Skip directly to site content Skip directly to search


Español  Other Languages


Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People
 Search
		×
			Vaccines site
			Vaccines site
				All CDC
				Submit
			For a full list of topics:A-Z Index
			Advanced Search
		Advanced Search


Advisory Committee on Immunization Practices (ACIP)


Facebook
        Twitter
        LinkedIn
        Syndicate





GRADE Analysis: Dengvaxia® Dengue Vaccine										Related Pages
										Introduction
Dengue viruses (DENV) transmitted by *Aedes aegypti*mosquitoes present a growing public health challenge (Shepard et al. 2016; Stanaway et al. 2016). DENV is endemic throughout the tropics and sub-tropics, with an estimated 3.8 (95% confidence interval [CI] 3.5–4.1) billion people (roughly 53% of the global population) living in areas that are suitable for DENV transmission with the vast majority in Asia, followed by Africa and the Americas (Messina et al. 2019).  Global estimates for 2013 suggest a total of 58 million symptomatic DENV infections (95% CI 24–122) and 13,586 fatal cases occurred (95% CI 4200–34,700), resulting in a total annual global cost of $8.9 billion (95% CI 3.7–19.7) (Shepard et al. 2016; Stanaway et al. 2016).
DENV are members of the genus *Flavivirus*, within the family *Flaviviridae*. There are 4 dengue virus serotypes (DENV-1, DENV-2, DENV-3 and DENV-4), all of which circulate globally, with most endemic coun­tries reporting circulation of all 4 serotypes in recent years.   The 4 dengue serotypes are serologically and genetically distinct, although they share several of their structural antigens. Following an infection with one DENV serotype, the antibodies induced are type-specific and also cross-reactive with other DENV sero­types (Wilder-Smith et al. 2019).
Clinical disease varies from a mild, undifferentiated febrile illness to severe disease with shock, hemorrhage and/or severe organ impairment such as hepatitis and encephalitis.  The case-fatality ratio for severe dengue is 10% or higher when untreated but can be reduced to less than 1% with good clinical management.  Age, co-morbidities, host genetics, and virus strain are risk factors for severe dengue with heterotypic secondary infections being the most prominent factor associated with severe dengue (Wilder-Smith et al. 2019). *Ae. aegypti*, the main vector of dengue, has proved highly difficult to control, and continues to expand its geographic range.  Dengue is a serious and ongoing public health problem in Puerto Rico and in other US territories and US affiliated states.
A vaccine to prevent dengue (CYD-TDV, Dengvaxia®) is licensed and available in 20 countries for people ages 9–45 years old. The World Health Organization recommends that the vaccine only be given to persons with confirmed prior dengue virus infection. **The vaccine manufacturer, Sanofi Pasteur, announced in 2017 that people who receive the vaccine and have not been previously infected with a dengue virus may be at risk of developing**severe dengue **if they get dengue after being vaccinated.**In May 2019, Dengvaxia® was approved by the U.S. Food and Drug Administration (FDA) in the United States for use in children 9-16 years old living in an area with endemic dengue with laboratory confirmed prior dengue virus infection.
Evidence Retrieval
The US Advisory Committee on Immunization Practices (ACIP) Dengue Vaccine Work Group reviewed Dengvaxia® safety and efficacy data in a systematic literature review in 2018. The search terms included Dengvaxia®, CYD-TDV, or live-attenuated dengue vaccine, and 5 database systems were reviewed (Medline, Embase, Cochrane Library, CINAHL, Scopus). A total of 710 results were identified; of these, 359 met initial inclusion criteria of including human data from clinical trials published after 2000. The remaining 351 findings were reviewed by at least two people to assess possible relevance. The majority of those were excluded as describing different live attenuated dengue vaccines or not including primary trial data. The final analysis included 30 papers that described Dengvaxia® safety or efficacy results from clinical trials. In this document we present the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
**Table 1: Policy Question and PICO, CYD-TDV Dengue Vaccine**
Table 1: Policy Question and PICO
Policy question
Should 3-doses of Dengvaxia® be administered routinely to persons 9-16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas to prevent virologically confirmed dengue, hospitalizations and severe dengue?Population
Persons 9 to 16 years of age living in dengue-endemic areas of the United States, territories, and freely associated statesIntervention
3 doses of Dengvaxia® administered at 6-month intervals, at 0, 6 and 12 monthsComparison
No dengue vaccinationOutcomes
Protection against virologically confirmed dengue, severe dengue, and hospitalization for dengue. The harms considered critical outcomes were serious adverse events, hospitalizations, severe dengue and deaths.
**Table 2. Summary of outcomes and rankings, CYD-TDV Dengue Vaccine**
Table 2. Summary of outcomes and rankings
Outcome
Importance
Include in evidence profileBenefitsVaccine efficacy for virologically confirmed dengue (VCD)
Critical
YesVaccine efficacy for severe VCD
Critical
YesVaccine efficacy for hospitalization for VCD
Critical
YesHarmsSerious adverse events
Critical
YesInjection site reactions
Important
NoSystemic reactions
Important
NoHospitalization
Critical
YesSevere dengue
Critical
YesDeath
Critical
Yes
Appendix 1: Studies included in Evidence Review
Appendix 1: Studies included in Evidence Review
Last name first author, Publication year
Study design
Country
Age in years
Total population
N Intervention
N comparison
Outcomes
Funding sourceCapeding, 2014
RCT (phase 3)
Indonesia, Malaysia, Philippines, Thailand, and Vietnam (CYD14)
2-14
10,275
6,851
3,424
Virologically confirmed dengue (VCD)
Sanofi PasteurVillar, 2015
RCT (phase 3)
Colombia, Brazil, Mexico, Honduras, Puerto Rico (CYD15)
9-16
20,869
13,920
6,949
VCD
Sanofi PasteurSabchareon, 2012
RCT (phase 2b)
Thailand (CYD23-57)
4-11
4,002
2,669
1,221
VCD
Sanofi PasteurHadinegoro, 2015
2 RCT
Combined (CYD14/CYD15)
9-14
30,063
20,046
10,017
VCD, hospitalization, severe dengue
Sanofi PasteurGailhardou, 2016
18 clinical trials (phase 1, 2, 3)
USA, Philippines, Mexico, Australia, Colombia, Honduras, Mexico, Puerto Rico, Vietnam, Peru, Singapore, Brazil, India, Thailand Malaysia, Australia, Indonesia
2-60
38,918
26,356
12,562
Serious adverse events, deaths
Sanofi PasteurSridhar, 2018
Case-cohort
Combined (CYD14/CYD15/CYD23-57)
9-16
3,578
2,384
1,194
VCD, hospitalization, severe dengue
Sanofi Pasteur

**Table 3a: Summary of studies reporting virologically confirmed dengue (VCD), CYD-TDV Dengue Vaccine**
Table 3a: Summary of studies reporting virologically confirmed dengue (VCD)
Authors last name, pub year
Age; DENV Serotype
Serostatus
n/N intervention
n/N comparison
Comparator vaccine
Efficacy/Relative Risk
Study limitations (Risk of Bias)Capeding, 2014
2-14
Seropositive
18/1811
34/880
Placebo
74.3 (53.2, 86.3)
Not seriousCapeding, 2014
2-14
Seronegative
23/838
18/423
Placebo
35.5 (-26.8, 66.7)
Not seriousVillar, 2015
9-16
Seropositive
8/2116
23/994
Placebo
83.7 (62.2, 93.7)
Not seriousVillar, 2015
9-16
Seronegative
9/500
9/284
Placebo
43.2 (-61.6, 80.0)
Not seriousSabchareon, 2012
4-11
Combined
45/2522
32/1251
Placebo
30.2 (-13.4, 56.6)
Not seriousHadinegoro, 2015
9-16
Seropositive
15/1560
40/763
Placebo
81.9 (67.2, 90.0)
Not seriousHadinegoro, 2015
9-16
Seronegative
16/387
17/208
Placebo
52.5 (5.9-76.1)
Not seriousHadinegoro, 2015
9-16; Serotype 1
Combined
135/17230
161/8596
Placebo
58.4 (47.7, 66.9)
Not seriousHadinegoro, 2015
9-16; Serotype 2
Combined
117/17230
110/8596
Placebo
47.1 (31.3, 59.2)
Not seriousHadinegoro, 2015
9-16; Serotype 3
Combined
66/17230
124/8596
Placebo
73.6 (64.4, 80.4)
Not seriousHadinegoro, 2015
9-16; Serotype 4
Combined
42/17230
124/8596
Placebo
83.2 (76.2, 88.2)
Not seriousSridhar, 2018
9-16 (MI)
Seropositive
192.7/1441.4
372.1/697.3
Placebo
76 (64, 84)
Not seriousSridhar, 2018
9-16 (MI)
Seronegative
174.3/353.6
148.9/193.7
Placebo
39 (-1, 63)
Not seriousSridhar, 2018
9-16 (MI); Serotype 1
Seropositive
71/1441.4
103.5/697.3
Placebo
67.4 (45.9, 80.4)
Not seriousSridhar, 2018
9-16 (MI); Serotype 2
Seropositive
57.1/1441.4
83.1/697.3
Placebo
67.3 (46.7, 79.9)
Not seriousSridhar, 2018
9-16 (MI); Serotype 3
Seropositive
40.5/1441.4
96/697.3
Placebo
80.0 (67.3, 87.7)
Not seriousSridhar, 2018
9-16 (MI); Serotype 4
Seropositive
20.9/1441.4
91.9/697.3
Placebo
89.3 (79.8, 94.4)
Not seriousSridhar, 2018
9-16 (MI); Serotype 1
Seronegative
23.6/365.4
23.6/365.4
Placebo
1.37 (0.59, 3.19)
Not seriousSridhar, 2018
9-16 (MI); Serotype 2
Seronegative
21.2/365.4
21.2/365.4
Placebo
2.41 (0.65, 8.95)
Not seriousSridhar, 2018
9-16 (MI); Serotype 3
Seronegative
10.1/365.4
10.1/365.4
Placebo
0.86 (0.23, 3.3)
Not seriousSridhar, 2018
9-16 (MI); Serotype 4
Seronegative
3.4/365.4
3.4/365.4
Placebo
0.94 (0.11, 8.1)
Not serious

**Table 3b: Summary of studies reporting hospitalization, CYD-TDV Dengue Vaccine**
Table 3b: Summary of studies reporting hospitalization
Authors last name, pub year
Age
Serostatus
n/N intervention
n/N comparison
Comparator vaccine
Efficacy/Relative Risk
Study limitations (Risk of Bias)Hadinegoro, 2015
9-16
Combined
27/17,230
70/7,596
Placebo
80.8 (70.1, 87.7)
Not seriousSridhar, 2018
9-16 (MI)
Seropositive
58.8/1502.9
137.7/729.8
Placebo
0.21 (0.14–0.31)
Not seriousSridhar, 2018
9-16 (MI)
Seronegative
64.2/375.1
25.3/207.2
Placebo
1.41 (0.74–2.68)
Not seriousSridhar, 2018
9-16 (MI); Serotype 1
Seropositive
15.4/1495.6
32.9/708.1
Placebo
0.22 (0.11, 0.45)
Not seriousSridhar, 2018
9-16 (MI); Serotype 2
Seropositive
15.8/1495.6
42.1/708.1
Placebo
0.18 (0.09, 0.34)
Not seriousSridhar, 2018
9-16 (MI); Serotype 3
Seropositive
14.9/1495.6
18.6/708.1
Placebo
0.38 (0.17, 0.82)
Not seriousSridhar, 2018
9-16 (MI); Serotype 4
Seropositive
3.6/1495.6
21.1/708.1
Placebo
0.07 (0.01, 0.38)
Not seriousSridhar, 2018
9-16 (MI); Serotype 1
Seronegative
23.6/365.4
9.1/196.9
Placebo
1.37 (0.59, 3.19)
Not seriousSridhar, 2018
9-16 (MI); Serotype 2
Seronegative
21.2/365.4
4.9/196.9
Placebo
2.41 (0.65, 8.95)
Not seriousSridhar, 2018
9-16 (MI); Serotype 3
Seronegative
10.1/365.4
6.4/196.9
Placebo
0.86 (0.23, 3.3)
Not seriousSridhar, 2018
9-16 (MI); Serotype 4
Seronegative
3.4/365.4
1.9/196.9
Placebo
0.94 (0.11, 8.1)
Not serious

**Table 3c: Summary of studies reporting severe dengue, CYD-TDV Dengue Vaccine**
Table 3c: Summary of studies reporting severe dengue
Authors last name, pub year
Age
Serostatus
n/N intervention
n/N comparison
Comparator vaccine
Efficacy/Relative Risk
Study limitations (Risk of Bias)Hadinegoro, 2015
9-16
Combined
3/17,230
22/8,596
Placebo
93.2 (77.3, 98.0)
Not seriousSridhar, 2018
9-16 (MI)
Seropositive
11.2/1502.9
33.4/729.8
Placebo
0.16 (0.07–0.37)
Not seriousSridhar, 2018
9-16 (MI)
Seronegative
14.8/375.1
3.6/207.2
Placebo
2.44 (0.47–12.56)
Not seriousSridhar, 2018
9-16 (MI); Serotype 1
Seropositive
12.9/1803.3
10.5/856.1
Placebo
0.57 (0.19, 1.74)
Not seriousSridhar, 2018
9-16 (MI); Serotype 2
Seropositive
8.6/1803.3
16/856.1
Placebo
0.24 (0.08, 0.74)
Not seriousSridhar, 2018
9-16 (MI); Serotype 3
Seropositive
10.5/1803.3
6.8/856.1
Placebo
0.72 (0.26, 2.0)
Not seriousSridhar, 2018
9-16 (MI); Serotype 4
Seropositive
1.1/1803.3
9/856.1
Placebo
NA
Not seriousSridhar, 2018
9-16 (MI); Serotype 1
Seronegative
13.1/551.7
4.5/294.9
Placebo
1.55 (0.37, 6.56)
Not seriousSridhar, 2018
9-16 (MI); Serotype 2
Seronegative
16.4/551.7
3/294.9
Placebo
3.21 (0.50, 20.68)
Not seriousSridhar, 2018
9-16 (MI); Serotype 3
Seronegative
9.5/551.7
1.2/294.9
Placebo
NA
Not seriousSridhar, 2018
9-16 (MI); Serotype 4
Seronegative
0.9/551.7
0/294.9
Placebo
NA
Not serious

**Table 3d: Summary of studies reporting severe adverse events, CYD-TDV Dengue Vaccine**
Table 3d: Summary of studies reporting severe adverse events
Authors last name, pub year
Age; Length of follow-up
Serostatus
n/N intervention
n/N comparison
Comparator vaccine
Efficacy/Relative Risk
Study limitations (Risk of Bias)Gailhardou, 2016
2-60; 28 days
Combined
218/26356
121/12562
Placebo
NA
Not seriousGailhardou, 2016
2-60; 6 months
Combined
23/26356
499/12562
Placebo
NA
Not seriousDayan G., personal communication
9-16; 28 days
Combined
123/19102
73/9484
Placebo
0.84 (0.63, 1.12)
Not seriousDayan G., personal communication
9-16; 6 months
Combined
534/19102
307/9484
Placebo
0.86 (0.75, 0.99)
Not serious
**Table 3e: Summary of studies reporting deaths, CYD-TDV Dengue Vaccine**
Table 3e: Summary of studies reporting deaths
Authors last name, pub year
Age
Serostatus
n/N intervention
n/N comparison
Comparator vaccine
Efficacy/Relative Risk
Study limitations (Risk of Bias)Gailhardou, 2016
2-60
Combined
23/26,356
14/12,522
Placebo
NA
Not seriousDayan G., personal communication
9-16
Combined
51/19102
26/9484
Placebo
0.97 (0.61, 1.56)
Not serious
**Table 4. GRADE assessment for 3 doses of Dengue vaccine administered at 6-month intervals compared to no vaccine for protection against virologically confirmed dengue, severe dengue, and hospitalization among children ages 9-16 yrs with confirmed previous dengue infection, CYD-TDV Dengue Vaccine**
Table 4. GRADE assessment for 3 doses of Dengue vaccine administered at 6-month intervals compared to no vaccine for protection against virologically confirmed dengue, severe dengue, and hospitalization among children ages 9-16 yrs with confirmed previous dengue infection
No of participants (studies) Reference
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Study event rates (%) with no vaccination
Study event rates (%) with 3 doses of Dengue vaccine administered at 6-month intervals
Relative effect
(95% CI)
Absolute effect/risk difference per 1000
(95% CI)
Certainty
ImportanceVirologically confirmed dengue among seropositives (follow up: 25 months; assessed with: active follow-up and laboratory testing)2323
(2 RCTs)
Handinegoro SR, et al.
RCTs
not seriousa,b
not serious
not serious
not seriousc
none
40/763 (5.2%)
15/1560 (1.0%)
**VE 81.9**
(67.2 to 90.0)
-42.8
(-59.4 to -26.3)
1
HIGH
CriticalHospitalization for VCD among seropositives (follow up: 6 years; assessed with: hospital surveillance)2232.7
(Case cohort using data from 3 RCTs)
Sridhar S, et al.
Case cohort using data from 3 RCTs
not seriousd
not serious
not serious
not serious
Upgrade for strong association
137.7/729.8 (18.9%)
58.8/1502.9 (3.9%)
**RR 0.21**
(0.14 to 0.31)
-149.6
(-179.6 to -119.5)
2
MODERATE
CriticalSevere VCD among seropositives (follow up: 6 years; assessed with: hospital surveillance)2232.7
(Case cohort using data from 3 RCTs)
Sridhar S, et al.
Case cohort using data from 3 RCTs
not seriousd
not serious
not serious
not serious
Upgrade for strong association
33.4/729.8 (4.6%)
11.2/1502.9 (0.7%)
**RR 0.16**
(0.07 to 0.37)
-38.3
(-54.19 to -22.5)
2
MODERATE
CriticalVirologically confirmed dengue among seronegatives (follow up: 25 months; assessed with: active follow-up and laboratory testing)595
(2 RCTs)
Handinegoro SR, et al.
RCTs
not seriousa
not seriouse
not serious
seriousf
Downgrade for imprecision
17/208 (8.2%)
16/387 (4.1%)
**VE 52.5**
(5.9 to 76.1)
-40.4
(-82.6 to 1.8)
2 MODERATE
CriticalHospitalization for VCD among seronegatives (follow up: 6 years; assessed with: hospital surveillance)582.3
(Case cohort using data from 3 RCTs)
Sridhar S, et al.
Case cohort using data from 3 RCTs
not seriousg
not serious
not serious
serioush
Downgrade for imprecision
25.3/207.2 (12.2%)
64.2/375.1 (17.1%)
**RR 1.41**
(0.74 to 2.68)
49.1
(-9.6 to 107.7)
4
VERY LOW
CriticalSevere VCD among seronegatives (follow up: 6 years; assessed with: hospital surveillance)582.3
(Case cohort using data from 3 RCTs)
Sridhar S, et al
Case cohort using data from 3 RCTs
not seriousg
not serious
not serious
seriousi
Downgrade for imprecision
3.6/207.2 (1.7%)
14.8/375.1 (3.9%)
**RR 2.44**
(0.47 to 12.56)
22.1
(-4.5 to 48.6)
4
VERY LOW
Critical**Serious adverse events among seropositive and seronegative (follow up: 6 months; assessed with: active surveillance)**28586
(9 RCTs)j
RCTs
not serious
not serious
not serious
not serious
none
73/9484 (0.8%)
123/19102 (0.6%)
**RR 0.86**
(0.75 to 0.99)
-1.3
(-3.4 to 0.8)
1
HIGH
Critical**Deaths among seropositives and seronegatives (follow up: 6 years; assessed with: hospital surveillance)**28586
(9 RCTs) j
RCTs
not serious
not serious
not serious
not seriousk
none
26/9484 (0.3%)
51/19102 (0.3%)
**RR 0.78**
(0.40 to 1.52)
-0.1
(-1.4 to 1.2)
1
HIGH
Critical
**CI:** Confidence interval; **RR:** Risk rati0
Dengvaxia® has been evaluated in two parallel Phase 3 clinical trials, known as CYD14 and CYD15. CYD14 was conducted in 5 countries in Asia (Indonesia, Malaysia, Philippines, Thailand, and Vietnam), with 5,234 participants aged 9-14 years at first vaccination (10,275 participants in the full trial population aged 2-14 years). CYD15 was conducted in 5 countries in Latin America (Brazil, Colombia, Honduras, Mexico, and Puerto Rico (US), with 20,869 participants aged 9-16 years at first vaccination. Participants were randomized to vaccine/placebo in a 2:1 ratio. Because the physical appearance of the vaccine and placebo was different, unmasked trial staff were responsible only for administration and were not involved in the follow-up. For trial endpoints the trials were observer-masked. All serology testing was also performed in a blinded manner. Immune status at baseline was only known for the immunogenicity subset with 2,000 participants per study, 4,000 total.
Active surveillance of participants lasted only until study month 25, after which surveillance was hospital-based. Thus, it is not possible to evaluate the duration of protection against virologically-confirmed dengue of any severity.
Based on the immunogenicity subset, vaccine efficacy among seropositives was 74.3% (95% CI 53.2-86.3) in CYD14, 83.7% (95% CI 62.2-93.7) in CYD15, 78.2% (95% CI 65.4-86.3) in the two trials pooled, and 81% (95%CI 67.2-90.0) in the two trials pooled with the age limited to 9-16 years. Data based on the supplemental analysis (see explanation in d below) affirms high vaccine efficacy in seropositives with point estimates ranging from 71-75%, depending on the method, and tight confidence intervals.
Data for long term hospitalization risk comes from a case cohort study using all VCD, hospitalization and severe dengue cases and randomly selected controls that represent 10% of the study cohort (n=3,300). As part of this supplemental study, three methods were used to assign dengue serostatus and re-analyze the Phase 3 trial data: multiple imputation (MI, month 0 onward), targeted minimum loss–based estimation (TMLE, month 0 onward), and measured anti–nonstructural protein 1 (NS1) titer (month 13 onward). Analyses from these methods provided similar results, therefore only results from multiple imputation (MI) are presented in the table. These methods are based on assays and statistical methods that are associated with misclassification of serostatus at baseline, which vary by assay. The false-positive rate (misclassifying seronegatives as seropositives) is high (31%), which would bias the result towards the null. Thus, the protective effect in seropositives may be greater than that estimated in these analyses. About 80% of participants in the case control study are seropositive, therefore the potential bias from the misclassified seronegatives is likely small.
Data based on the supplemental analysis provides variable point estimates for seronegatives. In 9-16 year-olds, vaccine efficacy is estimated at 39% (95%CI -1-63) using the multiple imputation method, 45% (95%CI 26-58) using the TMLE method, and 18% (95%CI -18-43) using the NS1 method. The confidence is downgraded for inconsistency.
Based on the immunogenicity subset, vaccine efficacy among seronegatives was 35.5% (95% CI -27.0-66.6) in CYD14, 43.2% (95%CI -61.6-80.0) in CYD15, 38.1% (95% CI -3.4-62.9) in the two trials pooled, and 52.5% (95% CI 5.9-76.1) in the two trials pooled with the age limited to 9-16 years. There were few seronegatives in the immune subset, making it hard to estimate vaccine efficacy with precision. The confidence is downgraded in the category of imprecision.
Data for long term hospitalization risk comes from a case control study using all VCD, hospitalization and severe dengue cases and randomly selected controls that represent 10% of the study cohort (n=3,300). The methods used for re-analysis of the Phase 3 trial data are based on assays and statistical methods that are associated with misclassification of serostatus at baseline, which vary by assay. The false-negative rate (misclassifying seropositives as seronegatives) is low and for this analysis there is limited bias due to misclassification.
Based on analyses of the immune subset for sero-negatives at baseline, the confidence intervals are very wide. All cross zero. The imprecision remains for most supplemental analyses with the longer-term follow-up, with the lower bound of the 95% CI crossing 0 for the multiple imputation method, TMLE and NS1 methods. The confidence is downgraded for imprecision.
The number of severe dengue cases among seronegatives was small. Multiple estimation methods were used including multiple imputation, TMLE, and NS1 testing at month 13. The estimates of increased risk of severe dengue among those vaccinated range from 1.4 (95%CI: 0.4-4.5) with TMLE to 6.2 (0.8-48.3), and the confidence intervals are wide and all estimates cross zero. The confidence is downgraded for imprecision.
Dayan GH, personal communication. 2019.
Did not rate down for imprecision because sample size meets optimal information size.
**Table 5: Summary of Evidence for Outcomes of Interest, CYD-TDV Dengue Vaccine**
Table 5: Summary of Evidence for Outcomes of Interest
Outcome
Importance
Included in evidence profile
CertaintyBenefitsVaccine efficacy for virologically confirmed dengue (VCD)
Critical
Yes
HighVaccine efficacy for hospitalization for VCD
Critical
Yes
ModerateVaccine efficacy for severe VCD
Critical
Yes
ModerateHarmsSerious adverse events
Critical
Yes
HighInjection site reactions
Important
NoSystemic reactions
Important
NoHospitalization
Critical
Yes
ModerateSevere dengue
Critical
Yes
ModerateDeath
Critical
Yes
High
References
Capeding MR, Tran NH, Hadinegoro SR, Ismail HI, Chotpitayasunondh T, Chua MN, et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet. 2014; 384(9951):1358-65.
Gailhardou S, Skipetrova A, Dayan GH, et al. Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials. Plos Negl Trop Dis; 2016.
Hadinegoro SR, Arredondo-García JL, Capeding MR, et al. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease. N Engl J Med. 2015 Sep 24;373(13):1195-206.
Messina, J. P., O. J. Brady, N. Golding, M. U. G. Kraemer, G. R. W. Wint, S. E. Ray, D. M. Pigott, F. M. Shearer, K. Johnson, L. Earl, L. B. Marczak, S. Shirude, N. Davis Weaver, M. Gilbert, R. Velayudhan, P. Jones, T. Jaenisch, T. W. Scott, R. C. Reiner, Jr., and S. I. Hay. 2019. ‘The current and future global distribution and population at risk of dengue’, Nat Microbiol.
Messina JP et al. Global spread of dengue virus types: mapping the 70 year history. Trends Microbiol. 2014 22(3): 138–146.
Sharp, T. M., K. Ryff, G. A. Santiago, H. S. Margolis, and S. Waterman. 2019. ‘Lessons Learned from Dengue Surveillance and Research Activities in Puerto Rico, 1899–2013’, Emerg Infect Dis, In press.
Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet. 2012 380 (9853):1559-67.
Sridhar S, Luedtke A, Langevin E,et al. Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy.. N Engl J. Med; 2019.
Stanaway, J. D., D. S. Shepard, E. A. Undurraga, Y. A. Halasa, L. E. Coffeng, O. J. Brady, S. I. Hay, N. Bedi, I. M. Bensenor, C. A. Castaneda-Orjuela, T. W. Chuang, K. B. Gibney, Z. A. Memish, A. Rafay, K. N. Ukwaja, N. Yonemoto, and C. J. Murray. 2016. ‘The global burden of dengue: an analysis from the Global Burden of Disease Study 2013’, Lancet Infect Dis.
Villar L, Dayan GH, Arredondo-García JL, et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med. 2015 Jan 8;372(2):113-23. doi: 10.1056/NEJMoa1411037. Epub 2014 Nov 3.
Wilder-Smith, A., E. E. Ooi, O. Horstick, and B. Wills. 2019. ‘Dengue’, Lancet, 393: 350-63.
Top of Page
							
					
						Page last reviewed:  December 16, 2021					Content source: 	National Center for Immunization and Respiratory Diseases homeACIP Home
Meeting Information
Committee Informationplus icon
Role of the ACIP in CDC’s Vaccine Recommendations
Charter
Economics Studies
Committee Membersplus icon
ACIP Membership Roster
Apply for ACIP Membership
Work Groupsplus icon
VaST Reportsplus icon
June 28, 2021
May 24, 2021
May 17, 2021
March 29, 2021
Recommendationsplus icon
Shared Clinical Decision-Making Recommendations
Evidence Based Recommendationsplus icon
About GRADE
Grade Evidence Tables
Evidence to Recommendations Frameworks Vaccines & ImmunizationsImmunization SchedulesVFC ResolutionsVaccine Information Statements (VISs)
  1600 Clifton Road, N.E., Mailstop A27
Atlanta, GA 30329-4027acip@cdc.gov


About CDC
					Contact Us
					800-232-4636
 Facebook Twitter Instagram LinkedIn Youtube Pinterest Snapchat
 CONTACT CDC
				Contact Us
							Call 800-232-4636
							Email Us
			ABOUT CDC
				About CDC
							Jobs
							Funding
			POLICIES
				Accessibility
							External Links
							Privacy
							Policies
							No Fear Act
							FOIA
							OIG
							Nondiscrimination
							Vulnerability Disclosure Policy
			CONNECT WITH US
				Facebook
								Twitter
								Instagram
								LinkedIn
							Youtube
								Pinterest
								Snapchat
								Email
			LANGUAGES
				Español
							繁體中文
							Tiếng Việt
							한국어
							Tagalog
							Русский
							العربية
							Kreyòl Ayisyen
							Français
							Polski
							Português
							Italiano
							Deutsch
							日本語
							فارسی
							English


U.S. Department of Health & Human Services
			Accessibility
			External Links
			Privacy
			Policies
			No Fear Act
			FOIA
			Nondiscrimination
			OIG
			Vulnerability Disclosure Policy
			USA.gov


Exit Notification / Disclaimer Policy Close
 Links with this icon  indicate that you are leaving the CDC website. The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
				Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
				You will be subject to the destination website's privacy policy when you follow the link.
				CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. Website Disclaimers
 Cancel Continue