West Nile fever

From Ganfyd

Contents 1 Introduction 2 Aetiology 3 Epidemiology 4 Clinical Features 4.1 Human infection 4.2 Animal infection 5 Diagnosis 6 Prevention and Prophylaxis 7 Treatment 7.1 Future 8 References 9 Related Links

Introduction

A viral illness now found essentially world wide with the potential for high population seroconversion rates approaching 10% in some countries due to transmission by Culex and Aedes albopictus mosquitoes from the usual avian hosts. It has become the commonest cause of viral encephalitis in many Western cultures recently even though only 1% of cases presented this way. Such presentations have a high mortality (up to 10%) and morbidity^[1]. Transmission through blood transfusions and organ transplantation can occur.

Aetiology

West Nile Fever is a viral infection caused by an arbovirus (a virus transmitted by arthropods) called West nile Virus (WNV), an RNA virus in the flavivirus family. It is closely related to other flaviviruses such as the Murray Valley encephalitis and Japanese encephalitis viruses. WNV is normally an infection of birds, though can infect humans and other animals such as horses. The insect vector is the mosquito. Over 40 species of mosquito are known to carry WNV, but the principal species are in the subgenus Culex. The exact ecology of WNV has not been elicited, due to the complex nature of multiple animal reservoirs and insect vectors. For example, two transmission cycles have been described in Europe: A rural cycle involving wetland birds and ornithophilic (bird biting) mosquitoes, and an urban cycle involving domestic birds and opportunistic (bird and human biting) mosquitoes.

Epidemiology

WNV was first isolated in 1937 in the West Nile area of Uganda, and has been subsequently been identified in birds across Africa, the Middle East and West Asia. More recently the virus has spread to Oceania (where the closely related Kunjin virus can be found), Central Asia, Europe (since the 1960's) and North America.

Europe currently experiences sporadic outbreaks of human & equine disease and these outbreaks are becoming larger, especially in temperate urban areas. Notable outbreaks include 393 cases in Romania in 1996, 800 cases in Russia in 1999 and 400 cases in Israel in 2000. There have also been sporadic cases identified in Portugal, Spain and France. The Netherlands and the Republic of Ireland have also had isolated cases though these are thought to be travel-associated and not acquired locally.

North America has experienced significant spread of the virus since it was first isolated in New York in 1999 (62 human cases, 7 deaths). The 1999 New York outbreak appears to have been introduced from either Egypt or Israel. The virus spread within 5 years to almost all states in the USA (except Alaska, Hawaii, Oregon and Washington). In 2003, 9858 human cases were identified though this may be due to enhanced awareness and surveillance rather than significantly increased virus activity. Canada has also been affected by WNV; 1388 cases were reported in Alberta, Manitoba, Ontario, Quebec and Saskatchewan in 2003.

The spread of the virus is probably due to a combination of the migratory patterns of birds and modern phenomena of travel, agriculture and climate change.

Clinical Features

Human infection

WNV has an incubation period of 3 - 15 days. Human infection is usually asymptomatic or causes a mild flu-like febrile illness, sometimes accompanied by

• Incubation 3 days to 2 weeks
• Fever
• Rash in 50%
• Headache/Retro-orbital pain
• Arthralgia/Polyarthropathy/Myalgia
• Nausea/Vomiting
• Conjunctivitis
• Pharyngitis
• Diarrhoea
• Upper respiratory tract symptoms
• Lymphadenopathy
• Rarely:
  • Splenomegaly
  • Hepatitis
  • Pancreatitis
  • Myocarditis
  • Risk factors for meningo-encephalitis, producing meningitis, encephalitis, or acute flaccid paralysis, appear to be:
    • Older age
    • Male
    • Hypertension
    • Diabetes mellitus
    • Lineage 2 infection

Complications such as hepatitis, myocarditis and pancreatitis have been described, but in less than 1% of cases severe neurological disease may develop. This can manifest as acute encephalitis, myelitis, aseptic meningitis or occasionally Guillain-Barré syndrome. This can lead to death in 5-12% of cases, the majority being in those over 50 years of age. CSF shows changes indicative of viral infection (high lymphocyte count, raised protein). Imaging of the brain may show evidence of encephalitis, though there are no pathognomonic changes.

Management is supportive, and Intensive Care has a major role in neurological cases. Ribavirin is known to inhibit the virus in cell culture, though it has only been used experimentally in vivo.

Animal infection

WNV can also infect horses and other mammals, and may manifest as encephalitis. Typical symptoms include ataxia with rear limb incoordination, fasciculation and weakness. A study of equine WNV infection in the USA reported a 26% fatality rate. The major animal reservoir of WNV is birds. In the Old World, there are few reports of visible disease and most infection is asymptomatic. In the New World large numbers of birds have died. A notable example is the death of many American Crows (Corvus brachyrhynchos) during the 1999 New York outbreak. Whether this is due to exposure of a naive population to a new virus or because of a species-specific susceptibility is unclear.

Diagnosis

Whilst clinical picture is important, there are no disease-specific signs and symptoms to aid diagnosis. Laboratory confirmation is usually based on the detection of IgM and IgG in serum. Other flaviviruses exhibit considerable cross-reactivity, so confirmation with a plaque reduction neutralisation test (PRNT) is often undertaken. RT-PCR of blood or CSF enables early diagnosis of WNV infection, but may be unsuccessful as samples need to be collected early in the illness. Detection of virus-specific antibody in CSF may provide an alternative method of early diagnosis.

Prevention and Prophylaxis

• Mosquito control

There is currently no licensed vaccine for use in humans. Live attenuated yellow fever WNV chimeric vaccines have been successful in animals and are currently undergoing human trials. A formalin-inactivated whole virus vaccine has been approved for use in horses. DNA vaccines coding for the structural WNV proteins have also been assessed for veterinary use and have been found to be protective in mice, horses and birds. There is also evidence that immunisation with Kunjin virus, the comparitively benign Australian relative of WNV, provides protective immunity against the North American strain.

The ecology of West Nile virus and its reservoirs & vectors is complex, but identification of local insect vectors that pass WNV between birds and from birds to mammals (such as Culex salinarius) may help to provide methods of disease control.

Treatment

• Supportive

Future

• Secondary suphonamides are being studied such as AP30451 in this and Yellow fever animal models. Some pyrazolines that inhibit RNA synthesis may have potential.

References

Related Links

• Department of Health WNV Information (UK)
• Health Protection Agency WNV Information (UK)
• CDC WNV Website (USA)
• Public Health Agency of Canada WNV Website (Canada)