Abstract

Although there is no recognized transmission of human arboviral infections in the UK, concerns about the possible spread of West Nile virus (WNV) have precipitated coordinated activities around both surveillance and response. The Department of Health has chaired a UK WNV task force since the end of 2000. This is a multidisciplinary group of senior representatives from Agencies and Government Departments involved in human and animal health, entomology and academic departments. Activities include surveillance for WNV infections in humans, and in dead birds, mosquitoes and horses. All have been negative for WNV. A WNV contingency plan was produced in 2004, and this could be used as a generic plan for an effective and coordinated response in the event of the emergence of a new vector-borne zoonotic infection.

Introduction

West Nile Virus (WNV) is an arbovirus and was first isolated from a woman with a fever in 1937 in the West Nile district of Uganda (Smithburn et al., 1940). It was first recognized as a cause of a human illness known as meningoencephalitis in Israel in 1957 and as a cause of horse disease in Egypt and France in the early 1960s (Murgue et al., 2001a).

Europe has had sporadic cases and outbreaks of WNV in human and horses since the 1960s (Hubálek & Halouza, 1999). However, over the past 10 years there have been significant outbreaks in the western hemisphere, including Bucharest, Romania in 1996 (393 cases) (Tsai et al., 1998), Volgograd, Russia in 1999 (over 800 cases) (Platonov et al., 2001) and Israel in 2000 (417 cases) (Chowers et al., 2002).

In France, the first reported WNV outbreak affecting horses and humans occurred during the summer of 1962. This occurred in the Carmague region which is characterized by wetlands and marshes, with a great number of migratory and resident bird species and large populations of mosquitoes. Sporadic cases followed this outbreak but after 1965 no cases in human or equine cases were reported until 2000. During 2000, there were 76 cases in horses, and WNV testing of over 5000 horses showed a WNV IgG seroprevalence rate of 8.3%, with 42% of those with IgG also being IgM positive. This suggested that WNV was not endemic in the affected area, rather that sporadic outbreaks were separated by long silent periods (Durand et al., 2002). Two gamekeepers were also found to have serological evidence of infection (Murgue et al., 2001b). Then in 2003, seven human cases of infection were identified late August in the Var District, which is adjacent to the Camargue. Three patients had encephalitis and four had fever. Five equine cases were also found; four had encephalitis and one was asymptomatic (Institut de Veille Sanitaire, 2003; Mailles et al., 2003). In 2004, 37 suspect cases in horses were reported and 14/18 had WNV infection (WNV IgM detection or positive RT-PCR), however, no human cases were found (Zeller et al., 2004). Two Irish tourists returning from the Algarve, Portugal in the summer of 2004 were diagnosed with WNV infections. They had been staying in an area of swamp bird reserves where there were many mosquitoes (Connell et al., 2004).

There has been a different epidemiological picture in the United States of America (USA). Despite being endemic for many other arboviruses, WNV had not been found in the USA until 1999, when WNV activity was reported for the first time in the New York City area (Nash et al., 2001). The infection then showed increases in terms of the annual case count, geographical spread and extension of the transmission period. During 2003, 9862 human cases were reported, and the infection was found in all states except Maine, Oregon, Washington, Alaska and Hawaii. However, in 2004 the number of cases reported fell dramatically (2539 cases) and showed little increase in 2005 (3000 cases) (Centers for Disease Control and Prevention).

Transmission cycle

Figure 1 shows the life cycle of WNV.

Figure 1

West Nile Virus transmission Cycle.

Figure 1

West Nile Virus transmission Cycle.

Birds are the natural host for WNV. The infection is transmitted to other birds by mosquitoes and the virus is maintained in the bird population. The virus is amplified by continuous transmission in this way between birds and mosquitoes and transmission is therefore increased where large numbers of mosquitoes are close to suitable bird populations. Mosquitoes involved in the transmission of WNV generally prefer to take blood meals from birds but will sometimes bite and infect humans and animals and act as ‘bridging vectors’. Humans and other animals such as horses are classified as ‘incidental’ or ‘dead end’ hosts, in that they are not important in maintaining transmission cycles since they rarely develop high enough levels of virus in their blood stream necessary to infect other mosquitoes. WNV is not transmitted from person-to-person through close contact. However, in a very small number of cases, WNV has been spread through blood transfusions (Pealer et al., 2003), organ transplants (Iwamoto et al., 2003), breastfeeding and in utero mother to child transmission (Centers for Disease Control and Prevention, 2002).

Clinical features of WNV infections

The incubation period is usually 3–15 days following the bite of an infected mosquito. Approximately 80% of those infected have no symptoms at all, and 20% have a mild influenza-like illness (fever, headache, myalgia, occasionally with rash, diarrhoea or lymphadenopathy) which generally lasts 2–5 days. A small proportion (less than 1%) goes on to develop more severe disease. Severe infection may present as an aseptic encephalitis, meningitis or meningoencephalitis. Patients may suffer headaches, fever, stiff neck, sore eyes, disorientation, muscle weakness, convulsions and coma. WNV infection spread throughout the USA, as an increasing number of syndromes and presentations have been reported. These include acute flaccid paralysis, cerebellar ataxia, Parkinsonism, cranial nerve abnormalities, optic neuritis and other neurological features, pancreatitis, hepatitis and myocarditis. Some patients suffer longer-term physical, functional and cognitive symptoms (Klee et al., 2004). Increasing age is the greatest risk factor for the development of serious disease and death (Weinberger et al., 2001).

WNV in England and Wales

In the UK, although there are suitable bird species to act as hosts for WNV and potential WNV bridge vectors are present (Medlock et al., 2005), the risk of cases occurring is thought to be low, mainly because the mosquito population densities are too small to maintain transmission (Crook et al., 2002). Mosquito-borne diseases, and indeed transmission of mosquito-borne viral infections, are virtually unknown in the UK, unlike in the USA and many parts of Europe.

However, this has not resulted in complacency. The Chief Medical Officer (CMO) for England has placed great emphasis on the risks of WNV, and when he published his strategy for combating infectious diseases ‘Getting ahead of the curve’ he highlighted WNV as an example of the way infections can emerge unexpectedly and unpredictably and pose a new threat to the population (Department for Health, 2002). In his annual report in 2002, the CMO included a chapter on WNV outlining the three main factors which would determine whether WNV became established in the UK (Department for Health, 2003).

  1. The mosquito population

    The distribution and abundance of different species of mosquito are crucial for the transmission of WNV and of the 32 species of mosquito recorded in Britain, at least seven species could potentially transmit WNV. Should WNV be introduced to the UK, the most likely vectors would be mosquitoes belonging to the most widely distributed Culex pipiens complex.

  2. The chances of the domestic bird population becoming infected

    Migratory birds have been instrumental in the periodic reintroduction of WNV to Europe. A study looking for evidence of infection with WNV virus amongst both migratory and nonmigratory birds has suggested that virus is already present in native birds in the UK (Buckley et al., 2003). However, the confirmation of these results was needed.

  3. Climate Change

    Insect vectors are very sensitive to meteorological conditions. Temperature and humidity influence significantly the transmission of WNV. Generally warmer weather accompanied by increased risk of flooding associated with climate change (Office of Science and Technology, 2004), would amplify the population density of vector mosquitoes. Warmer weather would also influence people's behaviour, leading to them spending more time outdoors in situations where they would be more prone to mosquito bites.

In the report, the CMO stressed the importance of assessing the risk of WNV and recommended enhanced surveillance of birds, humans and mosquitoes and the need for a WNV contingency plan.

In 2004, the Department of Health (DH) for England published ‘West Nile virus: a contingency plan to protect the public's health’ (Department of Health, 2004a). The plan sets out measures to enhance surveillance for the virus, to alert clinicians to the symptoms of WNV, and control mosquito populations. It includes sections on:

  1. background, and assessing the risk through surveillance of people, birds, mosquitoes and horses

  2. diagnosis, patient care and protection of healthcare professionals

  3. Public Health Action in partnership, outlining partnerships at a local, regional and national level of health, veterinary and environmental agencies

  4. environmental control including advice on the control of mosquitoes, and

  5. Action Plan, for use if WNV was found in the UK, including laboratory diagnosis, public health action, surveillance and environmental control

A coordinated response for WNV in the UK

The DH has had a UK WNV task force since the end of 2000. It is chaired by the DH, but is a multidisciplinary group bringing together senior representatives from Agencies and Government Departments involved in human and animal health, entomology and academic departments. Representatives from the Devolved Administrations (Wales, Scotland and Northern Ireland) also attend. It meets two to three times a year and provides a focus and coordinating body for research and surveillance activities for WNV.

Human enhanced surveillance and testing for WNV

So far, there have been two components of human surveillance for WNV infections acquired in England and Wales, as follows.

Retrospective surveillance

This involved examination of CSF from cases of encephalitis or meningitis in patients where no causative organism was found. This was coordinated by the Clinical Virology Network, and 123 CSF samples from patients aged over 50 years were tested for WNV. The patients came from most areas of England and Wales and all were negative for WNV.

Prospective surveillance of suspect cases

The Public Health Laboratory Service [which became part of the Health Protection Agency (HPA) in 2003] first alerted clinicians and microbiologists to the possibility of WNV infection in July 2001 and requested they send samples for testing (Public Health Laboratory service, 2001). Enhanced surveillance for cases acquired in England and Wales has been undertaken during the summer months since 2002 (Health Protection Agency, 2003). An article in the Communicable Disease Report at the start of the surveillance season requests Regional Epidemiologists contact clinicians in their regions to raise awareness of the possibility of WNV infection, particularly in those aged over 50 years, and microbiologists are asked to consider WNV in patients with otherwise unexplained neurological or compatible symptoms. The CMO also sends a letter to all clinicians in England reminding them of the need to think of WNV and alerting them to the WNV surveillance protocol on the Health Protection Agency website.

Each year enhanced surveillance for human WNV infection in England and Wales starts on 1 June and operates until the end of October, and case definitions were been revised in line with the EU case definitions (European Commission, 2005). The revised case definitions are shown in Table 1.

Table 1

Prospective surveillance: revised definition for suspected cases of West Nile Virus (WMV) infection in humans — indications for considering the diagnosis of WNV infection and requesting a WNV test (adapted from European Union case definition)

WNV Neurological Syndrome: A case of encephalitis or meningoencephalitis or aseptic meningitis or acute flaccid paralysis, defined by the specific criteria below, presenting from 1st June to 30th October 2005 
1. Encephalitis or meningoencephalitis 1. Fever >38° and 
Any person with suspected viral encephalitis with all the following criteria 2. Altered mental state (altered level of consciousness, agitation, lethargy) and/or other evidence of cortical involvement (e.g. focal neurological findings, seizures) and 
 3. Cerebrospinal fluid (CSF) pleocytosis with predominant lymphocytes and/or elevated protein with a negative Gram stain and culture and 
 4. No alternative microbiological cause identified 
2. Meningitis 1. Fever >38° and 
Any person with suspected viral (aseptic) meningitis with all the following criteria 2. Headache, stiff neck and/or other meningeal signs and 
 3. CSF pleocytosis with predominant lymphocytes and/or elevated protein with a negative Gram stain and culture and 
 4. No alternative microbiological cause identified 
3. Acute Flaccid Paralysis (AFP) 1. Fever >38° and 
Any person with suspected AFP (most cases are polio-like) with all the following criteria 2. Asymmetric limb weakness without sensory loss with diminished deep tendon reflexes and 
 3. Anterior horn cell disease and 
 4. May have facial nerve palsy and 
 5. No alternative microbiological cause identified 
WNV Neurological Syndrome: A case of encephalitis or meningoencephalitis or aseptic meningitis or acute flaccid paralysis, defined by the specific criteria below, presenting from 1st June to 30th October 2005 
1. Encephalitis or meningoencephalitis 1. Fever >38° and 
Any person with suspected viral encephalitis with all the following criteria 2. Altered mental state (altered level of consciousness, agitation, lethargy) and/or other evidence of cortical involvement (e.g. focal neurological findings, seizures) and 
 3. Cerebrospinal fluid (CSF) pleocytosis with predominant lymphocytes and/or elevated protein with a negative Gram stain and culture and 
 4. No alternative microbiological cause identified 
2. Meningitis 1. Fever >38° and 
Any person with suspected viral (aseptic) meningitis with all the following criteria 2. Headache, stiff neck and/or other meningeal signs and 
 3. CSF pleocytosis with predominant lymphocytes and/or elevated protein with a negative Gram stain and culture and 
 4. No alternative microbiological cause identified 
3. Acute Flaccid Paralysis (AFP) 1. Fever >38° and 
Any person with suspected AFP (most cases are polio-like) with all the following criteria 2. Asymmetric limb weakness without sensory loss with diminished deep tendon reflexes and 
 3. Anterior horn cell disease and 
 4. May have facial nerve palsy and 
 5. No alternative microbiological cause identified 

Clinicians are requested to send a form outlining the demographic and clinical details of the patient to the HPA Centre for Infections, and following samples are sent to the HPA Special Pathogens Laboratory.

  1. Paired serum or whole blood specimens. The acute phase specimen 0–8 days after onset and the convalescent phase sample 14–21 days after onset.

  2. CSF, ideally acute phase (<8 days of onset).

The case definitions based on laboratory investigations are shown in Table 2.

Table 2

Definitions of probable and confirmed West Nile Virus infection

Probable case 
 1. Single serum specimen: A positive WNV IgM test 
 2. CSF: detection of WNV IgM 
Confirmed case (positive for one or more of the following criteria): 
 1. Serum or CSF: isolation of WNV 
 3. Serum or CSF: detection of WNV genomic RNA sequences by RT-PCR 
 4. Serum or CSF: detection of neutralising WNV antibodies with significant titre 
 5. Paired Serum specimens: A fourfold rise in WNV specific antibody titre 
Probable case 
 1. Single serum specimen: A positive WNV IgM test 
 2. CSF: detection of WNV IgM 
Confirmed case (positive for one or more of the following criteria): 
 1. Serum or CSF: isolation of WNV 
 3. Serum or CSF: detection of WNV genomic RNA sequences by RT-PCR 
 4. Serum or CSF: detection of neutralising WNV antibodies with significant titre 
 5. Paired Serum specimens: A fourfold rise in WNV specific antibody titre 

deviation from EU definition

isolation of the virus or detection of nucleic acid is unusual and the most likely confirmatory testing is through detection of neutralising antibodies or a rising titre

Results of surveillance for human WNV infection

Between 2002 and 2005, a total of 36 surveillance forms were received and although most of these had meningitis or encephalitis, only seven fulfilled the case definition by having no foreign travel in the 3 weeks before the onset of symptoms and being aged over 50 years old. A further 38 patients were identified from the laboratory testing database as fulfilling the case definition, but on whom surveillance forms were not submitted. Of the 45 patients identified as fulfilling the case definition, 32 were reported as having encephalitis, six meningitis and seven had other symptoms (including confusion, fever and rash, VI nerve palsy).

All of the patients resident in England and Wales, including those who had a travel history in the 3 weeks before onset, or were aged under 50 years; those fulfilling the case definition were negative for WNV infection on laboratory testing.

Birds

The Veterinary Laboratories Agency funded by the Department for the Environment, Food and Rural Affairs (Defra) has been examining dead birds for WNV since 2001, and 1295 birds had been submitted up to the end of 2004. These include 87 different wild bird species. None of the 1250 tissue specimens tested have been positive for WNV.

Horses

Surveillance of neurological diseases in horses continues, and Defra is about to publish for consultation a generic plan for equine encephalitides which includes WNV. (Defra: A contingency plan for the UK: Specified Type Equine Exotic Disease (STEED) includes WNV, Western Equine Encephalitis, Eastern Equine Encephalitis, Venezuelan Equine Encephalitis, Borna Disease, Hendra and other viral encephalitides e.g. St Louis and Japanese Encephalitis). Although horses have been identified and reported with neurological features, WNV has not been found on investigation of these animals.

Mosquitoes

The DH has funded ongoing surveillance of mosquitoes in England for WNV since 2003. The sentinel sites in various parts of England were increased from four to six sites in 2004. Mosquitoes have been captured using mosquito magnet traps at the six sites and, in addition, suction traps at three of the sites. Over 13 000 mosquitoes have been collected and these include species which could act as possible vectors for WNV. Approximately half have been tested by PCR at the HPA Special Pathogen Laboratory, and WNV has not been detected. Work continues on optimal trapping methods to look for potential WNV vectors, especially female Culex pipiens.

Laboratory developments

Standard operating procedures have been developed for use by the Veterinary Laboratories Agency and the HPA had been upgrading their Standard operating procedures and validating their tests against different strains of WNV. There has also been standardization of test across agencies.

Other activities

Expert views

The views of the CMO's National Expert Panel on New and Emerging Infections were sought over whether more resources should be committed to vector-borne disease. This panel is an over-arching, horizon-scanning panel, reporting to the CMO and advising the DH.

Following presentations on the human health implications of vector-borne diseases, and a review of possible vectors a general discussion took place. The principal conclusions of the Panel were as follows.

  1. With the exception of Lyme disease, vector-borne diseases do not currently pose a significant public health threat in England and Wales.

  2. Vector-borne disease risks in the UK are unlikely to increase in the future.

  3. The risk of WNV emerging as a human disease is very low, but research and surveillance should continue.

  4. Vector-borne surveillance should be linked to the scale of potential public health disease risks, and should be targeted to specific defined ecological sites. At present, the public health risks posed do not justify wider surveillance of potential vectors

(Department of Health, 2004b)

Encephalitis study

The DH has agreed to fund a 3-year study by the HPA on the aetiology of encephalitis in England. This will investigate the cause of encephalitis in cases admitted to 14 neurological centres in England. Laboratories will be using an investigative protocol and WNV will be included in second line testing, but will move up the list of agents tested for if the patient is aged over 50 years.

West Nile exercise to test local responses

Exercise IBIS was an exercise to test the local multi-agency response to a WNV outbreak. The exercise took place in March 2005 and was organised by the HPA in collaboration with Defra to see how links between local veterinary and health partners would work in practice. The scenario was phased, and moved from an initial outbreak affecting horses, to human cases being confirmed and the suspicion of a local community outbreak. The linkages between all the partner agencies were tested from notification stage, through investigation and case searching, media handling and environmental vector control considerations. Many agencies were involved due to the complexity of the issue. For example, mosquito control measures may be needed to reduce or eliminate the vector risk for WNV. Therefore the involvement of agencies such as the Environment Agency, the Health and Safety Executive and English Nature, as well as local government, is crucial to assess all the potential risks and consequences of control measures, which may well include the use of pesticides or otherwise impact on the environment.

The exercise highlighted a number of issues: local cross-agency working, understanding of roles and responsibilities in different organisations and within an Incident Control team, the availability of resources and the importance of communications. The principles of dealing with such an incident would be applicable to any zoonotic disease requiring a multi-agency response.

Discussion

Although there is no recognized transmission of human arboviral infections in the UK, several concerns have precipitated coordinated activities around both surveillance and response. Firstly, increased transmission of WNV infection in France, the UK's closest geographical neighbour in Europe, and its introduction in the USA, prompted concerns that WNV could spread to the UK. However, the USA has a history of arboviral infections and specific factors seem to have operated to facilitate its spread. Also, the areas where transmission has occurred in France, and probably did in Portugal, provide a very different ecological environment from that found in the UK. In both these areas, temperatures exceed those in the UK and there is the combination of extensive wetland marshes and large numbers of migratory and nonmigratory birds with high population densities of mosquitoes. The second concern is that cases of WNV infection could be occurring but remain undiagnosed. Only around one in 150 of those infected with WNV develop serious neurological symptoms and so substantial transmission might be taking place without detection. There are around 700 hospital admissions of patients with encephalitis a year in England and 60% of these do not have the aetiology determined. Although only a small proportion of these occur in older patients, there is a suggestion that the numbers are increasing (Davison et al., 2003). We have undertaken enhanced surveillance for cases of WNV infection by looking at cases of viral encephalitis or meningitis each summer since 2002. People older than 50 years have a 10-fold higher risk of developing neurological illness (Weiss et al., 2001; Sampathkumar, 2003) and so by concentrating on older people with neurological features, we are trying to maximize resources. Despite reminding all clinicians of the features of WNV and the alerting them to this scheme, we capture relatively small numbers of patients through the surveillance scheme. More samples are referred directly to the laboratory but relatively few of these are from older patients with compatible symptoms and without a travel history. So far all samples have been negative for WNV. In addition, CSF from patients aged over 50 years with viral encephalitis or meningitis have also been examined, and WNV was not found in this group either. Although the occasional case of WNV infection may well have been missed, we feel if there were clusters of cases of neurological disease due to WNV we would have detected them.

No bird die-offs have been noted in England and Wales, but although birds have been found to show evidence of WNV infection in many parts of Europe (Malkinson & Banet, 2002), abnormal bird deaths do not appear to be a feature of the European outbreaks (Murgue et al., 2001a) unlike in the USA where mass bird die-off heralded WNV cases in humans (Yaremych et al., 2004). One study in England has reported finding evidence of WNV infection in resident and migratory birds in two sites in England. All birds were healthy and over 350 sera were tested, and 14.7% were Plaque Reduction Neutralization Test positive for WNV. A nested RT-PCR found the presence of WNV RNA in six magpies and one blackbird. Infectious virus was not detected (Buckley et al., 2003). The ongoing study of dead birds has not yet detected WNV.

In England and Wales, there is a coordinated response to WNV with ongoing surveillance of humans, horses, dead birds and mosquitoes, and the development of a specific WNV contingency plan. As we face more and more potential public health problems, it is a dilemma how much resource should be spent looking for WNV infection, especially given its sporadic and unpredictable mode of presentation observed in many other countries. It is not clear for how long these activities should be continued and whether we need more or less action in future. However, WNV has demonstrated the need for a multi-agency approach to surveillance and preparedness. There needs to be multi-agency working at the local, regional and national level and plans exercised to identify gaps and ensure the understanding of roles and responsibilities. If this is established for WNV, then this would lead to an effective and coordinated response in the event of the emergence of a new vector-borne zoonotic infection.

Acknowledgements

This paper is based on a presentation made at the FEMS symposium on Vector-borne Emerging and Re-emerging Pathogens and their Infections held in Istanbul, June 2005. I would like to thank the organisers for inviting me to the meeting.

I would like to acknowledge members of the Department of Health WNV task force including: Maggie Tomlinson, John Stephenson and Ailsa Wight (DH), Graham Lloyd, David Brown, Amanda Walsh (HPA), Paul Manser (Defra) Steve Lindsay (Durham University), Richard Harrington (BBSRC, Rothamstead Research), Bill Reilly (Health Protection Scotland) Steve Edwards and Ian Brown (Veterinary Laboratories Agency)

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Author notes

Editor: Alex van Belkum