Vector borne disease and Dengue

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


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


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


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


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


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


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.


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


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


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


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


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

Vector borne disease and Dengue

Health & Medicine

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