but can be relatively high for those who travel to an area suffering a high transmission outbreak. Acute chikungunya illness can be temporarily incapacitating, and for about 50% of patients progresses to long-lasting symptoms that can include potentially chronic polyarthralgia/arthritis. Although relatively rare, serious chikungunya disease and death occurs especially in vulnerable populations, e.g. the very young or old.
Desirable effects: How substantial are the desirable anticipated effects?	Trivial Small Moderate Large Varies Don't know	Immunogenicity: Data from a single phase 3 RCT demonstrated high and persistent seroresponse rate, 98.9% (95% confidence interval (CI): 96.7 to 99.8%) at 29 days after vaccination with a single dose of CHIK-LAVFootnote 1. Similar seroresponse rates were observed between persons 18 to 64 years old (98.6% (95%CI: 95.8 to 99.7%) and persons 65 years or older 100% (95% CI: 93.9 to 100.0%). Neutralizing antibody response level considered to be protective was maintained at 2 years after vaccination in 96.8% (95%CI: 94.3 to 98.5%) of 316 participants Footnote 24 and at 4 years after vaccination in 95.0% of 254 participantsFootnote 20. Seroreponse levels were similar between persons 18 to 64 years old and those 65 years or older. Vaccine efficacy (VE): VE was not directly measured. However, based on the totality of evidence, CATMAT judged that VE efficacy CHIK-LAV is likely high and used 95% efficacy across ages to estimate benefit. Estimated absolute benefit varied by age group and across outcomes, infection rates and travel durations (Appendix 2). For travel to an area where chikungunya disease endemic, the estimated absolute benefit of chikungunya vaccination is trivial for the prevention of clinical disease, hospitalization and death, across all trip durations up to 1 year. For long-term arthralgia, the absolute risk reduction varies from trivial for a two-week trip (0.01 fewer per 1,000, 95% CI: 0.01 to 0.02, low certainty evidence) to large for a year long trip (0.38 fewer per 1,000, 95% CI: 0.30 to 0.54). Persons aged 18 to 64: The estimated absolute benefit for prevention of long-term arthralgia ranged from moderate for a trip of 2 weeks to an area with a lower transmission outbreak (0.1 fewer cases per 1,000 [95% CI: 0.07 to 0.21 fewer]) to large (125.4 fewer per 1,000 [95% CI: 113.8 to 137.4 fewer]) for a 1-year trip to an area with a higher transmission outbreak. For clinical chikungunya, the anticipated benefits ranged from trivial to large depending on duration of travel and outbreak setting. Estimated absolute risk reduction for hospitalization and death were trivial across all travel durations to a lower transmission outbreak but were moderate with longer travel durations to a higher transmission outbreak. Persons 65 years or older: Estimated absolute benefit for prevention of long-term arthralgia and clinical chikungunya are the same as for persons aged 18 to 64 years. The estimated benefit for prevention of hospitalization and death were generally trivial to small for travel to a low transmission outbreak. For a higher transmission outbreak, estimated benefit ranged from moderate (hospitalization: 1.6 fewer per 10,000 [95% CI: 1.9 to 2.3], death: 1.1 fewer per 100,000 [95% CI:1.0 to 1.2] to large depending on travel duration).
Undesirable effects: How substantial are the undesirable anticipated effects?	Trivial Small Moderate Large Varies Don't know	Evidence for undesirable effects were derived from the phase 3 RCT, the US Food and Drugs Administration (FDA) clinical review memo, as well as information shared by the manufacturer. Post-marketing surveillance information was used to supplement this evidence. Estimated absolute undesirable effects associated with receipt of CHIK-LAV ranged from moderate to large (Appendix 2 – Table 8 and Table 12). Severe systemic adverse reactions of short duration (10 days or fewer) were common among vaccinees (2.1%) compared to placebo (0.1%) (20 more per 1000, 95% CI: 13 more to 26 more). Expressed by age, estimates were 22 more per 1000 (95% CI: 16 more to 28 more) for persons aged 18 to 64 and 9 more per 1000 (95% CI: 24 fewer to 25 more) for persons aged 65 and older. Chikungunya-like adverse reactions (CLARs) were observed more frequently among vaccine recipients (11.7%) compared to placebo (0.6%); the anticipated risk difference was 111 more per 1000 (95% CI: 47 more to 256 more) without an age-based difference. Reports of new or worsening arthritis of osteoarthritis symptoms did not differ greatly between the vaccinee recipients (0.6%) and placebo (0.4%) (2 more per 1000, 95% CI: 5 fewer to 6 more). The estimates by age were 1 more per 1,000 (95% CI: 6 fewer to 5 more) for persons 18 to 64 years old and 9 more per 1,000 (95% CI: 24 fewer to 25 more) for persons 65 years or older. There were two serious adverse events (SAEs) determined by the manufacturer to be related to CHIK-LAV among study participants. The Committee reviewed and considered another SAE event to be possibly related to vaccination. One of these events occurred in persons aged 18 to 64 years (absolute risk difference of 0.4 more per 1000), while the other two were in persons 65 years and older (absolute risk difference of 6 more per 1000). Additional considerations: Post-marketing surveillance identified 28 cases of serious adverse events following the administration of CHIK-LAV with most of these occurring in persons 65 years or older and in persons with a pre-existing health conditionFootnote 3. The independent contribution of age and comorbidity to the risk of SAE is unclear as there is a lack of understanding about the biological basis for this problem. Further studies are needed to better understand the occurrence of and biological mechanism for undesirable effects from CHIK-LAV, particular for rare events and occurrence of these in older persons.
Certainty of evidence: What is the overall certainty of the evidence of effects?	Very low Low Moderate High No included studies	The overall certainty of evidence was very low.
Importance of outcomes to/in/for/in relation to affected population: Is there important uncertainty about or variability in how much travellers value the main outcomes?	Important uncertainty or variability Possibly important uncertainty or variability Probably no important uncertainty or variability No important uncertainty or variability	The Committee identified the following outcomes as critical to decision making: Benefits (prevention of): clinical chikungunya disease, long-term arthralgia from chikungunya infection, hospitalization, and death. Harms: severe systemic adverse events of short duration, new or worsening arthritis or osteoarthritis symptoms, serious adverse events, chikungunya-like adverse reactions (CLARs). There is limited specific evidence related to how travellers value the identified critical outcomes. In a 2022 US Centers for Disease Prevention and Control surveyFootnote 25, risk of disease and of long-term joint pain following infection were reported as considerations that would influence decision making related to chikungunya vaccine. From a harms perspective, risk of potential side effects and as well costs were identified as factors that impacted reported willingness to receive vaccine. Based on this evidence, but also on the collective experience of the committee, CATMAT believes that most people would value prevention of chikungunya associated long-term arthralgia, hospitalization and death, and also would value avoidance of vaccine-associated adverse effects.
Balance of effects: Does the balance between desirable and undesirable effects favour the intervention (CHIK-LAV) or the comparison (No vaccination)?	Favours the comparison (No vaccination) Probably favours the comparison (No vaccination) Does not favour either the intervention (CHIK-LAV) or the comparison (No vaccination) Probably favours the intervention (CHIK-LAV) Favours the intervention (CHIK-LAV) Varies Don't know	The balance between desirable and undesirable effects varies by age, travel duration and risk of chikungunya infection (Appendix 2). Estimates of undesirable effects exceeded the thresholds for moderate effect size. For travel to an endemic area, the estimated benefits are trivial across most trip durations while estimated harms exceeded the threshold for a moderate effect size. The balance of effects at this transmission level favours the comparison (no vaccination). For travel to areas experiencing outbreaks: Estimated benefits for prevention of long-term arthralgia exceeded the moderate effect threshold at all travel durations and for low and high transmission outbreaks. Estimated benefits were overall greater for a high transmission outbreak, with thresholds for prevention of hospitalization and death being met at longer travel durations for younger persons, and at all travel durations for persons 65 years and older. In persons 18 to 64 years old, the balance of effects probably favours the intervention (CHIK-LAV) for all travel durations to a destination experiencing high transmission outbreak. In persons 65 years and older, the balance of effects is notably impacted by the estimated likelihood of SAE (from clinical evidence), supported by the post-marketing surveillance systems that have identified an SAE safety signal in older persons. CATMAT placed significant weight on the emergent evidence from post-marketing surveillance that suggest an important and related vaccine-related SAE signal in this age group. Hence, the evidence is judged to favour the comparison (no vaccination) based on current evidence and uncertainty. CATMAT also recognizes this information is evolving and will revisit recommendations if new evidence/analyses suggest these recommendations should be revisited. Additional considerations: Discussions between the patient and their healthcare provider are necessary to properly assess the individual's risk based on the likelihood of exposure, personal health risk factors and values and preferences.
Resource considerations: How large are the resource requirements (costs) to the individual?	Large costs Moderate costs Small costs Negligible costs Varies Don't know	In November 2024, when the vaccine was first available on the market in Canada, the cost of CHIK-LAV was estimated to be $225Footnote 23, with the possibility of additional costs for associated health care services. These costs are not covered by the public system and may not be covered by private health insurance. For families, the total cost may exceed that for the individual if multiple persons are eligible for and choose to receive vaccine.
Equity: What would be the impact on health equity?		Not applicable to interventions assessed at the individual level.
Acceptability: Is the intervention acceptable to key stakeholders?	No Probably no Probably yes Yes Varies Don't know	The vaccination schedule for CHIK-LAV consists of one dose prior to travel, as such will likely not require multiple visits to a health care provider. This option to receive CHIK-LAV is likely acceptable to younger adult travellers for whom it is a consideration. CATMAT believes most older persons (who are not recommended to receive vaccine) would accept a recommendation that suggests delaying travel to a chikungunya outbreak area given the generally short duration of outbreak events combined with their (usual) geographic scarcity.
Feasibility: Is the intervention feasible to implement for the individual?	No Probably no Probably yes Yes Varies Don't know	Travellers seeking vaccination would be required to seek healthcare provider and/or a clinic capable of providing the vaccine and may require more than one visit (consultation and vaccination if vaccine is not readily available). This may not be feasible in some underservices areas. The cost of the vaccine also may not be feasible for all travellers. CATMAT believes it is feasible for most older persons (who are not recommended to receive vaccine) to delay travel to a chikungunya outbreak area given the generally short duration of events combined with their (usual) geographic scarcity.

Table 14. Strength of CATMAT recommendations

Strength of recommendation based on factors not isolated to strength of evidence	Strong	Discretionary
Wording	"should/ should not" or "CATMAT recommends"	"clinicians may/ may not" or "CATMAT suggests"
Rationale	Known/anticipated advantages outweigh known/anticipated disadvantages("should"), or Known/anticipated disadvantages outweigh known/anticipated advantages ("should not")	Known/anticipated advantages are closely balanced with known/anticipated disadvantages, or uncertainty in the evidence of advantages and disadvantages exists
Implication	A strong recommendation applies to most travellers and should be followed unless a clear and compelling rationale for an alternative approach is present.	A discretionary recommendation may/may not be offered for some travellers in some circumstances. Alternative approaches may be reasonable.

Appendix 4. Assessment for applicability of good practice statement (GPS)

Table 15. Assessment of applicability of good practice statement for personal protective measures

Items to complete	Supporting information	Verification
Population and intervention components are clear.	Not applicable	Yes
Message is really necessary in regard to actual health care practice.	Personal protective measures against insect bites are an important tool to prevent exposure to vectors. Adherence to their use is often suboptimal.	Yes
Implementing the GPS results in a large net positive consequence.	Yes, reduction in exposure to vectors will reduce exposure to the pathogens they carry.	Yes
Collecting and summarizing the evidence is a poor use of a guideline panel's limited time, energy or resources. The opportunity cost of collecting and summarizing the evidence is large and can be avoided.	Yes, this recommendation is about advising travellers to protect themselves.	Yes
There is a well-documented clear and explicit rationale connecting the indirect evidence.	Yes, reducing exposure to vectors is reasonably expected to reduce risk of infection.	Yes
Clear and actionable	Not applicable	Yes

Final judgement: Development of GPS is appropriate

References