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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 Cholera, leprosy, tetanus
Viruses Influenza, chicken pox,
HIV, poliomyelitis, ebola Parasites
Filariasis, giardiasis, ameobasis
Fungi Fungal meningitis, mycosis
The Disease Triangle
DISEASE
HOST
ENVIRONMENTPATHOGEN
What are vector-borne diseases?
Definite host Intermediate host Reservoir 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
DISEASE
HOST
ENVIRONMENTPATHOGEN
VECTOR
Factors affecting the Emergence / Resurgence of Vector Borne Diseases
Genetic and Biological Human susceptibility to disease Pathogen adaptation
Physical Environmental Urbanization Climate change
Ecological Encroachment
Social / Political / Economical Poverty War Lack of political will / money
Strategies to curve disease incidence
Vector Control Options
• Biological Control• Immature and mature
stages• Predators / pathogens
• Genetic Control• Sterilization techniques
• Physical Control• Environmental
manipulation / reduction• Chemical Control
• Oils, insecticides• Personal Protection• Education
Challenges
Lack of surveillance / monitoring At all stages of
intervention Population dynamics
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
Mayo Foundation for Medical Research, 2012
Cann, 2007
The Vector Aedes aegypti
Urban Tropical / Subtropical Vector Control
WHO, 2012
Ae. aegypti
hype
rend
emic
Dengue in the Americas
Incidence Severity Understudied
From San Martin, et al., 2010
hypo
ende
mic
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?
• Diseases of Poverty• Lack of political will
• Not a priority• Vertical command structure
• Complicated diseases• No good vaccine• Uneducated populations
• Globalization• Urbanization• Vector importation• New emerging diseases
Transmission of Disease
Influencing factors
Environment
Human Host
Dengue Virus
UrbanizationSanitationVirulenceSerotype
Age
Gender
Ethnicity
Immune status
Vector
Climate
Density
Breeding Sites
Competitors
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 1.1Aim 1.2
Bureau of Public Health (BOG)n ≈ 5298
-Demographic -Clinical
Aim 2.1Aim 2.2
Academic Hospital Paramaribo Laboratory (AZPL)
-Demographic-Clinical
Aim 1.1Aim 1.2
Meteorological Service Suriname (MDS)
-Meteorological Aim 2.1
General Bureau of Statistics (ABS) -Census Aim 2.1Aim 2.2
Data Sources
Type of Information Inclusion / Exclusion Criteria
Case data Demographic Clinical Context
Additional Data Meteorological Census
Inclusion criteria 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 ClassificationDefinition Criteria
Probable
Clinical
-Acute febrile illness-Two or more of the following: headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leucopenia
-Compatible serology (reciprocal hemagglutination-inhibition antibody titer > 1280, comparable IgG EAI titer or positive IgM antibody test in serum specimen
Laboratory
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 Data cleaning / transforming
Prevalence In each district and resort
Incidence 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
Human Host
PriorInfection
Age
Gender
Ethnicity
ADE
Dengue Virus
Virulence Serotype
Increased risk for DHF
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
Ha: 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 Binary outcome: [Y = 0]: no DHF; [Y = 1]: DHF Stepwise forward selection of categorical indicator
variables Test for indicators and interaction variables (α = 0.5)
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)
Identify specific clustering(SatScan)
Local Moran’s IHo: No spatial association between the ith region and its neighborsHa: There is spatial association between the ith region and its neighbors
Create cluster map
Poisson regression analysis(log(pop)) is an offset for the population
OverdispersionHo: The data follow a Poisson distributionHa: The data do not follow a Poisson distribution
Map Predicted values
Yes No
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
# of containers w/ larvae or pupae100 houses inspected
Pupae / person survey
# 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
Environment
Human Host
Dengue Virus
Vector
Increased risk for DHF
VirulenceSerotype
Density
Competitors
PriorInfection
Age
Gender
Race
ClimateRainfall
Temperature
Humidity
Urbanization
Pop. DensityBreeding Sites
Sanitation
Larva
PupaeAdult
Acknowledgements
Dr. Lichtveld Dr. A. Jessurun at the Saint Vincent Hospital Dr. Hiwat and Dr. Jubithana at the Bureau of
Public Health
Questions & Comments