Jacqueline Lim - Dengue Vaccine Initiative

DVI Field Studies in 4 Focal Countries
Jacqueline Lim
kalim@ivi.int
Dengue Vaccine Initiative (DVI)
International Vaccine Institute, Seoul, Korea

DVI plans
Field site studies conducted in 4 likely early
adopter countries of dengue vaccine
Colombia (Medellin) Brazil (Salvador)
Thailand (Bang Phae) Vietnam (Nha Trang)
DVI plans to develop sound evidence for
decision-making to inform policy makers on
dengue vaccine introduction for developing
countries by conducting field studies in these 4
‘focal’ countries

Rationale for site selection
High levels of dengue virus transmission
Stable population with low rates of migration and
high rates of ethnic homogeneity
Easy accessibility
Excellent level of health services
Motivated and committed local dengue control
officers and provincial public health officials for
dengue research
Population size matching the sample size
calculated for the catchment area

DVI 4 “focal” countries
Population size 68 million 88 millio
n
% pop below Nat'l p
overty line
Thailand Vietnam Colombia Brazil
14%
(1998)
Study region Ratchaburi
(Bang Pha
e)
Catchment area po
pulation
Documented incide
nce in Nat'l surveilla
nce
29%
(2002)
Nha Tra
ng
45 million 192 millio
n
64%
(1999)
22%
(2003)
Medellin Salvador
49.506 38,989 56,977 10,842
0.6 - 1.8/1,
000
0.7 - 1.2/
1,000
2.1/1,000 4.5/1,000

Thailand & Colombia
To generate solid, high-quality data on the
dengue disease burden among children and
adults in a defined geographical area
To provide a complete package of evidence to
build a national investment case for dengue
vaccine
To be used as a model for other early-adopting
countries of dengue vaccine in the respective
regions to facilitate accelerated development and
introduction of safe and effective dengue
vaccines into public sector programs

Basic study information
Study Area with census and
mapping
(Catchment of study facility)
Serosurvey
Fever surveillance
(cases ascertained from
the facility)
- Cost of illness
Study Facility
2,000
2,000
50,000
Other random sampling:
1. Healthcare utilization survey
2. Willingness-to-Pay

Census data of the study area
For baseline demographic information of the
residents of the study area, existing census
and geographical data available at the subdistrict
health centers will be abstracted
In Nha Trang, Nagasaki Univ. is conducting
a study and just completed the census for
the city in 2010
For Colombia, census data are available

Passive fever surveillance
Dengue high transmission starts in June (Thailand)
and Sept/Oct (Colombia)
Protocol submitted to the Ethics Review Committees
of Thai MoPH & Mahidol Univ.
Thai protocol being modified for Colombia
Study subjects: patients between 1 and 55 years of
age who present to the study facility with current
fever or history of fever (

Passive fever surveillance
Acute sample of blood - taken when the patient
first visits the hospital with fever
Convalescent sample – subject is asked to return
to hospital for a convalescent sample collection
between 10-14 days from the first visit
Active follow-up - after the 14th day, if the patient
has not come to the hospital, phone calls or a
house visit will be made and the second blood
sample will be collected within 21 days from the
first visit

Surveillance lab-testing
Acute blood sample will be tested using
NS-1(rapid; compensation for enrolled subjects) and
ELISA dengue IgM/IgG and JE IgM/IgG
Convalescent blood sample will be tested
IgM/IgG ELISA
Positive samples by IgM or NS-1 or rising of IgG
(about 15% of the tested samples) will be tested with
RT-PCR

Serological survey
2000 randomly selected residents of the study
area between 1 and 55 years of age
To calculate sero-conversion rate of the catchment
population
To reflect the age distribution of the dengue
infection in Thailand, 60% of the serological
survey sample will come from children < 15 yearsof-age
and 40% will be from adults 15 - 55 years
of age
Use IgG to test blood samples with an interval of 6
months
Use PRNT among those samples with increased
IgG

Cost-of-illness study
To estimate the economic burden of dengue for
individuals and families, both from dengue illness and
from dengue avertive activities and the cost to society
for dengue treatment, including subsidies for
treatment in public facilities
- To estimate the direct medical, direct non-medical,
and indirect costs associated with dengue fever in all
dengue confirmed cases
- To assess the duration of dengue fever and whether
households have to borrow money as a result of the
illness
- Interview schedule: day 0 – day10/14 – day 28

Cost-of-illness study
To assess the government expenditure on
dengue vector control/prevention activities
- The cost of treating dengue fever at the
facility level & vector control costs - estimated
from operational records (at the district or
province-level data)
The patient survey data will be linked to their
hospital treatment record to estimate the full
cost of disease

Willingness-to-pay survey
Cost-of-illness analyses are complimentary with
clinical and epidemiological approaches to disease
burden estimation. Willingness-to-pay estimates
provide additional quantification of the private
benefit of disease reduction.
Based on 400 randomly selected households of the
study area
To inform policy makers of the need, demand for,
and feasibility of providing a vaccine against
dengue infection

Willingness-to-pay survey
To estimate private household benefits of a
dengue vaccine and assess socioeconomic
characteristics that influence vaccine demand,
including income, education, and household size
Two components:
1) qualitative rapid assessments conducted in
one-time single semi-structured open-ended
interviews of community residents, community
leaders, and health care providers &
2) quantitative household surveys

Willingness-to-pay survey
Data collected in the following domains:
- Quantitative estimates of private demand
- Quantitative estimates of the societal cost per dengue
case
- Perceptions of severity, vulnerability, and causes of
dengue
- Healthcare utilization pattern in the population in relation
to dengue fever
- Knowledge, attitudes, and behaviors in relation to current
interventions and programs for prevention of dengue fever
- Knowledge and attitudes regarding vaccination and past
vaccination programs

Healthcare utilization survey
Based on the same 400 randomly selected
households of the study area as the WTP survey
To characterize how the healthcare utilization
pattern differs between fever cases and non-fever
cases, as well as dengue and non-dengue cases
To estimate the proportion of resident that would not
seek care at the study facility
To identify the preference of healthcare service in
case of febrile illness/dengue fever

Data analysis I
Incidence of symptomatic dengue infection from the
hospital-based surveillance data
Sero-conversion rate – to estimate the occurrence of
asymptomatic dengue infection
Epidemiology of symptomatic and asymptomatic
(silent infection) dengue virus infections by age and
serotype
Clinical profile of individuals with dengue infection by
severity of the disease (severe vs. non-severe) and
the type of treatment (IPD and OPD)
Comparison to the national surveillance data to
estimate the level of under-reporting

Data analysis II
Direct and indirect cost-of-illness of the dengueconfirmed
cases that sought care at the facility
The economic burden by the treatment type
(hospitalized vs. outpatients), severity grade of
dengue, and age-group
The national-level cost for vector control to the
government
Private household demand for dengue vaccine from
statistical models that include the price offered and
household characteristics including education,
income, perceived dengue risk and perceived
dengue severity amongst other variables

Limitations
Underestimation of incidence of symptomatic
dengue - the community residents with
relevant symptoms seeking care from other
healthcare providers and facilities than the
facility under surveillance
Limited generalizability of the data collected
from these studies using randomized subsamples
of the catchment area population

Acknowledgements
DVI staff and advisors
International Vaccine Institute
Partners in DVI consortium
Our collaborators in the focal countries
- Faculty of Trop Med in Mahidol Univ.
- National Institute of Hygiene and
Epidemiology, Hanoi
- Khanh Hoa Health Services
- University of Antioquia
- Brazilian Ministry of Health