Introduction

Viruses are all around us and cause various types of diseases. As seen with the COVID pandemic and its implications, other viruses are also capable of causing detrimental effects on our health and the environment. In this article, we will be discussing a virus called West Nile Virus (WNV).

So, what is WNV? WNV is a zoonotic, RNA mosquito-borne flavivirus.¹ This means that the disease can spread between animals (mosquitoes) and humans. It is one of the 75 virus species of the Flaviviridae family. This virus was not considered very important to human health as it only caused mild infections, however, it is a major cause of morbidity (disease) and mortality (death) in different animals including birds, sheep, horses, cats, rodents, and reptiles. Additionally, in the last two decades, there has been a significant increase in human and equine cases.¹ Hence, to help treat this infection, it is important to understand the disease’s mechanism and transmission.

Basics of West Nile virus

WNV belongs to the genus Flavivirus, family Flaviviridae, and Japanese Encephalitis serocomplex, together with St. Louis encephalitis virus (SLEV), Murray Valley encephalitis virus (MVEV), and Alfuy virus (ALFV).^1,2

It was first identified in 1937, in the West Nile province of Uganda from a feverish patient.¹ It is carried over long distances across the earth through migratory birds and is characterised by high genetic diversity.² 

As mentioned previously, this virus affects animals more than humans. Susceptible bird species generally do not have severe clinical manifestations. However, it may cause severe neurological complications in some bird species, which may lead to death. Infected humans are often asymptomatic, however, 20% of cases can lead to a febrile illness known as West Nile Fever (WNF).²

Additionally, 1% of cases, specifically elderly or immunocompromised individuals, may experience severe and even fatal neurological disease known as the West Nile virus neuroinvasive disease (WNND).

WNV is maintained in a bird-mosquito-bird cycle, where infected mosquitoes (mainly the Culex genus) transmit this disease through bites. However, humans and other mammals can become incidental dead-end hosts.³

Transmission cycle

Mosquitoes are the primary means by which the WNV is transmitted. There is no single proven mechanism by which WNV develops, progresses, and persists.

However, various theories in mammals have been suggested. The infectious cycle starts through the bite of an infected mosquito, which then leads to the replication of the virus locally at the injection site. The mosquito’s saliva alters the host’s immune system, allowing the virus to replicate further.

This is achieved through the alteration of leukocyte (white blood cell) recruitment to the bite/injury site. The mosquito saliva also inhibits the production of interleukin 2 and IFNγ which are important in your immune response.¹

Hosts have an important role in enabling the continuous infectious cycle, as they allow for the transmission and spread of the virus. Various animals are susceptible to WNV infection, including:¹

• Indian elephant
• Indian rhinoceros
• Ring-tailed lemur
• Red panda
• Snow leopard
• Babirusa

However, only birds seem to produce high enough amounts of the virus to infect the mosquitoes making them a main reservoir.¹ 

Spread

Aside from mosquitoes and birds, WNV can be acquired in hospitals through:¹ 

• Organ transplants
• Needlesticks
• Blood transfusion
• Haemodialysis

Transmission through the oral-faecal route has been reported in American alligators and saltwater crocodiles. WNV transmission can also occur via direct contact between birds in commercial geese farming; this is thought to be linked to cannibalism and feather picking of infected birds.

Mosquito vector

Multiple species of mosquitoes are involved in the transmission of WNV, but those belonging to the Culex (Cx.) genus appear to be the primary carriers.¹ Examples of competent mosquito species include:

• Cx. univittatus (most competent vector to transmit WNV to humans)
• Aedes albopictus
• Cx. pipiens (most abundant in Africa)
• Cx.Tritaeniorhynchus (most abundant in Africa)

Research has reported WNV was detected in around 150 mosquito species, however, the key vectors (spreaders) for this virus in the USA are Cx. tarsalis, Cx. pipiens, and Cx. quinquefasciatus.

The life stages of the vectors (mosquitoes) are summarised below:^4,5

Eggs

Female mosquitoes lay their eggs on the inner wet walls of containers with water. They lay around 100 eggs at a time which stick to the walls like glue.

Larva

Upon contact with water, the larvae emerge from the egg; hence, rainwater or the addition of water can trigger them to hatch. After moulting 3 times, they become a pupa.

Pupa

The pupae continue to develop until the adult flying mosquito body emerges from the pupal skin and then they leave the water.

Adult

After emerging from the water, male mosquitoes feed on nectar from flowers, while females feed on humans and animals for blood for egg production. After feeding, female mosquitoes locate water sources to lay more eggs.

Multiple factors can affect the successful growth and reproduction of the mosquito population, including:

Mosquito diet

Certain studies suggest that diet can affect the mosquito’s lifespan. For example, a male mosquito (An. coluzzii) feeding on papayas showed longer survival and higher mating rates compared to mosquitoes feeding on bananas.

Environment

Temperature or use of larvicides can affect mosquito survival.

Availability of food

Larval competition for food affects development time and survival.

Intrinsic mosquito genetics

The mosquito’s competence as a vector is mainly determined by its genetics. Some mosquitoes may have advantageous genes which will make them more susceptible to WNV infection. Their genes also influence how successfully they can transmit WNV to other hosts.⁶

Avian hosts

As mentioned previously, birds are the main amplifiers and reservoirs for the WNV. Multiple bird species were found to be infected, including but not limited to:¹

• Domestic geese
• Owls
• Pigeons
• Vultures
• Crows
• Cranes
• Pelicans
• Turtle doves
• Bald eagle
• Flamingos

These hosts play an important role in the amplification of the virus, as well as its spread. Certain species (e.g., the American crows) can be the main amplifier, which leads to more mosquitoes being infected. As these birds migrate, they can spread the virus into different regions of the globe.^1,2

Human and mammalian hosts

Humans are usually asymptomatic to the WNV, however, some cases can turn febrile or even severe. Children, the elderly, and patients with chronic diseases are more susceptible to more severe forms of the disease. The primary clinical signs appear at the end of the incubation period (2-14 days after infection). Some of the symptoms include:¹

• Fever (temperature > 38˚C)
• Headache
• Lethargy and alteration of mental state (depression and personality change)
• Rash
• Photophobia
• Vomiting
• Nausea
• Anorexia
• Myasthenia

The transmission of the WNV is still under study. In one research study, the virus was detected in the urine during the critical phase of infection, suggesting the virus can be transmitted through contact with contaminated material.¹ This indicates–although rare–human-to-human transmission through aerosols or bodily fluids is possible.

Prevention and control

Currently, there is no specific cure for WNV infections. However, the following control measures can be taken.¹

Vaccination

Currently, there are no vaccines available for humans for the WNV, however, horses have successful vaccines which are commercially available.

Vector control

Using pesticides and mosquito larvicide (Bacillus thuringiensis) to destroy the breeding ground for mosquitoes.

Personal protective measures

Using mosquito repellent, protective clothing, and mosquito nets, eliminating stagnant and standing water (breeding ground for mosquitoes).

Other

Screening blood and organ donors. Continuous research for developing successful vaccines.

Surveillance and monitoring

Monitoring the transmission of WNV can help limit and control the disease. For instance, understanding the migration cycles of hosts (birds) can help predict the transmission path for this virus.

Moreover, studying local species can provide insight into their diversity and spreading patterns. For example, WNV L2 has historically circulated in Sub-Saharan Africa and Madagascar before finding its way to Europe. Malagasy strains of WNV appear to be very different from other strains, suggesting a local cycle is sustained by resident birds and mosquitoes independent of the annual movements of migratory birds.² 

Mosquitoes can also be transmitted by ships, wind or aeroplanes, human movement and bird trade which can affect the transmission of WNV.¹

Furthermore, rice fields, stagnant water, and wetlands provide a rich environment for the rapid increase in mosquito numbers, which results in WNV outbreaks. Hence, hosts, vectors and environmental factors can all play a role in the viral spread. Taking these factors into account is vital to employ efficient control measures and help monitor WNV spread.

Summary

West Nile Virus (WNV) is a zoonotic virus with a complex life cycle. It requires an interaction between mosquito vectors, reservoirs/hosts, and the end-stage hosts. All of which interact with the environment. WNV is a widespread disease with detrimental effects on certain species like birds.

Understanding its transmission and development is key to limiting its impacts and controlling its spread. However, more research is still needed to provide a better overall understanding of transmission and pathology. Further research is also required to provide a vaccine for humans, especially susceptible patients, and main reservoirs/other mammals.