Recommendations on use of QDENGA (dengue vaccine) in jurisdictions where it is authorized for travellers

Published: May 2025

On this page

• Preamble
• Key points for the health care provider
• Recommendations
  • Documentation of previously confirmed dengue infection
  • Individual-based exposure and values and preferences assessment
• Background
  • Clinical features
  • Epidemiology in travellers
  • Dengue diagnosis and pre-vaccination screening tests
• QDENGA
• Methods
• Results
• Conclusions and research needs
• Acknowledgements
• Conflicts of interest
• Appendix 1: German Standing Committee on Vaccination (STIKO) Grading of Recommendations, Assessment, Development and Evaluation (GRADE) summary of findings tables
• Appendix 2: Evidence to decision framework
• Appendix 3: Assessment for applicability of good practice statement
• 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 health care provider

• Dengue is caused by a mosquito-transmitted flavivirus. It is a perennial risk through much of the tropical and sub-tropical world, with recurrent and intensifying epidemics that may increase the likelihood of travel-associated infection.
• Dengue is a relatively common cause of mild or moderate febrile illness in travellers. Severe or complicated disease among travellers is rare.
• There are no authorized dengue vaccines available in Canada.
• A dengue vaccine, QDENGA, is authorized by the European Medicines Agency (EMA) including for use by travellers to endemic areas^{Footnote 1}. It also is authorized in several dengue endemic countries.
• Canadians visiting countries where QDENGA is authorized may have access to this vaccine and could receive recommendations to be vaccinated.

Recommendations

1. CATMAT recommends against vaccination with QDENGA for Canadian travellers who do not have documentation of laboratory confirmed prior dengue infection.

(Strong recommendation, very low certainty evidence for increased risk of severe disease in seronegative vaccine recipients)

Remarks:

• QDENGA has not been authorized in Canada, and hence a conservative approach to its use is warranted.

Rationale:

• Cumulative vaccine efficacy at three years against virologically confirmed dengue among vaccinees seronegative at baseline was 0.54 (95% confidence interval [CI] 0.42 to 0.64, low certainty evidence).
• Increased risk of severe dengue among vaccinated persons who were seronegative at baseline (relative risk [RR] = 2.47; 95% CI 0.12 to 51.36) cannot be ruled out (very low certainty evidence).
• QDENGA effectiveness was evaluated in dengue-endemic settings, i.e. where recurrent exposure to mosquito-transmitted virus might help sustain protective immunity. Effectiveness has not been specifically assessed for persons travelling to endemic areas, i.e. those who reside in non-endemic regions such as Canada, and for whom recurrent exposures and "natural" immunologic boosting is unlikely^{Footnote 2}.
• CATMAT placed significant weight on the absence of definitive evidence to rule out the possibility of increased harms among seronegative vaccine recipients. Therefore, despite very low to low certainty in estimates, CATMAT strongly recommends against vaccination for persons whose serostatus is unknown or negative.
• Additional evidence may improve certainty or yield different effect estimates, in which case this recommendation will be revisited.

2. Vaccination with a complete primary series of QDENGA may be considered for Canadian travellers previously infected with dengue (laboratory confirmed).

(Discretionary recommendation, low to very low certainty evidence)

Remarks:

• QDENGA has not been directly evaluated for safety and effectiveness among travellers who live in non-endemic areas or in adults over 60 years of age or children less than four years of age.
• Travellers estimated to be at relatively higher risk for dengue infection based on travel destination, duration and individual level risk factors are more likely to benefit from vaccination with QDENGA.
• Discussions between the traveller and their healthcare provider are necessary to properly assess the individual's risk based on the likelihood of exposure and personal health risk factors (see section Individual-based dengue exposure and values and preferences assessment). The consultation should also include discussion of anticipated benefits and harms, as well as other factors including resources required (time, cost), accessibility and complementary strategies to vaccination to help the traveller reach an informed decision that aligns with their values and preferences.
• If a traveller indicates a desire to receive QDENGA vaccination in a country where it is authorized, they should receive the full series (two doses over three months) before travel to an endemic area.

Rationale:

• Cumulative vaccine efficacy at three years against virologically confirmed dengue among vaccinees seropositive at baseline was 0.65 (95% CI 0.59 to 0.70, low certainty evidence).
• In this population, vaccination may offer protection against severe disease associated with subsequent secondary infection by another serotype (RR = 0.1; 95% CI 0.01 to 0.86) (very low certainty evidence).
• Data to allow a fulsome evaluation of the safety and effectiveness of a partial vaccine series among travellers is not available.
• The discretionary recommendation reflects:
  • anticipated differences in patient values and preferences related to vaccination with QDENGA;
  • the committee's judgement that adhering to a two-dose schedule at a 3-month interval would not be feasible for many travellers; and,
  • the committee's judgement that effective screening for previous infection would not be feasible for many travellers.

3. Clinicians should NOT request dengue serology to screen travellers for previous exposure to dengue virus to assess suitability for vaccination (good practice statement).

This reflects the limited testing capacity in Canada, the potential for cross reactivity with other flaviviruses, the expected low true seropositivity likelihood for most travellers, the cost of testing which may be borne by the traveller and the overall low risk for severe dengue among travellers.

4. Clinicians should advise all travellers to dengue-endemic areas to adhere to 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 dengue 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 envelope 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.

Documentation of previously confirmed dengue infection

Travellers should only be considered to have had dengue virus infection if they can provide a laboratory report confirming this. There are no time limits on when a previous infection was documented. Laboratory reports should specify the following:

• the name of the individual tested and an appropriate personal identifier;
• the date;
• the type of test used to make the diagnosis;
• the result of the test, and
• the address/location of the laboratory that performed the test.

CATMAT does not consider clinical diagnosis by a healthcare provider in the absence of confirmatory testing (see Table 1 for testing information) sufficient to validate infection with dengue for the purpose of following the vaccination recommendations made herein.

CATMAT recommends against screening individuals for dengue infection for the purpose of informing decision-making related to use of QDENGA. This reflects the potential for cross reactivity, the expected low true seropositivity likelihood for most travellers, the limited testing capacity in Canada, the cost of testing and the overall low risk for severe dengue among travellers.

Individual-based dengue exposure and values and preferences assessment

Travellers should consult with their healthcare provider prior to travel for an individualized assessment of their risk of exposure to dengue and to discuss travel health interventions aligned with their values and preferences.

Exposure assessment

Evaluate information related to burden of disease at the risk destination(s)

• Dengue virus transmission can show significant spatial and temporal variability.
  • Where available, individual country/location information can be reviewed to estimate current level of transmission. If such is not readily available, review the areas with risk of dengue from the U.S. Centers for Disease Control and Prevention. In areas characterized as suffering frequent or continuous dengue risk, transmission can be assumed to be relatively high.

Assess duration of travel or residence and likelihood of future travel to areas at risk/potential risk for dengue transmission/outbreaks

• Cumulative duration of potential exposure (during single or multiple trips) should be considered, as longer exposure times should be associated with increased risk of infection. In general, vaccination is not indicated for relatively short duration travel, e.g., a month or less in the aggregate (over a three-year period).

Discuss likelihood of exposure to Aedes mosquitoes and likelihood of adherence to prevention measures

• The main mosquito vector of dengue is Aedes aegypti. This species often bites: indoors; in urban areas; and, during the day.
• Staying in mosquito-protected indoor settings (e.g., houses or buildings with protected entry points, well maintained screening) should reduce exposure risk.
  • Where mosquitoes can't be excluded indoors, consider using insect repellents to reduce risk of exposure when inside.
• Regular use of bite protection measures like repellents will reduce the burden of bites received from dengue mosquitoes.

Values and preferences

Explore/Consider traveller values and preferences

• Travellers likely have differing values and preferences related to dengue and its prevention. This includes risk tolerance for the possibility of an adverse event after vaccination and for dengue-related disease.
• Assess if a traveller is likely to be able to receive a full series (two doses over three months) of QDENGA before travel to an endemic area.

Background

Dengue is a common arboviral infection in tropical and subtropical areas of the world^{Footnote 3}. It's caused by dengue viruses, of which there are four distinct serotypes: DENV-1 through DENV-4. Dengue tends to be most prevalent in urban environments, where the principal vector (Aedes aegypti) makes use of human associated habitats and humans to live and feed, respectively.

Worldwide, the burden of dengue has been estimated as about 400 million infections, 100 million symptomatic cases and 40,000 deaths annually^{Footnote 4}. Among travellers, dengue infection is a relatively common cause of febrile illness. Severe disease probably occurs in 1% or less of diagnosed cases among travellers^{Footnote 5Footnote 6}.

Currently, prevention of travel-associated dengue relies on reducing exposure to mosquitoes. This means use of repellents, staying in mosquito protected accommodations and other individual level interventions (see CATMAT statement measures to prevent arthropod bites). Additionally, mosquito control measures undertaken by local authorities, which recently have started to include the release of genetically modified mosquitoes, can reduce risk.

Over the last several years, two dengue vaccines have been licensed for use in endemic areas. Neither of these vaccines have been licensed/authorized for use in Canada.

The initial dengue vaccine to become commercially available, Dengvaxia, is not intended for general use by travellers. This vaccine was recommended "for children aged 9–16 having evidence of a previous dengue infection and living in areas where dengue is endemic…" by the United States (US) Advisory Committee on Immunization Practices^{Footnote 7}. Since June 2024, Dengvaxia is no longer available in the US due to discontinuation of production by the manufacturer^{Footnote 8}.

More recently QDENGA, a tetravalent live-attenuated dengue vaccine, has been authorized by several regulatory authorities, including the European Medicines Authority (EMA)^{Footnote 1}. QDENGA is not authorized for use in Canada, nor in the United States. However, the EMA authorization includes travellers as a potential use group as does recent World Health Organization guidance^{Footnote 9Footnote 10}. It is thus possible that Canadian travellers or expatriates could receive the vaccine in anticipation of future travel-related exposures. In view of this possibility, CATMAT developed the advice contained herein, with a target audience of health care providers who provide advice to Canadian travellers.

Clinical features

Most dengue infections are asymptomatic, but for those who develop symptoms the incubation period is usually 4 to 10 days. The illness itself is non-specific with flu-like symptoms that last between about 2 and 7 days. High-grade fever usually occurs alongside symptoms such as headache, nausea and vomiting, swollen glands, joint, bone or muscle pains, rash, and pain^{Footnote 3}.

Around the time of defervescence, if the patient does not feel better and symptoms do not improve, the clinical course may proceed to a more severe, life-threatening stage of dengue^{Footnote 11}. Special attention should be given to a set of clinical warning signs indicative of possible progression to severe dengue: a sharp drop in body temperature accompanied by symptoms such as intense abdominal pain, persistent vomiting, dizziness or drowsiness, mucosal bleed, or change in mental state. Most warnings signs are an indication of an increase in capillary permeability, as such immediate inpatient management is necessary to initiate intensive support therapy. With early recognition and proper medical care, serious outcomes, including death can usually be averted. Table 2 provides information to classify dengue, with symptoms for each category of dengue disease.

In a person who has already experienced primary infection, severe dengue can occur following a secondary infection by another serotype of this virus. The relative risk for severe disease is higher for a secondary infection than for a primary or tertiary one, possibly by a factor of approximately two^{Footnote 13}. The risk of severe dengue also varies depending on a variety of other factors such as age of host, individual immune responses and genetic factors, interval between primary and secondary infection, history of exposure to other flavivirus, season and duration of travel, and transmission intensity at the destination country^{Footnote 6}.

There is evidence from Dengvaxia trials and post-marketing surveillance that infection in a dengue-naïve person who fails to seroconvert to all serotypes after vaccination can also lead to a higher risk of severe dengue. Presently, there is insufficient evidence to rule this out as a possibility with QDENGA.

Epidemiology in travellers

Dengue infection is relatively common among travellers, for example serosurveys of patients returning from endemic areas suggest infection rates from about 1% to < 10%. Most of these infections are asymptomatic. Severe dengue is relatively uncommon among travellers, and dengue-associated deaths are rare^{Footnote 5Footnote 6}. For example, over the period of 2010-2021, 7,528 probable travel-associated cases of dengue were reported in the United States. Of these, 88 cases were reported as severe dengue (1.1%) and 19 deaths occurred (0.25%)^{Footnote 14}. Expressed against travel volume (by air) to endemic areas^{Footnote 15}, the overall burden of reported disease ranged from approximately 20 to 40 symptomatic cases per million trips, with modest differences in estimates between regions, e.g., from about 20 events per million trips for Asia and the Caribbean to about 30 events per million trips for Central America^{Footnote 14}. Using the above cited values for reported cases set against travel volumes^{Footnote 15}, the estimated risk of death from dengue is 1 per 13.2 million trips to endemic areas.

Dengue diagnosis and pre-vaccination screening tests

Dengue diagnosis relies on a combination of clinical and laboratory findings set against a history of recent travel to an area where the disease is present. Due to the variable presentation of the infection, no clinical criteria can reliably diagnose dengue or distinguish it from other febrile illnesses affecting travellers, however the presence of fever in a patient returning from an endemic area in the past 7 to 10 days should raise the suspicion of dengue. Frequent findings include a characteristic rash ("white islands on a red sea"), thrombocytopenia, transaminitis, lymphopenia or lymphocytosis. Petechiae may be observed, and disease may rarely progress to hemorrhage and hypovolemic shock. Only laboratory diagnostics can confirm a dengue infection.

Diagnostics in Canada are either polymerase chain reaction (PCR) or serological. PCR detection of the virus is confirmatory and can typically be achieved from blood taken within 5-7 days of symptom onset, after which viremia is unlikely to be present. Serological diagnosis can be achieved by the detection of IgM and IgG. Seroconversion (an increase in acute and convalescent IgG) or presence of dengue IgM is suggestive of a recent dengue infection, however IgM to dengue virus may persist for months and exposure history must be considered when interpreting IgM results. Static IgG antibody titres suggest remote infection. Cross-reactivity between antibodies against members of the flavivirus family is common and IgG ELISA assays may be falsely positive for dengue in patients with prior flavivirus infections or vaccination (e.g. yellow fever, Japanese Encephalitis, Tick-borne Encephalitis vaccines). Neutralization assays performed by the Canadian National Microbiology Laboratory (NML) are more specific for dengue and should be considered the gold-standard when diagnosing dengue infection (acute or remote) by serology.

Other assays for the diagnosis of dengue may exist abroad. Antigen assays (e.g., NS1 antigen) may be used to detect acute dengue within 5 to 7 days of symptom onset. A positive dengue NS1 antigen is considered confirmatory for acute dengue virus infection.

CATMAT recommends against screening individuals for dengue infection for the purpose of informing decision-making related to use of QDENGA. This reflects the potential for cross reactivity, the expected low true seropositivity likelihood for most travellers, the limited testing capacity in Canada, the cost of testing and the overall low risk for severe dengue among travellers (also see Table 1).

QDENGA

QDENGA is a live-attenuated tetravalent vaccine that expresses the surface proteins of all four serotypes on a DENV-2 backbone^{Footnote 9Footnote 16}. The primary series consists of two doses provided over a three-month period. Efficacy and sero-bridging studies, summarized in assessments by the WHO and the EMA indicate the vaccine elicits a seroresponse in persons aged 5 years to 60 years^{Footnote 9Footnote 10}. Studies have not been done with persons older than 60 years of age.

Methods

This rapid review was undertaken to address a single question: Should Canadian travellers be advised to receive dengue vaccine (Takeda: QDENGA) in countries where it is authorized for travellers?

A full systematic review and metanalyses were not done. Rather, a review of existing guidelines related to QDENGA was undertaken to identify a suitable analysis that could be used to develop CATMAT recommendations.

Results

Other guidelines

CATMAT reviewed available QDENGA guidelines from several European jurisdictions and the World Health Organization^{Footnote 10Footnote 16Footnote 17Footnote 18Footnote 19Footnote 20Footnote 21Footnote 22Footnote 23}. From among the retrieved sources, CATMAT decided that the methodology and QDENGA guideline developed by the German Standing Committee on Vaccination (STIKO)^{Footnote 23} most closely matched the approach as would apply if CATMAT developed QDENGA recommendations de novo. Thus, the STIKO guideline and supporting analyses, in addition to CATMAT's own judgments, were used to develop recommendations.

Evidence

Efficacy studies were conducted in endemic countries with children aged 4 years to 16 years. In this setting, efficacy against serologically confirmed disease (Appendix 1, Table 3) was estimated to be 80% in the first year and had decreased to about 60% by three years after the second dose. Importantly, efficacy was lower at all time intervals post-vaccination in patients who were dengue naïve at the time of immunization compared to those who were not (Appendix 1, Table 3). When further stratified by serotype, estimates of efficacy were higher for DENV-1 and 2 than DENV-3 and 4. Indeed, vaccination was not statistically associated with protection in naïve patients for DENV-3 and 4 (Appendix 1, Table 4).

While there was evidence that vaccine protected against severe dengue, the certainty of the evidence was very low reflecting, among other factors, the very low number of events in treatment and control groups (Appendix 1, Table 5). Further, for DENV-3 specifically, the likelihood of severe dengue among naïve patients was estimated to be higher (RR 2.47, 95% CI: 0.12–51.36) than for the control group (very low certainty evidence)^{Footnote 23}.

A summary of CATMAT's evidence assessment and recommendations based on work by STIKO^{Footnote 23} is provided in Appendix 2.

Conclusions and research needs

Data is lacking on harms and benefits of dengue vaccine in travellers, who are likely to be seronegative, visiting endemic regions. The possibility of increased risk of severe disease following vaccination in seronegative travellers cannot be ruled out. In the immunosuppressed population, dengue vaccine is contraindicated as the benefits or harms of the vaccine are unknown and there is theoretical possibility that decreased immune response to the vaccine could increase the likelihood for severe disease if subsequently infected.

Additional studies are necessary to further investigate: vaccine effectiveness for all dengue serotypes and in seronegative travellers; vaccine benefits and harms in important subgroups including immunosuppressed population and older populations with comorbidities; and severe infection, hospitalization and severe dengue disease. Monitoring for duration of immunity and the risk of disease enhancement is also desirable to gain a comprehensive understanding of the long-term effects of dengue vaccine.

Acknowledgements

This statement was prepared by the CATMAT Dengue Working Group: M Libman, Y Bui, C Greenaway, T Nguyen, P Lagacé-Wiens, S Schofield, and was approved by CATMAT.

CATMAT acknowledges and appreciates support received from the German Standing Committee on Vaccination (STIKO), both for permission to leverage their analyses/guideline for development of this statement, but also for providing support and clarifying information as required during the development of this statement.

CATMAT gratefully acknowledges the contribution of: M Laplante, N Santesso, and the Public Health Agency of Canada Library.

CATMAT

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

Former member: A Acharya

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: E Ebert (National Defence and the Canadian Armed Forces), 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).

Conflicts of interest

None declared.

Appendix 1: STIKO GRADE summary of findings tables (vaccine efficacy of QDENGA compared to placebo vaccination in people of any age)

The tables below are based on the STIKO GRADE summary of findings tables (PDF).

For Table 3, the following applies.

Population: male and female, all ages, irrespective of endemic settings

Intervention: 2 doses of QDENGA vaccine given three months apart

Comparison: placebo vaccination

Outcome: virologically confirmed dengue (VCD) (serotype-specific reverse PCR or NS-1-Ag-test)

For Table 5, the following applies.

Population: Male and female, all ages, irrespective of endemic settings

Intervention: 2 doses of QDENGA vaccine given three months apart

Comparison: placebo vaccination

Outcome: severe dengue (serotype-specific reverse PCR or NS1-Ag-test) according to WHO classification from 2009

Appendix 2: Evidence to decision framework

Question: Should Canadian travellers be advised to receive dengue vaccine (Takeda: QDENGA) in countries where it is authorized?

Population: Canadians travelling to areas where the vaccine (QDENGA) is authorized.

Intervention: Vaccination with QDENGA according to recommended doses and schedule

Comparison: No vaccination

Main outcomes: Virologically confirmed dengue, severe dengue due to any serotype, local and systemic reactions, fever, severe adverse outcomes including death

Setting: International travel

Perspective: Individual

Background: Dengue is a common arboviral infection caused by a mosquito-transmitted flavivirus. The main vector is the Aedes aegypti. Dengue is endemic in over 100 tropical and subtropical countries with an estimated 100 to 400 million cases occurring annually. Travellers are at risk of dengue infection in most tropical and subtropical parts of the world, especially in urban areas. Dengue is a relatively common cause of mild or moderate febrile illness in travellers. Severe or complicated disease among travellers is rare, with a higher likelihood if travellers who suffer a second infection are older individuals and/or have comorbidities.

There are no authorized dengue vaccines in Canada. However, a dengue vaccine, QDENGA, is authorized by the European Medicines Agency (EMA) including for use by travellers to endemic areas. It also is authorized in several dengue endemic countries. This vaccine consists of two vaccine doses, to be administered at an interval of 3 months. There is another dengue vaccine, Dengvaxia, that has been available in some endemic countries. However, it is not authorized for use by travellers and is not considered in this guideline.

Conflict of interests: None

Assessment

Type of recommendation

Strong recommendation against the intervention (for travellers who have not previously been infected with dengue).

Discretionary recommendation for the intervention (for travellers who have previously been infected with dengue).

Conclusions

Recommendation

CATMAT recommends against vaccination with QDENGA for Canadian travellers who do not have documentation of laboratory confirmed prior dengue infection.

(Strong recommendation, very low certainty evidence for increased risk of severe disease in seronegative vaccine recipients)

Remarks:

• QDENGA has not been authorized in Canada, and hence a conservative approach to its use is warranted.

Rationale:

• Cumulative vaccine efficacy at three years against virologically confirmed dengue among vaccinees seronegative at baseline was 0.54 (95% CI 0.42 to 0.64, low certainty evidence).
• Increased risk of severe dengue among vaccinated persons who were seronegative at baseline (RR = 2.47; 95% CI 0.12 to 51.36) cannot be ruled out (very low certainty evidence).
• QDENGA effectiveness was evaluated in dengue-endemic settings, i.e. where recurrent exposure to mosquito-transmitted virus might help sustain protective immunity. Effectiveness has not been specifically assessed for persons travelling to endemic areas, i.e. those who reside in non-endemic regions such as Canada, and for whom recurrent exposures and "natural" immunologic boosting is unlikely^{Footnote 2}.
• CATMAT placed significant weight on the absence of definitive evidence to rule out the possibility of increased harms among seronegative vaccine recipients. Therefore, despite very low to low certainty in estimates, CATMAT strongly recommends against vaccination for persons whose serostatus is unknown or negative.
• Additional evidence may improve certainty or yield different effect estimates, in which case this recommendation will be revisited.

Vaccination with a complete primary series of QDENGA may be considered for Canadian travellers previously infected with dengue (laboratory confirmed).

(Discretionary recommendation, low to very low certainty evidence)

Remarks:

• QDENGA has not been directly evaluated for safety and effectiveness among travellers who live in non-endemic areas or in adults over 60 years of age or children less than four years of age.
• Travellers estimated to be at relatively higher risk for dengue infection based on travel destination, duration and individual level risk factors are more likely to benefit from vaccination with QDENGA.
• Discussions between the traveller and their healthcare provider are necessary to properly assess the individual's risk based on the likelihood of exposure and personal health risk factors (see section Individual-based dengue exposure and values and preferences assessment). The consultation should also include discussion of anticipated benefits and harms, as well as other factors including resources required (time, cost), accessibility and complementary strategies to vaccination to help the traveller reach an informed decision that aligns with their values and preferences.
• If a traveller indicates a desire to receive QDENGA vaccination in a country where it is authorized, they should receive the full series (two doses over three months) before travel to an endemic area.

Rationale:

• Cumulative vaccine efficacy at three years against virologically confirmed dengue among vaccinees seropositive at baseline was 0.65 (95% CI 0.59 to 0.70, low certainty evidence).
• In this population, vaccination may offer protection against severe disease associated with subsequent secondary infection by another serotype (RR = 0.1; 95% CI 0.01 to 0.86) (very low certainty evidence).
• Data to allow a fulsome evaluation of the safety and effectiveness of a partial vaccine series among travellers is not available.
• The discretionary recommendation reflects:
  • anticipated differences in patient values and preferences related to vaccination with QDENGA;
  • the committee's judgement that the lack of evidence related to the safety and effectiveness of an incomplete series is important; and,
  • the committee's judgement that effective screening for previous infection would not be feasible for many travellers.

Clinicians should NOT request dengue serology to screen travellers for previous exposure to dengue virus to assess suitability for vaccination (good practice statement).

This reflects the limited testing capacity in Canada, the potential for cross reactivity with other flaviviruses, the expected low true seropositivity likelihood for most travellers, the cost of testing which may be borne by the traveller and the overall low risk for severe dengue among travellers.

Clinicians should advise all travellers to dengue-endemic areas to adhere to 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 dengue 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 envelope 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.

Appendix 3: Assessment for applicability of good practice statement

Good practice statement (GPS): Clinicians should not request dengue serology to screen travellers for previous exposure to dengue virus to assess suitability for vaccination.

Final judgement: Development of GPS is appropriate

Good practice statement: Clinicians should advise all travellers to dengue-endemic areas to adhere to personal protective measures against insect bites

Final judgement: Development of GPS is appropriate