Vector Borne Disease and the Environment: A
Transdisciplinary Cumulative Risk Model Associated
with Dengue
Diana Hamer, MSc, PhD(c)
Different Trends in Disease…

WHO, 2011
The Range of Infectious Diseases


Bacteria




HOST

Influenza, chicken pox,
HIV, poliomyelitis, ebola

Parasites




The Disease Triangle

Viruses




Cholera, leprosy,
tetanus

Filariasis, giardiasis,
ameobasis

DISEASE

Fungi


Fungal meningitis,
mycosis

PATHOGEN

ENVIRONMENT
What are vector-borne diseases?






Definite host
Intermediate host
Reservoir host

HOST

Vector: an agent that
carries and transmits and
infectious pathogen into
another organism


Mosquitos and flies, other
arthropods, bats, copepods,
cats, fleas, ticks, rats, dogs

VECTOR

DISEASE
PATHOGEN

ENVIRONMENT


Factors affecting
the Emergence /
Resurgence of
Vector Borne
Diseases

Genetic and Biological





Physical Environmental





Urbanization
Climate change

Ecological




Human susceptibility to
disease
Pathogen adaptation

Encroachment

Social / Political /
Economical




Poverty
War
Lack of political will / money
Strategies to curve disease incidence
Vector Control Options
•

Biological Control
•
•

•

•

Lack of surveillance /
monitoring


Sterilization techniques


Environmental manipulation /
reduction

Chemical Control
•

•

Immature and mature stages
Predators / pathogens

Physical Control
•

•



Genetic Control
•

•

Challenges

Oils, insecticides

Personal Protection
Education

Population dynamics




At all stages of
intervention
Migration, poverty,
urbanization

Climate change


Increase in habitats,
vector expansion
Reemergence of Vector Borne Diseases


Global Problems with local challenges



Dengue Fever in Florida




Reemerged in 2009
(Monroe County)
Currently
Martin & St. Lucie County
Significance


Dengue Worldwide




First recognized in 1950
Currently 2.5 million at risk
50 - 100 million dengue fever / year

DengueMap-CDC-HealthMap Collaboration
Dengue: The Spectrum of Disease

• No clinical signs

•
•
•
•

Fever
Headache
Myalgia / athralgia
Leukopenia

• Rash
• Petechiae

• Thrombocytopenia
• Hematemesis

• Plasma leakage
• Hypovolemia
Dengue Virus (DENV)




Genus flavivirus
+, single stranded RNA
4 types (DENV1-4)




Homotypic immunity
Heterotypic immunity
Antibody-dependent enhancement
Cann, 2007
Mayo Foundation for Medical Research, 2012
The Vector


Aedes aegypti




Urban
Tropical / Subtropical
Vector Control

Ae. aegypti

WHO, 2012
Dengue in the Americas



hy
po

hy
pe

re
n

en
de
m

ic

de
m
ic



Incidence
Severity
Understudied

From San Martin, et al., 2010
Suriname




Population
Climate
Ae. aegypti endemic




Hyperendemic dengue

Bureau of Public Health
(BOG)
Dengue in Suriname


Frequency and severity (BOG)
A Neglected Tropical Disease
•

Shifting the focus to prevent the emergence and resurgence of
infectious diseases
•

Where do you start?
•

•

Lack of political will
•
•

•

Not a priority
Vertical command structure

Complicated diseases
•
•

•

Diseases of Poverty

No good vaccine
Uneducated populations

Globalization
•
•
•

Urbanization
Vector importation
New emerging diseases
Transmission of Disease
Influencing factors
Competitors

Age
Human Host

Ethnicity
Gender
Immune status

Density
Breeding Sites

Dengue Virus

Serotype

Virulence

Vector

Climate

Environment
Sanitation

Urbanization
Hypotheses






Hypothesis 1:
There is a statistical association between demographic
and clinical factors and the progression of dengue into
the severe forms for the disease in Suriname
Hypothesis 2:
Spatio-temporal trends and relationships of factors
influencing dengue incidence and severity will identify
disease hotspots in Suriname
Hypothesis 3:
Prediction models and dengue disease cluster analysis can
identify effective prevention methods and risk reduction
strategies for dengue in Suriname
Study Population
Data Sources


Electronic databases

Source

Type of Information Aims

Saint Vincent Hospital Paramaribo (SVZ)
n ≈ 2092

-Demographic
-Clinical

Aim 1.1
Aim 1.2

Bureau of Public Health (BOG)
n ≈ 5298

-Demographic
-Clinical

Aim 2.1
Aim 2.2

Academic Hospital Paramaribo
Laboratory (AZPL)

-Demographic
-Clinical

Aim 1.1
Aim 1.2

Meteorological Service Suriname (MDS)

-Meteorological

Aim 2.1

General Bureau of Statistics (ABS)

-Census

Aim 2.1
Aim 2.2
Data Sources
Type of Information


Case data



Inclusion / Exclusion Criteria


Demographic
Clinical Context

Inclusion criteria





Additional Data



Meteorological
Census



Probable (hospital or clinic)
cases of dengue fever
Admitted into a hospital /
clinic - 2001 to 2012

Exclusion criteria



No available date of birth
No source or address
Case Classification
Definition

Criteria

Probable
Clinical

-Acute febrile illness
-Two or more of the following: headache, retro-orbital pain,
myalgia, arthralgia, rash, hemorrhagic manifestations,
leucopenia

Laboratory

-Compatible serology (reciprocal hemagglutination-inhibition
antibody titer > 1280, comparable IgG EAI titer or positive
IgM antibody test in serum specimen

Confirmed

-Clinically compatibility and
-DENV isolation in cell culture
-RT-PCR detection of nucleic acid in serum

Peeling et al. 2010
Methodology: Hypothesis 1








Aim 1.1: Characterize the incidence, prevalence and severity
of dengue – with an emphasis of pediatric dengue – in
Suriname from 2001 to 2012
Frequency distributions, incidence and mortality of DF & DHF

Aim 1.2: Examine the demographic and clinical factors that
influence the development of severe dengue
Univariate analysis to identify difference between groups
Multivariate analysis to test for associations

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 2


Aim 2.1: Integrate clinical and demographic information
of all dengue cases reported in Suriname since 2001 into
a GIS platform





Generate a Geodatabase
Identify historic spatial and temporal trends

Aim 2.2: Identify spatial and temporal historic clusters of
DF and DHF from 2001 to 2012



Global clusters / local clusters
Poisson-model to assess spatial random distribution

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 3


Aim 3.1: Characterize dengue-related entomological and
environmental data in previously identified high
transmission risk areas





Use the maps to identify areas of high dengue transmission
And conduct entomological and environmental surveys to
further assess the situation

Aim 3.2: Propose effective, low-cost dengue intervention
activities based on local information to reduce the risk of
dengue transmission in Suriname

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Data Analysis
Hypothesis 1




Aim 1.1: Characterize the incidence, prevalence and severity
of dengue – with an emphasis of pediatric dengue – in
Suriname from 2001 to 2012
 Prevalence
Data cleaning / transforming




Incidence




In each district and resort
District and resort with
available census data

Stratified by gender, age,
ethnicity, type

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 1


Aim 1.2: Examine the demographic and clinical factors
that influence the development of severe dengue
ADE

Prior
Infection

Increased risk
for DHF

Age
Human Host

Dengue Virus

Virulence

Ethnicity

Gender

Serotype

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 1 (Aim 1.2)


Univariate analysis


Predetermined sample





Presence of absence of severe disease (DHF)
P1 : did not develop DHF; P2 : did develop DHF

Chi-square test for homogeneity


Ho: Pi = Pj



H a: Pi ≠ Pj



Significance: p < 0.05

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 1 (Aim 1.2)


Multivariate analysis



Test for association of indicators on the development of DHF
Logistic regression model





Test for indicators and interaction variables (α = 0.5)





Binary outcome: [Y = 0]: no DHF; [Y = 1]: DHF
Stepwise forward selection of categorical indicator variables
Maximum Likelihood method / likelihood ratio
Odds ratio (95% confidence interval)

Chi Square goodness of fit (α = 0.5)


Significance: p < 0.05

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 2


Aim 2.1: Integrate clinical and demographic information
of all dengue cases reported in Suriname since 2001 into
a GIS platform


Geodatabase includes



Suriname basemap (administrative level)
Layers





Cases of DF and DHF
Hospitals and clinics in Suriname

Attribute table (for data exploration)





Demographic and clinical information of cases
Weekly meteorological data- relative humidity, precipitation, average
temp
Additional district / resort characteristics- SES, access to piped water, etc.

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 2


Aim 2.2: Identify spatial and temporal historic clusters of
DF and DHF from 2001 to 2012


Identify IF clusters exist
Global clustering – obtain Moran’s I (-1 to +1)
Yes

No

Identify specific clustering
(SatScan)

Poisson regression analysis
(log(pop)) is an offset for the population

Local Moran’s I

Overdispersion

Ho: No spatial association between the ith region
and its neighbors
Ha: There is spatial association between the ith
region and its neighbors

Ho: The data follow a Poisson distribution
Ha: The data do not follow a Poisson distribution

Create cluster map

Map Predicted values

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 3


Aim 3.1: Characterize dengue-related entomological and
environmental data in previously identified high
transmission risk areas


Epidemiological Maps




Sample size
Unit classification
Replicates


Wet v dry season



Environmental Surveys


Unit Classification






Residential v non-residential
Rural v urban
Local characteristics

Container classification





Non traditional v traditional
Non disposable v disposable
Size & location
Water source

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 3 (Aim 3.1)


Surveys



Immature Ae. aegypti
Larval and Pupae indices
Container
Index

# of containers w/ larvae or pupa
# of containers examined

x 100

House Index

# of houses w/ larvae or pupae
# of houses inspected

x100

Breteau Index
Pupae / person
survey

# of containers w/ larvae or pupae
100 houses inspected
# of pupae in a community
# of people in a community

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Hypothesis 3


Aim 3.2: Propose effective, low-cost dengue intervention
activities based on local evidence-based information to
reduce the risk of dengue transmission in Suriname





Historical cases of dengue help identify spatial and temporal
patterns of transmission
The importance of environmental and entomological data
collection in elucidating populations at higher risk of
transmission
Epidemiological, entomological and environmental surveillance
is necessary to move from an ad hoc basis to a more
prevention oriented approach

Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
Increased risk
for DHF

Prior
Infection
Age

Competitors
Human Host
Adult
Larva

Pupae

Race
Gender
Temperature

Density

Rainfall

Vector

Dengue Virus

Serotype
Breeding Sites

Virulence

Climate

Humidity

Environment
Sanitation

Urbanization
Pop. Density
Acknowledgements




Dr. Lichtveld
Dr. A. Jessurun at the Saint Vincent Hospital
Dr. Hiwat and Dr. Jubithana at the Bureau of Public
Health
Questions & Comments

Vector borne disease and Dengue

  • 1.
    Vector Borne Diseaseand the Environment: A Transdisciplinary Cumulative Risk Model Associated with Dengue Diana Hamer, MSc, PhD(c)
  • 2.
    Different Trends inDisease… WHO, 2011
  • 3.
    The Range ofInfectious Diseases  Bacteria   HOST Influenza, chicken pox, HIV, poliomyelitis, ebola Parasites   The Disease Triangle Viruses   Cholera, leprosy, tetanus Filariasis, giardiasis, ameobasis DISEASE Fungi  Fungal meningitis, mycosis PATHOGEN ENVIRONMENT
  • 4.
    What are vector-bornediseases?     Definite host Intermediate host Reservoir host HOST Vector: an agent that carries and transmits and infectious pathogen into another organism  Mosquitos and flies, other arthropods, bats, copepods, cats, fleas, ticks, rats, dogs VECTOR DISEASE PATHOGEN ENVIRONMENT
  • 5.
     Factors affecting the Emergence/ Resurgence of Vector Borne Diseases Genetic and Biological    Physical Environmental    Urbanization Climate change Ecological   Human susceptibility to disease Pathogen adaptation Encroachment Social / Political / Economical    Poverty War Lack of political will / money
  • 6.
    Strategies to curvedisease incidence Vector Control Options • Biological Control • • • • Lack of surveillance / monitoring  Sterilization techniques  Environmental manipulation / reduction Chemical Control • • Immature and mature stages Predators / pathogens Physical Control • •  Genetic Control • • Challenges Oils, insecticides Personal Protection Education Population dynamics   At all stages of intervention Migration, poverty, urbanization Climate change  Increase in habitats, vector expansion
  • 7.
    Reemergence of VectorBorne Diseases  Global Problems with local challenges  Dengue Fever in Florida   Reemerged in 2009 (Monroe County) Currently Martin & St. Lucie County
  • 8.
    Significance  Dengue Worldwide    First recognizedin 1950 Currently 2.5 million at risk 50 - 100 million dengue fever / year DengueMap-CDC-HealthMap Collaboration
  • 9.
    Dengue: The Spectrumof Disease • No clinical signs • • • • Fever Headache Myalgia / athralgia Leukopenia • Rash • Petechiae • Thrombocytopenia • Hematemesis • Plasma leakage • Hypovolemia
  • 10.
    Dengue Virus (DENV)    Genusflavivirus +, single stranded RNA 4 types (DENV1-4)    Homotypic immunity Heterotypic immunity Antibody-dependent enhancement Cann, 2007 Mayo Foundation for Medical Research, 2012
  • 11.
    The Vector  Aedes aegypti    Urban Tropical/ Subtropical Vector Control Ae. aegypti WHO, 2012
  • 12.
    Dengue in theAmericas   hy po hy pe re n en de m ic de m ic  Incidence Severity Understudied From San Martin, et al., 2010
  • 13.
  • 14.
  • 15.
    A Neglected TropicalDisease • Shifting the focus to prevent the emergence and resurgence of infectious diseases • Where do you start? • • Lack of political will • • • Not a priority Vertical command structure Complicated diseases • • • Diseases of Poverty No good vaccine Uneducated populations Globalization • • • Urbanization Vector importation New emerging diseases
  • 16.
    Transmission of Disease Influencingfactors Competitors Age Human Host Ethnicity Gender Immune status Density Breeding Sites Dengue Virus Serotype Virulence Vector Climate Environment Sanitation Urbanization
  • 17.
    Hypotheses    Hypothesis 1: There isa statistical association between demographic and clinical factors and the progression of dengue into the severe forms for the disease in Suriname Hypothesis 2: Spatio-temporal trends and relationships of factors influencing dengue incidence and severity will identify disease hotspots in Suriname Hypothesis 3: Prediction models and dengue disease cluster analysis can identify effective prevention methods and risk reduction strategies for dengue in Suriname
  • 18.
  • 19.
    Data Sources  Electronic databases Source Typeof Information Aims Saint Vincent Hospital Paramaribo (SVZ) n ≈ 2092 -Demographic -Clinical Aim 1.1 Aim 1.2 Bureau of Public Health (BOG) n ≈ 5298 -Demographic -Clinical Aim 2.1 Aim 2.2 Academic Hospital Paramaribo Laboratory (AZPL) -Demographic -Clinical Aim 1.1 Aim 1.2 Meteorological Service Suriname (MDS) -Meteorological Aim 2.1 General Bureau of Statistics (ABS) -Census Aim 2.1 Aim 2.2
  • 20.
    Data Sources Type ofInformation  Case data   Inclusion / Exclusion Criteria  Demographic Clinical Context Inclusion criteria    Additional Data   Meteorological Census  Probable (hospital or clinic) cases of dengue fever Admitted into a hospital / clinic - 2001 to 2012 Exclusion criteria   No available date of birth No source or address
  • 21.
    Case Classification Definition Criteria Probable Clinical -Acute febrileillness -Two or more of the following: headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leucopenia Laboratory -Compatible serology (reciprocal hemagglutination-inhibition antibody titer > 1280, comparable IgG EAI titer or positive IgM antibody test in serum specimen Confirmed -Clinically compatibility and -DENV isolation in cell culture -RT-PCR detection of nucleic acid in serum Peeling et al. 2010
  • 22.
    Methodology: Hypothesis 1      Aim1.1: Characterize the incidence, prevalence and severity of dengue – with an emphasis of pediatric dengue – in Suriname from 2001 to 2012 Frequency distributions, incidence and mortality of DF & DHF Aim 1.2: Examine the demographic and clinical factors that influence the development of severe dengue Univariate analysis to identify difference between groups Multivariate analysis to test for associations Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 23.
    Hypothesis 2  Aim 2.1:Integrate clinical and demographic information of all dengue cases reported in Suriname since 2001 into a GIS platform    Generate a Geodatabase Identify historic spatial and temporal trends Aim 2.2: Identify spatial and temporal historic clusters of DF and DHF from 2001 to 2012   Global clusters / local clusters Poisson-model to assess spatial random distribution Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 24.
    Hypothesis 3  Aim 3.1:Characterize dengue-related entomological and environmental data in previously identified high transmission risk areas    Use the maps to identify areas of high dengue transmission And conduct entomological and environmental surveys to further assess the situation Aim 3.2: Propose effective, low-cost dengue intervention activities based on local information to reduce the risk of dengue transmission in Suriname Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 25.
  • 26.
    Hypothesis 1   Aim 1.1:Characterize the incidence, prevalence and severity of dengue – with an emphasis of pediatric dengue – in Suriname from 2001 to 2012  Prevalence Data cleaning / transforming   Incidence   In each district and resort District and resort with available census data Stratified by gender, age, ethnicity, type Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 27.
    Hypothesis 1  Aim 1.2:Examine the demographic and clinical factors that influence the development of severe dengue ADE Prior Infection Increased risk for DHF Age Human Host Dengue Virus Virulence Ethnicity Gender Serotype Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 28.
    Hypothesis 1 (Aim1.2)  Univariate analysis  Predetermined sample    Presence of absence of severe disease (DHF) P1 : did not develop DHF; P2 : did develop DHF Chi-square test for homogeneity  Ho: Pi = Pj  H a: Pi ≠ Pj  Significance: p < 0.05 Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 29.
    Hypothesis 1 (Aim1.2)  Multivariate analysis   Test for association of indicators on the development of DHF Logistic regression model    Test for indicators and interaction variables (α = 0.5)    Binary outcome: [Y = 0]: no DHF; [Y = 1]: DHF Stepwise forward selection of categorical indicator variables Maximum Likelihood method / likelihood ratio Odds ratio (95% confidence interval) Chi Square goodness of fit (α = 0.5)  Significance: p < 0.05 Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 30.
    Hypothesis 2  Aim 2.1:Integrate clinical and demographic information of all dengue cases reported in Suriname since 2001 into a GIS platform  Geodatabase includes   Suriname basemap (administrative level) Layers    Cases of DF and DHF Hospitals and clinics in Suriname Attribute table (for data exploration)    Demographic and clinical information of cases Weekly meteorological data- relative humidity, precipitation, average temp Additional district / resort characteristics- SES, access to piped water, etc. Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 31.
    Hypothesis 2  Aim 2.2:Identify spatial and temporal historic clusters of DF and DHF from 2001 to 2012  Identify IF clusters exist Global clustering – obtain Moran’s I (-1 to +1) Yes No Identify specific clustering (SatScan) Poisson regression analysis (log(pop)) is an offset for the population Local Moran’s I Overdispersion Ho: No spatial association between the ith region and its neighbors Ha: There is spatial association between the ith region and its neighbors Ho: The data follow a Poisson distribution Ha: The data do not follow a Poisson distribution Create cluster map Map Predicted values Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 32.
    Hypothesis 3  Aim 3.1:Characterize dengue-related entomological and environmental data in previously identified high transmission risk areas  Epidemiological Maps    Sample size Unit classification Replicates  Wet v dry season  Environmental Surveys  Unit Classification     Residential v non-residential Rural v urban Local characteristics Container classification     Non traditional v traditional Non disposable v disposable Size & location Water source Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 33.
    Hypothesis 3 (Aim3.1)  Surveys   Immature Ae. aegypti Larval and Pupae indices Container Index # of containers w/ larvae or pupa # of containers examined x 100 House Index # of houses w/ larvae or pupae # of houses inspected x100 Breteau Index Pupae / person survey # of containers w/ larvae or pupae 100 houses inspected # of pupae in a community # of people in a community Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 34.
    Hypothesis 3  Aim 3.2:Propose effective, low-cost dengue intervention activities based on local evidence-based information to reduce the risk of dengue transmission in Suriname    Historical cases of dengue help identify spatial and temporal patterns of transmission The importance of environmental and entomological data collection in elucidating populations at higher risk of transmission Epidemiological, entomological and environmental surveillance is necessary to move from an ad hoc basis to a more prevention oriented approach Significance • Background • Transmission of Disease • Hypotheses • Study Population • Methodology • Data Analysis
  • 35.
    Increased risk for DHF Prior Infection Age Competitors HumanHost Adult Larva Pupae Race Gender Temperature Density Rainfall Vector Dengue Virus Serotype Breeding Sites Virulence Climate Humidity Environment Sanitation Urbanization Pop. Density
  • 36.
    Acknowledgements    Dr. Lichtveld Dr. A.Jessurun at the Saint Vincent Hospital Dr. Hiwat and Dr. Jubithana at the Bureau of Public Health
  • 37.