Study of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01374516
• Collaborator: (none)
• Enrollment: 20,869
• Locations: 22
• Arms: 2
• Actual Duration (Months): 80.9
• Patients Per Site: 948.6
• Patients Per Site Per Month: 11.7

Study Details

Study Description

Brief Summary

The aim of the study was to assess the efficacy of Sanofi Pasteur's CYD dengue vaccine in preventing symptomatic virologically-confirmed dengue cases for dengue-endemic areas of Latin America.

Primary Objective:

To assess the efficacy of CYD dengue vaccine after 3 vaccinations at 0, 6, and 12 months in preventing symptomatic virologically-confirmed dengue (VCD) cases, regardless of the severity, due to any of the four serotypes in children and adolescents aged 9 to 16 years at the time of inclusion.

Secondary Objectives:

• To describe the efficacy of CYD dengue vaccine in preventing symptomatic VCD cases after the third dose to the end of the Active Phase, after at least 1 dose, and after 2 doses.

• To describe the occurrence of hospitalized VCD cases and the occurrence of severe (clinically severe or as per World Health Organization (WHO) criteria) VCD cases, throughout the Surveillance Expansion Period (SEP) and throughout the trial (from Day 0 until the end of the study).

• To describe the antibody response to each dengue serotype after Dose 2, after Dose 3, and 1 and 5 years after Dose 3.

• To describe the occurrence of serious adverse events (SAEs), including SAEs of special interest in all participants throughout the trial period.

Condition or Disease	Intervention/Treatment	Phase
Dengue Fever; Dengue Hemorrhagic Fever; Dengue	Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus; Biological: Placebo: (NaCl) 0.9% solution	Phase 3

Detailed Description

Participants were randomized to either receive 3 injections of CYD dengue vaccine or a placebo at 0, 6, and 12 months.

A subset of participants from each country (N=2000) was also evaluated for reactogenicity and immunogenicity.

For each participant, the Active Phase of dengue case detection began after the first injection (Dose 1) and continued until 13 months after the third injection (Dose 3). It was assumed that 12 months of surveillance should result in the detection of a sufficient number of VCD cases to allow for an assessment of efficacy.

The Hospital Phase began after the Active Phase. Participants with a febrile illness and requiring hospitalization were screened for dengue until the end of the study.

Participants who consented to participate in the SEP were actively followed for dengue case detection (i.e. at least weekly contact and capturing any acute febrile illness, not just hospitalized febrile cases, as in the Active Phase). The SEP was designed to maximize the detection of symptomatic VCD (hospitalized or not) in order to describe CYD dengue vaccine efficacy and safety in preventing symptomatic dengue in the long-term. Participants who declined participating in the SEP continued surveillance as in the Hospital Phase until trial completion.

Symptomatic VCD cases occurring more than (>) 28 days after dose 3 (during the Active Phase) are defined as:

• Acute febrile illness (i.e. temperature >=38 degree Celsius (°C) on at least 2 consecutive days)

• Virologically confirmed by dengue Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and/or dengue non-structural (NS)1 enzyme-linked immunosorbent assay (ELISA) Ag test.

Severity was assessed using a definition consistent with the 1997 WHO Classification Dengue Hemorrhagic Fever and by an independent Data Monitoring Committee (IDMC) severity criteria.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20869 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Efficacy and Safety of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America
• Actual Study Start Date: Jun 8, 2011
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Mar 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CYD Dengue Vaccine Group Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus; 0.5 mL, Subcutaneous; Other Names: CYD Dengue Vaccine
Placebo Comparator: Placebo Group Participants were to receive a placebo vaccine at 0, 6, and 12 months.	Biological: Placebo: (NaCl) 0.9% solution; 0.5 mL, Subcutaneous

Outcome Measures

Primary Outcome Measures

1. Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo [28 days and up to 13 months post-injection 3]

   Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction (RT-PCR) and/or dengue non-structural (NS) protein 1 antigen enzyme-linked immunosorbent assay (ELISA). Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.

Secondary Outcome Measures

1. Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo [Day 0 up to 13 months post-injection 3]

   Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.

2. Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo [28 days post-injection 1 and up to 13 months post-injection 3]

   Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.

3. Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo [28 days post-injection 2 and up to 13 months post-injection 3]

   Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.

4. Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo [Day 0 to the end of study (up to 72 months)]

   Dengue hemorrhagic fever (DHF) cases were defined as number of participants with at least one symptomatic VCD episode meeting the 1997 WHO criteria. (a) Fever: acute onset, high (>= 38°C) and continuous, lasting 2 to 7 days and (b) any of the pre-listed hemorrhagic manifestations and laboratory findings of thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/ or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhage.

5. Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo [From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)]

   The 1997 WHO criteria are: a) Fever: acute onset, high (>= 38°C) and continuous, for 2 to 7 days and (b) any of the following: thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hematocrit increased by 20% or more or pleural effusion and/or ascites and/or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participant, usually in the form of skin and/or other hemorrhages; Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness; and Grade IV: Profound shock with undetectable blood pressure and pulse.

6. Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo [Day 0 up to the end of study (up to 72 months)]

   Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature >=38°C on at least 2 consecutive days) requiring hospitalization.

7. Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo [From consent to participate in the Surveillance Expansion Period to end of the study (up to 72 months)]

   Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature >=38°C on at least 2 consecutive days) requiring hospitalization.

8. Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo [Day 0 to the end of study (up to 72 months)]

   The severity of VCD cases was assessed by an Independent Data monitoring Committee (IDMC) based on a medical review of cases and any of the following criteria:1) Platelet count <=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20 mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by Glasgow Coma Scale (GCS) score 5) Liver impairment (AST >1000 IU/L or prothrombin time [PT] International normalized ratio [INR] >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.

9. Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo [From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)]

   The severity of VCD cases was assessed by an IDMC based on a medical review of cases and any of the following criteria:-1) Platelet count <=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20 mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. Unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by GCS score 5) Liver impairment (AST >1000 IU/L or PT INR >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.

10. Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo [Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit [V] 07) and 60 months (Visit [V] 12) post-injection 3]

    Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (parental strains) were measured by the plaque reduction neutralization test in a pre-defined subset of participants.

11. Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo [Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3]

    Geometric mean titers for each of the 4 dengue virus serotypes (parental strains) were assessed using the plaque reduction neutralization test in a pre-defined subset of participants.

12. Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo [Within 7 days after each and any injection]

    Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (9-11 years): Pain: incapacitating, unable to perform usual activities; Erythema and Swelling, >= 50 mm. Grade 3 Solicited injection site reactions (12-16 years): Pain: significant, prevents daily activity; Erythema and Swelling, >100 mm.

13. Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo [Within 14 days after each and any injection]

    Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 reactions: Fever: >= 39°C; Headache, Malaise, Myalgia, and Asthenia: significant, prevents daily activity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Years to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged 9 to 16 years on the day of inclusion and resident of the site zone

• Participant in good health, based on medical history and physical examination

• Assent form or informed consent form has been signed and dated by the participant (based on local regulations), and informed consent form has been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations)

• Participant was able to attend all scheduled visits and comply with all trial procedures.

Exclusion Criteria:

• Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination).

• Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination

• Planned participation in another clinical trial during the present trial period

• Self-reported or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroids therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)

• Self-reported seropositivity for Human Immunodeficiency Virus (HIV) infection

• Self-reported systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances

• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion

• Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response

• Planned receipt of any vaccine in the 4 weeks following any trial vaccination

• Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily

• Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures

• Identified as a site employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member (i.e., immediate, husband, wife and their children, adopted or natural) of the site employees or the Investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Fortaleza	CE	Brazil	60430 270
2		Vitória	ES	Brazil	29040 09
3		Goiania	GO	Brazil	74675 020
4		Campo Grande	MS	Brazil	79074 460
5		Natal	RN	Brazil	59025 600
6		Aguazul	Casanare	Colombia
7		Yopal	Casanare	Colombia
8		Girardot	Cundinamarca	Colombia
9		Acacias	Meta	Colombia
10		Armenia	Quindío	Colombia
11		Calarcá	Quindío	Colombia
12		La Tebaida	Quindío	Colombia
13		Montenegro	Quindío	Colombia
14		Bucaramanga	Santander	Colombia
15		Tegucigalpa	Municipalidad Del Distrito Central	Honduras
16		Temixco	Morelos	Mexico
17		Municipio De Cd. Mante	Tamaulipas	Mexico
18		Veracruz Puerto	Veracruz	Mexico
19		Tizimin	Yucatán	Mexico
20		Valladolid	Yucatán	Mexico
21		Guayama		Puerto Rico	00784
22		San Juan		Puerto Rico	00918

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director, Sanofi Pasteur Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01374516
• Other Study ID Numbers: CYD15; UTN: U1111-1116-4986
• First Posted: Jun 16, 2011
• Last Update Posted: Mar 21, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Sanofi Pasteur, a Sanofi Company: Dengue Virus; Dengue fever; Dengue Hemorrhagic Fever; CYD dengue vaccine; Flavivirus; Dengue Disease
• Additional relevant MeSH terms: Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Fever; Hyperthermia; Vaccines

Study Results

Participant Flow

Recruitment Details	Study participants were enrolled from 08 June 2011 to 16 March 2012 at 5 clinical centers in Brazil, 9 in Colombia, 1 in Honduras, 5 in Mexico, and 2 in Puerto Rico.
Pre-assignment Detail	A total of 20869 participants were enrolled and randomized in the study.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Period Title: Vaccination Phase (Up to 25 Months)
STARTED	13920	6949
COMPLETED	13281	6640
NOT COMPLETED	639	309
Period Title: Vaccination Phase (Up to 25 Months)
STARTED	13281	6640
COMPLETED	10932	5387
NOT COMPLETED	2349	1253

Baseline Characteristics

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group	Total
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).	Total of all reporting groups
Overall Participants	13920	6949	20869
Age (Count of Participants)
<=18 years	13920 100%	6949 100%	20869 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Age Continuous	12.5 (2.14)	12.5 (2.13)	12.5 (2.14)
Sex: Female, Male (Count of Participants)
Female	7048 50.6%	3532 50.8%	10580 50.7%
Male	6872 49.4%	3417 49.2%	10289 49.3%
Region of Enrollment (Number) [Number]
Colombia	6497 46.7%	3246 46.7%	9743 46.7%
Brazil	2370 17%	1178 17%	3548 17%
Mexico	2312 16.6%	1152 16.6%	3464 16.6%
Honduras	1866 13.4%	933 13.4%	2799 13.4%
Puerto Rico	875 6.3%	440 6.3%	1315 6.3%

Outcome Measures

1. Primary Outcome

Title	Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction (RT-PCR) and/or dengue non-structural (NS) protein 1 antigen enzyme-linked immunosorbent assay (ELISA). Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time Frame	28 days and up to 13 months post-injection 3

Outcome Measure Data

Analysis Population Description

Number of symptomatic VCD cases were assessed in the Per-Protocol Analysis Set for Efficacy, defined as participants who had no protocol deviations.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	12574	6261
Number [Cases]	176	221

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Placebo Group
	Comments	The statistical methodology was based on the use of the two-sided 95% confidence interval (CI) of the vaccine efficacy (expressed in %). The CI was calculated using the exact method conditional on the total number of cases in both groups (exact method by Breslow & Day). The vaccine efficacy of the CYD dengue vaccine was considered significant if the lower bound of its 95% CI was greater than 25%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine Efficacy
	Estimated Value	60.8
	Confidence Interval	(2-Sided) 95%; 52.0 to 68.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time Frame	Day 0 up to 13 months post-injection 3

Outcome Measure Data

Analysis Population Description

Number of symptomatic VCD cases were assessed in the Full Analysis Set for Efficacy, which included all participants who received at least 1 injection.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	13914	6940
Number [Cases]	277	385

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Placebo Group
	Comments	The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy (expressed in %) calculated using the exact method conditional on the total number of cases in both groups.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine Efficacy
	Estimated Value	64.7
	Confidence Interval	(2-Sided) 95%; 58.7 to 69.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time Frame	28 days post-injection 1 and up to 13 months post-injection 3

Outcome Measure Data

Analysis Population Description

Number of symptomatic VCD cases were assessed in the Full Analysis Set for Efficacy, which included participants who received at least 1 dose of study vaccine.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	13914	6940
Number [Cases]	273	380

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Placebo Group
	Comments	The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy (expressed in %) calculated using the exact method conditional on the total number of cases in both groups.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine Efficacy
	Estimated Value	64.7
	Confidence Interval	(2-Sided) 95%; 58.7 to 69.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time Frame	28 days post-injection 2 and up to 13 months post-injection 3

Outcome Measure Data

Analysis Population Description

Number of symptomatic VCD cases were assessed in the Other Efficacy Analysis Set, which included participants who received at least 2 doses of study vaccine.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	13506	6765
Number [Cases]	236	306

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Placebo Group
	Comments	The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy (expressed in %) calculated using the exact method conditional on the total number of cases in both groups.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine Efficacy
	Estimated Value	61.9
	Confidence Interval	(2-Sided) 95%; 54.7 to 68.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	Dengue hemorrhagic fever (DHF) cases were defined as number of participants with at least one symptomatic VCD episode meeting the 1997 WHO criteria. (a) Fever: acute onset, high (>= 38°C) and continuous, lasting 2 to 7 days and (b) any of the pre-listed hemorrhagic manifestations and laboratory findings of thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/ or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhage.
Time Frame	Day 0 to the end of study (up to 72 months)

Outcome Measure Data

Analysis Population Description

Number of WHO dengue hemorrhagic fever cases were assessed in the Safety Analysis Set, which included all participants who received at least one dose of study vaccine. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	12809	6380
Due to Any of the 4 Serotypes: Any Grade	7	15
Due to Any of the 4 Serotypes: Grade I	0	2
Due to Any of the 4 Serotypes: Grade II	7	13
Due to Any of the 4 Serotypes: Grade III	0	0
Due to Any of the 4 Serotypes: Grade IV	0	0

6. Secondary Outcome

Title	Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	The 1997 WHO criteria are: a) Fever: acute onset, high (>= 38°C) and continuous, for 2 to 7 days and (b) any of the following: thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hematocrit increased by 20% or more or pleural effusion and/or ascites and/or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participant, usually in the form of skin and/or other hemorrhages; Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness; and Grade IV: Profound shock with undetectable blood pressure and pulse.
Time Frame	From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)

Outcome Measure Data

Analysis Population Description

Number of WHO dengue hemorrhagic fever cases were assessed in the Full Analysis Set for Surveillance Expansion Period, which included all participants who received at least 1 injection and accepted to be included in the Surveillance Expansion Period.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	11063	5430
Due to Any of the 4 Serotypes: Any Grade	2	0
Due to Any of the 4 Serotypes: Grade I	0	0
Due to Any of the 4 Serotypes: Grade II	2	0
Due to Any of the 4 Serotypes: Grade III	0	0
Due to Any of the 4 Serotypes: Grade IV	0	0

7. Secondary Outcome

Title	Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature >=38°C on at least 2 consecutive days) requiring hospitalization.
Time Frame	Day 0 up to the end of study (up to 72 months)

Outcome Measure Data

Analysis Population Description

Number of hospitalized dengue hemorrhagic fever cases were assessed in the Safety Analysis Set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Measure Participants	12809	6380
Number [Cases]	46	71

8. Secondary Outcome

Title	Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature >=38°C on at least 2 consecutive days) requiring hospitalization.
Time Frame	From consent to participate in the Surveillance Expansion Period to end of the study (up to 72 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed in the Safety Analysis Set.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Measure Participants	13915	6939
Number [Cases]	5	2

9. Secondary Outcome

Title	Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	The severity of VCD cases was assessed by an Independent Data monitoring Committee (IDMC) based on a medical review of cases and any of the following criteria:1) Platelet count <=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20 mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by Glasgow Coma Scale (GCS) score 5) Liver impairment (AST >1000 IU/L or prothrombin time [PT] International normalized ratio [INR] >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.
Time Frame	Day 0 to the end of study (up to 72 months)

Outcome Measure Data

Analysis Population Description

Number of clinically severe VCD cases were assessed in the Safety Analysis Set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	12809	6380
Number [Cases]	9	16

10. Secondary Outcome

Title	Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Description	The severity of VCD cases was assessed by an IDMC based on a medical review of cases and any of the following criteria:-1) Platelet count <=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20 mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. Unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by GCS score 5) Liver impairment (AST >1000 IU/L or PT INR >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.
Time Frame	From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)

Outcome Measure Data

Analysis Population Description

Number of clinically severe VCD cases were assessed in the Full Analysis Set for Surveillance Expansion Period. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	11061	5431
Number [Cases]	42	34

11. Secondary Outcome

Title	Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo
Description	Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (parental strains) were measured by the plaque reduction neutralization test in a pre-defined subset of participants.
Time Frame	Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit [V] 07) and 60 months (Visit [V] 12) post-injection 3

Outcome Measure Data

Analysis Population Description

Antibody titers against each dengue virus serotype strain were assessed in Full Analysis Set for Immunogenicity(FASI),which included a subset of participants who received at least one dose of vaccine and had a blood sample drawn and result available after the dose.Here, 'number analyzed'=participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Subset of participants who received at least one dose of CYD Dengue vaccine.	Subset of participants who received at least one dose of placebo vaccine.
Measure Participants	1301	643
Dengue virus Serotype 1: Pre-Inj.1	72.8 0.5%	70.5 1%
Dengue virus Serotype 1: Post-Inj. 2	92.7 0.7%	71.8 1%
Dengue virus Serotype 1: Post-Inj. 3	94.9 0.7%	74.2 1.1%
Dengue virus Serotype 1; 1 year Post-Inj. 3 (V 07)	85.6 0.6%	73.6 1.1%
Dengue virus Serotype 1; 5 year Post-Inj. 3 (V 12)	90.0 0.6%	81.1 1.2%
Dengue virus Serotype 2; Pre-Inj. 1	76.1 0.5%	73.8 1.1%
Dengue virus Serotype 2; Post-Inj. 2	97.5 0.7%	75.1 1.1%
Dengue virus Serotype 2; Post-Inj. 3	98.5 0.7%	77.2 1.1%
Dengue virus Serotype 2; 1 year Post-Inj. 3 (V 07)	94.1 0.7%	78.9 1.1%
Dengue virus Serotype 2; 5 year Post-Inj. 3 (V 12)	93.5 0.7%	83.1 1.2%
Dengue virus Serotype 3; Pre-Inj. 1	76.5 0.5%	73.6 1.1%
Dengue virus Serotype 3; Post-Inj. 2	98.5 0.7%	75.7 1.1%
Dengue virus Serotype 3; Post-Inj. 3	98.4 0.7%	78.0 1.1%
Dengue virus Serotype 3; 1 year Post-Inj. 3 (V 07)	92.7 0.7%	76.2 1.1%
Dengue virus Serotype 3; 5 year Post-Inj. 3 (V 12)	95.4 0.7%	82.7 1.2%
Dengue virus Serotype 4; Pre-Inj. 1	68.2 0.5%	65.0 0.9%
Dengue virus Serotype 4; Post-Inj. 2	96.9 0.7%	67.0 1%
Dengue virus Serotype 4; Post-Inj. 3	98.1 0.7%	68.9 1%
Dengue virus Serotype 4; 1 year Post-Inj. 3 (V 07)	94.9 0.7%	69.0 1%
Dengue virus Serotype 4; 5 year Post-Inj. 3 (V 12)	96.3 0.7%	78.9 1.1%

12. Secondary Outcome

Title	Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo
Description	Geometric mean titers for each of the 4 dengue virus serotypes (parental strains) were assessed using the plaque reduction neutralization test in a pre-defined subset of participants.
Time Frame	Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3

Outcome Measure Data

Analysis Population Description

Antibody titers against each dengue virus serotype strain were assessed in FASI, which included a subset of participants who received at least one dose of vaccine and had a blood sample drawn and result available after the dose. Here,'number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Subset of participants who received at least one dose of CYD Dengue vaccine.	Subset of participants who received at least one dose of the placebo vaccine.
Measure Participants	1301	643
Dengue virus Serotype 1; Pre-Inj. 1	128	119
Dengue virus Serotype 1; Post Inj. 2	458	128
Dengue virus Serotype 1; Post Inj. 3	395	121
Dengue virus Serotype 1; Year 1 Post Inj. 3 (V 07)	266	146
Dengue virus Serotype 1; Year 5 Post Inj. 3 (V 12)	284	210
Dengue virus Serotype 2; Pre-Inj. 1	138	115
Dengue virus Serotype 2; Post Inj. 2	622	124
Dengue virus Serotype 2; Post Inj. 3	574	129
Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07)	371	145
Dengue virus Serotype 2; Year 5 Post-Inj. 3 (V 12)	297	201
Dengue virus Serotype 3; Pre-Inj. 1	121	114
Dengue virus Serotype 3; Post Inj. 2	556	117
Dengue virus Serotype 3; Post Inj. 3	508	124
Dengue virus Serotype 3; Year 1 Post Inj. 3 (V 07)	292	137
Dengue virus Serotype 3; Year 5 Post Inj. 3 (V 12)	346	224
Dengue virus Serotype 4; Pre Inj. 1	43.6	39.0
Dengue virus Serotype 4; Post Inj. 2	261	40.9
Dengue virus Serotype 4; Post Inj. 3	241	44.3
Dengue virus Serotype 4; Year 1 Post Inj. 3 (V 07)	174	51.5
Dengue virus Serotype 4; Year 5 Post Inj. 3 (V 12)	144	73.6

13. Secondary Outcome

Title	Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo
Description	Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (9-11 years): Pain: incapacitating, unable to perform usual activities; Erythema and Swelling, >= 50 mm. Grade 3 Solicited injection site reactions (12-16 years): Pain: significant, prevents daily activity; Erythema and Swelling, >100 mm.
Time Frame	Within 7 days after each and any injection

Outcome Measure Data

Analysis Population Description

Solicited injection site reactions were assessed in a subset of the Safety Analysis Set, which included all participants who received at least one dose of study vaccine and who were evaluated for reactogenicity. Here, 'number analyzed' = participants with available data for specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	1333	664
Injection-site Pain (Post any injection)	650 4.7%	270 3.9%
Injection-site Erythema (Post-any injection)	83 0.6%	44 0.6%
Injection-site Swelling (Post-any injection)	77 0.6%	27 0.4%
Injection-site Pain (Post-injection 1)	430 3.1%	173 2.5%
Grade 3 Injection-site Pain (Post-injection 1)	11 0.1%	6 0.1%
Injection-site Erythema (Post-injection 1)	55 0.4%	31 0.4%
Grade 3 Injection-site Erythema (Post-injection 1)	0 0%	1 0%
Injection-site Swelling (Post-injection 1)	47 0.3%	18 0.3%
Grade 3 Injection-site Swelling (Post-injection 1)	0 0%	1 0%
Injection-site Pain (Post-injection 2)	332 2.4%	105 1.5%
Grade 3 Injection-site Pain (Post-injection 2)	7 0.1%	0 0%
Injection-site Erythema (Post-injection 2)	25 0.2%	11 0.2%
Grade 3 Injection-site Erythema (Post-injection 2)	1 0%	0 0%
Injection-site Swelling (Post-injection 2)	25 0.2%	6 0.1%
Grade 3 Injection-site Swelling (Post-injection 2)	0 0%	0 0%
Injection-site Pain (Post-injection 3)	288 2.1%	104 1.5%
Grade 3 Injection-site Pain (Post-injection 3)	11 0.1%	2 0%
Injection-site Erythema (Post-injection 3)	19 0.1%	10 0.1%
Grade 3 Injection-site Erythema (Post-injection 3)	0 0%	0 0%
Injection-site Swelling (Post-injection 3)	20 0.1%	8 0.1%
Grade 3 Injection-site Swelling (Post-injection 3)	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo
Description	Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 reactions: Fever: >= 39°C; Headache, Malaise, Myalgia, and Asthenia: significant, prevents daily activity.
Time Frame	Within 14 days after each and any injection

Outcome Measure Data

Analysis Population Description

Solicited systemic reactions were assessed in a subset of the Safety Analysis Set, which included all participants who received at least one dose of study vaccine and who were evaluated for reactogenicity. Here, 'number analyzed' = participants with available data for specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Measure Participants	1333	664
Fever (Post any injection)	220 1.6%	123 1.8%
Headache (Post any injection)	727 5.2%	379 5.5%
Malaise (Post any injection)	536 3.9%	261 3.8%
Myalgia (Post any injection)	576 4.1%	267 3.8%
Asthenia (Post any injection)	496 3.6%	251 3.6%
Fever (Post-injection 1)	86 0.6%	42 0.6%
Grade 3 Fever (Post-injection 1)	21 0.2%	7 0.1%
Headache (Post-injection 1)	528 3.8%	273 3.9%
Grade 3 Headache (Post-injection 1)	67 0.5%	27 0.4%
Malaise (Post-injection 1)	324 2.3%	170 2.4%
Grade 3 Malaise (Post-injection 1)	32 0.2%	15 0.2%
Myalgia (Post-injection 1)	386 2.8%	180 2.6%
Grade 3 Myalgia (Post-injection 1)	29 0.2%	10 0.1%
Asthenia (Post-injection 1)	326 2.3%	148 2.1%
Grade 3 Asthenia (Post-injection 1)	36 0.3%	17 0.2%
Fever (Post-injection 2)	72 0.5%	42 0.6%
Grade 3 Fever (Post-injection 2)	10 0.1%	7 0.1%
Headache (Post-injection 2)	386 2.8%	182 2.6%
Grade 3 Headache (Post-injection 2)	27 0.2%	15 0.2%
Malaise (Post-injection 2)	270 1.9%	106 1.5%
Grade 3 Malaise (Post-injection 2)	17 0.1%	8 0.1%
Myalgia (Post-injection 2)	273 2%	101 1.5%
Grade 3 Myalgia (Post-injection 2)	21 0.2%	5 0.1%
Asthenia (Post-injection 2)	231 1.7%	105 1.5%
Grade 3 Asthenia (Post-injection 2)	24 0.2%	7 0.1%
Fever (Post-injection 3)	89 0.6%	52 0.7%
Grade 3 Fever (Post-injection 3)	13 0.1%	5 0.1%
Headache (Post-injection 3)	378 2.7%	158 2.3%
Grade 3 Headache (Post-injection 3)	33 0.2%	12 0.2%
Malaise (Post-injection 3)	246 1.8%	96 1.4%
Grade 3 Malaise (Post-injection 3)	18 0.1%	7 0.1%
Myalgia (Post-injection 3)	255 1.8%	116 1.7%
Grade 3 Myalgia (Post-injection 3)	19 0.1%	5 0.1%
Asthenia (Post-injection 3)	208 1.5%	110 1.6%
Grade 3 Asthenia (Post-injection 3)	17 0.1%	8 0.1%

Adverse Events

Time Frame	Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months).
Adverse Event Reporting Description	Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
Arm/Group Title	CYD Dengue Vaccine Group		Placebo Group
Arm/Group Description	Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.		Participants received 3 doses of placebo vaccine; one each at 0, 6, and 12 months.
All Cause Mortality
	CYD Dengue Vaccine Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/13915 (0.3%)		27/6939 (0.4%)
Serious Adverse Events
	CYD Dengue Vaccine Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1765/13915 (12.7%)		911/6939 (13.1%)
Blood and lymphatic system disorders
Anaemia	0/13915 (0%)	0	4/6939 (0.1%)	4
Anaemia Of Pregnancy	2/13915 (0%)	2	0/6939 (0%)	0
Aplastic Anaemia	1/13915 (0%)	1	0/6939 (0%)	0
Haemorrhagic Anaemia	1/13915 (0%)	1	0/6939 (0%)	0
Idiopathic Thrombocytopenic Purpura	2/13915 (0%)	2	1/6939 (0%)	1
Iron Deficiency Anaemia	1/13915 (0%)	1	0/6939 (0%)	0
Lymphadenitis	7/13915 (0.1%)	7	4/6939 (0.1%)	4
Lymphadenopathy	2/13915 (0%)	2	1/6939 (0%)	1
Lymphoid Tissue Hyperplasia	1/13915 (0%)	1	0/6939 (0%)	0
Thrombocytopenia	1/13915 (0%)	1	1/6939 (0%)	1
Thrombocytopenic Purpura	2/13915 (0%)	2	0/6939 (0%)	0
Cardiac disorders
Tachycardia	1/13915 (0%)	1	0/6939 (0%)	0
Wolff-Parkinson-White Syndrome	0/13915 (0%)	0	1/6939 (0%)	1
Congenital, familial and genetic disorders
Arteriovenous Malformation	1/13915 (0%)	1	0/6939 (0%)	0
Atrial Septal Defect	1/13915 (0%)	1	0/6939 (0%)	0
Cryptorchism	0/13915 (0%)	0	1/6939 (0%)	1
Hereditary Spherocytosis	1/13915 (0%)	1	0/6939 (0%)	0
Phimosis	0/13915 (0%)	0	3/6939 (0%)	3
Sickle Cell Trait	0/13915 (0%)	0	1/6939 (0%)	1
Ear and labyrinth disorders
Tympanic Membrane Perforation	0/13915 (0%)	0	1/6939 (0%)	1
Vertigo	1/13915 (0%)	1	0/6939 (0%)	0
Endocrine disorders
Basedow's Disease	1/13915 (0%)	1	0/6939 (0%)	0
Hypothalamo-Pituitary Disorder	1/13915 (0%)	1	0/6939 (0%)	0
Eye disorders
Keratoconus	0/13915 (0%)	0	1/6939 (0%)	1
Retinal Detachment	1/13915 (0%)	1	0/6939 (0%)	0
Visual Impairment	0/13915 (0%)	0	1/6939 (0%)	1
Gastrointestinal disorders
Abdominal Adhesions	0/13915 (0%)	0	1/6939 (0%)	1
Abdominal Pain	26/13915 (0.2%)	26	9/6939 (0.1%)	9
Abdominal Pain Lower	3/13915 (0%)	3	1/6939 (0%)	1
Abdominal Pain Upper	1/13915 (0%)	1	1/6939 (0%)	1
Acute Abdomen	0/13915 (0%)	0	1/6939 (0%)	1
Anal Haemorrhage	1/13915 (0%)	1	0/6939 (0%)	0
Colitis	3/13915 (0%)	3	4/6939 (0.1%)	4
Constipation	1/13915 (0%)	1	0/6939 (0%)	0
Diarrhoea	5/13915 (0%)	5	4/6939 (0.1%)	4
Dyspepsia	1/13915 (0%)	1	0/6939 (0%)	0
Enteritis	2/13915 (0%)	3	0/6939 (0%)	0
Enterocolitis	1/13915 (0%)	1	0/6939 (0%)	0
Faecaloma	2/13915 (0%)	2	1/6939 (0%)	1
Food Poisoning	0/13915 (0%)	0	2/6939 (0%)	2
Gastritis	12/13915 (0.1%)	13	5/6939 (0.1%)	5
Gastritis Haemorrhagic	2/13915 (0%)	2	0/6939 (0%)	0
Gastrointestinal Haemorrhage	1/13915 (0%)	1	0/6939 (0%)	0
Gingivitis	1/13915 (0%)	1	0/6939 (0%)	0
Haematemesis	1/13915 (0%)	1	0/6939 (0%)	0
Inguinal Hernia	5/13915 (0%)	5	2/6939 (0%)	2
Inguinal Hernia, Obstructive	1/13915 (0%)	1	0/6939 (0%)	0
Intestinal Functional Disorder	1/13915 (0%)	1	0/6939 (0%)	0
Intestinal Obstruction	1/13915 (0%)	1	3/6939 (0%)	3
Intussusception	1/13915 (0%)	1	0/6939 (0%)	0
Irritable Bowel Syndrome	1/13915 (0%)	1	1/6939 (0%)	1
Malocclusion	1/13915 (0%)	1	0/6939 (0%)	0
Pancreatitis	1/13915 (0%)	1	1/6939 (0%)	1
Pancreatitis Acute	0/13915 (0%)	0	2/6939 (0%)	2
Peptic Ulcer	2/13915 (0%)	2	0/6939 (0%)	0
Peritonitis	2/13915 (0%)	2	0/6939 (0%)	0
Stomatitis	1/13915 (0%)	1	0/6939 (0%)	0
Umbilical Hernia	0/13915 (0%)	0	1/6939 (0%)	1
Umbilical Hernia, Obstructive	1/13915 (0%)	1	0/6939 (0%)	0
Varices Oesophageal	0/13915 (0%)	0	1/6939 (0%)	1
Vomiting	1/13915 (0%)	1	1/6939 (0%)	1
Vomiting In Pregnancy	1/13915 (0%)	1	0/6939 (0%)	0
General disorders
Catheter Site Phlebitis	0/13915 (0%)	0	1/6939 (0%)	1
Cyst	0/13915 (0%)	0	1/6939 (0%)	1
Death	1/13915 (0%)	1	0/6939 (0%)	0
Device Intolerance	0/13915 (0%)	0	1/6939 (0%)	1
Discomfort	0/13915 (0%)	0	1/6939 (0%)	1
Drowning	0/13915 (0%)	0	2/6939 (0%)	2
Malaise	0/13915 (0%)	0	1/6939 (0%)	1
Medical Device Complication	0/13915 (0%)	0	1/6939 (0%)	1
Pyrexia	9/13915 (0.1%)	9	2/6939 (0%)	2
Soft Tissue Inflammation	1/13915 (0%)	1	0/6939 (0%)	0
Sudden Death	2/13915 (0%)	2	0/6939 (0%)	0
Hepatobiliary disorders
Autoimmune Hepatitis	1/13915 (0%)	1	0/6939 (0%)	0
Bile Duct Stone	1/13915 (0%)	1	0/6939 (0%)	0
Cholecystitis	7/13915 (0.1%)	7	6/6939 (0.1%)	6
Cholecystitis Acute	5/13915 (0%)	5	2/6939 (0%)	2
Cholecystitis Chronic	3/13915 (0%)	3	2/6939 (0%)	2
Cholelithiasis	9/13915 (0.1%)	9	13/6939 (0.2%)	15
Cholestasis Of Pregnancy	0/13915 (0%)	0	1/6939 (0%)	1
Gallbladder Disorder	1/13915 (0%)	1	0/6939 (0%)	0
Hepatitis	2/13915 (0%)	2	0/6939 (0%)	0
Hepatitis Acute	2/13915 (0%)	2	1/6939 (0%)	1
Hepatitis Toxic	1/13915 (0%)	1	0/6939 (0%)	0
Hydrocholecystis	0/13915 (0%)	0	1/6939 (0%)	1
Jaundice	0/13915 (0%)	0	2/6939 (0%)	2
Immune system disorders
Allergy To Arthropod Sting	1/13915 (0%)	1	1/6939 (0%)	1
Anaphylactic Reaction	1/13915 (0%)	1	0/6939 (0%)	0
Anti-Neutrophil Cytoplasmic Antibody Positive Vasculitis	1/13915 (0%)	1	0/6939 (0%)	0
Antiphospholipid Syndrome	1/13915 (0%)	1	0/6939 (0%)	0
Drug Hypersensitivity	1/13915 (0%)	1	2/6939 (0%)	2
Food Allergy	0/13915 (0%)	0	1/6939 (0%)	1
Infections and infestations
Abdominal Abscess	0/13915 (0%)	0	1/6939 (0%)	1
Abortion Infected	1/13915 (0%)	1	2/6939 (0%)	2
Abscess	2/13915 (0%)	2	0/6939 (0%)	0
Abscess Limb	6/13915 (0%)	6	1/6939 (0%)	1
Abscess Neck	1/13915 (0%)	1	1/6939 (0%)	1
Abscess Of Salivary Gland	0/13915 (0%)	0	1/6939 (0%)	1
Abscess Oral	0/13915 (0%)	0	2/6939 (0%)	2
Acute Sinusitis	0/13915 (0%)	0	1/6939 (0%)	1
Acute Tonsillitis	1/13915 (0%)	1	4/6939 (0.1%)	4
Adenoiditis	0/13915 (0%)	0	1/6939 (0%)	1
Amniotic Cavity Infection	2/13915 (0%)	3	1/6939 (0%)	1
Amoebiasis	0/13915 (0%)	0	1/6939 (0%)	1
Amoebic Dysentery	2/13915 (0%)	2	1/6939 (0%)	1
Anal Abscess	1/13915 (0%)	1	0/6939 (0%)	0
Anogenital Warts	1/13915 (0%)	1	1/6939 (0%)	1
Appendicitis	261/13915 (1.9%)	261	138/6939 (2%)	138
Appendicitis Perforated	5/13915 (0%)	5	2/6939 (0%)	2
Arthritis Bacterial	3/13915 (0%)	3	2/6939 (0%)	2
Arthritis Infective	1/13915 (0%)	1	0/6939 (0%)	0
Asymptomatic Hiv Infection	1/13915 (0%)	1	0/6939 (0%)	0
Bacterial Infection	3/13915 (0%)	3	1/6939 (0%)	1
Bartholin's Abscess	2/13915 (0%)	2	3/6939 (0%)	3
Breast Abscess	4/13915 (0%)	4	3/6939 (0%)	3
Breast Cellulitis	6/13915 (0%)	6	0/6939 (0%)	0
Bronchiolitis	0/13915 (0%)	0	1/6939 (0%)	1
Bronchitis	8/13915 (0.1%)	8	0/6939 (0%)	0
Bronchopneumonia	6/13915 (0%)	6	1/6939 (0%)	1
Carbuncle	1/13915 (0%)	1	1/6939 (0%)	1
Cellulitis	50/13915 (0.4%)	50	35/6939 (0.5%)	35
Chikungunya Virus Infection	8/13915 (0.1%)	8	3/6939 (0%)	3
Chorioamnionitis	3/13915 (0%)	3	2/6939 (0%)	2
Chronic Sinusitis	1/13915 (0%)	1	0/6939 (0%)	0
Chronic Tonsillitis	1/13915 (0%)	1	2/6939 (0%)	2
Cutaneous Anthrax	2/13915 (0%)	2	1/6939 (0%)	1
Cystitis	1/13915 (0%)	1	0/6939 (0%)	0
Dengue Fever	101/13915 (0.7%)	104	94/6939 (1.4%)	94
Endometritis	3/13915 (0%)	3	1/6939 (0%)	1
Endometritis Decidual	3/13915 (0%)	3	2/6939 (0%)	2
Enterocolitis Infectious	1/13915 (0%)	1	1/6939 (0%)	1
Erysipelas	2/13915 (0%)	2	3/6939 (0%)	3
External Ear Cellulitis	1/13915 (0%)	1	0/6939 (0%)	0
Eye Infection Toxoplasmal	1/13915 (0%)	1	0/6939 (0%)	0
Flavivirus Infection	3/13915 (0%)	3	0/6939 (0%)	0
Gastroenteritis	34/13915 (0.2%)	34	21/6939 (0.3%)	21
Gastroenteritis Bacterial	2/13915 (0%)	2	0/6939 (0%)	0
Gastroenteritis Viral	3/13915 (0%)	3	2/6939 (0%)	2
Gastrointestinal Bacterial Infection	0/13915 (0%)	0	1/6939 (0%)	1
Gastrointestinal Infection	3/13915 (0%)	3	1/6939 (0%)	1
Gastrointestinal Viral Infection	0/13915 (0%)	0	1/6939 (0%)	1
Genital Infection Female	1/13915 (0%)	1	0/6939 (0%)	0
Genitourinary Tract Infection	0/13915 (0%)	0	2/6939 (0%)	2
Granuloma Inguinale	1/13915 (0%)	1	0/6939 (0%)	0
H1n1 Influenza	1/13915 (0%)	1	0/6939 (0%)	0
Hiv Infection	2/13915 (0%)	2	1/6939 (0%)	1
Hiv Infection Cdc Category A3	1/13915 (0%)	1	0/6939 (0%)	0
Helminthic Infection	1/13915 (0%)	1	1/6939 (0%)	1
Hepatitis A	3/13915 (0%)	3	1/6939 (0%)	1
Hepatitis Viral	2/13915 (0%)	2	0/6939 (0%)	0
Herpes Zoster	1/13915 (0%)	1	1/6939 (0%)	1
Herpes Zoster Ophthalmic	0/13915 (0%)	0	1/6939 (0%)	1
Infected Bites	1/13915 (0%)	1	1/6939 (0%)	1
Infectious Mononucleosis	2/13915 (0%)	2	1/6939 (0%)	1
Infective Myositis	1/13915 (0%)	1	0/6939 (0%)	0
Influenza	3/13915 (0%)	3	1/6939 (0%)	1
Leptospirosis	2/13915 (0%)	2	1/6939 (0%)	1
Lower Respiratory Tract Infection	2/13915 (0%)	2	1/6939 (0%)	1
Lung Infection	1/13915 (0%)	1	0/6939 (0%)	0
Malaria	0/13915 (0%)	0	1/6939 (0%)	1
Mastitis	4/13915 (0%)	4	3/6939 (0%)	3
Mastitis Postpartum	1/13915 (0%)	1	3/6939 (0%)	3
Mastoiditis	1/13915 (0%)	1	0/6939 (0%)	0
Meningitis Bacterial	2/13915 (0%)	2	1/6939 (0%)	1
Meningitis Viral	1/13915 (0%)	1	1/6939 (0%)	1
Mononucleosis Syndrome	1/13915 (0%)	1	0/6939 (0%)	0
Mumps	0/13915 (0%)	0	1/6939 (0%)	1
Mycoplasma Infection	1/13915 (0%)	1	0/6939 (0%)	0
Nasopharyngitis	0/13915 (0%)	0	2/6939 (0%)	2
Orchitis	5/13915 (0%)	5	2/6939 (0%)	2
Osteomyelitis	2/13915 (0%)	3	1/6939 (0%)	1
Osteomyelitis Chronic	4/13915 (0%)	4	1/6939 (0%)	1
Otitis Media	0/13915 (0%)	0	2/6939 (0%)	2
Otitis Media Chronic	0/13915 (0%)	0	1/6939 (0%)	2
Pancreatitis Mumps	1/13915 (0%)	1	0/6939 (0%)	0
Panencephalitis	0/13915 (0%)	0	1/6939 (0%)	1
Parasitic Gastroenteritis	2/13915 (0%)	2	0/6939 (0%)	0
Pelvic Inflammatory Disease	10/13915 (0.1%)	11	4/6939 (0.1%)	4
Perineal Abscess	1/13915 (0%)	1	0/6939 (0%)	0
Perineal Infection	0/13915 (0%)	0	1/6939 (0%)	1
Periorbital Cellulitis	2/13915 (0%)	2	1/6939 (0%)	1
Peritonsillar Abscess	2/13915 (0%)	2	2/6939 (0%)	2
Pharyngotonsillitis	3/13915 (0%)	3	0/6939 (0%)	0
Pilonidal Cyst	5/13915 (0%)	6	1/6939 (0%)	1
Pneumonia	18/13915 (0.1%)	18	13/6939 (0.2%)	13
Pneumonia Bacterial	4/13915 (0%)	4	0/6939 (0%)	0
Pneumonia Mycoplasmal	1/13915 (0%)	1	0/6939 (0%)	0
Post Procedural Infection	1/13915 (0%)	1	1/6939 (0%)	1
Postoperative Wound Infection	6/13915 (0%)	8	4/6939 (0.1%)	4
Postpartum Sepsis	4/13915 (0%)	4	0/6939 (0%)	0
Pulmonary Tuberculosis	2/13915 (0%)	2	1/6939 (0%)	1
Pyelonephritis	10/13915 (0.1%)	12	0/6939 (0%)	0
Pyelonephritis Acute	7/13915 (0.1%)	7	1/6939 (0%)	1
Retroperitoneal Abscess	1/13915 (0%)	1	0/6939 (0%)	0
Salmonellosis	2/13915 (0%)	2	0/6939 (0%)	0
Scarlet Fever	0/13915 (0%)	0	1/6939 (0%)	1
Secondary Syphilis	2/13915 (0%)	2	0/6939 (0%)	0
Sepsis	0/13915 (0%)	0	1/6939 (0%)	1
Sinusitis	1/13915 (0%)	1	1/6939 (0%)	1
Skin Infection	1/13915 (0%)	1	0/6939 (0%)	0
Soft Tissue Infection	1/13915 (0%)	1	0/6939 (0%)	0
Subcutaneous Abscess	13/13915 (0.1%)	13	2/6939 (0%)	2
Syphilis	2/13915 (0%)	2	0/6939 (0%)	0
Tonsillitis	2/13915 (0%)	2	2/6939 (0%)	2
Tonsillitis Bacterial	2/13915 (0%)	2	1/6939 (0%)	1
Tooth Abscess	6/13915 (0%)	6	2/6939 (0%)	3
Toxoplasmosis	0/13915 (0%)	0	2/6939 (0%)	2
Tracheitis	1/13915 (0%)	1	0/6939 (0%)	0
Tuberculosis	1/13915 (0%)	1	0/6939 (0%)	0
Typhoid Fever	1/13915 (0%)	1	0/6939 (0%)	0
Upper Respiratory Tract Infection	3/13915 (0%)	3	3/6939 (0%)	3
Urinary Tract Infection	118/13915 (0.8%)	127	59/6939 (0.9%)	69
Urinary Tract Infection Bacterial	1/13915 (0%)	1	0/6939 (0%)	0
Urosepsis	1/13915 (0%)	1	0/6939 (0%)	0
Vaginal Infection	1/13915 (0%)	1	1/6939 (0%)	1
Varicella	3/13915 (0%)	3	1/6939 (0%)	1
Viral Cardiomyopathy	1/13915 (0%)	1	0/6939 (0%)	0
Viral Infection	10/13915 (0.1%)	10	7/6939 (0.1%)	7
Visceral Leishmaniasis	1/13915 (0%)	1	0/6939 (0%)	0
Vulval Abscess	1/13915 (0%)	1	1/6939 (0%)	1
Wound Infection	5/13915 (0%)	5	0/6939 (0%)	0
Injury, poisoning and procedural complications
Abdominal Injury	2/13915 (0%)	2	0/6939 (0%)	0
Accident	0/13915 (0%)	0	1/6939 (0%)	1
Accident At Home	2/13915 (0%)	2	0/6939 (0%)	0
Accident At Work	2/13915 (0%)	2	1/6939 (0%)	1
Acetabulum Fracture	0/13915 (0%)	0	1/6939 (0%)	1
Adverse Event Following Immunisation	1/13915 (0%)	1	0/6939 (0%)	0
Alcohol Poisoning	0/13915 (0%)	0	1/6939 (0%)	1
Animal Bite	3/13915 (0%)	3	3/6939 (0%)	3
Ankle Fracture	2/13915 (0%)	2	1/6939 (0%)	1
Arthropod Sting	1/13915 (0%)	1	1/6939 (0%)	1
Avulsion Fracture	1/13915 (0%)	1	0/6939 (0%)	0
Burns Second Degree	6/13915 (0%)	6	2/6939 (0%)	2
Burns Third Degree	2/13915 (0%)	2	0/6939 (0%)	0
Chemical Poisoning	2/13915 (0%)	2	0/6939 (0%)	0
Chest Injury	3/13915 (0%)	3	2/6939 (0%)	2
Clavicle Fracture	1/13915 (0%)	1	1/6939 (0%)	1
Endotracheal Intubation Complication	1/13915 (0%)	1	0/6939 (0%)	0
Epiphyseal Fracture	1/13915 (0%)	1	0/6939 (0%)	0
Eye Injury	2/13915 (0%)	2	1/6939 (0%)	1
Eye Penetration	1/13915 (0%)	1	0/6939 (0%)	0
Face Injury	1/13915 (0%)	1	0/6939 (0%)	0
Facial Bones Fracture	1/13915 (0%)	1	0/6939 (0%)	0
Fall	28/13915 (0.2%)	28	11/6939 (0.2%)	12
Femur Fracture	5/13915 (0%)	5	2/6939 (0%)	2
Fibula Fracture	0/13915 (0%)	0	1/6939 (0%)	1
Foot Fracture	0/13915 (0%)	0	2/6939 (0%)	2
Forearm Fracture	21/13915 (0.2%)	21	7/6939 (0.1%)	7
Foreign Body	1/13915 (0%)	1	3/6939 (0%)	3
Foreign Body In Eye	0/13915 (0%)	0	1/6939 (0%)	1
Genital Injury	1/13915 (0%)	1	0/6939 (0%)	0
Gun Shot Wound	24/13915 (0.2%)	24	15/6939 (0.2%)	15
Hand Fracture	5/13915 (0%)	5	3/6939 (0%)	3
Head Injury	16/13915 (0.1%)	17	3/6939 (0%)	3
Humerus Fracture	6/13915 (0%)	6	5/6939 (0.1%)	5
Injury	0/13915 (0%)	0	1/6939 (0%)	1
Intentional Overdose	2/13915 (0%)	2	0/6939 (0%)	0
Joint Dislocation	3/13915 (0%)	3	2/6939 (0%)	2
Joint Injury	5/13915 (0%)	5	2/6939 (0%)	2
Limb Crushing Injury	1/13915 (0%)	1	0/6939 (0%)	0
Limb Injury	4/13915 (0%)	4	3/6939 (0%)	3
Limb Traumatic Amputation	4/13915 (0%)	4	0/6939 (0%)	0
Lower Limb Fracture	3/13915 (0%)	3	3/6939 (0%)	3
Lumbar Vertebral Fracture	0/13915 (0%)	0	1/6939 (0%)	1
Meniscus Lesion	3/13915 (0%)	3	0/6939 (0%)	0
Multiple Fractures	6/13915 (0%)	6	1/6939 (0%)	1
Multiple Injuries	12/13915 (0.1%)	12	3/6939 (0%)	3
Muscle Injury	0/13915 (0%)	0	1/6939 (0%)	1
Nerve Injury	1/13915 (0%)	1	0/6939 (0%)	0
Open Wound	0/13915 (0%)	0	1/6939 (0%)	1
Perineal Laceration	0/13915 (0%)	0	1/6939 (0%)	1
Pneumothorax Traumatic	0/13915 (0%)	0	1/6939 (0%)	1
Poisoning	1/13915 (0%)	1	0/6939 (0%)	0
Poisoning Deliberate	15/13915 (0.1%)	16	10/6939 (0.1%)	10
Post Procedural Haemorrhage	1/13915 (0%)	1	0/6939 (0%)	0
Post-Traumatic Pain	0/13915 (0%)	0	1/6939 (0%)	1
Postoperative Wound Complication	0/13915 (0%)	0	1/6939 (0%)	1
Procedural Complication	1/13915 (0%)	1	0/6939 (0%)	0
Radius Fracture	8/13915 (0.1%)	8	3/6939 (0%)	3
Road Traffic Accident	108/13915 (0.8%)	109	39/6939 (0.6%)	39
Skull Fracture	1/13915 (0%)	1	0/6939 (0%)	0
Soft Tissue Injury	1/13915 (0%)	1	0/6939 (0%)	0
Spinal Cord Injury	0/13915 (0%)	0	1/6939 (0%)	1
Spinal Cord Injury Cervical	1/13915 (0%)	1	0/6939 (0%)	0
Sports Injury	8/13915 (0.1%)	8	3/6939 (0%)	3
Stab Wound	5/13915 (0%)	5	1/6939 (0%)	1
Tendon Injury	1/13915 (0%)	1	0/6939 (0%)	0
Tendon Rupture	2/13915 (0%)	2	1/6939 (0%)	1
Testicular Injury	1/13915 (0%)	1	0/6939 (0%)	0
Thermal Burn	1/13915 (0%)	1	0/6939 (0%)	0
Tibia Fracture	5/13915 (0%)	5	3/6939 (0%)	3
Toxicity To Various Agents	7/13915 (0.1%)	7	4/6939 (0.1%)	4
Traumatic Brain Injury	5/13915 (0%)	5	1/6939 (0%)	1
Traumatic Fracture	0/13915 (0%)	0	1/6939 (0%)	1
Ulna Fracture	3/13915 (0%)	3	0/6939 (0%)	0
Ulnar Nerve Injury	0/13915 (0%)	0	1/6939 (0%)	1
Upper Limb Fracture	1/13915 (0%)	1	1/6939 (0%)	1
Vascular Access Complication	1/13915 (0%)	1	0/6939 (0%)	0
Wound	5/13915 (0%)	5	2/6939 (0%)	2
Wrist Fracture	2/13915 (0%)	2	1/6939 (0%)	1
Investigations
Investigation	1/13915 (0%)	1	0/6939 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/13915 (0%)	0	1/6939 (0%)	1
Diabetes Mellitus Inadequate Control	0/13915 (0%)	0	2/6939 (0%)	3
Diabetic Ketoacidosis	2/13915 (0%)	3	0/6939 (0%)	0
Hypoglycaemia	1/13915 (0%)	1	0/6939 (0%)	0
Type 1 Diabetes Mellitus	1/13915 (0%)	1	1/6939 (0%)	1
Musculoskeletal and connective tissue disorders
Ankle Deformity	1/13915 (0%)	1	0/6939 (0%)	0
Arthropathy	2/13915 (0%)	2	0/6939 (0%)	0
Back Pain	4/13915 (0%)	4	2/6939 (0%)	2
Epiphysiolysis	1/13915 (0%)	1	0/6939 (0%)	0
Intervertebral Disc Protrusion	0/13915 (0%)	0	1/6939 (0%)	1
Juvenile Arthritis	0/13915 (0%)	0	2/6939 (0%)	2
Knee Deformity	1/13915 (0%)	1	1/6939 (0%)	1
Myopathy	0/13915 (0%)	0	1/6939 (0%)	1
Myositis	2/13915 (0%)	2	0/6939 (0%)	0
Pathological Fracture	1/13915 (0%)	1	0/6939 (0%)	0
Rhabdomyolysis	0/13915 (0%)	0	1/6939 (0%)	1
Rheumatic Fever	2/13915 (0%)	2	1/6939 (0%)	1
Rheumatoid Arthritis	0/13915 (0%)	0	1/6939 (0%)	1
Sacroiliitis	1/13915 (0%)	1	0/6939 (0%)	0
Synovial Cyst	0/13915 (0%)	0	1/6939 (0%)	1
Systemic Lupus Erythematosus	2/13915 (0%)	2	2/6939 (0%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign Hydatidiform Mole	1/13915 (0%)	1	1/6939 (0%)	1
Benign Ovarian Tumour	1/13915 (0%)	1	0/6939 (0%)	0
Benign Pancreatic Neoplasm	0/13915 (0%)	0	1/6939 (0%)	1
Bone Giant Cell Tumour	0/13915 (0%)	0	1/6939 (0%)	1
Bone Sarcoma	0/13915 (0%)	0	1/6939 (0%)	1
Brain Neoplasm Malignant	0/13915 (0%)	0	1/6939 (0%)	1
Chondrosarcoma	1/13915 (0%)	2	0/6939 (0%)	0
Chronic Myeloid Leukaemia	1/13915 (0%)	1	0/6939 (0%)	0
Desmoid Tumour	1/13915 (0%)	1	0/6939 (0%)	0
Fibroadenoma Of Breast	1/13915 (0%)	1	0/6939 (0%)	0
Haemangioma Of Skin	0/13915 (0%)	0	1/6939 (0%)	1
Hodgkin's Disease	2/13915 (0%)	2	0/6939 (0%)	0
Leukaemia	1/13915 (0%)	1	0/6939 (0%)	0
Osteochondroma	1/13915 (0%)	1	0/6939 (0%)	0
Osteoma	1/13915 (0%)	1	0/6939 (0%)	0
Osteosarcoma Metastatic	0/13915 (0%)	0	1/6939 (0%)	1
Osteosarcoma Recurrent	0/13915 (0%)	0	1/6939 (0%)	1
Ovarian Adenoma	1/13915 (0%)	1	0/6939 (0%)	0
Ovarian Germ Cell Teratoma Benign	2/13915 (0%)	2	1/6939 (0%)	1
Pituitary Tumour Benign	2/13915 (0%)	2	0/6939 (0%)	0
Thyroid Cancer	1/13915 (0%)	1	0/6939 (0%)	0
Uterine Leiomyoma	2/13915 (0%)	2	0/6939 (0%)	0
Nervous system disorders
Acute Disseminated Encephalomyelitis	0/13915 (0%)	0	1/6939 (0%)	1
Acute Polyneuropathy	1/13915 (0%)	1	0/6939 (0%)	0
Arachnoid Cyst	1/13915 (0%)	1	0/6939 (0%)	0
Atonic Seizures	1/13915 (0%)	1	0/6939 (0%)	0
Cerebellar Syndrome	1/13915 (0%)	1	0/6939 (0%)	0
Complicated Migraine	1/13915 (0%)	1	1/6939 (0%)	1
Convulsion	21/13915 (0.2%)	31	10/6939 (0.1%)	11
Dizziness	0/13915 (0%)	0	1/6939 (0%)	1
Encephalitis	1/13915 (0%)	1	1/6939 (0%)	1
Epilepsy	26/13915 (0.2%)	86	8/6939 (0.1%)	27
Grand Mal Convulsion	2/13915 (0%)	2	2/6939 (0%)	4
Guillain-Barre Syndrome	0/13915 (0%)	0	2/6939 (0%)	2
Haemorrhage Intracranial	1/13915 (0%)	1	1/6939 (0%)	1
Haemorrhagic Cerebral Infarction	1/13915 (0%)	1	0/6939 (0%)	0
Headache	2/13915 (0%)	2	2/6939 (0%)	2
Hydrocephalus	1/13915 (0%)	1	0/6939 (0%)	0
Hypersomnia	0/13915 (0%)	0	1/6939 (0%)	1
Hypertensive Encephalopathy	1/13915 (0%)	1	1/6939 (0%)	1
Idiopathic Generalised Epilepsy	0/13915 (0%)	0	1/6939 (0%)	1
Intracranial Aneurysm	1/13915 (0%)	1	0/6939 (0%)	0
Migraine	5/13915 (0%)	5	2/6939 (0%)	2
Migraine With Aura	0/13915 (0%)	0	1/6939 (0%)	1
Migraine Without Aura	2/13915 (0%)	2	0/6939 (0%)	0
Neuropathy Peripheral	0/13915 (0%)	0	1/6939 (0%)	1
Partial Seizures	1/13915 (0%)	1	1/6939 (0%)	1
Post-Traumatic Headache	1/13915 (0%)	1	0/6939 (0%)	0
Status Epilepticus	3/13915 (0%)	3	1/6939 (0%)	3
Status Migrainosus	0/13915 (0%)	0	1/6939 (0%)	1
Syncope	6/13915 (0%)	6	2/6939 (0%)	2
Viith Nerve Paralysis	5/13915 (0%)	5	3/6939 (0%)	3
Pregnancy, puerperium and perinatal conditions
Abnormal Product Of Conception	1/13915 (0%)	1	0/6939 (0%)	0
Abortion	14/13915 (0.1%)	14	6/6939 (0.1%)	6
Abortion Complete	9/13915 (0.1%)	9	4/6939 (0.1%)	4
Abortion Complicated	0/13915 (0%)	0	1/6939 (0%)	1
Abortion Incomplete	22/13915 (0.2%)	22	9/6939 (0.1%)	9
Abortion Incomplete Complicated	1/13915 (0%)	1	0/6939 (0%)	0
Abortion Missed	3/13915 (0%)	3	2/6939 (0%)	2
Abortion Of Ectopic Pregnancy	0/13915 (0%)	0	1/6939 (0%)	1
Abortion Spontaneous	48/13915 (0.3%)	51	30/6939 (0.4%)	34
Abortion Spontaneous Complete	8/13915 (0.1%)	8	6/6939 (0.1%)	6
Abortion Spontaneous Complicated	0/13915 (0%)	0	1/6939 (0%)	1
Abortion Spontaneous Incomplete	16/13915 (0.1%)	16	2/6939 (0%)	2
Abortion Spontaneous Incomplete Complicated	1/13915 (0%)	1	0/6939 (0%)	0
Abortion Threatened	14/13915 (0.1%)	14	3/6939 (0%)	4
Amniorrhexis	1/13915 (0%)	1	0/6939 (0%)	0
Antepartum Haemorrhage	2/13915 (0%)	2	0/6939 (0%)	0
Blighted Ovum	11/13915 (0.1%)	11	1/6939 (0%)	1
Cephalo-Pelvic Disproportion	1/13915 (0%)	1	0/6939 (0%)	0
Cervical Incompetence	2/13915 (0%)	2	0/6939 (0%)	0
Complication Of Delivery	4/13915 (0%)	4	0/6939 (0%)	0
Delivery	1/13915 (0%)	1	0/6939 (0%)	0
Eclampsia	5/13915 (0%)	5	0/6939 (0%)	0
Ectopic Pregnancy	3/13915 (0%)	3	3/6939 (0%)	3
Failed Induction Of Labour	1/13915 (0%)	1	0/6939 (0%)	0
False Labour	39/13915 (0.3%)	45	14/6939 (0.2%)	14
Foetal Distress Syndrome	1/13915 (0%)	1	4/6939 (0.1%)	4
Gestational Hypertension	12/13915 (0.1%)	12	7/6939 (0.1%)	7
Hellp Syndrome	2/13915 (0%)	2	1/6939 (0%)	1
High Risk Pregnancy	1/13915 (0%)	1	1/6939 (0%)	1
Hyperemesis Gravidarum	3/13915 (0%)	3	0/6939 (0%)	0
Intra-Uterine Death	1/13915 (0%)	1	3/6939 (0%)	3
Intrapartum Haemorrhage	1/13915 (0%)	1	0/6939 (0%)	0
Oligohydramnios	12/13915 (0.1%)	12	4/6939 (0.1%)	4
Placental Insufficiency	1/13915 (0%)	1	0/6939 (0%)	0
Postpartum Haemorrhage	8/13915 (0.1%)	8	5/6939 (0.1%)	5
Pre-Eclampsia	34/13915 (0.2%)	35	23/6939 (0.3%)	23
Premature Baby	2/13915 (0%)	2	0/6939 (0%)	0
Premature Delivery	6/13915 (0%)	6	1/6939 (0%)	1
Premature Labour	17/13915 (0.1%)	17	6/6939 (0.1%)	6
Premature Rupture Of Membranes	13/13915 (0.1%)	13	2/6939 (0%)	2
Premature Separation Of Placenta	1/13915 (0%)	1	0/6939 (0%)	0
Prolonged Labour	1/13915 (0%)	1	3/6939 (0%)	3
Puerperal Pyrexia	0/13915 (0%)	0	1/6939 (0%)	1
Retained Placenta Or Membranes	2/13915 (0%)	2	2/6939 (0%)	2
Retained Products Of Conception	2/13915 (0%)	2	1/6939 (0%)	1
Ruptured Ectopic Pregnancy	0/13915 (0%)	0	1/6939 (0%)	1
Stillbirth	6/13915 (0%)	6	5/6939 (0.1%)	5
Threatened Labour	7/13915 (0.1%)	7	9/6939 (0.1%)	10
Psychiatric disorders
Abnormal Behaviour	1/13915 (0%)	1	0/6939 (0%)	0
Acute Psychosis	2/13915 (0%)	2	1/6939 (0%)	1
Acute Stress Disorder	1/13915 (0%)	1	0/6939 (0%)	0
Adjustment Disorder	1/13915 (0%)	1	0/6939 (0%)	0
Aggression	1/13915 (0%)	1	1/6939 (0%)	1
Anorexia Nervosa	1/13915 (0%)	1	0/6939 (0%)	0
Anxiety Disorder	1/13915 (0%)	1	1/6939 (0%)	1
Bipolar I Disorder	2/13915 (0%)	4	0/6939 (0%)	0
Bipolar Disorder	2/13915 (0%)	2	3/6939 (0%)	3
Completed Suicide	2/13915 (0%)	2	2/6939 (0%)	2
Conduct Disorder	1/13915 (0%)	1	1/6939 (0%)	1
Conversion Disorder	3/13915 (0%)	3	1/6939 (0%)	1
Dependence	1/13915 (0%)	1	0/6939 (0%)	0
Depression	18/13915 (0.1%)	18	9/6939 (0.1%)	9
Depression Suicidal	0/13915 (0%)	0	2/6939 (0%)	2
Dissociative Disorder	1/13915 (0%)	1	0/6939 (0%)	0
Drug Abuse	2/13915 (0%)	2	1/6939 (0%)	1
Drug Dependence	1/13915 (0%)	1	0/6939 (0%)	0
Intentional Drug Misuse	1/13915 (0%)	1	1/6939 (0%)	1
Intentional Self-Injury	6/13915 (0%)	6	2/6939 (0%)	2
Intermittent Explosive Disorder	1/13915 (0%)	1	0/6939 (0%)	0
Major Depression	6/13915 (0%)	6	2/6939 (0%)	2
Obsessive Rumination	0/13915 (0%)	0	1/6939 (0%)	1
Psychotic Disorder	1/13915 (0%)	1	0/6939 (0%)	0
Schizophrenia	1/13915 (0%)	1	2/6939 (0%)	2
Schizophrenia, Undifferentiated Type	1/13915 (0%)	1	0/6939 (0%)	0
Somatoform Disorder	1/13915 (0%)	1	1/6939 (0%)	1
Substance Abuse	14/13915 (0.1%)	15	9/6939 (0.1%)	13
Suicidal Ideation	2/13915 (0%)	2	0/6939 (0%)	0
Suicide Attempt	19/13915 (0.1%)	19	8/6939 (0.1%)	14
Renal and urinary disorders
Calculus Ureteric	1/13915 (0%)	1	0/6939 (0%)	0
Calculus Urethral	1/13915 (0%)	1	0/6939 (0%)	0
Calculus Urinary	3/13915 (0%)	3	1/6939 (0%)	1
Cystitis Haemorrhagic	0/13915 (0%)	0	1/6939 (0%)	1
Glomerulonephritis	0/13915 (0%)	0	1/6939 (0%)	1
Haematuria	1/13915 (0%)	1	0/6939 (0%)	0
Lupus Nephritis	1/13915 (0%)	1	1/6939 (0%)	1
Nephritic Syndrome	1/13915 (0%)	1	0/6939 (0%)	0
Nephrolithiasis	15/13915 (0.1%)	15	5/6939 (0.1%)	5
Post Streptococcal Glomerulonephritis	0/13915 (0%)	0	1/6939 (0%)	1
Renal Colic	2/13915 (0%)	2	3/6939 (0%)	5
Renal Failure	1/13915 (0%)	1	0/6939 (0%)	0
Renal Tubular Necrosis	0/13915 (0%)	0	1/6939 (0%)	1
Tubulointerstitial Nephritis	0/13915 (0%)	0	1/6939 (0%)	1
Urogenital Haemorrhage	1/13915 (0%)	1	0/6939 (0%)	0
Reproductive system and breast disorders
Adenomyosis	1/13915 (0%)	1	0/6939 (0%)	0
Balanitis	1/13915 (0%)	1	0/6939 (0%)	0
Bartholinitis	1/13915 (0%)	1	0/6939 (0%)	0
Breast Disorder	2/13915 (0%)	2	0/6939 (0%)	0
Breast Mass	4/13915 (0%)	4	1/6939 (0%)	1
Breast Pain	1/13915 (0%)	1	0/6939 (0%)	0
Coital Bleeding	0/13915 (0%)	0	1/6939 (0%)	1
Dysfunctional Uterine Bleeding	3/13915 (0%)	5	1/6939 (0%)	1
Dysmenorrhoea	2/13915 (0%)	2	1/6939 (0%)	1
Endometriosis	1/13915 (0%)	1	0/6939 (0%)	0
Epididymitis	1/13915 (0%)	1	0/6939 (0%)	0
Female Genital Tract Fistula	1/13915 (0%)	1	0/6939 (0%)	0
Gynaecomastia	0/13915 (0%)	0	1/6939 (0%)	1
Haematocolpos	1/13915 (0%)	1	0/6939 (0%)	0
Haematosalpinx	0/13915 (0%)	0	1/6939 (0%)	1
Haemorrhagic Ovarian Cyst	1/13915 (0%)	1	1/6939 (0%)	1
Metrorrhagia	0/13915 (0%)	0	1/6939 (0%)	1
Ovarian Cyst	7/13915 (0.1%)	7	5/6939 (0.1%)	5
Ovarian Cyst Ruptured	2/13915 (0%)	2	1/6939 (0%)	1
Ovarian Torsion	0/13915 (0%)	0	1/6939 (0%)	1
Ovulation Pain	1/13915 (0%)	1	0/6939 (0%)	0
Pelvic Pain	3/13915 (0%)	3	0/6939 (0%)	0
Polycystic Ovaries	1/13915 (0%)	1	0/6939 (0%)	0
Retrograde Menstruation	0/13915 (0%)	0	1/6939 (0%)	1
Testicular Disorder	0/13915 (0%)	0	1/6939 (0%)	1
Testicular Torsion	12/13915 (0.1%)	12	3/6939 (0%)	3
Uterine Cyst	1/13915 (0%)	1	0/6939 (0%)	0
Uterine Haemorrhage	2/13915 (0%)	2	0/6939 (0%)	0
Vaginal Haemorrhage	3/13915 (0%)	3	0/6939 (0%)	0
Varicocele	2/13915 (0%)	2	0/6939 (0%)	0
Vulval Haematoma	1/13915 (0%)	1	0/6939 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema	2/13915 (0%)	2	0/6939 (0%)	0
Acute Respiratory Failure	1/13915 (0%)	1	0/6939 (0%)	0
Adenoidal Hypertrophy	2/13915 (0%)	2	0/6939 (0%)	0
Alveolitis Allergic	1/13915 (0%)	1	0/6939 (0%)	0
Asphyxia	2/13915 (0%)	2	0/6939 (0%)	0
Aspiration	0/13915 (0%)	0	1/6939 (0%)	1
Asthma	19/13915 (0.1%)	24	17/6939 (0.2%)	22
Asthmatic Crisis	12/13915 (0.1%)	14	7/6939 (0.1%)	8
Bronchial Obstruction	1/13915 (0%)	1	0/6939 (0%)	0
Epistaxis	0/13915 (0%)	0	1/6939 (0%)	1
Haemothorax	1/13915 (0%)	1	0/6939 (0%)	0
Nasal Septum Deviation	0/13915 (0%)	0	1/6939 (0%)	1
Nasal Turbinate Hypertrophy	1/13915 (0%)	1	0/6939 (0%)	0
Oropharyngeal Pain	1/13915 (0%)	1	0/6939 (0%)	0
Pleurisy	1/13915 (0%)	1	0/6939 (0%)	0
Pneumothorax	1/13915 (0%)	1	1/6939 (0%)	1
Pulmonary Artery Stenosis	1/13915 (0%)	1	0/6939 (0%)	0
Pulmonary Embolism	1/13915 (0%)	1	0/6939 (0%)	0
Pulmonary Oedema	1/13915 (0%)	1	0/6939 (0%)	0
Respiratory Tract Haemorrhage	1/13915 (0%)	1	0/6939 (0%)	0
Status Asthmaticus	5/13915 (0%)	6	2/6939 (0%)	2
Tonsillar Cyst	0/13915 (0%)	0	1/6939 (0%)	1
Tonsillar Hypertrophy	5/13915 (0%)	5	2/6939 (0%)	2
Skin and subcutaneous tissue disorders
Angioedema	0/13915 (0%)	0	1/6939 (0%)	1
Dermatitis Atopic	1/13915 (0%)	1	0/6939 (0%)	0
Erythema	1/13915 (0%)	1	0/6939 (0%)	0
Erythema Nodosum	1/13915 (0%)	1	0/6939 (0%)	0
Henoch-Schonlein Purpura	1/13915 (0%)	1	0/6939 (0%)	0
Hypertrophic Scar	1/13915 (0%)	1	0/6939 (0%)	0
Mechanical Urticaria	1/13915 (0%)	1	0/6939 (0%)	0
Rash Erythematous	0/13915 (0%)	0	1/6939 (0%)	1
Skin Fissures	1/13915 (0%)	1	0/6939 (0%)	0
Subcutaneous Nodule	1/13915 (0%)	1	0/6939 (0%)	0
Urticaria	4/13915 (0%)	4	0/6939 (0%)	0
Social circumstances
Physical Assault	9/13915 (0.1%)	9	4/6939 (0.1%)	4
Sexual Abuse	7/13915 (0.1%)	7	4/6939 (0.1%)	4
Substance Use	1/13915 (0%)	1	0/6939 (0%)	0
Victim Of Crime	2/13915 (0%)	2	0/6939 (0%)	0
Victim Of Homicide	5/13915 (0%)	5	1/6939 (0%)	1
Victim Of Sexual Abuse	1/13915 (0%)	1	1/6939 (0%)	1
Surgical and medical procedures
Abortion Induced	0/13915 (0%)	0	1/6939 (0%)	1
Abortion Induced Complete	1/13915 (0%)	1	0/6939 (0%)	0
Caesarean Section	2/13915 (0%)	2	1/6939 (0%)	1
Cholecystectomy	1/13915 (0%)	1	0/6939 (0%)	0
Obesity Surgery	0/13915 (0%)	0	1/6939 (0%)	1
Scoliosis Surgery	1/13915 (0%)	1	0/6939 (0%)	0
Surgery	0/13915 (0%)	0	1/6939 (0%)	1
Umbilical Hernia Repair	0/13915 (0%)	0	1/6939 (0%)	1
Vascular disorders
Hypertensive Crisis	1/13915 (0%)	1	0/6939 (0%)	0
Secondary Hypertension	2/13915 (0%)	2	0/6939 (0%)	0
Other (Not Including Serious) Adverse Events
	CYD Dengue Vaccine Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1038/1333 (77.9%)		515/664 (77.6%)
General disorders
Asthenia	500/1333 (37.5%)	771	253/664 (38.1%)	366
Injection Site Erythema	83/1333 (6.2%)	99	44/664 (6.6%)	52
Injection Site Pain	650/1333 (48.8%)	1056	270/664 (40.7%)	384
Injection Site Swelling	77/1333 (5.8%)	92	27/664 (4.1%)	32
Malaise	539/1333 (40.4%)	853	264/664 (39.8%)	383
Pyrexia	238/1333 (17.9%)	270	127/664 (19.1%)	142
Infections and infestations
Influenza	76/1333 (5.7%)	80	37/664 (5.6%)	40
Nasopharyngitis	150/1333 (11.3%)	163	60/664 (9%)	70
Musculoskeletal and connective tissue disorders
Myalgia	578/1333 (43.4%)	921	267/664 (40.2%)	400
Nervous system disorders
Headache	753/1333 (56.5%)	1385	388/664 (58.4%)	652

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.