Mapping the growing global burden of dengue to help countries plan for the next decade of dengue control

Lead Research Organisation: London School of Hygiene & Tropical Medicine
Department Name: Epidemiology and Population Health

Abstract

Dengue is one of the fastest growing global infectious diseases with an 8-fold increase in reported cases since 2000. Because a large proportion of dengue virus infections are asymptomatic and the quality of disease surveillance is constantly changing, computational models have been central to estimating the global burden of dengue. However, a key limitation of current models is that they do not accurately estimate how this burden changes year-on-year. This prevents model-based burden estimates of dengue having the same impact they do in the fields of HIV, TB and malaria where they are actively used to track progress towards international targets. This year, new goals for reducing the global burden of dengue between 2021-2030 will be set. Data gaps and limitations of current modelling approaches constraint our ability to track country progress, understand how existing interventions are working and suggest how control programmes need to change to meet these new targets.

In this fellowship I will develop novel detailed global dengue models that allow a new generation of predictions of the past present and future global burden of dengue to be made. These models can be used to answer three main aims:

Aim 1: How has the global growth in dengue burden changed since 2000?
By pairing a new global dengue database with geostatistical and mathematical modelling techniques I will generate unbiased burden estimates of the growth in dengue burden 2000-2020.

Aim 2: How effective have policy changes to reduce dengue deaths been?
Through an analysis of over 4 million individual-level patient records in São Paulo (Brazil) and the Philippines, I will investigate how changes in treatment seeking, diagnosis and clinical management have reduced the risk of dengue death. This will measure the impact of current interventions on mortality and identify where further gains could be made.

Aim 3: By how much will dengue burden grow 2021-2030 in each country?
By projecting the models from Aim 1 into the future taking into account changes in climate, urbanisation and growing levels of immunity to dengue, robust predictions of dengue burden 2021-2030 can be made. A dengue control feasibility assessment will then identify the specific barriers each country faces in meeting their 2021-2030 targets.

This fellowship aims to improve our understanding of how the global burden of dengue is changing at a pivotal time. Aim 1 will focus on developing a new generation of dengue models to estimate past changes in incidence 2000-2020 to understand why we were unable to contain dengue expansion. Aim 2 will answer key questions about the effectiveness of current efforts to reduce dengue deaths. Aim 3 will estimate future growth in dengue incidence allowing countries to decide how to best address this growing problem. All the data, models and predictions will be hosted on a new dedicated website that allows researchers and government officials to explore these estimates in detail and with full transparency. Beyond dengue, these models will also provide fundamental insights into how modern emerging infectious diseases are capable of uncontained global spread and help design new strategies against future pandemics.

Technical Summary

Dengue is one of the fastest growing uncontained emerging infectious diseases. Computational models play an important role in estimating disease burden because of the limitations of epidemiological data. This year, new goals for reducing the global burden of dengue between 2021-2030 will be set, but current models are insufficient for tracking progress. In this fellowship I will develop the next generation of global dengue models that take into account the spatio-temporal variation in multiple types of epidemiological data to predict the past, present and future global burden of dengue.

A systematic search will assemble incidence and prevalence data at a sub-national level with geospatial models used to make predictions for data deficient areas. A Bayesian multi-serotype dengue transmission model fit to dengue incidence and prevalence data will then give consensus estimates of how dengue burden has changed 2000-2020. These predictions will give insights into how dengue was able to spread so rapidly and help design strategies to contain future arboviral pandemics.

With data on >4 million individual-level dengue patient records I will characterise spatio-temporal trends and causal determinants of delayed treatment seeking and misdiagnosis. Using multivariate regression approaches I will then assess the contribution of each of these to the risk of severe disease and death after accounting for relevant confounders. This will give new insights into how to prevent dengue deaths through non-therapeutic approaches.

Projecting these models using future climate, urbanisation and immunity scenarios will allow new predictions of future changes in dengue burden. A national feasibility assessment will then rank countries in their ability to meet 2021-2030 goals based on epidemiological, operational and financial barriers. This work can be used to define target product profiles of novel interventions and identify under or over-achieving control programmes.

Publications

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Brady O (2021) What Is the Impact of Lockdowns on Dengue? in Current infectious disease reports

 
Description WHO target product profile for Wolbachia
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a guidance/advisory committee
Impact The target product profile (TPP) document that will arise from this process when it is complete in Q2 2023 will assist the following stakeholders: 1. Country ministries of health- this provides internationally recognised guidance on what an acceptable and ideal Wolbachia replacement product will look like including setting transparent expectations for cost, speed, effectiveness and durability. 2. Product developers- outlines minimum standards that products must meet, allowing early viability assessments of potential products and streamlining product development to avoid wasted resources. 3. Members of the public- this TPP will allow accelerated uptake of a key intervention against dengue and ensure the product is available at a price point that is equitable for all dengue endemic countries.
URL https://www.who.int/news-room/articles-detail/call-for-public-consultation-development-target-produc...
 
Description Developing target characteristics for mosquito suppression and replacement programmes using modelling
Amount $50,000 (USD)
Funding ID OPP1183567 
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 11/2021 
End 12/2022
 
Description Supporting a global database and risk map of arboviral diseases for the Global Arboviruses Initiative
Amount $175,000 (USD)
Organisation World Health Organization (WHO) 
Sector Public
Country Global
Start 07/2022 
End 08/2023
 
Title Data and covariates from "Human movement and environmental barriers shape the emergence of dengue" 
Description Contains municipality level dengue data for Mexico and Brazil and a range of environmental and mobility covariates summarised at the admin2 level for use in the linked paper. Further details on each covariate available in the full paper. 
Type Of Material Database/Collection of data 
Year Produced 2023 
Provided To Others? Yes  
Impact This dataset provides a rich back catalogue to understand long term dengue emergence in Brazil and Mexico at a very fine spatial scale. This database supports a forthcoming publication on dengue emergence in these context and makes the data and covariates fully available to improve reproducibility and reuse of this dataset. 
URL https://figshare.com/articles/dataset/Data_and_covariates_from_Human_movement_and_environmental_barr...
 
Description Covid-19 impact on dengue collaboration 
Organisation Beijing Normal University
Country China 
Sector Academic/University 
PI Contribution We have jointly worked on two papers assessing the impact of COVID-19 restrictions on dengue transmission in China and globally. Myself and Huaiyu Tian designed the experiments, analysis strategy and wrote the manuscript, while Huaiyu's team collected the data and conducted the analyses.
Collaborator Contribution We have jointly worked on two papers assessing the impact of COVID-19 restrictions on dengue transmission in China and globally. Myself and Huaiyu Tian designed the experiments, analysis strategy and wrote the manuscript, while Huaiyu's team collected the data and conducted the analyses.
Impact Two main publications (both listed under publications): 1. Assessing the impact of border closures on dengue in China: Li, Naizhe, et al. "Assessing the impact of COVID-19 border restrictions on dengue transmission in Yunnan Province, China: an observational epidemiological and phylogenetic analysis." The Lancet Regional Health-Western Pacific 14 (2021): 100259. 2. Assessing the global impact of COVID-19 restrictions on dengue burden: Chen, Yuyang, et al. "Measuring the effects of COVID-19-related disruption on dengue transmission in southeast Asia and Latin America: a statistical modelling study." The Lancet infectious diseases 22.5 (2022): 657-667.
Start Year 2021
 
Description Global Arbovirus Initiative 
Organisation World Health Organization (WHO)
Country Global 
Sector Public 
PI Contribution After the launch of the GAI we joined forces to conduct a systematic review of arbovirus mapping studies. I then chaired a meeting at ASTMH in Seattle in October 2022 that convened arbovirus modellers and epidemiologists to discuss the initial results of the systematic review and built new collaborations to improve maps of arboviruses.
Collaborator Contribution The GAI secretariat set up the meeting and has convened the attendees and overall helped shape all these new collaborators into an effective working group. They also provide direct financial contributions to our activities that funds personnel to conduct the work.
Impact Manuscript under preparation on the systematic review of arbovirus mapping studies. Two further manuscripts planned. Outputs from each of these manuscripts are planned to be hosted on a new WHO arbovirus dashboard that improves global situational awareness of arboviruses and stimulates further data sharing.
Start Year 2022
 
Description Neglected Tropical Diseases Modelling consortium 
Organisation Neglected Tropical Diseases Modelling Consortium
Sector Charity/Non Profit 
PI Contribution I was invited to chair a session on dengue at the annual meeting of the NTD consortium in Geneva, Switzerland. I organised discussions, took notes and produced a summary of discussion on future research needs for dengue control which will form part of a wider publication by the NTD modelling consortium.
Collaborator Contribution The NTD modelling consortium brought together modellers, implementation researchers and country programme managers to discuss unmet needs across different NTDs. They aim to produce a combined publication using the outputs from our separate discussion groups.
Impact Manuscript under preparation. Involved researchers and governmental personnel from modelling, epidemiology, clinicians and implementation research disciplines.
Start Year 2022