Vector competence of British mosquitoes to flaviviruses

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.

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.

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.