The purpose of this research paper is to give an overview of the West Nile Virus; its origin, transmission, symptoms and treatment. An overview of the disease is given, before discussing its origin in Uganda and epidemiology and spread throughout the world, including its spread into the Western Hemisphere. Transmission of the virus is discussed, highlighting the virus’ avian host and arthropod transmission vector – in particular the Culex mosquito. A key outbreak is discussed in detail – giving insight into the virus’ impact in New York City in 1999. Theories are also given as to how the virus spread to America. Clinical manifestations of the virus are then identified, highlighting that the virus can shift from its initial state to meningitis and encephalitis. Treatment and vaccines are explored – identifying that there is currently no specific treatment or vaccine available, and that treatment is currently supportive. Conclusions are then given, identifying current gaps in knowledge that are hindering the development of viable treatment and vaccines in animals and humans.
West Nile Virus (WNV) causes substantial human disease. It is a member of the genus Flavivirus and is within the family Flaviviridae – which contains 3 genera known as the flavirviruses, where WNV is classified (Colpitts et al, 2012). Originally isolated in Africa, the disease has spread to other continents including Europe and the Americas and has displayed outbreaks throughout. A key outbreak in New York in 1999 showed the first cases of WNV in the Western Hemisphere. A mosquito-borne disease with avian hosts, WNV is spread through an infected mosquito biting a human or animal. Effects can be asymptomatic and can lead to flu like symptoms – with few people leading on to develop West Nile meningitis, West Nile Encephalitis and other more serious clinical manifestations. Currently, there is no specific treatment or vaccine for WNV other than hospitalisation and supportive care. In today’s world, incidence of WNV is still spreading through the developed world and it is hard to curb this due to knowledge gaps and the lack of treatment and working vaccine.
Origin and Epidemiology of West Nile Virus
WNV was first isolated from a symptomatic patient in the West Nile district in Uganda in 1937. Although the patient initially presented symptoms of yellow fever, diagnostic tests showed a different reason for the symptoms (Sejvar, 2003). Epidemiology of WNV was characterised in the early 1950’s and 1960’s due to several outbreaks in the Mediterranean basin. Further outbreaks in Egypt between 1951 and 1954 gave further understanding to the epidemiology, ecology and clinical presentation of WNV. The presence of the virus in Egypt led to the discovery that the virus was only able to be isolated from mosquitoes – suggesting that this arthropod was the primary vector (Sejvar, 2003).
An outbreak of WNV in 1957, occurring in Israel, showed presentation of severe neurologic manifestations whereas neurologic illness as a result of WNV had rarely been reported before this time. Subsequent outbreaks in France and South Africa also showed neurologic illness – however this appeared to be infrequent. Large outbreaks of WNV were infrequent through the late 1970s and 1980s until around 1996, where a large outbreak was observed in Romania – the first WNV outbreak to occur within a predominantly urban area (Sejvar, 2003). Following this, there were several epidemics in Morocco, Tunisia, Italy and Israel. At this time, it appeared that outbreaks of WNV were becoming much more prevalent, as well as more recent outbreaks showing increased rates of severe central nervous system disease and higher fatality rates since the outbreak in Romania. A key outbreak to be discussed later was in New York City in 1999, when the virus was first detected within this region (Sejvar, 2003).
Transmission of West Nile Virus
WNV has been shown to maintain itself throughout the world through an enzootic cycle – whereby the virus is primarily transmitted between mosquito vectors (most commonly the Culex species) and avian hosts. When infected birds develop high levels of the virus within their bloodstream, mosquitos can become infected by biting the avian host. After around a week, the infected mosquitos are able to pass the virus onto any avian hosts they feed from. The most common way in which WNV is transmitted to humans is due to the bite of an infected mosquito. Mosquitos are also seen to bite some animals including horses – however both human and the animals bitten by the infected arthropods are classified as ‘dead end’ hosts (McLean et al, 2006). This is due to the fact that their bloodstream does not develop high enough levels of virus in order to pass it on to other mosquitos that may bite them. Although bites are the most common method of transmission, a small number of cases have been transmitted via blood transfusion and organ donation as well as congenitally from mother to baby (WHO, 2018).
Transmission appears to depend on the local ecology and human behaviour that leads to exposure to infected mosquitos. During epidemics in Africa, up to 55% of the affected populations became infected, whereas outbreaks in Europe and North American saw much lower percentages. As a comparison, the New York outbreak in 1999 only saw around 2.6% of residents infected – even though it was seen as an area of intense transmission outside of Africa (Hayes et al, 2005). Incidence of WNV also appears to be seasonal in the more temperate zones of Europe, North America and the Mediterranean Basin – with activity peaking between July and October. The virus’ ‘transmission season’ has lengthened as the virus has moved south within the United States, where disease can be seen from April to December. Transmission in countries within Southern Africa has shown to increase after spring and summer rainfall within the early months of the year (Hayes et al, 2005).
Within the United States, age is not a factor in susceptibility to WNV infection – but the incidence of the more severe forms of the infection and fatalities appear to increase with age and are observed to be slightly higher in male patients. As may be expected, the key risk factor in acquiring WNV is contact with infected mosquitos (Hayes et al, 2005). Transmission cannot occur without avian hosts, infected mosquitos and humans/animals of which to pass WNV onto. Areas with higher rates of infection tend to see higher levels of these even in developed countries. Romanian outbreaks saw people more at risk if people had mosquitos within the home and if they had flooded basements – a breeding ground for said arthropods (Hayes et al, 2005). The New York outbreak showed that cases appeared to be clustered within an area that had higher vegetation cover than other locations within the city – with this area being a favourable habitat for mosquitos (Hayes et al, 2005).
New York 1999 Outbreak
In August 1999, two patients displayed symptoms of encephalitis in a hospital in northern Queens. A following six cases were then identified, all originating from previously healthy patients. All patients initially seen were from the northern Queens area and with no common exposure to WNV due to travel, the infection source was theorised to have been in the city itself. All patients reporting illness had engaged in outdoor activities around their homes during the evening; this lead to an environmental investigation which revealed the presence of Culex mosquito breeding sites and larvae in the patient’s neighbourhoods. Because of these findings, an arthropod-borne virus was suspected – but common viruses were ruled out, except for St. Louis encephalitis, a virus common in North America. Before and during this investigation, deaths of birds had been reported within the New York City area – which were originally assumed to be unrelated to the outbreak in human patients. This is due to the fact that St. Louis encephalitis does not usually kill avian hosts (Nash et al, 2001).
Four weeks after becoming aware of the outbreak in humans, American crows and other birds tested positive for WNV. Following this, there were 719 reports of patients with symptoms of meningitis and encephalitis – and laboratory evidence of WNV infection became apparent in patients tested (Nash et al, 2001). This outbreak represented the first known occurrence of WNV in the Western Hemisphere and was unusual, as outbreaks usually caused milder febrile illness (Nash et al, 2001), whereas 62 patients were hospitalised in this case, 7 of whom died (Rappole, 2001).
How WNV got to New York City is unknown. It was theorised to have originated from migrating birds – which makes sense given the disease having an avian host. Because of this, WNV rapidly spread across America, across many states from its assumed origin in New York (Rappole, 2001). Another theory for the spread of WNV to New York in 1999 is immigration. It is thought that immigrants may have brought the disease to the city, or infected mosquitoes could have been brought over to America with immigrants. Again however, it is still unknown exactly as to how the virus was introduced to the USA (Murray et al, 2010). The disease still persists in America today, with an estimated 3 million cases between 1999 and 2010 (Peterson et al, 2012).
Clinical Manifestations of West Nile Virus
Most infected with West Nile virus are asymptomatic and symptoms are only seen to develop in around 20-40% of patients. Typical incubation period for the disease is around 2-14 days before symptoms present. For most symptomatic patients, they present with flu-like symptoms. The virus itself is characterised by malaise, fatigue, skin rash, myalgia, headache, fever, diarrhoea and vomiting. In less that 1% of patients, the disease progresses to West Nile meningitis and/or West Nile encephalitis (Campbell et al, 2002).
West Nile meningitis presents initially usually with fever and evidence of meningeal irritation; headaches, photophobia and a stiff neck. If the brain parenchyma is involved, West Nile encephalitis develops and thus other clinical features are present. Patients show disorientation, altered levels of consciousness, tremors, involuntary movements and other focal neurological symptoms. Although patients with West Nile fever can recover in a matter of days to months, there is a much poorer outcome in those with West Nile encephalitis than those with West Nile meningitis. In a recent study only 25% of surviving patients with this West Nile Encephalitis were able to return home without requirements for increased care, compared to 76% of those who had suffered with West Nile Meningitis (Campbell et al, 2002).
Treatment and Vaccines
At present, there is no specific therapy for WNV, however the main action initially for treatment of those with suspected meningoencephalitis is hospitalisation. Currently, no controlled studies on a various number of drugs have been reported for the virus (Campbell et al, 2002). Pain relief is however often used to reduce fever and relieve some of the symptoms of WNV. When patients are hospitalised, supportive treatments such as intravenous fluids and pain medication are used. Thus, it can be said that the only treatment for WNV is supportive. In New York in 1999 and New Jersey in 2000, five patients were admitted to intensive care and two patients required mechanical ventilation as supportive treatment (Petersen et al, 2002).
There is also currently no vaccine for the virus available. Efforts to develop both human and veterinary vaccines have been made – using both traditional and innovative approaches. At present, there is an approved whole virus vaccine for use in horses, and DNA vaccines coding for the structural proteins of WNV have seen to be protective in mice, horses and birds. Further studies have also found that vaccination for the Kunjin virus, an Australian variant of WNV provides protective immunity against the North American strain of WNV (Hall et al, 2004). More recently, in 2015, clinical trials of a new vaccine for WNV began. As of yet, no formal results have been released (Clinicaltrials.gov, 2016).
Today, WNV can still be seen to be continuously spreading across Europe, America and other regions of the world. Although outbreaks on WNV in Europe have been sporadic, events have increased and the virus has been seen to be introduced into new areas. Whilst progress has been made regarding scientific knowledge of WNV, knowledge gaps exist that limit the ability to forecast changes in the risks of occurrence of outbreaks that would aid prevention and control of transmission. Knowledge on how WNV has been introduced to America and Europe is still only theorised. Migrating birds is the assumed method of transmission however many questions surrounding this are still unanswered. Questions are also raised when observing the virus disappearing from previously infected area (Rizzoli et al, 2015). The lack of specified treatments and lack of vaccine for the virus create another knowledge gap concerning WNV. The continual spread of WNV throughout previously WNV free areas implies future economic burden and struggles in disease prevention and vector control. These gaps in knowledge reflect an urgent need to both continue and boost WNV research efforts, with increased surveillance of WNV also needed epidemiologically (Rizzoli et al, 2015). If these knowledge gaps could be filled, and a vaccine identified, increasing incidence of the virus could possibly be curbed, and the virus could be better controlled. In conclusion, incidence of WNV across the developed world can be seen to be increasing and it is paramount that efforts are increased in order to prevent this.