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Safety Overview of
CYD-TDV Dengue Vaccine:
Pooled Analysis of Data from
18 Clinical Trials
Dr. Tawee Chotpitayasunondh,MD
20 July 2017, National Vaccine Institute
| 2
Reduction in
symptomatic dengue
65.6% (95% CI: 60.7–69.9)
Reduction in
hospitalized dengue
80.8% (95% CI: 70.1–87.7)
CONSISTENT EFFICACY PROFILE OF CYD 14 & CYD 15 STUDIES
IN SUBJECTS 9–16 YEARS OF AGE DURING ACTIVE PHASE
1.Hadinegoro, 2015, N Engl J Med.
Key Efficacy Results 25-month active phase* Pooled efficacy analyses‡1
*Data come from the 2 pivotal, phase III, large-scale efficacy trials CYD14 and CYD15, which were designed to fully assess efficacy; postdose 1; 1Full Analysis Set
for Efficacy (FASE): all subjects who received at least one injection. †dengue hemorrhagic fever, Severe Dengue, IDMC criteria. CI=confidence interval;
DENV=dengue virus.
Reduction in
severe dengue †
93.2% (95% CI: 77.3–98.0)
For each serotype:
DENV-1: 58.4% (95% CI: 47.7–66.9)
DENV-2: 47.1% (95% CI: 31.3–59.2)
DENV-3: 73.6% (95% CI: 64.4–80.4)
DENV-4: 83.2% (95% CI: 76.2–88.2)
By dengue serostatus:
Seropositive: 81.9% (95% CI: 67.2–90.0)
Seronegative: 52.5% (95% CI: 5.9–76.1)
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
Pooled analysis of safety data from
18 clinical trials
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Integrated safety analyses performed in 9 to 60 yo population create significant size of safety
database
13 Clinical trials with final immunization schedule from phase II to phase III were included
in the pooled safety analyses
20,667 subjects of 9 to 60 years
~19,700 received all 3 doses
Allowing to detect very common, common, and uncommon adverse events (AEs) that
occur with an incidence ≥ 0.1%, in accordance with WHO guidelines
*Integrated safety analysis pooling data from 13 studies that used the final formulation and final vaccination schedule (CYD12, 13, 22, 24, 28, 30, 47, 23, 17, 32, 14, 15, 51).
AE=adverse event; AR=adverse reaction.
METHODOLOGY:- INTEGRATED SAFETY ANALYSES FROM CLINICAL TRIALS STUDIES
CONDUCTED ENROLLING INDIVIDUALS UP TO 60 YEARS OF AGE
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
Criteria of safety assessment
• Solicited* (local vs systemic reactions)
• Injection-site reactions : pain, erythema and swelling (monitored for 7 days after vaccination)
• Systemic reactions : fever, headache, myalgia, asthenia,
malaise (monitored for 14 days after vaccination)
• Unsolicited** (monitored for 28 days after vaccination)
• Immediate AE : AEs occurring within 30 minutes of
an injection
• Adverse event of special interest (AESI)
*considered as being vaccine-related (adverse reactions)
**relatedness was assessed by the investigators (can be considered as
adverse events or adverse reactions)
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
Overall safety profile (stratified by age groups)
Results showed that the overall reactogenicity and safety profile for the CYD-TDV vaccine was comparable to placebo
across all age groups (2–8 years; 9–60 years) with similar reported rates and nature of events.
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
0.2
74
49.6
66.5
44.3
0
64.1
36.5
59
39
0 10 20 30 40 50 60 70 80 90 100
Immediate unsolicited AR
Solicited AR
Solicited injection site reaction
Solicited systemic reaction
Unsolicited non-serious AE
Placebo (n=1780)
CYD vaccine (n=4615)
Percentage of subjects presenting with at least 1 reaction or event
*Integrated safety analysis pooling data from 13 studies that used the final formulation and final vaccination schedule (CYD12, 13, 22, 24, 28, 30, 47, 23, 17, 32, 14, 15, 51).
AE=adverse event; AR=adverse reaction.
Gailhardou et al, PLoSNTD, 2016
RESULTS:- SAFETY OVERVIEW AFTER ANY DENGUE VACCINE OR PLACEBO DOSE –
SUBJECTS AGED 9–60 YEARS SAFETY POOLED ANALYSIS*
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%, 95% CI
Solicited
injection site
reaction
Adults aged 18–60 years
Subjects aged 9–17 years
Grade 3
solicited
injection site
reaction
Adults aged 18–60 years
Subjects aged 9–17 years
Pain
Adults aged 18–60 years
Subjects aged 9–17 years
Erythema
Adults aged 18–60 years
Subjects aged 9–17 years
Swelling
Adults aged 18–60 years
Subjects aged 9–17 years
RESULTS OVERVIEW OF SAFETY : SOLICITED INJECTION SITE
REACTIONS1 (AGE 9–60 YEARS) - SAFETY POOLED ANALYSIS*
46.9
51.0
0.7
1.5
45.2
49.2
7.9
8.4
2.4
6.9
-5 15 35 55
44.3 49.4
49.2 52.8
0.4 1.3
1.1 2.0
42.7 47.7
47.5 51.0
6.6 9.3
7.4 9.4
1.7 3.3
6.0 7.8
*Integrated safety analysis pooling data from 13 studies that used the final formulation and final vaccination schedule (CYD12, 13, 22, 24, 28, 30, 47, 23, 17, 32, 14, 15, 51).
AE=adverse event; AR=adverse reaction.
• Pain was the most common in all age groups
• Most solicited injection site reaction were grade 1 severity
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
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RESULTS OVERVIEW OF SAFETY : SOLICITED SYSTEMIC REACTIONS1
(AGE 9–60 YEARS) - SAFETY POOLED ANALYSIS*
%, 95% CI
Solicited
systemic
reaction
Adults aged 18–60 years
Subjects aged 9–17 years
Grade 3 Adults aged 18–60 years
Subjects aged 9–17 years
Fever Adults aged 18–60 years
Subjects aged 9–17 years
Headache Adults aged 18–60 years
Subjects aged 9–17 years
Malaise Adults aged 18–60 years
Subjects aged 9–17 years
Myalgia Adults aged 18–60 years
Subjects aged 9–17 years
Asthenia Adults aged 18–60 years
Subjects aged 9–17 years
65.6
67.0
10.8
11.1
4.9
16.4
51.4
54.1
44.3
40.9
42.2
42.0
28.3
34.2
0 20 40 60
63.1 67.9
65.3 68.7
9.2 12.4
10.0 12.2
3.9 6.1
15.1 17.8
48.9 54.0
52.3 55.9
41.8 46.8
39.2 42.7
39.7 44.7
40.2 43.8
26.1 30.7
32.5 35.9
*Integrated safety analysis pooling data from 13 studies that used the final formulation and final vaccination schedule (CYD12, 13, 22, 24, 28, 30, 47, 23, 17, 32, 14, 15, 51).
AE=adverse event; AR=adverse reaction.
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
Headache, malaise, myalgia were most frequently reported in both groups
• Rates were similar between the age groups except for fever.
• (more frequent in children and adolescents than adults)
Results : Serious Adverse Events
• Frequency and nature of SAEs observed up to 28 days post injection and between day >28 and 6 months post injection of any dose were similar in both groups and were common medical conditions that could be expected as a function of age
• No safety concern observed in the review of SAEs during longer-term follow up (up to year-3 post dose 1)
• Six (CYD) and eight(Placebo) deaths* reported within 6 months after any injection in the CYD-TDV and placebo groups in participants aged 2-60 years; all were assessed as not related
*In the CYD-TDV group the deaths were due to road traffic accidents (n = 3), tracheal injury (n = 1), deliberate poisoning (n = 1) and accidental asphyxia by strangulation (n = 1). In the placebo group the deaths were due to drowning (n = 2), T-cell lymphoma (n = 1), road traffic accident (n = 1), bronchoscopic aspiration (n = 1), head injury (n = 1), lupus nephritis (n = 1) and metastatic osteosarcoma (n = 1).
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
Results : AESI (1)
Allergic reactions and anaphylaxis (within 7 days of vaccination)
• Non-serious potential allergic reactions (mainly rashes) among participants aged 9–60 years in the main trials were found within 7 days after any injection
• 46 (0.7%) in the CYD-TDV
• 15 (0.5%) in the placebo groups
• Similar profile observed in participants aged 2-8 years
• Overall, no severe or serious immediate anaphylactic reactions
were reported in any age group
Viscerotropic or neurotropic events* (within 30 days of vaccination)
• No confirmed cases of viscerotropic or neurotropic disease were reported.
*Viscerotropic and neurotropic diseases are very rare events that have been reported for YFV vaccines such as Stamaril [37]. The event rate after vaccination with a licensed YFV vaccine has been reported to be 0.4/100,000 doses for viscerotropic events and 0.8/100,000 doses for neurotropic events [38].
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
Safety profiles after each dose
Rates were lower after the second or third dose than the first dose.
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
No influence of Baseline dengue sero-status on safety
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
Dengue Vaccine Viremia • From pooled analysis of viremia data available, <6.0% (38/683) had
detectable vaccine viremia after dose 1 or 2 of the CYD-TDV vaccine, but with low level (34 after dose 1, 4 after dose 2)
• None of Participants with viremia experienced immediate AEs, post-vaccination dengue-like syndrome, AEs leading to trial discontinuation, AESIs, or SAEs
• Rate of all adverse reactions or events were similar between viremic and non-viremic participants
• No safety concerns were identified in participants with vaccine viremia
PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004821 July 14, 2016
This participant did not have virologically-confirmed dengue disease and had no reports of safety outcomes.
Focusing on Dengue hospitalization and severe dengue after vaccination
*CYD14 was conducted in Asia-Pacific in subjects 2–14 years of age. †Efficacy surveillance phase year 1=day 0 to dose 3; year 2=dose 3 to month 25; cumulative results=day 0 to year 5.
RR=relative risk; VCD=virologically confirmed dengue.
CYD14 - OVERALL RESULTS BY STUDY YEAR - HOSPITALIZED
VCD (ANY SEVERITY) IN SUBJECTS ≥ 9 YOA
0.39
(0.12, 1.17) 0.08
(0.01, 0.25)
0.57
(0.18;1.86) 0.42
(0.28, 0.62)
25-Month Active Phase + Year 31 + Year 42 + Year 53
Vaccine Group Control Group
RR
(95% CI)
0.73
(0.34, 1.61)
0.2 <0.1 0.3
0.6
0.4 0.3 0.5
1.1
0.5
0.8 0.7 0.7
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
Year 1 Year 2 Year 3 Year 4 Year 5 Cumulative Results
Ann
ua
l In
cid
ence R
ate
(%
)
| 26
0.54
(0.23, 1.30)
Active Phase Surveillance† Long Term Safety Follow-up Period
Database cleaned, not locked
1. Hadinegoro SR, et al N Engl J Med 2015; 373:1195-1206
2. Hadinegoro SR, et.al. Long-Term Safety of the CYD-TDV Dengue Vaccine in Asia-Pacific Dengue Endemic Countries.
Poster presented at: 5th Pan American Dengue Research Network Meeting. 2016 Apr 20-23 Panama, Panama.
3. Capeding et al - ACVR, April 24-26, 2017, US
| 27
CYD14 RESULTS: KAPLAN-MEIER FOR HOSPITALIZED VCD DUE TO ANY SEROTYPE IN
CYD14 STUDY IN ≥9 YEARS OF AGE GROUP
No at risk:
Vaccine group
Control group
(≥9 yo)
3315
1657
3297
1644
3285
1619
3263
1606
413
220
3215
1580
This still show reduce against hospitalized VCD in vaccinees ≥9 years of age over
the 5-year study period.
9-14y CYD
9-14y Control
*CYD14 was conducted in Asia-Pacific in subjects 2–14 years of age. †Efficacy surveillance phase ;year 1=day 0 to dose 3; year 2=dose 3 to month 25; cumulative results=day 0 to year 5.
RR=relative risk; VCD=virologically confirmed dengue.
CYD14 - OVERALL RESULTS BY STUDY YEAR - HOSPITALIZED
VCD (ANY SEVERITY) IN SUBJECTS < 9 YOA
0.36
(0.16, 0.78) 0.53
(0.25, 1.12)
1.58
(0.61, 4.83) 0.85
(0.63, 1.16)
25-Month Active Phase + Year 31 + Year 42 + Year 53
Vaccine Group Control Group
RR
(95% CI)
1.19
(0.65, 2.28)
0.4 0.4 0.6
1.1
1.0
0.7
1
0.8
0.4
0.9 0.9 0.8
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
Year 1 Year 2 Year 3 Year 4 Year 5 Cumulative Results
Ann
ua
l In
cid
ence R
ate
(%
)
| 28
1.09
(0.59, 2.11)
Active Phase Surveillance† Long Term Safety Follow-up Period
Database cleaned, not locked
1. Hadinegoro SR, et al N Engl J Med 2015; 373:1195-1206
2. Hadinegoro SR, et.al. Long-Term Safety of the CYD-TDV Dengue Vaccine in Asia-Pacific Dengue Endemic Countries.
Poster presented at: 5th Pan American Dengue Research Network Meeting. 2016 Apr 20-23 Panama, Panama.
3. Capeding et al - ACVR, April 24-26, 2017, US
| 29
CYD14 RESULTS: KAPLAN-MEIER FOR HOSPITALIZED VCD DUE TO ANY SEROTYPE IN
CYD14 STUDY IN <9 YEARS OF AGE GROUP
No at risk:
Vaccine group
Control group
(< 9 yo)
3533
1767
3498
1735
3476
1712
3438
1698
562
262
3377
1673
This still show reduce against hospitalized VCD in vaccinees <9 years of age
over the 5-year study period.
2-8y CYD
2-8y Control
Annual incidence=cases among M * 100 converted to annual rate; cases=number of participants with at least 1 hospitalized symptomatic VCD episode.
RR=relative risk; VCD=virologically confirmed dengue.
| 31
RR (%)
(95% CI)
Vaccine Group Control Group
0.166
(0.05, 0.48)
0.214
(0.10, 0.43) 0.533
(0.25, 1.16)
0.334
(0.10, 1.05)
<0,1 <0,1 0.1 <0,1 <0,1
0.2
0.4
0.2
0.1
0.2
0.0
0.1
0.2
0.3
0.4
0.5
0.6
Y1 (AP) Y2 (AP) Y3 (Y1 of HP) Y4 (Y2 of HP) Entire Study
Ann
ua
l In
cid
ence R
ate
(%
)
0.291
(0.19, 0.44)
Cortes et al – ASTMH, 2016
CYD15: RESULTS BY STUDY YEAR HOSPITALIZED VCD (ANY SEVERITY)
Active Phase: from D0 to the end of the Active Phase Hospital Phase: from the end of the Active until the cut off date Aug. 13th 2015
9-16yrs (CYD)
9-16yrs (Control)
CYD15 - CUMULATIVE HOSPITALIZED CASES (NON-SEVERE & SEVERE)
DUE TO ANY SEROTYPE FROM Post Dose1 UP TO 50 MONTHS
| 32
1. Cortes M, et al. Poster presentation at the 65th Annual Meeting of the ASTMH, 13–17 Nov 2016, Atlanta, Georgia, USA.
CYD23/57 - KAPLAN-MEIER CURVES FOR HOSPITALIZED OR SEVERE DENGUE IN ≥9 YEARS SUBJECTS IN THE ENTIRE STUDIES FOR CYD57
9-11y CYD
9-11y Control
There is greater protection, that appears to be stable, against hospitalized or severe VCD in subjects ≥9 years of age observed over time.
1. Limkittikul et al, Presentation at ACPID2016, 7-10 Nov 2016, Bangkok - Thailand
Y6
No difference in the clinical pattern of hospitalized cases and severe cases***
In the hospital phase compared to the active phase
In vaccinees compared to controls
No clinically relevant difference of frequency and duration of signs and symptoms
HOSPITALIZED VCD: NO DIFFERENCES IN THE CLINICAL / VIROLOGICAL OR IMMUNOLOGICAL PROFILE BETWEEN VACCINEES AND PLACEBO RECIPIENTS
Clinical Profile
Non-serotype specific dengue case viraemia*
*Among hospitalized VCD cases of any severity, any serotype no difference. Quantified viremia ≥LLOQ (log10 PFU/mL); median (Q1, Q3); at any time. The time to collect acute sample was calculated between start date of fever and date of acute sample taken. LLOQ=lower limit of quantification; VCD=virologically confirmed dengue. **A panel of 38 cytokines/chemokines associated with inflammatory of immunosuppressive responses were tested in the sera of hospitalized/severe cases *** Severe case - WHO classification: All DHF Grade I and Grade II, except 2 DHF III in CYD57 (CYD Group, less than 9 years, year 1 of LTFU)
Immune profile: 38 panel cytokines/chemokines**
1. Hadinegoro SR, et al. N Engl J Med 2015;373(13):1195–1206. 2. Harenberg A, et al. PLoS Negl Trop Dis 2016;10(7): e0004830.
Dengue viremia in CYD VS Control group
4.15
2.55
4.53
3.35
0
1
2
3
4
5
6
7
Active Phase HospitalPhase (Y3)
4.84
3.3 3.84 3.21
0
1
2
3
4
5
6
7
Active Phase Hospital Phase(Y3)
Qu
anti
fied
vir
emia
log1
0 p
fu/m
L
VACCINE EFFICACY ACCORDING TO AGE AS A CONTINUOUS VARIABLE active phase CYD14 and CYD15
*Using kernel smoothing
VE against symptomatic virologically-confirmed dengue cases during the whole Active Phase due to any of the 4 serotypes according to age using kernel smoothing - FASE - CYD14 & CYD15 (2-16 years)
Solid line corresponds to point estimate and the dotted lines represent the 95% CI
Vac
cin
e Ef
fica
cy (
%)
Age in Years (CYD14+CYD15) Thisyakorn et al, 8th Asian Congress of Pediatric Infectious
Diseases (ACPID) - 7-9 November 2016, Bangkok, Thailand
What is ADE theory ??
• Primary dengue infection confers life- long homotypic protective
immunity.
• Secondary infection (Heterotypic antibody)
: Antibody from 1ry infection with DENV , are not sufficient
to neutralize 2nd infection by different DENV serotype.
• ADE has been demonstrated in vitro and animal model.
• Heterotypic immunity will protect new serotype for 6 months.
• If ADE occur , it should be 12 month after 1ry infection.
(Nature Communications 8, Article number: 15674 (23 June,2017)doi:10.1038/ncomms15674)
49
Antibody-dependent enhancement of dengue infection
(ADE Theory)
It will happen in sequential dengue infection.
Investigations on disease outcome and immune profile
| 50
● The pattern of hospitalized cases, including severe disease, remains similar to that observed in the control group during the active phase.
● No increased breakthrough Dengue viremia in vaccinee VS placebo1
1. Hadinegoro SR, et al. Efficacy and long-term safety of a dengue vaccine in regions of endemic disease. N Engl J Med 2015;373:1195–206.
4.15
2.55
4.53
3.35
0
1
2
3
4
5
6
7
Active Phase Hospital Phase (Y3)
CYD
Control
4.84
3.3 3.84
3.21
0
1
2
3
4
5
6
7
Active Phase Hospital Phase (Y3)
Qu
anti
fied
vir
emia
log1
0 p
fu/m
L
51
Infection-ending T-cell responses misdirected by
original antigenic sin (ADE Theory)
| 52
● No differences in immune profiles between hospitalized vaccinees and placebos , no excess of deleterious cytokines, which would rule out excess ADE activity in vaccines versus placebos1
1. Harenberg A, et al. Cytokine Profile of Children Hospitalized with Virologically-Confirmed Dengue during Two Phase III Vaccine Efficacy Trials. PLoS Negl Trop Dis. 2016;10(7):e0004830.
● The few differences at the individual cytokine level support a positive effect of the vaccine
• IL-1Ra, at higher levels in severe dengue, is also significantly higher in the placebo group
• On the other hand, sCD40L, at higher levels in non-severe cases is higher in the vaccine group
Investigations on disease outcome and immune profile
NO EVIDENCE OF DISEASE ENHANCEMENT WAS OBSERVED IN PHASE IIb TRIAL (CYD23/57)
• Clinical characteristics of dengue episodes were similar between the vaccine group and the control/placebo group, irrespective of serotype.
• No SAE related to vaccine was observed after 2 years of follow-up after the first injection, in the presence of nonprotective immune responses to DENV-2.
– There was also no observed increase in DENV-2 dengue cases due to vaccination.
• In line with the WHO guidelines, participants will be followed for safety for 4 years post–dose 3.
WHO, 2011, Dengue Vaccine Guidelines. Sabchareon, 2012, Lancet.
VIREMIA AND IMMUNE PATTERN
Similar levels of viremia observed in vaccine vs control groups (CYD14 and CYD15).
No cytokine/chemokine pattern associated with increased disease enhancement in vaccine vs placebo.
CLINICAL, VIROLOGICAL AND IMMUNOLOGICAL PRESENTATION INSIGHTS: NO IMPORTANT DIFFERENCE IN CLINICAL SIGNS, SYMPTOMS & BIOLOGY DURING
ONGOING LTFU VERSUS ACTIVE PHASE & PLACEBO GROUP IN SUBJECTS 2–16 YEARS OF AGE (IN CYD14 & CYD15) 1
LTFU=long-term follow-up; VCD=virologically confirmed dengue.
LENGTH OF HOSPITALIZATION
Similar for both the 25-month active phase and the ongoing LTFU phase in CYD14, CYD15, and CYD23/57.
FREQUENCIES OF SIGNS AND SYMPTOMS
No clinically important differences observed for the frequencies of various signs and symptoms during the 25-month efficacy phase and the ongoing LTFU phase in CYD14, CYD15, and CYD23/57.
DURATION OF FEVER AND CLINICAL SYMPTOMS
Similar for both the 25-month efficacy phase and the ongoing LTFU phase in CYD14, CYD15, and CYD23/57.
1. Hadinegoro SR, et al. N Engl J Med 2015;373(13):1195–1206. 2. Harenberg A, et al. PLoS Negl Trop Dis 2016;10(7): e0004830.
ADE of Zika infection in Dengue primed
Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus (No ADE)
• DENV-immune serum, has been shown in vitro that antibody-dependent
enhancement (ADE) of ZIKV infection can occur.
• in vivo study, two cohorts of rhesus macaques (N=8) infect with ZIKV;
- one cohort (N=4) has been exposed to DENV 2.8 years earlier ,
- second control cohort (N=4) is naïve to flaviviral infection.
• Results,
- pre-existing DENV immunity does not result in more severe ZIKV disease.
- But results show a reduction in the number of days of ZIKV viremia in
DENV immune comparing to naïve macaques group.
- No ADE of ZIKV pathogenesis in DENV immune macaques.
(Nature Communications 8, Article number: 15674 (23 June,2017)doi:10.1038/ncomms15674)
Viral load and cytokine response profile does not support
ADE in dengue-primed Zika-infected patients: Brazil 2016.
• The mechanism of severe Dengue disease is poorly understood.
• Most studies focus on the process of antibody-dependent
enhancement (ADE) as a primary risk factor.
• ZIKV in DENV-endemic areas, Zika outcomes remains unknown.
• Neither dengue nor Zika viremia was higher in 65 Brazilian
patients with prior DENV infection, and measure 10 cytokines.
• Conclusion: No signs of ADE were observed in vivo in patients
with acute ZIKV infection who had prior exposure to DENV.
(Clin Infect Dis , 20 June 2017. DOI:https://doi.org/10.1093/cid/cix558)
Safety data from Dose 1 School-Based EPI Implementation in Philippines (Phase IV)
Round 1 Dengue Vaccine School-based Immunization Coverage Report by Region
Region Total no.
of Schools
Total no. of Grade 4 enrolled
pupils (Masterlist)
Tot. no. of pupils w/ approved parental consent
Total no. of pupils
vaccinated
Vaccination
Acceptance Rate
Uptake Rate
NCR 524 203,631 118,968 104,412 58% 88%
3 2,963 232,707 205,058 205,058 91% 97%
4A 2,680 292,772 209,120 182,520 71% 87%
Total 6,167 729,110 539,549 491,990 74% 91%
J. Lecciones, PIDSP, Feb2017, Philippines
Top 10 AEFI** rates experienced among minor AEFI cases Dengue SBI Round1
J. Lecciones, PIDSP, Feb2017, Philippines
Top 10 AEFI** rates experienced among minor AEFI cases Dengue SBI Round2
J. Lecciones, PIDSP, Feb2017, Philippines
Take Home Message
• The vaccine showed an acceptable safety profile with no related deaths in the CYD dengue vaccine group reported during the entire study.
• No clinically important differences noted in the frequencies of various signs and symptoms during the entire long-term follow-up between CYD and control groups for any age group.
เราจะเลอืกเช่ืออะไรระหว่าง Evidence based กบั Personal opinion
Eupatorium pertoliatum 200C ใช้ในการป้องกนัไข้เลอืดออกของ กรมพฒันาแพทย์แผนไทยและแพทย์ทางเลอืก กระทรวงสาธารณสุข
Brazil (Public Programme)
Philippines (Public Programme)
Mexico
El Salvador
Paraguay
Costa Rica
Guatemala
Peru
Indonesia
Ongoing regulatory submission in other endemic countries.
Thailand
Bolivia
Singapore
Dengvaxia® approved in 17 countries
Cambodia
Venezuela
Malaysia
Argentina
Honduras
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