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.
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.
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.
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
Mackenzie-Impoinvil L
(2015)
Evaluation of a temperate climate mosquito, Ochlerotatus detritus (=Aedes detritus), as a potential vector of Japanese encephalitis virus.
in Medical and veterinary entomology
Metelmann S
(2019)
The UK's suitability for Aedes albopictus in current and future climates.
in Journal of the Royal Society, Interface
Richardson J
(2016)
Drivers for emerging issues in animal and plant health.
in EFSA journal. European Food Safety Authority
Seechurn N
(2024)
Field-based assessments of the seasonality of Culex pipiens sensu lato in England: an important enzootic vector of Usutu and West Nile viruses.
in Parasites & vectors
Solomon T
(2016)
Zika virus and neurological disease--approaches to the unknown.
in The Lancet. Infectious diseases
Stokes JE
(2016)
A freedom from disease study: Schmallenberg virus in the south of England in 2015.
in The Veterinary record
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 |