Les IMEA IRD/UMI233 rencontres NORD SUDimea.fr/sites/default/files/RNS12/Jean-lang-Dengue... · CYD Dengue Vaccine November 2018 Les 12èmes rencontres NORD SUD IMEA - IRD/UMI233

CYD Dengue Vaccine November 2018

Les 12èmes rencontres NORD–SUD

IMEA - IRD/UMI233 - 21/11/2018

| 2 | 2

Dengue is a public health priority

WHO estimates1

3.9 billion people live in dengue-endemic countries (about half of the world’s population)

390 million people are infected per year

96 million symptomatic infections per year

500,000 people with severe dengue require hospitalization each year

2.5% of people with severe

dengue die

WHO objectives by 2020:2 mortality by ≥50% morbidity by ≥25%

1. WHO, Dengue Fact Sheet, 2018. 2. WHO, Global Strategy for Dengue Prevention and Control, 2012.


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Global burden of dengue disease mainly in inter-tropical areas

Stanaway JD, Shepard DS, Undurraga EA, Halasa YA, Coffeng LE, Brady OJ, Hay SI, Bedi N, Bensenor IM, Castañeda-Orjuela CA, Chuang TW, Gibney KB, Memish ZA, Rafay A, Ukwaja KN, Yonemoto N, Murray CJL. The global burden of dengue: an analysis from the Global Burden of Disease Study 2013. Lancet Infect Dis. 2016 Jun;16(6):712-723. doi:

10.1016/S1473-3099(16)00026-8.

Age-standardized incidence rates of dengue (per 100 000 person-years), in 2013

meeting with SAG 30th April 2018 3


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https://www.sciencedirect.com/topics/medicine-and-dentistry/dengue-fever

Dengue epidemiology in EU Overseas Territories varies by region

4

• EU dengue endemic areas include tropical Latin America, the Caribbean and the Indian & Pacific Oceans

• Caribbeans & Latin America: high level transmission/endemicity demonstrated by incidence rates during epidemics, seroprevalence, 4-serotype circulation

• Widespread presence of the vector: Aedes aegypti (most competent) • Increasingly large epidemics in recent decades with IR suspected dengue as high as 4,000-11,000/100,0001

• Reported seroprevalence among adults ≥ 18 years-old2,3,4 > 80%, and >90% in certain settings • Serotype distribution reflects historical variations and multiple serotype circulation at any given time

• EU territories outside the Americas: limited data suggest lower endemicity • In Indian Ocean (La Reunion, Mayotte) seroprevalence among adults < 50% 1, 2

• La Reunion 2017-2018: unusual persistent circulation sign of changing epidemiology3

• In the Pacific Ocean, French Polynesia or New Caledonia, reported IR < 100/100,0004

• In Madeira island, one reported outbreak in 2012-13 (first sustained transmission of dengue in the European Union since the 1920s) with more than 1000 cases reported (no severe clinical forms reported, and no fatalities)

1. L’Azou M et al. PLoS Negl Trop Dis 2014;8(11): e3235.

2. L’Azou M, et al. Am J Trop Med Hyg. 2015;92(6):1137-1140. 3. Meynard J. Bull Épidémiologique Hebd. 2009;33:357 4. Wood H, et al. Am J Trop Med Hyg. 2014;91(3):642-644. 5. Leslie T et al. PLoS ONE 2014 ;9(6): e95002.

6. Larrieu S, et al. Trans R Soc Trop Med Hyg. 2014;108(1):57-59. 7. Sissoko D, et al.. PLoS One. 2010;5(11)::e14141. 8. Sante Publique France. Surveillance de la dengue à la Réunion. PEpi 19 mars 2018. 9. Arima Y, et al. Western Pac Surveill Response J. 2011;2(2):4-8


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Dengue Epidemic at La Réunion Depuis début 2018

• Plus de 24 000 syndromes dengue-like

rapportés en consultation de ville (réseau sentinelle et médecins généralistes)

• 6635 cas autochtones (confirmés ou probables) signalés par les laboratoires de ville et hospitaliers de La Réunion

• 144 cas hospitalisés dont 23 cas de dengue sévères

• 5 décès (trois classés comme directement liés et deux comme indirectement liés à la dengue)

• DENV-2

| 5

Situation épidémiologique au 30 Octobre 2018 (N°76)

http://invs.santepubliquefrance.fr/fr/Publications-et-outils/Points-epidemiologiques/Tous-les-numeros/Ocean-Indien/2018/Surveillance-de-la-dengue-a-la-Reunion.-Point-epidemiologique-au-30-octobre-2018


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Dengue Epidemic at La Réunion

6

Cas hospitalisés (données de 131/139 cas rapportés au 2/10/18)



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Although dengue affects people of all ages, the majority of cases in endemic countries occur in preadolescence to adulthood.

1,1 6,5 8,4 6,4

75,2 66,3 83 82,6

23,7 27,2 8,6 11

0

20

40

60

80

100

Thailand Colombia Brazil* Mexico*0–9 years 10–64 years 65+ years

1–9 years 10–59 years 60+ years



Proportion of dengue cases by age group, 2010–2014 (4- to 5-year average data)

Perc

enta

ge (%

)

*Laboratory-confirmed cases. 1Ministry of Public Health Bureau of Epidemiology. Surveillance Report 506. Available at : http://www.boe.moph.go.th/boedb/surdata/disease.php?dcontent=old&ds=262766. Published March 2014. Accessed February 16, 2016. Limkittikul K, et al. PLoS Negl Trop Dis. 2014;8(11):e3241. doi:10.1371/journal.pntd.0003241.

2Villar LA et al. PLoS Negl Trop Dis. 2015;9(3):e0003499. Sandra Liliana Bello Pérez. Comportamiento epidemiológico del dengue en Colombia año 2011. Event report/INS/Colombia 2011. Courtesy of Dr. Bello. Marcela Mercado Reyes. Informe del evento dengue año, 7th period 2014. Event report/INS/Colombia 2014. Available at: http://www.ins.gov.co/lineasdeaccion/SubdireccionVigilancia/Informe%20de%20Evento%20Epidemiolgico/Forms/AllItems.aspx?Paged=TRUE&p_SortBehavior=0&p_FileLeafRef=Colera%202006%2epdf&p_ID=68&PageFirstRow=31&&View. Published June 2014. Accessed February 16, 2016. Mera C, et al. Inf Quinc Epidemiol Nac. 2003;8(5):73-88. Rodríguez JM, et al. Rev Fac Med (Bogotá). 2006;54(2):88-95. Pérez SLB. Comportamiento epidemiológico del dengue en Colombia año 2011. Event report/INS/Vigilancia y Control en Salud Pública. 2011:1-16. Reyes MM. Informe del evento dengue año 2013. Event report/INS/Vigilancia y Control en Salud Pública. 2013:1-30. Reyes MM. Informe del evento dengue, hasta el periodo epidemiologico nueve, Colombia, 2014 (Periodo IX 2014). Event report/INS/Vigilancia y Control en Salud Pública. 2014:1-34.

3Teixeira MG, et al. PLoS Negl Trop Dis. 2013;7(12):e2520. Siqueira JB Jr, et al. Secretaria de Vigilancia em Saude - Ministerio da Saude. Dengue no Brasil: tendencias e mudancas na epidemiologia, com enfase nas epidemias de 2008 e 2010. Available at: http://pt.slideshare.net/adrianomedico/dengue-tendncias-e-mudanas-na-epidemiologia-com-nfase-nas-epidemias-de-2008-e-2010. Published 2010. Accessed February 16, 2016. Secretaria de Vigilancia em Saude - Ministerio da Saude. SINAN. Courtesy of Pr. Dr. Joao Bosco.

4Dantés HG, et al. PLoS Negl Trop Dis. 2014;8(11):e3158. Sistema Nacional de Vigilancia Epidemiologica. Panorama epidemiológico de fiebre por dengue y fiebre hemorrágica por dengue. Secretaria de Salud/Mexico. Available at: http://www.epidemiologia.salud.gob.mx/doctos/panodengue/PANORAMAS_2013/Pano_dengue_sem41_sem2013.pdf. Published October 2013. Accessed February 16, 2016. San Martin JL, et al. Am J Trop Med Hyg. 2010;82(1):128-135. Mexican public health data. Instituto Nacional de Estadistica y Geografica/Mexico. Available at: http://www.inegi.org.mx/. Accessed February 16, 2016.

1 2 3 4


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Vector

• Mosquito-borne virus.1 • Primary vector: Aedes aegypti. • Secondary vector: Aedes

albopictus.

• Transmission is both endemic and epidemic in many countries.2,3

Host Anyone can be infected.1

Identified risk factors for more severe dengue: age, pregnancy near the term, chronic health status, second infection 4

Virus Arbovirus of the Flaviviridae

family.1 4 disease-causing viral

serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.1

1. WHO, 2009, Dengue Guidelines. 2. Gubler, 2011, Trop Med Health. 3. Wang, 2000, J Virol. 4. Guzmán et al., Lancet Infectious Diseases 2002

DENV=dengue virus.

SPGLB.DENG.15.05.0092

Dengue is a complex disease with interactions between virus, vector and host


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Management of dengue disease is complicated by the unpredictability of disease progression

• Severe disease cannot be predicted and may develop without warning signs.1

| 1. WHO, 2009, Dengue Guidelines.

WHO=World Health Organization.

Dengue without warning signs

Fever + any 2: • Nausea or vomiting • Rash • Aches and pains • Tourniquet test – positive • Leukopenia

Dengue with warning signs

• Abdominal pain or tenderness • Persistent vomiting • Fluid accumulation • Mucosal bleed • Lethargy or restlessness • Liver enlargement • Increased hematocrit with

decreased platelet count

SEVERE DENGUE/DHF • Plasma leakage, shock, and/or

fluid accumulation • Severe bleeding • Severe organ impairment

?

WHO dengue case classification and levels of severity1


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| 10 Oral Explanation 18 September 2018

Risk of severe dengue is higher upon secondary infection • Relative risk of getting severe disease in 2ary infection as compared to 1ary can

exceed 20 (Mizumoto et al)

Mizumoto et al. J Vector Borne Dis. 2014 Jul-Sep;51(3):153-64


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Sanofi Pasteur dengue vaccine

• The Sanofi Pasteur vaccine is a 4-serotype, recombinant, live, attenuated vaccine1,2: • 4 genetic constructs with 1 for each serotype • Genes encoding prM/E structural proteins from each

dengue serotype combined with genes encoding C and NS proteins from YFV 17D vaccine strain

• Combination into a single vaccine3: • Freeze-dried • Without adjuvant or preservatives

17D Yellow fever Dengue

Chimeric Virus

17D yellow fever Dengue

Recombinant virus

1. Guirakhoo, 2001, J Virol. 2. Guirakhoo, 2000, J Virol. 3. Guy, 2011, Vaccine.

*Vaccine referred to in the literature as chimeric yellow fever 17D-tetravalent dengue vaccine (CYD-TDV). C=capsid; DENV=dengue virus; E=envelope; NS=nonstructural; prM=precursor membrane; YFV 17D=yellow fever vaccine 17D.


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Overview of the clinical program

5 phase I trials in 3 countries

(USA, Mexico, Philippines) N=400 CYD vaccinees

Ages: 2–45 years

14 phase II trials in 13 countries

(USA, Australia, Latin America, Asia) N=5400 CYD vaccinees

Ages: 12 months–45 years

6 phase III trials in 12 countries

(Australia, Latin America, Asia) N=23,000 CYD vaccinees Ages: 9 months–60 years

25 clinical studies supporting the dossier, in 15 countries. More than 40,000 subjects included in clinical studies. Nearly 29,000 individuals children, adolescent and adults

received the vaccine.*

*As of August 2015. SP=Sanofi Pasteur. 1. B Guy et al. Expert Review of vaccines, 2017,

Phase I Non endemic Phase II Endemic Phase III


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Two phase III randomized efficacy studies and 1 phase IIb proof of concept efficacy study included >35,000 participants in endemic countries

1. Sabchareon, 2012, Lancet. 2. Villar, 2015, N Engl J Med. 3. Capeding, 2014, Lancet. 4. Hadinegoro, 2015, N Engl J Med.

Phase III efficacy Latin America (CYD15)2 • Countries: Colombia, Mexico, Honduras,

Puerto Rico, Brazil • Age group: 9–16 years • Sample size: 20,869 (Brazil: 3,548; Colombia: 9,743;

Honduras: 2,799, Mexico: 3,464; Puerto Rico: 1,315)

Phase III efficacy Asia-Pacific (CYD14)3 • Countries: Thailand, Indonesia, Malaysia, Vietnam,

Philippines • Age group: 2–14 years • Sample size: 10,275 (Indonesia: 1,870; Malaysia:

1401; Philippines: 3,501; Thailand: 1,170; Vietnam: 2333)

Phase IIb efficacy Asia-Pacific (CYD23/57*) proof-of-concept study1,4

• Country: Thailand • Age group: 4–11 years • Sample size: 4002

*CYD57 is the long-term follow-up of CYD23.


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Pooled results in the targeted age indication

(9- to 16-year-olds)3

Consistent efficacy profile during the 25-month efficacy phase

1. Capeding, 2014, Lancet 2. Villar, 2015, N Engl J Med. 3. Hadinegoro, 2015, N Engl J Med.

*Per protocol, 12 months postdose 3 for CYD14 and CYD15 individual studies; †Intent to treat, 25 months postdose 1 for hospitalized dengue, severe dengue and all pooled results for CYD14 and CYD15; World Health Organization (WHO) 1997 criteria, intent to treat.

ASIA (CYD14)1

2- to 14-year-olds LATIN AMERICA (CYD15)2

9- to 16-year-olds

56.5% (95% CI: 43.8–66.4)

60.8%

(95% CI: 52.0–68.0)

Efficacy against symptomatic dengue*†

70.0% (95% CI: 35.7–86.6)

95.5% (95% CI: 68.8–99.9)

Efficacy against severe dengue† 93.2%

(95% CI: 77.3–98.0)

67.2% (95% CI: 50.3–78.6)

80.3% (95% CI: 64.7–89.5)

Reduction in hospitalized dengue†

80.8% (95% CI: 70.1–87.7)

65.6% 95% CI: 60.7–69.9)

SPGLB.DENG.15.05.0092


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15

6 years follow-up completed CYD14 in Asia (9-14 yo)

LB-5388: Six-Year Safety of the Recombinant Live-Attenuated Chimeric-Yellow Fever-Dengue Virus Tetravalent Dengue Vaccine (CYD-TDV) in Phase III Efficacy Trials in Asia and Latin America. Carrasquilla G, et al. ASTMH 2018.


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16

6 years follow-up completed CYD14 in Asia (2-8 yo)



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17

6 years follow-up completed CYD15 in Latam and the Caribbean (9-16 yo)



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VE is impacted by age and baseline serostatus in phase 3

| 18

Vaccine efficacy by age (years)

1. Capeding MR, et al (2014). Lancet; . 2. Villar L, et al (2015). N Engl J Med 3. Hadinegoro SR, et al (2015). N Engl J Med; 4. Sridhar S, et al (2018). N Engl J Med

*Serostatus assessed at baseline with the plaque reduction neutralisation test (PRNT50) in immunogenicity subset. CI, confidence interval; N, number of subjects included in the analysis; VE, vaccine efficacy.

CYD141

0 20 40 60 80

100

2–5

33.7 59.5

74.4

VE

, % (9

5% C

I)

6–11 12–14

0 20 40 60 80

9–11

VE

, % (9

5% C

I)

12–16

CYD152 61.7 67.6

Vaccine efficacy in 9−16-year-olds3 Pooled analysis of CYD14 and CYD15

Vaccine efficacy, % (95% CI)

Seropositive* N=2323

Seronegative* N=595

100 0 20 40 60 80

65.6

52.5

60.7 69.9

5.9 76.1

Overall N=25,826

90.0 67.2 81.9

• Vaccine efficacy is impacted by age and baseline serostatus3

• An increased risk of hospitalization and severe dengue with vaccination was seen in <9-year-olds, mainly driven by data in 2−5-year-olds in the CYD14 study3

• Supplemental analyses conducted to investigate the effects of age and previous dengue infection on vaccine efficacy4


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Design of the Supplemental Analysis according to serostatus All subjects provided M13 samples as a possible surrogate of Baseline serostatus

Safety Outcomes (Hospitalized/Severe Dengue)

Efficacy Outcomes Suppl. Analysis

Surrogate of baseline (M13) True baseline (M0)

1) Capeding et al (2014). Lancet.; 2) Villar et al (2015). NEJM; 3) Nascimento et al (2018). Journal of Virological Methods

Surveillance Expansion Phase


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Dengue Anti-NS1 IgG ELISA Assay

Rationale: NS1 protein in Dengue Virus is different than NS1 protein in Yellow Fever Virus.

CYD Dengue Vaccine has gene encoding NS1 from Yellow Fever CYD Dengue Vaccine is not expected to induce meaningful antibodies against the Dengue NS1 protein

Presence of Dengue NS1 antibodies differentiate previous exposure to natural dengue infection from previous exposure to CYD vaccination

Nascimento et al (2018). Journal of Virological Methods


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Hazard ratio/Relative risk of hospitalized and severe dengue

Risk of hospitalized and severe dengue in seronegative 9−16-year-olds up to 5 years after first injection

Sridhar S, et al. N Engl J Med 2018: DOI:10.1056/NEJMoa1800820 & Supplementary appendix.

Hospitalized

Severe*

Vaccine n (M)

Control n (M)

64.2 (375.1)

14.8 (375.1)

Hazard ratio/ Relative risk

Unfavorable Favorable 0.01 100 0.1 1 10

25.3 (207.2)

3.6 (207.2)

1.41

2.44

0.74 2.68

0.47 12.56

*As per IDMC assessment. Hazard ratio/Relative risk of hospitalized and severe virologically confirmed dengue in seronegative participants aged 9–16 years old. Pooled analysis of CYD14 (9−14-year-olds), CYD15 (9−16-year-olds) and CYD23/57 (9−11-year-olds) studies. MI-M0 estimate. n and M are averages from 10 iterations of multiple imputations with n representing the number of participants that were cases of symptomatic VCD and M the total number of participants selected in the subcohort. Error bars: 95% confidence intervals. IDMC, Independent Data Monitoring Committee; MI-M0, Multiple Imputation, Month 0.


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SAGLB.DENG.18.06.0675 Date of preparation: June 2018

Hazard ratio/Relative risk of hospitalized and severe dengue

Consistent reduction in the risk of hospitalized/severe dengue in seropositive 9−16-year-olds up to 5 years after first injection


*As per IDMC assessment. Hazard ratio/Relative risk of hospitalized and severe virologically confirmed dengue in seropositive participants aged 9–16 years old. Pooled analysis of CYD14 (9−14-year-olds), CYD15 (9−16-year-olds) and CYD23/57 (9−11-year-olds) studies. MI-M0 estimate. n and M are averages from 10 iterations of multiple imputations with n representing the number of participants that were cases of symptomatic VCD and M the total number of participants selected in the subcohort. Error bars: 95% confidence intervals. IDMC, Independent Data Monitoring Committee; MI-M0, Multiple Imputation, Month 0.

Hospitalized

Severe*

Vaccine n (M)

Control n (M)

58.8 (1502.9)

11.2 (1502.9)

Hazard ratio/ Relative risk


137.7 (729.8)

33.4 (729.8)

0.21

0.16

0.14 0.31

0.07 0.37


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Relative risk of hospitalized dengue

Consistent reduction in the risk of hospitalized dengue according to serotype in 9−16-year-olds

0.18

0.22 Serotype

Serotype 1

Vaccine n (N)

Control n (N) Relative risk/

Hazard ratio


Serotype 2

Serotype 3

Serotype 4

15.4 (1495.6)

32.9 (708.1)

15.8 (1495.6)

42.1 (708.1)

14.9 (1495.6)

18.6 (708.1)

0.38

3.6 (1495.6)

21.1 (708.1)

0.07

0.11 0.45

0.09 0.34

0.17 0.82

0.01 0.38

Relative risk of hospitalized dengue in seropositive participants aged 9–16 years old. Pooled analysis of CYD14 (9−14-year-olds), CYD15 (9−16-year-olds) and CYD23/57 (9−11-year-olds) studies. MI-M0 estimate. Error bars: 95% confidence intervals. MI-M0, Multiple Imputation, Month 0; n/N, number of symptomatic cases/total number of participants in cohort.



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Comparable vaccine efficacy across the individual efficacy trials in seropositive 9−16-year-olds

| 24


Vaccine efficacy against symptomatic dengue for seropositive individuals during 25-month Active Phase

Vaccine n (M)

Control n (M)


0 100 20 40 60 80

Study

CYD14 50.9 (294.6)

102 (151.2)

75 60 85

CYD15 141.8 (1146.8)

270.1 (546.1)

76 62 85

Vaccine efficacy against symptomatic virologically confirmed dengue up to Month 25 for seropositive 9−16-year-old participants. CYD14: 9−14-year-olds; CYD15: 9−16-year-olds. MI-M0 estimate. n and M are averages from 10 iterations of multiple imputations with n representing the number of participants that were cases of symptomatic VCD and M the total number of participants selected in the subcohort; estimates are from M0–M25. CI, confidence interval; MI-M0, Multiple Imputation, Month 0.


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CYD-TDV vaccination protects against each and any dengue serotypes in seropositive subjects 9-16 years of age

Vaccine efficacy against symptomatic dengue for seropositive individuals during 25-month Active Phase

Vaccine n (M)

Control n (M)


0 100 20 40 60 80

71.0 (1441.4)

103.5 (697.3)

67 46 80

57.1 (1441.4)

20.9 (1441.4)

Vaccine efficacy against symptomatic virologically confirmed dengue up to Month 25 for seropositive 9−16-year-old participants. MI-M0 estimate. n and M are averages from 10 iterations of multiple imputations with n representing the number of participants that were cases of symptomatic VCD and M the total number of participants selected in the subcohort; estimates are from M0–M25. CI, confidence interval; MI-M0, Multiple Imputation, Month 0.


Serotype

Serotype 1

Serotype 2

Serotype 3

Serotype 4

40.5 (1441.4)

83.1 (697.3)

96.0 (697.3)

91.9 (697.3)

67 47 80

80 67 88

89 94 80


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Population level effects: reduction in attributable risk with vaccination for seropositive 9−16-year-olds

| 26


Attributable risk and cumulative incidence estimates over a 5-year period

Hospitalized dengue

Severe dengue

Vaccinated Non-vaccinated

4.8 (3.4, 6.9)

Attributable risk per 1000 (95% CI)

Unfavorable Favorable −10 30 −20 −30 0 10 20

−5.0

0.6

Estimated incidence per 1000 (95% CI)

18.8 (15.4, 23.1)

3.8 (2.6, 5.4)

0.8 (0.3, 1.7)

−15.1

−4.1

−25.4

−9.6

Attributable risk: difference in the incidence of hospitalized/severe dengue between vaccinated and non-vaccinated groups over a 5-year period

All incidence and attributable risks figures are presented cumulatively over the study period up to Month 60 or 66, which means, for a duration of at least 5 years post dose 1. Results are based on the incidence and seroprevalence observed in the clinical trials in 9−16-year-olds (pooled studies). MI-M0 estimate. CI, confidence interval; MI-M0, Multiple Imputation, Month 0.


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Sanofi Pasteur first-in-class dengue vaccine

• No dengue-specific treatment is available

• CYD-TDV is a first-in-class vaccine for the prevention of dengue disease due to the four serotypes

• Recommendation of vaccinating previously infected individuals aged 9-45 years living in endemic areas targeting the population with the highest risk for severe and hospitalized dengue

| 27 Sridhar S, et al. N Engl J Med 2018: DOI:10.1056/NEJMoa1800820 & Supplementary appendix.

Clinical outcome

Vaccine efficacy (VE)/ Risk reduction (RR)

in seropositives 9-16 yo (95% CI)

Symptomatic dengue (VE)

(M0-M25) 76%

(64, 84)

Hospitalized dengue (RR)

(M0-M66) 79%

(69, 86)

Severe dengue (RR)

(M0-M66) 84%

(63, 93)


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| 28

• Subnational or national mass vaccination strategy in areas of high seroprevalence

• Population surveys to identify areas with high seroprevalence where public impact is maximized and harm minimized

• Mass vaccination in identified high seroprevalence areas without serological screening

WHO Updated position on the use of the first licensed dengue vaccine Sep 2018

Pre-vaccination screening

Preferred approach

• Serological screening prior to vaccination • Dengue IgG ELISA could potentially be used for

screening • Currently available Rapid Diagnostic Tests could

be considered in high transmission settings • Strategy may also be considered in low to

moderate transmission settings. In settings with low transmission (high numbers of seronegatives) a test with high specificity is needed

Population seroprevalence without screening

Alternative approach

ELISA, enzyme-linked immunosorbent assay; WHO, World Health Organization.

For countries considering vaccination as part of their dengue control program: WHO has acknowledged the public health role of the CYD-TDV vaccine and the strong protective benefit in

seropositive individuals for the subsequent dengue infection In order to maximize the public health impact and minimize risk with dengue vaccination, WHO has

recommended two main approaches:

World Health Organization, « Dengue Vaccine WHO position paper( September 2018 http://apps.who.int/iris/bitstream/handle/10665/274315/WER9336.pdf?ua=1) .


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http://apps.who.int/iris/bitstream/handle/10665/274315/WER9336.pdf?ua=1


In Conclusion

Vaccination confers protection against hospitalized and severe dengue with subsequent infection for more than 5 years (~80%)

Based on the evidence, WHO has recommended two main dengue vaccination approaches in endemic settings in order to minimize the risk and maximize the public health impact 2

1. Sridhar S, et al. N Engl J Med 2018: DOI:10.1056/NEJMoa1800820 & Supplementary appendix 2. World Health Organization, « Dengue Vaccine WHO position paper( September 2018

http://apps.who.int/iris/bitstream/handle/10665/274315/WER9336.pdf?ua=1) 3. Bonaparte et al, Poster, XVIII Congreso Latinoamericano de Pediatria, September 2018, Asuncion, Paraguay

1

2

3

VE against virologically-confirmed dengue cases demonstrated against each and any serotype in 9 years and above previously infected by dengue virus1,

Despite limitations, the currently available dengue RDTs could be considered for the identification of prior dengue infected individuals in endemic settings, assuming local assessment of performance and expanded evaluation of cross-reactivity3

4


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Les IMEA IRD/UMI233 rencontres NORD SUDimea.fr/sites/default/files/RNS12/Jean-lang-Dengue... · CYD Dengue Vaccine November 2018 Les 12èmes rencontres NORD SUD IMEA - IRD/UMI233