West Nile virus (WNV) presents a significant public health threat due to its ability to cause serious neurological conditions. While the majority of infections result in mild or asymptomatic disease, a small proportion of individuals will face infection of the brain or spinal cord - the central nervous system, which can cause conditions such as encephalitis or paralysis. This article explores the impact of WNV on public health, the effects of the spread of infection to the central nervous system, and the efforts to prevent and manage the disease. 

Introduction to West Nile Virus

West Nile Virus (WNV) is a disease caused by the Flavivirus, which can be transmitted to humans through the bite of an infected mosquito. It was first identified in Uganda in the 1930s and has since spread globally, causing outbreaks in regions of Africa, Europe, Asia and North America.¹ It mainly causes asymptomatic disease, or very mild, flu-like symptoms, as the human immune system is effective in clearing the virus. However, occasionally it can infect the nervous system, which results in serious neurological complications.

Life cycle of the virus²

WNV between mosquito vectors, which spread the virus between different hosts, and birds, known as amplifier hosts as the virus can replicate in the bloodstream to reach high levels. 

This cycle can continue until the virus reaches a “dead-end” host. These include humans and other mammals such as horses. The virus is able to replicate and cause health issues within dead-end hosts, but the levels of virus seen in the blood are not high enough for it to then be picked up by a mosquito and spread further. 

Symptoms³ 

The virus can be present the an infected individual for around 4-14 days during its incubation period before any clinical symptoms arise. These symptoms come on suddenly and can vary from very middle to debilitating, lasting from a few days to months, depending on the severity of the infection. Some cases of neurological infection are left with permanent health complications.

Initial symptoms include 

• Headache 
• Muscle pain (myalgia)
• Low-grade fever
• Vomiting 
• Eye pain
• Anorexia 
• Rash of the trunk of the body 
• A general feeling of sickness (malaise)

Most people infected with WNV experiencing mild symptoms will make a full recovery with no need for medical intervention. This may be less likely for older and/or immunocompromised individuals, as their immune system is less capable of clearing the infection. 

In rare cases, WNV infection of the nervous system can cause neurological issues such as meningitis, encephalitis and acute flaccid paralysis. The symptoms of a more advanced WNV infection include:

• Severe muscle weakness, particularly affecting the arms and legs, which worsens rapidly
• Difficulty breathing and swallowing 
• Seizures
• Altered mental status

These symptoms often progress quickly, requiring hospitalization to help support the individual as their body clears the infection.

Diagnosis⁴

If a doctor suspects a WNV infection, they will order a blood test to check for antibodies produced by the body which are designed specifically in response to this virus to fight it off. A lumbar puncture, using a needle inserted in the lower back, may also be used to check for signs of infection in cerebrospinal fluid. This is often used in more severe, neurological cases. 

Most WNV cases go undiagnosed due to the mild symptoms and similarities to other, more common illnesses. It has been shown that in blood donors who had shown WNV infection, 38% had already sought medical help for their illness, but only 5% were accurately diagnosed.⁵

Neurological complications of WNV

West Nile neuroinvasive disease occurs in a minority of WNV infections when the virus is able to move from the site of infection and into either the brain or the spinal cord, known as the central nervous system (CNS). This leads to much more severe disease, and a number of neurological conditions can arise as a result, leading to death in around 10% of neuroinvasive cases.⁶ Around 1/200 cases go on to develop these complications, although due to the issues with diagnosing WNV, it is likely much more rare than this.

How does WNV infiltrate the CNS?

There are a number of methods used by the virus to gain access to the CNS. When the individual is bitten by an infected mosquito, their body launches an immune response to deal with both the invading virus and the damage to the skin caused by the bite. In normal conditions, cells and other chemicals are not able to cross the blood-brain barrier, which protects the brain from toxins in the blood among other functions.⁷ However, in the heightened immune state, the permeability of the barrier has been increased by chemicals produced in the body in response to the virus. This means that the West Nile viral particles can move across the barrier and into the brain easily, causing neuroinvasive infection.

Another method used by WNV is known as the “trojan horse” mechanism.⁶ In this case, the virus infects the individual’s immune cells and stays alive within them. As the cells move around the body as part of the immune response, they transport the virus along with it, giving it access to other areas of the body without being detected and killed by the immune system, including the CNS. 

The virus has also shown the ability to infect neurons outside of the central nervous system, called peripheral neurons. These are more susceptible to infection and easier for the virus to access, and from here they can infect the CNS.⁶ This is called retrograde axonal transport.⁸

Results of neuroinvasive disease

Meningitis 

Meningitis occurs when WNV infection in the CNS causes inflammation to the meninges, which are the membranes surrounding the brain and spinal cord, acting as a protective barrier.⁹

Symptoms of West Nile meningitis include 

• Fever 
• Headache
• Stiffness in the neck
• Light sensitivity

Encephalitis 

WNV infection can cause encephalitis when the invasion of the virus into the CNS causes damage and swelling to the parenchyma, meaning the brain tissue itself is involved in the inflammation¹⁰. This causes more severe symptoms, such as:

• High fever
• Severe headache
• Disorientation 
• Tremors 
• Seizures
• Coma 

Cases of West Nile encephalitis can lead to profound neurological dysfunction and lasting side effects even after recovery from the infection due to the direct involvement of the brain tissue.

The damage and inflammation that causes encephalitis can be caused by a combination of the harm caused by the virus and that caused by the immune response as it tries to control the infection. 

Acute flaccid paralysis 

This is characterized by the sudden weakness of an individual’s extremities, such as their arms and legs. Muscles involved in swallowing and breathing can also be affected, which can lead to severe complications and complete loss of ability to eat, drink or breathe in some cases, leading to hospitalization. This has a sudden onset and tends to affect one side of the body more significantly. 80% of cases of paralysis occur in combination with either meningitis or encephalitis.⁶

As the virus is capable of using nerve cells to move around the body, it can infect neurons all over the body, which can lead to extensive damage throughout the whole body. Only ⅓ of cases of acute flaccid paralysis make a full recovery with muscle strength reaching close to its baseline level before infection. ⅓ make a partial recovery, and the last ⅓ make little to no improvement, even with the help of physical therapy.⁶

The individual’s immune system can also play a role in the damage caused by acute flaccid paralysis, similar to cases of encephalitis. Its reaction to the virus can cause further inflammation, which in turn damages neurons. The combination of the virus-killing healthy cells and the immune system-killing infected cells can contribute to the extensive damage of WNV.

Treatment for severe cases

There are no vaccines to prevent infection or antiviral drugs to treat an active infection available for human use. The process of managing the infection is supportive, meaning it focuses on relieving the symptoms and dealing with complications associated with WNV. while the majority of people with WNV will not display symptoms and therefore require no treatment, for those who face severe illness, particularly with neuroinvasive cases, supportive care is crucial. 

The treatment is specific to the requirements of the patients and can include:

• Anticonvulsants to control seizures caused by WNV encephalitis 
• Pain management to alleviate headaches and muscle pain 
• Respiratory support may be necessary for patients with acute flaccid paralysis as a result of weakness in respiratory muscles. This can include ventilation
• Rehabilitation to help regain function and mobility in cases of paralysis
• Further monitoring of symptoms by healthcare professionals to prevent new, severe complications

Supportive care allows the immune system time to completely clear the virus without the use of specific antiviral medications. The lack of medication to treat WNV highlights the necessity for good infection prevention measures, particularly in areas that have experienced previous outbreaks, such as the United States. 

Prevention and control of WNV⁶

Pest control approaches are the most widely effective methods to prevent West Nile outbreaks, including surveillance of diagnosed cases, removal of mosquito breeding sites and management of both adult mosquitoes and larvae using pesticides. There have been no cases of adverse health effects resulting from these control operations. 

During outbreaks, the focus turns to controlling the adult mosquito population to reduce the number of mosquitoes which are capable of becoming infected through biting infected birds, and therefore reducing the spread of the virus. 

While human infection usually comes from mosquito bites, there are other methods of transmission which mostly stem from a lack of adequate diagnosis of the infection. These include 

• Blood transfusion and organ transplantation 
• Occupational exposure 
• Breastfeeding and cross-placental transmission from mother to foetus 

This highlights the importance of correct diagnosis of the disease, and proper testing of potential organ and blood donations to prevent the spread of the virus between individuals. 

Summary 

• West Nile Virus is spread to humans primarily through the bite of infected mosquitoes. 
• 80% of cases are mild or asymptomatic 
• If the virus can invade the central nervous system, it can cause neurological issues such as meningitis, encephalitis and acute flaccid paralysis. 
• There are no antiviral treatments for West Nile virus, but symptoms can be treated medically to allow the body time to fight off the infection naturally 
• Proper diagnosis and antiviral measures to prevent the spread of WNV are vital