Economic analysis and health impacts of routine vaccination

with TAK-003 dengue vaccine in San Juan, Puerto Rico

Guido España, Manar Alkuzweny, Alex Perkins

University of Notre Dame

June 22nd, 2023
Conflicts of interest & Disclosures

• GE and AP have previously received research funding from 

GlaxoSmithKline to support unrelated research on dengue vaccine

development.

• AP currently receives research funding and consulting fees from

Emergent Biosciences to support unrelated research on 

chikungunya vaccine development.

• As of June 2023, GE is an employee of CDC. This work was 

performed while working at the University of Notre Dame. The 

findings and conclusions in this presentation are those of the 

author(s) and do not necessarily represent the views of the CDC.

2
Abbreviation Full term/Meaning

VCD Virologically confirmed disease

VE Vaccine efficacy

DENV (e.g., DENV-3) Dengue virus (e.g., serotype 3 dengue virus)

HPV Human papillomavirus

PICO Policy question articulated as Population, Intervention, 

Comparison, Outcomes

Additional hospitalizations Hospitalization induced by vaccine-enhanced disease

ICER Incremental cost-effectiveness ratio ($/QALY, $/hospitalization 

averted)

QALY Quality adjusted life years

3

Terminology
We modeled six scenarios to answer each of the 

policy (PICO) questions. 

• Age group scenarios: 

• 4 – 16 years 

• 17 – 60 years

• 4 – 60 years

• For each age group we modeled:

• Without required pre-vaccination screening (vaccinate 

seropositives and seronegatives)

• With required pre-vaccination screening (vaccinate 

seropositives only)

4
Outcomes of interest included benefits, harms, and 

costs. 

• Epidemiological outcomes: 

• VCD* and hospitalizations averted 

• Dengue hospitalizations among vaccinated seronegative 

persons infected with DENV-3 and DENV-4.

• Health Outcomes:

• QALYs gained 

• Economic outcomes:

• ICER ($/QALY)

• ICER ($/hospitalization averted)

*VCD refers to medically attended cases only 5
We calibrated an agent-based model to reproduce patterns 

of serotype circulation, force of infection, and age-specific 

incidence.

• We created a synthetic population to represent demographic and

geographic characteristics of San Juan, Puerto Rico.

• Our model simulates individual daily activities of humans and 

mosquitoes.

• Model calibrated using 30 years of historical dengue surveillance data 

to reproduce observed force of infection and age-specific 

incidence.

6
The serotype distribution simulated over 10 year time horizon of vaccination 

was modeled on 30 (1986-2016) years of data from San Juan, Puerto Rico.

*Model based on 1,000 bootstraps with different proportion of serotypes in every simulation. Average reflects the mean proportion of serotypes among 

entire model. These estimates are preliminary and are subject to change.

Serotype Average proportion in 

model*

• DENV-1 14% (5% - 25%)

• DENV-2 35% (17% - 51%)

• DENV-3 29% (11% – 46%)

• DENV-4 22% (9% - 40%)

7
The estimated seroprevalence among persons 9 years of 

age was approximately 40%. 

• 30% of individuals aged 5–9 years were seropositive.

• People aged 20, 75% of people had ≥1 infection by the end of the

calibration.

Age group

8
We simulated the vaccine roll-out based on previous 

introduction of HPV vaccine in the US*.

• Vaccine coverage increased gradually from 0% to ~40% in 10 years 

and was distributed evenly across age ranges in the scenario.

• We simulated additional scenarios of 2x and 0.5x the final coverage.

*https://www.cdc.gov/nchs/data/hus/2020-2021/VaxTn.pdf 9
Vaccine efficacy and vaccine protection assumptions

10
Model and trial estimates of vaccine efficacy for VCD and 

hospitalization among seropositive participants.

54

100

70 68 67

96

74

100

0

20

40

60

80

100

1 2 3 4

63

85

43

60

56

80

52

71

0

20

40

60

80

100

1 2 3 4

VCD Hospitalization

Takeda – ACIP WG presentation September13th – 100% VE values are assumed. Vaccine efficacy

Biswal (Takeda). ACIP, February 17, 2023.

11
Model and trial estimates of vaccine efficacy for VCD and 

hospitalization among seronegative participants.

VCD Hospitalization

30

96

30

-1

45

88

-16

-106

-150

-100

-50

0

50

100

1 2 3 4

85

99

-30

39

78

100

-88

100

-150

-100

-50

0

50

100

1 2 3 4

Takeda – ACIP WG presentation September 13th – 100% VE values are assumed. Vaccine efficacy

Biswal (Takeda). ACIP, February 17, 2023.

12
Vaccine protection assumptions 

• Protection varies for each serotype (DENV 1-4) and serostatus (seronegative

or seropositive).

• The duration of protection was estimated as

• VCD for seronegatives (13.1yrs) and for seropositives (17.4yrs)

• Hospitalization for seronegatives (19.3) and for seropositives (25.6).

• Equal level of protection against infection and disease given infection. 

• In scenarios with pre-vaccination screening, the coverage of pre-vaccination 

screening is the same as the vaccine rollout coverage (without screening). The 

test has 80% sensitivity and 98% specificity for detecting previous dengue 

infection.

• We simulated outcomes of VCD and hospitalizations over 10 years in 

scenarios with vaccination compared to scenarios without vaccination.

• We assumed that all individuals testing positive are vaccinated.

14
Epidemiological outcomes*: VCD and hospitalizations 

averted (Benefits)

*Results are preliminary and are subject to change. 15
No pre-vaccination screening increased the proportion 

of total VCD averted compared to screening. 

0

2

4

6

8

10

12

14

16

18

20

1 2 3

% of symptomatic VCD averted in the total 

population

3

8

9

1

6

7

*Results are preliminary and are subject to change. 16
No pre-vaccination screening increased the proportion of 

total hospitalizations averted compared to screening. 

0

2

4

6

8

10

12

14

16

18

20

1 2 3

% of hospitalizations averted in the total 

population

3 3

13

15

10

12

*Results are preliminary and are subject to change. 17
Epidemiological outcomes: Additional hospitalizations 

(Harms)

18
Outcomes: Additional hospitalizations (Harms)

• We used the ratio of averted hospitalizations to additional 

hospitalizations as a relative measure of harm. 

• Additional hospitalizations only occurred among seronegative persons 

who received the vaccine and were infected with DENV-3 or DENV-4 

post-vaccination.

19
Screening increased the ratio of averted to additional 

hospitalizations compared to no pre-vaccination screening.

0

10

20

30

40

50

60

70

80

90

100

1 2 3

Ratio of hospitalizations averted to

additional hospitalizations

*

6:1

15:1

35:1

18:1

102:1

69:1

*among seronegative persons who received the vaccine and were infected with DENV-3 post-vaccination. Note: Results are preliminary and are subject to change.

20
Economic outcomes*

21
We estimated the Incremental Cost-Effectiveness

Ratio to determine cost-effectiveness

• We estimated the quality-adjusted life-years (QALYs) gained with

routine vaccination using disability weights (Zeng et al. 2018)

• The unit cost per fully vaccinated individual was varied from 100

to 600 USD (330 USD baseline).

QALYintervention – QALYno intervention

Costintervention – Costno intervention

= ICER

*The cost per fully vaccinated individual was estimated as 150 USD per dose with an additional 15 USD for vaccine administration costs per dose. All 

costs were estimated for the year 2022.

22
Economic outcomes* by scenario for a public 

payer perspective, over 10 years, 3% discounting.

Age 

group

Pre-vaccination 

screening

QALYs 

gained

ICER $ / QALY 

gained

ICER $ / 

hospitalization 

averted

4-16 Yes 17 181,918 16,800

4-16 No 35 254,751 46,813

17-60 Yes 89 396,574 48,986

17-60 No 118 314,597 39,886

4-60 Yes 106 384,830 48,305

4-60 No 134 326,412 45,495

23

*Results are preliminary and are subject to change.
Summary

• Our model simulations show some benefits from vaccination in terms of

symptomatic cases and hospitalizations averted.

• These benefits depend on the serostatus of the vaccinees and the

circulating serotypes.

• Overall, pre-vaccination screening reduces the potential negative

outcomes in seronegative individuals.

• ICERs per QALY gained and ICER per hospitalization averted were higher 

when implementing pre-vaccination screening except in the 4–16 age 

group where screening was more cost-effective.

• Cost-effectiveness of the intervention depended on the 

seroprevalence, which is lower for younger age groups.

24
Limitations

• Our model projections are not predictions on the serotype circulation or 

the burden of disease.

• Our results on the benefits and cost-effectiveness of the intervention 

depend on the circulation of specific serotypes during the projection 

period.

• We are not including QALYs loss due to death in the cost-effectiveness 

analysis.

24
Acknowledgements

This analysis is based on previous analyses described in the 

manuscript by España et al.: “Model-based assessment of public 

health impact and cost-effectiveness of dengue vaccination

following screening for prior exposure. PLOS NTDs 2019” (España 

et al., 2019). The manuscript was prepared in collaboration with 

other authors: Yutong Yao, Kathryn B. Anderson, Meagan C. 

Fitzpatrick, David L. Smith, Amy C. Morrison, Annelies

Wilder-Smith, and Thomas W. Scott.
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España, G., Yao, Y., Anderson, K. B., Fitzpatrick, M. C., Smith, D.

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