Vector competence of British mosquitoes to flaviviruses

Lead Research Organisation: University of Liverpool
Department Name: Institute of Infection and Global Health

Abstract

Are British mosquitoes capable of transmitting viruses to livestock and people? There is great uncertainty whether British mosquitoes are capable of transmitting arthropod-borne viruses ("arboviruses"). On one hand, the UK has some mosquito species that are implicated in the transmission of arboviruses in mainland Europe, and the climate and environment in some of these locations are similar to those in the UK. On the other hand, mosquito-borne viruses are not known to have been transmitted in the UK (apart from a small number that are 'mechanically' transmitted on the insects' mouthparts). Furthermore, regional differences in competence of mosquitoes to different viruses have been reported. Therefore, it is not clear whether the UK has the right mosquitoes but the wrong conditions for virus transmission; whether our mosquitoes simply cannot transmit viruses; or whether our mosquitoes are capable of transmitting viruses, but the opportunity has not yet arisen. Given the impact of global change on the emergence of infectious diseases, it is paramount that UK vectors are assessed for their potential to transmit arboviruses, in order to mount informed mitigation procedures in advance of, or in the event of, an outbreak. Furthermore, the ability of mosquitoes to spread arboviruses is sensitive to temperature, making such viruses likely to be affected by climate change; it is important to understand the effects of temperature in order to assess future risks.
Our main aim here is to determine whether native British mosquitoes and invasive mosquito species present in the UK can be infected and transmit viruses that affect livestock and humans, and how this ability, if present, is affected by temperature. Ten mosquito-borne arboviruses have been reported in Europe with some at similar latitude to the UK. Field observations have shown potential native vectors, particularly West Nile virus (WNV) vectors, to be present in the UK. In 2011, Culex modestus, a major vector of WNV, was found actively propagating in the UK, representing the first known introduction and establishment of an invasive mosquito species. While the mere presence of these mosquitoes suggests a risk for arbovirus transmission, further support for the potential of these mosquitoes to serve as vectors must be demonstrated in detailed laboratory experiments since there is genetic and environmental variation in the ability of these mosquitoes to transmit these viruses.
While the emergence(s) of several mosquito-borne viruses is plausible, we have chosen Japanese encephalitis virus (JEV) and WNV for evaluation in UK mosquitoes. JEV was selected for this study because we have already infected Ochlerotatus detritus, a mosquito from the UK, and found this mosquito able to transmit JEV. Though JEV occurs mostly on the Asian continent inter-continental introductions of arboviruses do occur, and with increased human mobility, may become more common. In fact, evidence for JEV has recently been reported in European mosquitoes. WNV was selected for this study because it arguably poses the most imminent threat to UK. WNV is widely distributed across the globe, being found in Africa, West Central Asia, the Middle East, Europe and recently North America. The virus infects a wide range of mosquitoes and vertebrate hosts. Due to its spread in North America and in Europe, particularly southern France, and its occurrence in similar latitudes to the UK elsewhere in Europe, this virus is of major interest to the UK.
We will use an infection model where mosquitoes from the field will be directly infected with recently isolated strains of viruses. Mosquitoes will be assessed for: their ability to transmit virus; the viral dosage required to achieve infection; and the effect of temperature on their vector competence.

Technical Summary

Historically, the UK has been free of viruses biologically-transmitted by mosquitoes. This persists despite the presence of potential mosquito vectors in the UK, and the transmission of arboviruses in neighbouring mainland European countries. Given global changes to climate, landscape, and human and animal demography change, this naive situation is threatened.
While several UK native mosquito species and the recently introduced mosquito, Culex modestus, have been named as potential vectors of certain epizootic and zoonotic viruses, vector competence (VC) studies have not been undertaken that firmly implicate these species. The aim of this project is to determine the competence of three UK mosquitoes for two major arboviruses, Japanese encephalitis virus (JEV) and West Nile virus (WNV), using infection assays on field-collected native and invasive mosquitoes.
To determine VC, mosquitoes will be assessed for their ability to harbour an infection, disseminate the infection to secondary tissues and transmit the virus by bite.
Oral infectious dose needed to infect 50% of a mosquito population will be determined in order to quantify the competence threshold for virus.
Temperature has been shown to affect VC by increasing susceptibility of the vector or reducing the extrinsic incubation period. We will assess these temperature effects in infection bioassays.
This study aims to identify competent vectors of WNV and JEV in the UK and determine the effect of temperature on their ability to spread these viruses.

Planned Impact

Non-academic beneficiaries of this project include the general public and livestock industry, vector control agencies, the UK economy and policy makers, including the government.

GENERAL PUBLIC AND UK LIVESTOCK INDUSTRIES: The main aim of this project is to help preserve the quality of UK health (animal and human) by providing needed information on the ability of UK mosquitoes to serve as vectors for deadly pathogens. In the event of an outbreak, our work will provide information required for more effective, or faster, vector control or surveillance, leading to direct public benefits.

VECTOR CONTROL AGENCIES: Information of the existence of possible disease vectors will, we believe, be useful to local councils (which often have responsibility for dealing with mosquitoes as pests), and commercial companies developing insect surveillance and control tools (such as Brandenburg Ltd, described as 'the world's leading manufacturer of flying and biting insect control systems', with which Baylis is collaborating on the development of improved traps for biting midges). Brandenburg already produces and sells a trap for mosquitoes.

UK ECONOMY: Arboviruses have the potential to cause significant costs for national economies. The outbreak of BTV-8 in northern Europe is a good example, with costs exceeding £1 billion in France in 2007, mainly through lost trade and the costs of control; high costs were experienced in many affected counties. In this proposal we focus on two mosquito-borne viral diseases, both of which can cause heavy public health burdens and exorbitant animal production losses to certain parts of the livestock industry. JE epidemics in Japan have resulted in pig reproductive losses of 50-70%. Horse losses during a United States WN epidemic resulted in costs of US$ 1.5 million incurred in medical and animal disability costs. The human societal costs of severe JE and WN outbreaks can be hundreds of millions of dollars. This study can assist in mitigation of outbreaks that impact livestock and humans by identifying UK mosquitoes that are particularly competent to an arbovirus and targeting those mosquitoes for control.

POLICY MAKERS: We will arm policy makers with information that will be useful for (i) more accurate assessment of the risk presented by arboviruses to the UK; (ii) reducing the chances of an outbreak occurring; (iii) more effectively dealing with an outbreak if one occurs. At present the Department of Health's UK contingency plan for West Nile (DoH product 40168) makes clear that critical information is lacking on UK mosquito vectors (para 20); despite this, it proceeds to suggest that in an outbreak breeding sites (which are species-specific) would be targeted (para 47). This project will provide important information for improving the specificity of contingency plans.
The UK government is currently promoting the creation of new wetlands as nature reserves. A good example is Wallasea island, being created in the Thames (from soil from Cross Rail) as a new wetland; and described as the biggest mad-made nature reserve in Europe (The Guardian, 17/9/2012). While beneficial for biodiversity, it should also be regarded in the light of the invasion of Cx modestus (a known West Nile vector in mainland Europe) on either side of the Thames Estuary; and also the possible creation of a fourth London airport nearby (which could be a portal for WN entry to the UK). While not criticising such moves, we believe that our research will provide important new information to be taken into consideration in the taking of these decisions.

Publications

10 25 50
 
Description A widespread, endemic UK mosquito species, Aedes detritus, is a competent vector of West Nile and Japanese encephalitis viruses (WNV, JEV) - but not capable of transmission of Chikungunya or dengue viruses. We have also shown that Aedes detritus can be infected with Usutu virus, but at a very low level of vector competence.

In addition, we have demonstrated that Culex torrentium and pipiens pipiens, both common in northern UK and European latitudes, are vector competent for West Nile virus.

Culex modestus, a common vector in mainland Europe which has recently established in south east England, is capable of transmitting WNV and JEV at high frequency. The aforementioned, Culex pipiens pipiens and Culex modestus have also been shown to be competent for JEV.

Given that Aedes detritus is both widespread and commonly bites humans and birds, and shown here to have a high vector competence for WNV and JEV, we concluded it was the greatest risk to the population. Accordingly, we incubated the infected mosquitoes at four temperatures (18oC, 21oC, 24oC and 27oC) for 11 time points (0, 1, 3, 5, 7, 10, 14, 17, 21, 24 and 28 days post infection) to assess its ability to transmit the viruses at temperatures relevant to the British climate. We found low transmission of both viruses at 18oC indicating some risk of transmission in the UK during for example a warm summer. Relative to the common tropical vector Culex quinquefasciatus, however, we found that Aedes detritus is a less efficient vector across all temperatures, which, in addition to the cooler climate in the UK, indicates that there is not a major risk of these viruses establishing.
Exploitation Route We have driven expansion of research into vector competence of native temperate vectors, which was lacking, especially in the UK. In relation to public health, we have shown at least some risk of virus transmission in the UK by our native vectors, therefore, this information would be extremely useful in minimising the risk of further infections should an outbreak (e.g. from travellers returning from abroad) occur. We have identified which viruses common British mosquitoes are capable of transmitting and given the prior knowledge of their habitat, targeted control programmes can be effected in such an event.
Sectors Agriculture

Food and Drink

Environment

Healthcare

 
Description Chapter 5. People and the Built Environment
Geographic Reach National 
Policy Influence Type Citation in other policy documents
URL https://www.theccc.org.uk/tackling-climate-change/preparing-for-climate-change/climate-change-risk-a...
 
Description Chapter 7: global security
Geographic Reach National 
Policy Influence Type Citation in other policy documents
URL https://www.theccc.org.uk/tackling-climate-change/preparing-for-climate-change/climate-change-risk-a...
 
Description Health. Climate Change Impacts.
Geographic Reach National 
Policy Influence Type Citation in other policy documents
URL http://www.nerc.ac.uk/research/partnerships/lwec/products/report-cards/health/report-card/
 
Description Risk assessment of Chikungunya
Geographic Reach National 
Policy Influence Type Citation in other policy documents
URL https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/594791/Chikungunya_risk_as...
 
Description Zika: Predicted establishment of Aedes sp. in the UK
Geographic Reach Europe 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description A conflict of interests: How do viruses manipulate their mosquito-vector to increase their own transmission?
Amount £181,248 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2022 
End 09/2026
 
Description Do arboviruses manipulate their mosquito vectors' behaviour to increase transmission?
Amount £182,600 (GBP)
Organisation Majlis Amanah Rakyat (MARA) 
Sector Public
Country Malaysia
Start 11/2020 
End 10/2024
 
Description GCRF MRC Foundation Awards
Amount £400,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 03/2019
 
Description Health Protection Research Unit (2) in Emerging Infections and Zoonoses
Amount £4,000,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 03/2020 
End 03/2025
 
Description Health Protection Research Unit in Emerging Infections and Zoonoses
Amount £3,900,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 03/2014 
End 03/2019
 
Description Usutu virus risk to the UK: Determining local vector competence and modelling climate suitability
Amount £468,971 (GBP)
Funding ID BB/W002906/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 05/2022 
End 12/2025
 
Description VecPrime: immune priming to vaccinate vectors
Amount £97,302 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2018 
End 12/2019
 
Description Vector in the machine: How accurately can mosquito transmission of viruses be predicted by machine learning?
Amount £181,248 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2022 
End 09/2026
 
Description Collaboration with Liverpool School of Tropical Medicine 
Organisation Liverpool School of Tropical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-authoring of papers on mosquito infections with LSTM staff
Collaborator Contribution LSTM provide facilities for our mosquito infection work
Impact Papers on mosquito infections associated with this grant
Start Year 2007
 
Description Collaboration with Public Health England 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution Collaborating on mosquito infection work, in part through Health Protection Research Unit in Emerging and Zoonotic Infection (joint venture of University of Liverpool, Liverpool School of Tropical Medicine, and Public Health England)
Collaborator Contribution Intellectual - ideas, suggestions for research activity
Impact Through the HPRU our work is passed rapidly to the HAIRS committee
Start Year 2015
 
Description Manipulating mosquito immune memory and fertility 
Organisation University of Liverpool
Department Institute of Integrative Biology
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributing mosquito experiments to larger projects on immune memory and fertility across a range of insect species important to health and agriculture (pollinators and pests), specifically: mosquitoes, bees, and drosophila
Collaborator Contribution Collaborators provide expertise in agricultural insects
Impact VecPrime grant (~£100k) Ongoing grant applications, including to the upcoming 'Bezos Earth Fund'
Start Year 2018
 
Description Uppsala University 
Organisation Uppsala University
Country Sweden 
Sector Academic/University 
PI Contribution Sharing of a staff member. Jenny Hesson has moved to part-time employment at both University of Liverpool and University of Uppsala (as returned to Sweden for family reasons)
Collaborator Contribution Sharing of a staff member. Jenny Hesson has moved to part-time employment at both University of Liverpool and University of Uppsala (as returned to Sweden for family reasons)
Impact Evidence that the mosquito Culex torrentium is a competent vector of West Nile virus
Start Year 2016
 
Description Big Bang Northwest 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact "Bug" stall at Big Bang North West event for regional schools
Year(s) Of Engagement Activity 2016
 
Description Cafe Scientifique - Insects: why they rule the world 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A presentation to 6th formers at a local school
Year(s) Of Engagement Activity 2014
 
Description Climate change impacts on health presentation to Civil Service Environment Network 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Short presentation to the CSEN on the origins of pandemics, and how climate change is a driver of their emergence. The key message was that climate change is an important driver, but there are others and it cannot be considered in isolation
Year(s) Of Engagement Activity 2022
URL https://www.civilserviceenvironmentnetwork.org/
 
Description Interviews and articles for New Scientist and The Independent 
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 Interviews with reporters from New Scientist and The Independent, articles were written in both and further media sources wrote articles based on these.
Year(s) Of Engagement Activity 2020
URL https://www.newscientist.com/article/2248273-climate-change-may-push-zika-virus-into-southern-and-ea...
 
Description Panellist, BBSRC webinar for COP26. Climate change bites; & associated blog post 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact As part of its contribution to COP26, BBSRC organised an online panel event, chaired by BBC's Victoria Gill. I was an invited panellist, taking part in the Q&A. There was also a blogged Q&A
Year(s) Of Engagement Activity 2022
URL https://medium.com/@UKRI/biting-bugs-are-set-to-benefit-from-climate-change-heres-why-that-s-a-probl...
 
Description Public engagement talk 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Talk on ZIka virus to members of the pubic in an informal (pub) setting.
Year(s) Of Engagement Activity 2017
 
Description Talk on emerging equid diseases at Newmarket 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Presentation on emerging vector-borne diseases of horses to an audience at Newmarket. Done as part of an HBLB-funded workshop. Audience mainly concerned about risks to racehorses.
Year(s) Of Engagement Activity 2019
 
Description Talk to civil service environment network 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Talk to civil service environment network, titled "exploring the relationship between climate change and pandemics", By Matthew Baylis and Marcus Blagrove. Will be avaliable online
Year(s) Of Engagement Activity 2022
URL https://www.civilserviceenvironmentnetwork.org/
 
Description Talk/Workshop to local school children as part of 'National Science Week' 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Workshop including mosquito talks and microscopy. Also a DNA extraction exercise
Year(s) Of Engagement Activity 2017