A systems biology approach to infectious disease transmission: linking individuals populations and ecosystems

Lead Research Organisation: University of Glasgow
Department Name: School of Life Sciences

Abstract

Did you ever wonder (and wish) that mosquitoes would bite your dog instead of you? Ecological theory tells us that animals should evolve to specialize on diets that most increase their survival and reproduction. In the case of blood-feeding insects, this evolution may explain why some species bite only humans, whereas others prefer domesticated or wild animals. Evidence shows that the survival and reproduction of most blood-feeding insects, including mosquitoes, bed bugs, fleas, and biting flies, depends on the species of vertebrate that they bite. The survival of parasites within these insects, many of whom cause severe disease in humans and animals, is also influenced by vertebrate species choice; with the blood of some animals enhancing parasite growth, and others blocking it. Given this is the case, what would happen if the range of animal hosts available to blood-feeding insects was suddenly changed on a landscape scale, and how would this change impact the spread of human and animal disease? This experiment is occurring in nature, where the variety of animal species available to blood-feeding insects is rapidly changing as human populations expand; reducing the availability of other vertebrates in favour of themselves and their livestock. The downstream impacts of this narrowing of vertebrate species choice are not yet known; particularly with respect to how it will impact the biodiversity and abundance of biting insects, and the spread of the diseases they carry. Understanding how these changes in vertebrate host species composition influence the survival, population growth and parasite transmission potential of biting insects is the central aim of this project. Using this information to formulate and test mathematical models that predict how insect abundance and disease risk will change in response to specific human-induced land-use changes is my ultimate goal. In Africa, a continent inflicted by the world's deadliest insect-borne diseases; changes in land-use practices are starting to take place. Large-scale urbanization and intensive agricultural development are not yet common, but will become increasingly so within the next decade. Thus here more than anywhere, study of the impact of vertebrate species diversity on blood-feeding insects has the potential to provide pre-emptive solutions to detrimental ecological and epidemiological consequences associated with changes in land use. I will conduct a series of novel laboratory analyses, biologically realistic behavioural assays, and intensive field collections in order to test whether the survival and reproduction of the common African mosquitoes Anopheles gambiae s.s. and An. arabiensis is influenced by the availability of host species that they prefer (humans and cows) relative to those that are secondary (goats, chickens and dogs). I will test whether the ability of these two mosquito species to compete with one another is determined by the relative abundance of their preferred host species (humans for An. gambiae, and cows for An. arabiensis). Finally I will investigate whether the development of malaria parasites within these mosquitoes is influenced by the type of blood (human, cow, goat, chicken or dog) that they consume when they are infected. Information gathered in the experiments will be used to formulate a mathematical model of mosquito and parasite population growth as a function of host species composition. I will use this model to examine how skewing the composition of vertebrate hosts towards humans (as expected under urbanization), or to a mixture of livestock and humans (as expected under agricultural expansion) will influence mosquito abundance, biodiversity, and malaria transmission intensity. Finally, these models will be fit to actual landscapes within a malaria-endemic region of east Africa to predict how current and forecasted changes in land-use activities could impact Anopheline population dynamics and human health.

Technical Summary

To predict the behaviour of complex biological systems such as organisms, populations and ecosystems; the links between genes, physiology, organism fitness, and population dynamics must be identified. Few biological systems have been sufficiently characterized to permit this, with a rare exception being human infectious diseases that have been studied extensively at the molecular, organismal, and population level. Here I will combine the rich multi-scale data available for human malaria parasite with new experiments that address linkages betsween processes occurring at different scales to evaluate the ability of biological properties associated with individual resource use to inform population, community and epidemiological dynamics. I will begin with lab experiments that test how the fitness of individual mosquito vectors and their parasites depends on the vertebrate species from which they take blood. Field studies will follow to examine how vertebrate behaviour influences the feeding success and mortality of individual mosquitoes; and how intra- and interspecific competition between larvae of vectors An. gambiae and An. arabiensis are influenced by the vertebrate host choice of their parents. These individual-based behavioural and fitness data will be used to parameterize a spatially-explicit demographic model of mosquito and parasite dynamics. Within a Geographic Information System, I will simulate known vertebrate host distributions from 6 Tanzanian sites; and examine the model's ability to predict the rank-order of independently-collected, hierarchical epidemiological properties of each site including vector survival, reproduction, abundance, species composition, and finally parasite transmission. This integrative approach uniting experiments, field observation, and mathematical modelling will provide a unique opportunity to test our ability to predict the dynamics of a complex infectious disease system as a function of lower-order biological phenomena.

Publications

10 25 50

 
Description - the impact of livestock on protecting people from malaria mosquitoes in Africa
- tested ecological and evolutionary predictions about the reasons why African malaria mosquitoes specialize on humans instead of other animals.
- the use of semi-field systems for the study of mosquito vector ecology
- that the type of blood which malaria-infected mosquitoes consume during the time that parasites are developing will determine how infectious they become
Exploitation Route Understanding of role of environmental change on malaria risk
How mosquito vectors may change their behaviour in response to the use of interventions
How semi-field systems can be established and used to investigate the ecology, behaviour and control of mosquito vectors
Sectors Environment,Healthcare,Other

URL http://www.gla.ac.uk/researchinstitutes/bahcm/staff/heatherferguson/
 
Description Yes - as the lead case study of impact from the David Philips Fellowship programme: http://www.bbsrc.ac.uk/research/impact/david-phillip-fellowships.aspx
Sector Other
Impact Types Societal

 
Description International Expert Panel carrying out Risk Assessment for Controlling Mosquito Vectors with Engineered Nucleases
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact As part of this international expert panel we performed a risk assessment for planned trials of Genetically Modified Mosquitoes to reduce malaria transmission in Africa. Field trials have not yet taken place, but our recommendations will be used to guide regulation and planning of these trials in the future
URL https://publications.csiro.au/rpr/pub?pid=csiro:EP153254
 
Description Participation in working group to develop guidelines for contained field trials of genetically modified mosquitoes
Geographic Reach Africa 
Policy Influence Type Membership of a guideline committee
Impact These guidelines were developed to inform best practice for safe testing of genetically modified mosquitoes for vector-borne disease control within contained field cages in Africa. This approach has not yet been approved for use in but progress towards field testing is ongoing. If successful, this intervention could significantly reduce the burden of malaria in Africa, which still kills ~440,000 people each year, mainly children under 5
URL http://online.liebertpub.com/doi/pdf/10.1089/vbz.2007.0273
 
Description BBSRC DTP Studentship
Amount £82,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2014 
End 09/2017
 
Description FP7 Research Infrastructures
Amount € 154,000 (EUR)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 02/2009 
End 01/2013
 
Description Fp7 Callfor Africa
Amount € 657,873 (EUR)
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 02/2011 
End 01/2016
 
Description Gates Foundation Anopheles funestus ecology
Amount £2,040,000 (GBP)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 09/2017 
End 08/2019
 
Description Global Challenges Research Fund Foundation Award
Amount £659,977 (GBP)
Funding ID MR/P025501/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2017 
End 03/2019
 
Description RO1
Amount $1,051,700 (USD)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 03/2011 
End 02/2016
 
Description Travel Grant
Amount £1,500 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2009 
End 08/2009
 
Description USAID Grand Challenges to Combat Zika
Amount £780,129 (GBP)
Funding ID AID-OAA-F-16-00095 
Organisation United States Agency for International Development 
Sector Public
Country United States
Start 10/2016 
End 09/2018
 
Description Understanding the Impacts of the current El Nino
Amount £232,828 (GBP)
Funding ID NE/P004407/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 04/2016 
End 08/2017
 
Title Development of large-scale semi-field systems for study of mosquito vector ecology and control 
Description In collaboration with the Ifakara Health Institute in Tanzania, I developed a novel large-scale Semi-field system in which populations of the most important African malaria vector species can be established and experimentally studied under realistic environmental conditions (Ferguson et al 2008). This novel facility provides an unparalleled opportunity to conduct experimental study of mosquitoes behaviour and ecology that would be otherwise intractable under open field conditions. Numerous studies are now taking place within this facility, and are shedding new insights in topics ranging from fundamental studies of the evolutionary and ecological forces that cause mosquitoes to bite humans, up to applied investigations of the effectiveness of new vector control tools (e.g. repellants, traps). These research facilities have been further expanded at the Ifakara Health Institute, and are now being established in several locations around the world for study of malaria vectors. Based on our experience, we have provided guidance on how to construct and maintain these faciltiies 
Type Of Material Improvements to research infrastructure 
Year Produced 2008 
Provided To Others? Yes  
Impact Our team published 3 papers describing the development and use of these faciltiies Ferguson, H.M., Ng'habi, K.R., Walder, T., Kadungula, D., Moore, S.J., Lyimo, I., Russell, T., Kihonda, J., Urassa, H., Mshinda, H., Killeen, G.F. and B.G.J. Knols. (2008) Establishment of a large semi-field system for experimental study of African malaria vector ecology and control in Tanzania. Malaria Journal, 7(158) Ng'habi, K.R.N., Mwasheshi, D., Knols, B.G.J., and Ferguson, H.M. (2010) Establishment of a self-propagating population of the African malaria vector Anopheles arabiensis under semi-field conditions. Malaria Journal, 9(1), p. 356. 
 
Description Ifakara Health Institute, Tanzania 
Organisation Ifakara Health Institute
Country Tanzania, United Republic of 
Sector Charity/Non Profit 
PI Contribution We collaborate with the Ifakara Health Institute on research related to the ecology, surveillance and control of mosquito vectors of malaria. My team contributes through collaboration on the developing of new mosquito trapping technologies, leading research into malaria vector ecology and their response to control measures, and strengthening research capacity through the provision of postgraduate training and mentorship to PhD students and Fellows from the Institute
Collaborator Contribution Our partners at IHI contribute to this research by co-leadership and development of research on vector ecology and surveillance, hosting and leadership of our field-based collaborations in rural Tanzania, and provision of capacity strengthening by providing training to postgraduate students and postdoctoral researchers from the University of Glasgow
Impact 1) Publications - Through this collaboration, I have published 29 co-authored publications with postgraduate students and scientists from the Ifakara Health Institute Doi: 10.1186/s12936-016-1513-1 Doi: 10.1371/journal.pgen.1006303 Doi: 10.1371/journal.pmed.1002002 Doi: 10.1186/s13071-016-1394-8 Doi: 10.1186/s12936-014-0536-8 Doi: 10.1186/s13071-015-1066-0 Doi: 10.1186/s12936-015-1025-4 Doi: 10.1186/s12936-014-0523-0 Doi: 10.1371/journal.pntd.0003310 Doi: 10.1098/rspb.2012.2823 Doi: 10.1371/journal.pntd.0002510 Doi: 10.1186/1475-2875-11-425 Doi: 10.3389/fphys.2012.00199 Doi: 10.1111/j.1420-9101.2011.02442.x Doi: 10.1186/1475-2875-11-106 Doi: 10.1186/1475-2875-11-118 Doi: 10.1098/rspb.2011.0153 Doi: 10.1186/1475-2875-10-289 Doi: 10.1186/1475-2875-9-356 Doi: 10.1016/j.pt.2009.01.005 Doi: 10.4269/ajtmh.2009.09-0192 Doi: 10.1186/1475-2875-7-158 Doi: 10.1016/j.anbehav.2008.01.014 Doi: 10.1186/1756-3305-1-45 Doi: doi:10.1242/jeb.005033 Doi: 10.1371/journal.pmed.0040229 Doi: 10.1186/1475-2875-5-62 Doi: 10.1016/j.tree.2005.02.003 Doi: 10.1186/1475-2875-4-49 2) Patents 2) Patent applications A joint patent application has been filed between the University of Glasgow and Ifakara Health Institute for the mosquito trap we co-developed Patent application title: "Insect Trap2 PCT application PCT/EP2015/075354 filed 31/10/2015 - this application is pending PCT application published 6 May 2016, with reference WO2016/066847 3) Mentorship and funding support for early career scientists I have co-sponsored the Wellcome Trust Fellowships for 3 early career scientists from the Ifakara Health Institute 2013: Sponsor and supervisor. Training Fellow in International Health and Tropical Medicine "Understanding the potential for malaria vector behavioural adaptations" Principal Investigator: Dr. Nicodem Govella, Ifakara Health Institute, Tanzania (£348,602, 2014-2017) Sponsor. Intermediate Fellow in International Health and Tropical Medicine. "Targeting residual malaria vectors in communities where insecticidal bed nets are already widely used". Dr. Fredros Okumu, Ifakara Health Institute, Tanzania (£660,705, 2014-19) 2010: Sponsor and supervisor, Wellcome Trust Training Fellowship in Public Health and Tropical Medicine, "Evolutionary and ecological response of African malaria vectors to insecticide- treated nets: vector population replacement?" Principal Investigator: Dr Kija Ng'habi, Ifakara Health Institute, Tanzania. (£285,864, 2010-2013) 4) Postgraduate student training I have supervised the postgraduate training of 5 students from the Ifakara Health Institute Mr. Halfan Ngowo, M.Sc: Investigating the seasonal abundance and biting behaviours of primary and secondary malaria vectors in Tanzania. 2015-2016 Dr. Deodatus Maliti (University of Glasgow), PhD: Ecological determinants of African malaria vector behaviour and their implications for control. Dr. Issa Lyimo (University of Glasgow), PhD: The ecological determinants of host choice in Anopheline mosquitoes and its consequences for malaria parasite transmission, 2007-2010. *Ms. Valeliana Mayagaya (University of Dar es Salaam), MSc:The impacts of host species composition on malaria vectors and transmission risk in Kilombero Valley, Tanzania, 2007-2010. Dr. Kija Ng'habi (Wageningen University, Netherlands), PhD: Ecological, behavioural and genetic determinant of gene flow in African malaria mosquitoes, 2006-2010. 5) Additional funding I have secured ~£1.8 million in additional funding for collaborative research with the Ifakara Health Institute following my original BBSRC Fellowship 2017: Principal Investigator, MRC Global Challenges Research Fund Foundation Award, "Development of a new tool for malaria mosquito surveillance to improve vector control" (£659,977, 2017-2019) Co-applicant, USAID Grand Challenges to Combat Zika, "Affordable, scalable , low technology Transluthrin emanators for protection against Zika transmission in low-income countries" (Total: £1,385,460 HMF Component: £73,827, 2016-2018) Co-applicant, NERC- DFID Understanding the Impacts of the Current El Nino call. "Impact of El Niño on malaria vector dynamics in Tanzania: observation, improvement and unleashing forecasting potential" (£232,828, HMF Component: £8121, 2016-2017) 2011: Co-applicant, NIH RO1 Grant: "Ecological and genetic determinants of malaria transmitting behaviors in the African vector Anopheles arabiensis", (Total $2,459,000 USD, HMF Component: £638,000, 2011-2016) Co-applicant, European Union FP7 Call for Africa Programme, "African Vector Control: New tools", (Total €12 million, HMF Component: £515,651, 2011-2016) 2009: Principal Investigator, Royal Society International Travel Grant, "Semi-field systems for the study of vector ecology", (£1500) Co-applicant, UBS Optimus Foundation Grant, "Road-testing Innovative Surveillance Technologies for Rabies in Southern Tanzania" (780,000 Swiss Francs, 2009-2011)
Start Year 2006
 
Description BBC the Inquiry Podcast 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I took part as one of 4 expert witnesses being interviewed for the BBC radio documentary "The Inquiry" - in which we gave testimony on our opinion of whether we should try to eliminate all mosquitoes to stop vector-borne disease. This was broadcast on the BBC World Service, and is available to download as a podcast.
Year(s) Of Engagement Activity 2016
URL http://www.bbc.co.uk/programmes/p03j0k30
 
Description International expert panel to conduct risk assessment for field trials with genetically modified mosquitoes 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I have took part in international work groups and expert panels which developed guidelines and risk assessments for planned trials of genetically-modified mosquitoes for malaria control in Africa
Year(s) Of Engagement Activity 2015
URL https://publications.csiro.au/rpr/pub?pid=csiro:EP153254
 
Description Newspaper article in the Scottish Herald 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact My research on mosquito vectors was the subject of a feature article on the role of mosquitoes in transmitting diseases, and whether we should eliminate them, as published in the Scottish Herald (and Evening Times) in Jan 2016
Year(s) Of Engagement Activity 2016
URL http://www.heraldscotland.com/news/14242612._quot_It_s_not_mosquitoes_per_se_that_are_the_enemy__but...
 
Description Public debate on GM mosquitoes at British Ecological Society Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact As part of the British Ecological Society's Annual Conference I took in a public date about the use of GM products in the environment. I was one of 5 on an expert panel, and had the role of describing the prospective use of GM mosquitoes for the control of vector-borne disease. I gave a summary presentation on the current status of this field, and took questions from the audience in the discussion session at the end
Year(s) Of Engagement Activity 2015
URL http://miriamgrace.co.uk/1/post/2016/01/the-bes-gm-debate.html
 
Description Working group to develop recommendations on contained trials of Genetically Modified mosquitoes 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I have took part in international work groups and expert panels which developed guidelines and risk assessments for planned trials of genetically-modified mosquitoes for malaria control in Africa
Year(s) Of Engagement Activity 2008
URL http://online.liebertpub.com/doi/pdf/10.1089/vbz.2007.0273