Preparing for vector-borne virus outbreaks in a changing world: an One Health Approach

The Netherlands, with its dense population of humans and livestock, international transport and travel hubs, and water-dominated landscape is particularly vulnerable to infectious disease outbreaks. The One Health Consortium aims to understand if and how changes in climate, farming, water management and travel lead to mosquito-borne disease outbreaks, to be better prepared.

Interacting changes
Infectious disease outbreaks are increasingly common due to multiple, interacting global changes and developments in the human, animal or environment domains.

These changes can trigger processes that disturb the fragile balance in the complex human-animal-environment ecosystem, up to the point where the conditions are created for (new) infectious disease outbreaks, in animals and/or humans. In these situations, the state of the system has reached a pathogen-specific vulnerability threshold ( ‘tipping point’), making the system receptive to outbreaks of that pathogen if it is introduced. The Netherlands, with its dense population of humans and food animals, international transport and travel hubs (Schiphol, Rotterdam), and unique water-dominated landscape is particularly vulnerable to the occurrence of such tipping points and hence, outbreaks of (newly emerging) infectious diseases. In this project we will consider four change scenarios that could lead to the occurrence of such tipping points and disease emergence:

changes in the climate,
changes in water management,
changes in farming methods and
changes concerning international travel and import risks.
Despite this expected vulnerability, emerging disease outbreaks in the Netherlands are still relatively rare. We currently study these outbreaks – when they occur – reactively, individually and within relatively isolated silos (e.g., human vs animal vs ecological health, academic research vs public health research, public vs private sector). This ad-hoc, reactive and fragmented approach is ineffective and inefficient. Instead, the partners collaborating in this project will adopt a pro-active, integrated, multisectoral, One Health approach in studying emerging infectious disease outbreaks.

We will develop and implement a forward-looking integrated research agenda, measuring and modelling how projected demographic, climatological, ecological, and planological changes will impact the risk of emergence of infectious diseases in the Netherlands, and translate this understanding into effective, integrated outbreak preparedness and response actions.

Focus on vector-borne diseases (VBD)
To prevent spreading our efforts and resources too thinly, we will focus our research agenda on a specific category of infectious diseases, namely vector-borne diseases (VBD), which are particularly relevant to the Netherlands, due to its water-dominated ecosystems and abundant wildlife as potential amplifying hosts. VBD are infectious diseases that are transmitted through arthropods (e.g. mosquitoes). They have been expanding massively in (sub)tropical regions of the world through trade and habitat changes.

Scientific and societal breakthroughs we aim to achieve
Our ambition is to prepare for VBD outbreaks in a rapidly changing environment. The One Health Consortium will do this by

providing pathogen specific and generic early warning indicators that measure whether our human-livestock-wildlife ecosystem is (becoming) vulnerable for VBD outbreaks,
developing novel catch all tools for outbreak detection and risk assessment,
translating the knowledge into interventions based on in depth knowledge of the entire ecosystem and interactions in which such outbreaks may occur.
Our approach consists of four complementary, interacting pillars. The One Health Consortium will gain a deep understanding of suitability of ecosystems in the Netherlands for VBD introduction, circulation, and expansion, and – conversely – the actionable factors that determine ecosystem resilience.

Pillar A: Ecosystem mapping

PhDs will be involved in studies aimed at mapping at high-resolution the complex interplay between factors that drive arbovirus introduction, circulation and expansion in the Netherlands. They will be involved in a series of uniquely interconnected research studies addressing reservoir hosts, disease hosts, viruses, vectors, and their interactions, and through their work provide critical baseline data for the PhDs in pillar B, responsible for model development.

Wild-animals are important as reservoir for arboviruses, both by introducing viruses through migration, and by serving as amplifiers of locally present viruses, if conditions are favourable. In addition, specific vectors are needed for arbovirus establishment. The group of PhDs involved in this work will jointly design smart surveillance strategies, involving well-trained citizen scientists coordinated by Vogeltrekstation, as well as studies in dead birds and other wild-life reported to the Dutch Wildlife Health Centre. Where needed, this will be complemented with targeted sampling of rodents, bats, and wild herbivores to provide information regarding circulation of (emerging) arboviruses. Dried blood spot samples, throat- and cloacal swabs will be tested for antibodies and/or target viruses, using protein microarrays and multiplex PCRs, developed as part of this project (Pillar D).

Analytical methods will be harmonized across species, including humans. Spatial and temporal avian host dynamics will be studied through citizen-science projects combined with detailed longitudinal studies in selected host species and in relation to virus exposure. We will gather data on density and movements of competent avian hosts for (invasive) mosquito vectors for animal and human AVD by combining and modifying existing citizen science projects (Sovon, Vogeltrekstation, Eurobirdportal, Trektellen) to monitor avian host occurrence in time and space. For rodents, bats and mammals, data will be gathered through “Waarneming.nl” and the Network Ecological Monitoring of CBS and through direct consultation of landowners that use large grazers as management tool.

If an actual VBD outbreak occurs in the Netherlands during the project period, the efforts and associated resources will be realigned to target the specific disease, if agreed with the funder and in collaboration with co-financing partners with a mandate for outbreak response. Sanquin and the blood bank of Curacao will prepare a rapid response protocol for population exposure testing during a health threat, and will provide access for establishing baselines for systems serology studies. To do this, joint preparedness protocols will be developed under coordination of PhD project 21.

PhD projects 1 through 5 are tightly linked and will collaborate closely to optimise sampling of various taxa and to allow for cross-taxa analyses and integration of data from virus phylogeny and pathogenicity to vector and host population dynamics and, ultimately, risk mapping and early warning.

PhD vacancies
PhD position 1: Citizen science for mosquito surveillance

PhD position 2: Wildlife surveillance

PhD position 3: Impact of emerging arboviruses on wild bird populations

PhD position 4: Tracking of movement, density and mortality of susceptible amplifying hosts (birds, rodents, bats, mammals)

PhD position 5: Dynamic risk based early warning risk maps

PhD position 6: Travelers as sentinel and source of arboviruses

PhD position 7: Citizens and surveillance with focus on high schools

PhD position 8: Arbovirus impact in livestock

Pillar B: Forecasting and early detection

PhDs will be involved in studies aimed at mapping the complex interplay between factors at high-resolution that drive arbovirus introduction, circulation and expansion in the Netherlands. They will be involved in a series of uniquely interconnected research studies addressing reservoir hosts, disease hosts, viruses, vectors, and their interactions, building from field and experimental data (collected in Pillars A and D), supplemented with data relevant to model VBD life-cycles collected from public sources (e.g., KNMI, CBS, literature, data from the EDEN/EDENext EU-funded projects). We will develop a method and practical tools for early warning to quantify and predict when the critical emergence threshold will be reached for VBD. The model-based approach will be used to analyse scenarios that could lead to disease emergence: 1) changes in climate, 2) changes in water management, 3) changes in farming practices, and 4) changes in importation risk. Critical knowledge gaps for the change scenario’s will be addressed through targeted experimental studies that generate essential data for the scenario modelling.

PhD vacancies
PhD position 9: Tracing and retracing mosquito-borne disease emergence

PhD position 10: Tools to explore risk of emergence of vector-borne diseases in ecosystems

PhD position 11: Generic early warning indicators for vector-borne infections

PhD position 12: Predictors of tipping points of mosquito populations in a changing world

PhD position 13: Vector competence studies in change scenario’s

PhD position 14: Vector immunity in change scenario’s

PhD position 15: Experimental work on effects of global change scenarios on vector population parameters

Pillar C: Impact and severity assessment

In Pillar C we address key knowledge gaps that are crucial to model the potential impact of an outbreak through a suite of in vitro and in vivoexperiments in mosquitoes and (reservoir and disease) hosts, respectively. The work in pillar c will address a select group of critical parameters to answer key questions for risk assessment: 1) what vector and vertebrate species can be infected, 2) can the virus efficiently spread between vectors, animals and humans, and 3) can the virus cause (severe) disease in animals or humans?

PhD vacancies
PhD position 16: Prediction of host range and reservoir potential

PhD position 17: Understanding the role of vector, host and virus variations in transmission and disease

PhD position 18: Models to study and prioritize neuropathogenic arboviruses

PhD position 19: Role of host innate immune responses and arbovirus innate immune evasion in transmissibility, host range and disease outcome

PhD position 20: Arbovirus systems serology: antibody profiling for exposure and impact assessment

Pillar D: Interventions

The findings from the studies in pillars a, b, and c will be used to guide development of targeted early warning systems and tools for rapid assessment of risk of emerging VBD to humans and animals, to be transferred to institutes with primary responsibility for early warning.

A cross-cutting toolkit of advanced assays will be developed, including targeted and metagenomic NGS, protein microarrays, eDNA metabarcoding, targeted to field studies and for rapid outbreak response. To allow deployment for use in regions with limited research infrastructure, such as the Dutch Caribbean, fieldable versions of the key assays will be developed. A suite of bio-informatic tools, coupled with a data sharing and analysis platform will be developed for the entire project in collaboration with the European data infrastructure EBI/ELIXIR and the COMPARE project.

PhD vacancies
PhD position 21: From theory to practice: what to do, when and where?

PhD position 22: Serological tools for surveillance across species

PhD position 23: Pathogen detection, metagenomics and genomic epidemiology for early warning surveillance

PhD position 24: Modulating mosquito immunity

PhD position 25: Arbovirus pathogenesis and development of innovative vaccine candidates

PhD position 26: Universal vaccines

Partners in this project:

Erasmus Medical Center

Utrecht University

Wageningen University Research

Leiden University Medical Center

Radboud University Medical Center

NIOO

Avans Hogescholen

Leiden University

Utrecht University Medical Center

Deltares

RIVM

KNMI

Red Cross Blood bank foundation

Sanquin

Techncasium

NVWA

CEAB-CSIC (Spain)

SOVON