Transmission of arboviral diseases using a multiplexed serological - - PowerPoint PPT Presentation

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Transmission of arboviral diseases using a multiplexed serological - - PowerPoint PPT Presentation

Transmission of arboviral diseases using a multiplexed serological survey in French Guiana Claude FLAMAND, FETP, PhD Head of epidemiology unit of Institut Pasteur in French Guiana Pasteur International Network Meeting American Region Sa o


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Transmission of arboviral diseases using a multiplexed serological survey in French Guiana

Claude FLAMAND, FETP, PhD

Head of epidemiology unit of Institut Pasteur in French Guiana Pasteur International Network Meeting – American Region Sāo Paulo, 3 -5 July 2019

EPIARBO Project

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Aedes mosquitoes : A history of global expansion

2 Kraemer & al. (ELife, 2015)

  • Ae. aegypti
  • Ae. albopictus

vectors vectors

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Increasing risk of transmission of arbovirus

3 vectors vectors

https://www.cdc.gov/chikungunya/geo/index.html

Chikungunya global distribution Zika global distribution

Growing number of major outbreaks of DENV All four DENV serotypes in much global tropical and sub-tropical regions Large outbreak of Chikungunya in the Caraibbean and the Americas in 2013-2014 Large outbreak of Zika virus in the Americas in 2015 Yellow fever in Brazil and Angola in 2016-2017

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Knowledge gaps in arbovirus spread and maintenance

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Common features of arbovirus Epidemiological gaps

 Frequent clinical misdiagnosis  Transmission dynamics poorly understood  True Burden rarely known  Outbreak occurence prediction remain difficult  Control efforts limited to ressource-intensive vector control activities and difficult to target  Low specificity of serosurveys in the context of co-circulation

  • f closely related pathogens

 Substantial asymptomatic infection  Changing epidemiology  Serological cross-reaction  Impact of environmental drivers may vary according to geographical area and spatial scale

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  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane

French overseas department, South America

Population size : 250,000 inhabitants (~1‰ Brazil)

Amazonian forest complex (3 inhab./km2) Two main inhabited geographical regions

 A costal urbanized strip (90% population)  Remote and river area along the frontiers

High levels of immigration : ~40% of the population Various ethnic groups

 Creoles, European, Brazilians, Marrons, Amerindians,

Chinese,…

Total fertility rate : 3.5 children p. women (6,700 births/year)

French Guiana

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  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane

Presence of competent vector : Aedes aegypti Regular major DENV outbreaks (1991 – 2013)

 ~2-5% of the population (CC)

Recent outbreaks of emergent arbovirus

 CHIKV (2014), ZIKV (2016)

No seroprevance data available

 Impact of past epidemics  Estimating future transmission risks  Surveillance system coverage  Assessing the impact of prevention strategies

Implementation of an househould serosurvey

 Burden of diseases and spatial distribution of viruses

Justification and objectives

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Epidemiological cross-sectional study

 General population household survey  2 500 residents of FG (~1600 households)  Target Population : [ 2 years – 75 years ]  Stratified 2-stage sample design based on the size of municipality  Questionnaire (Sociodemographic, environment, human behavior

Serum sample : Multiplexed microsphere-based IgG Immunassay (Relative fluorescence intensity)

 DENV ; CHIKV ; ZIKV ; MAYV ; YF ; WN  Seroneutralization tests (subsample)

Age-stratified Modelling approach

 Reconstruction of history of circulation and the extent of cross-reactivity

Methodology

  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane
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Spatial distribution of enrolled subjects (N =2,697)

  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane
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Exploring serological cross-correlations

  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane

Alphaviruses Flaviviruses

DENV1-DENV4

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From antibodies titer levels to serological status

  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane

The example for CHIKV and MAYV

 CHIK serological status clearly identified  MAYV response strongly impact CHIKV response  Differences of antibodies responses according to age and location data  Estimating location-specific forces of infection modulated by risk factors

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Model-based classification of the infection status

  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane

Infection status (MAYV, CHIKV) Titers (in log scale)

(0,0) tM = s0

M + N(0, eM)

tC = s0

C + N(0, eC)

(1,0) tM = s0

M + sM + N(0, eM)

tC = s0

C + sM  C tM +

N(0, eC) (0,1) tM = s0

M + sC  M tC

+N(0, eM) tC = s0

C + sC + N(0, eC)

(1,1) tM = s0

M + sM +N(0, eM)

tC = s0

C + sC + N(0, eC)

 Determining infection status for

MAYV and CHIK from individual RFI

 Understanding how an infection

boosts the RFI for an assay and cross-react with the other assay

 Reconstructing the history of

circulation using risk factors

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Validation with seroneutralization results

  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane

Model-based classification vs simple optimized cut-off

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Estimating the burden of arboviruses

DENV 69.7% [66.2% – 71.0%] High level of infection Small variations in the areas exposed to Aedes aegypti ZIKV 23.1% [19.5% – 27.2%] Large transmission in the most important municipalities North-Western area+ CHIKV 20.3 [17.5% – 22.5%] West Maroni river highly infected North-western area++ Household transmission ++ MAYV 2.7% [ 2.1% – 3.4%] Sylvatic constant transmission Inland and amazonian forest area ++ Male >20 years ++

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Conclusions and perspectives

Determining the level of circulation of priority arboviruses at a country-level in South America Contribution of modelling techniques to assess viral circulation from detailed age-stratified seroprevalence data dealing with cross- reactivity issues Investigating DENV serotype-specific and YF seroprevalence Elucidating spatial differences in risks exploring more determinants

 population mobility, entomological risks, insecticide resistance, …

Development opportunity to elaborate new research projects and establish partnerships to improve the understanding of transmission dynamics in South America

  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane
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Aknowledgements

Fundings

  • C. Fritzell
  • S. Bailly
  • S. Cauchemez
  • H. Salje
  • J. Paireau
  • E. Hoze
  • B. Nikolay
  • S. Matheus
  • D. Rousset
  • A. Enfissi
  • M. Kazanji
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www.pasteur-cayenne.fr

  • C. Flamand – Unité d’épidémiologie,, Institut Pasteur de la Guyane