Research project Aedes mosquitoes, spreading Zika, Dengue, and Chikungunya, are proliferating in many of the most densely populated regions of the world, contributing to increasing disease burdens.
Considering the current lack of effective control mechanisms, disease risks can be expected to increase as human population grows, global mobility increases, and climate change allows vector establishment in previously unaffected areas. Today, we lack validated methods for making predictions of Aedes mosquito population abundance, partly because Aedes population and invasion dynamics are still poorly understood. Understanding the dynamics of Aedes is critical for assessing outbreak risks of Zika, Dengue and Chikungunya virus in relation to local and global drivers of disease propagation. This project will develop mathematical-epidemiological methods for establishing validated estimates of Aedes mosquito abundance and predict the mid- to long-term dynamics of future Zika outbreaks at the global scale in different climate and development futures. The project is nested within the ongoing ZikaPLAN and the ISIPEDIA projects which secures data access and involvement of top-level international experts in many disciplines, and stakeholder dissemination to climate policy. By interfacing process-based models of Aedes ecology and Zika epidemiology with predictions of future demographic and climatic change, this project will enable more reliable projections than any study to date.
Purpose and aims
This project will develop mathematical models and provide novel validated estimates of Aedes mosquito abundance and project the future long-term dynamics of Zika epidemiology at the global scale in order to inform research, policy and control efforts.
The project aims to:
1. Develop methods to estimate global mosquito densities of Aedes aegypti and Aedes albopictus across the globe in present time, and project its future distribution and abundance under climate change
2. Develop models of mosquito-mediated transmission of Zika to predict the mid- & longer-term future epidemiological scenarios of outbreaks across the globe with climate change, and assess its sensitivity to future changes in human mobility, and population growth scenarios;
3. Simulate future Zika outbreak frequencies in non-endemic fringe zones, such as Europe.
Survey of the field
Many diseases transmitted by the Aedes mosquitos, Aedes aegypti and Aedes albopictus, have shown a marked expansion and intensification since the mid-20th century. This is particularly true for Zika, Dengue, and Chikungunya, nowadays thriving in many densely populated human settlements across the tropical and sub-tropical regions (1-3). There are currently no effective vaccines or treatments for Zika, Dengue, or Chikungunya. Instead, the dominating public health responses are symptomatic treatment, surveillance, outbreak preparedness, and vector control.
The recent large outbreak of Zika in Latin America was proclaimed by the WHO a “Public Health Emergency of International Concern” in February 2016 (4). Particularly alarming has been the discovery of neurological consequences of Zika infection, such as microcephaly in infants, and Guillain-Barré Syndrome. Zika has, in addition to being detected in blood during the viremic phase, also been detected in semen up to 2 months after infection, and as a consequence sporadic sexual transmission has been observed (5). Currently the epidemic in Latin America is in its third epidemic wave.
Chikungunya and Dengue are also transmitted by Aedes vectors. Similarly to Zika, immunity to Chikungunya will be induced after first infection. Chikungunya is currently expanding its transmission zones, and outbreaks have recently been reported, in Brazil, Africa, and the Caribbean. In addition, a larger outbreak carried by Aedes albopictus occurred in Italy 2007 (6). Dengue, phylogenetically closely related to Zika, has been estimated to carry a disease burden of almost 400 million infections per year worldwide (7). The high disease burden of dengue, endemic in most tropical and subtropical countries, can be explained by the fact that – unlike for Zika—dengue virus has four serotypes, thus up to 4 infections per person before complete immunity can occur. In Europe, the Portuguese island of Madeira had a large dengue outbreak in 2012 with more than 2000 confirmed cases. This followed some years after the introduction and establishment of the principal vector Aedes aegypti in 2005 (8). Our preliminary findings show that 2012 was a peak year for the vector abundance in Madeira due to favourable weather conditions (in preparation Liu-Helmersson). We also identified, using phylogenetic trees and global mobility data, that the virus was introduced from Venezuela (8).
Aedes aegypti and Aedes albopictus are ectothermic vectors. As such, their competence, survival, and the vectorial capacity and competence to replicate and transmit virus is highly determined by climatic conditions (9, 10). While Aedes aegypti has a more tropical habituation area and need warmer conditions to effectively replicate virus, Aedes albopictus has adapted also to temperate climate zones by winter diapause. Aedes aegypti, however, is the principal vector contributing to most outbreaks, as it is a more competent vector in suitable climate conditions, because it feeds exclusively on human blood, with a preference for feeding on many humans before finishing a single blood meal. Using ecological niche modelling and methods appropriate for noisy scattered data, a global estimate of the distribution of both vectors has been established (1) showing temperature as the most important predictor (abundance estimates are still absent).
Nowadays, compartmental and process-based models are a cornerstone of infectious disease research, policy, and control (11). They rest on building causal-loop models using mathematical differential equations or stochastic simulation models. The models describe complex vector and human dynamics in relation to external forcing, and the corresponding disease transmission and propagation patterns over time and space. The models continuously track births, deaths, and transition rates of humans and vectors, and the population at risk by dynamically capturing susceptible, infected and immune populations. Today, no long-term simulation of Aedes vectors exists that take into account the complexity of their life cycle in relation to environmental and climate conditions. Moreover, only one long-term simulation of the future Zika disease transmission of Zika exists (12). The study reports that the future of Zika may be characterized by long non-epidemic periods of about 20-30 years between larger outbreaks. However, the study was based on simplifications that could considerably change the disease dynamics and invalidate the prediction. A stochastic compartment model was used with mobility connectivity between particularly neighbouring (local to regional) spatial compartments and only a simple seasonal parameterisation of climate influences on vectors was used without accounting for heterogeneity in disease distribution. The simulation into the future did not assess sensitivity to several externally influential variables expected to change considerably over time (18), such as changes in population density & climate change. In fact, climate change projections show a rather consistent global pattern of the amplitude of change to the mid 21th century, at that time rather independently of greenhouse gas emission reductions (13).
The current prevailing paradigm and way of including climate change data into health impact models is to use a range of climate model outputs and scenarios to describe the climate impact and its uncertainty, similar to the research we have been involved in through the ISIMIP community and the DengueTools project (9, 10,14).
This project will build on the aforementioned studies and bridge the scientific gaps by developing mathematical and stochastic methods and establishing novel estimates of Aedes and Zika proliferation from current time to the end 21th century. It will take into consideration the most important drivers of disease spread and intensification at a local and global scale. It will further evaluate the sensitivity of the estimates to different development pathways of future change, and by so, provide more reliable estimates of future risks posed by Aedes and Zika.
1. Kraemer MU, Sinka ME, Duda KA, Mylne AQ, Shearer FM, Barker CM, et al. The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus. Elife. 2015;4:e08347.
2. Musso D, Cao-Lormeau VM, Gubler DJ. Zika virus: following the path of dengue and chikungunya? Lancet. 2015;386(9990):243-4.
3. Struchiner CJ, Rocklov J, Wilder-Smith A, Massad E. Increasing Dengue Incidence in Singapore over the Past 40 Years: Population Growth, Climate and Mobility. PloS one. 2015;10(8):e0136286.
4. Heymann DL, Hodgson A, Sall AA, Freedman DO, Staples JE, Althabe F, et al. Zika virus and microcephaly: why is this situation a PHEIC? Lancet. 2016;387(10020):719-21.
5. Oster AM, Russell K, Stryker JE, Friedman A, Kachur RE, Petersen EE, et al. Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus - United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(12):323-5.
6. Angelini R, Finarelli AC, Angelini P, Po C, Petropulacos K, Silvi G, et al. Chikungunya in northeastern Italy: a summing up of the outbreak. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2007;12(11):E071122 2.
7. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504-7.
8. Wilder-Smith A, Quam M, Sessions O, Rocklov J, Liu-Helmersson J, Franco L, et al. The 2012 dengue outbreak in Madeira: exploring the origins. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2014;19(8):20718.
9. Liu-Helmersson J, Stenlund H, Wilder-Smith A, Rocklov J. Vectorial capacity of Aedes aegypti: effects of temperature and implications for global dengue epidemic potential. PloS one. 2014;9(3):e89783.
10. Liu-Helmersson J. QMB, Wilder-Smith A., Stenlund H., Ebi K., Massad E., Rocklöv J. Climate Change and Aedes Vectors: 21st Century Projections for Dengue Transmission in Europe. eBioMedicine [Internet]. 2016.
11. Anderson RM, R. Infectious Diseases of Humans: Dynamics and Control: Oxford University Press; 1991.
12. Lessler J, Chaisson LH, Kucirka LM, Bi Q, Grantz K, Salje H, et al. Assessing the global threat from Zika virus. Science. 2016;353(6300):aaf8160.
13. IPCC. Climate Change 2013: The Physical Science Basis. Contribution of Working Group I to the Fifth Assessment Report of the Intergovernmental Panel on Climate Change. Cambridge, United Kingdom and New York, NY, USA: Cambridge University Press; 2013. 1535 p.
14. Caminade C, Kovats S, Rocklov J, Tompkins AM, Morse AP, Colón-González FJ, et al. Impact of climate change on global malaria distribution. Proceedings of the National Academy of Sciences.