Originally discovered in Uganda in 1937, the West Nile virus is a potentially debilitating disease that has affected thousands of individuals who exhibit both intraocular and central nervous system manifestations.1-5 Decades after its discovery, with the help of migratory birds and mosquito populations, there was a steady increase of West Nile virus occurrences in the human population around the world. There were a number of outbreaks in Israel during the 1950s, as well as France in the 1960s, “which were characterized by encephalitis in humans and horses”.5 The United States experienced a massive outbreak in 2003, in which the CDC reported that there were 9,862 human cases of the virus, including 264 deaths due to complications.3 The prevalence of the virus during the 1990s and early 2000s around the world led scientists scrambling in researching to learn everything they can about the virus. Geography plays a huge role in the transmission of the virus, due to the fact that it relies primarily on presence of infected birds and mosquitos. Among areas that were affected by the virus, the climate was commonly described as temperate and subtropical, which are thriving environments for a large number of different species of birds and mosquitos.1
The transmission cycle for the West Nile virus primarily exists between infected birds and mosquitos, however, a viral load found in the mosquito saliva can be transmissible as a result of a bug bite.1,5 Studies have shown that the virus is not specific to a particular aviary species, however, the virus is most commonly found and transferred by the Culex mosquito species. The West Nile virus is classified in the Flaviviridae family, which is approximately 50 microns and spherical in shape.1 Among the many different studies of the virus, scientists have not come to a complete consensus in the process in which the virus spreads throughout the entire body. After an infected mosquito bites a human host, the viral RNA, which is composed of approximately 11,000 nucleotides first infects dendritic cells, such as Langerhans cells.3,5 The virus then is spread throughout the entire system through the lymphatics, thus infecting vital organs such as the spleen, liver, and kidneys. The virus undergoes a complex replication process as it gradually makes its way throughout the body’s organ system. A breakdown of the blood brain barrier can lead to serious complications such as meningoencephalitis, which is more commonly found in older patients. The lineage of the virus that has infected the individual will be a good indication on the severity of the symptoms he/she will exhibit. Current studies have discovered five different lineages of the virus, however, lineage Ia, Ib, and II are the most common.5 Lineage Ia originated from Europe, the Middle East, and Africa, and is most commonly associated with severe human neurologic conditions.5 In contrast, mild symptoms are usually exhibited by lineage Ib and II which originate in Africa. In the transmission cycle of the virus, humans are considered dead end hosts, due to the fact that an infected human cannot pass the virus to another individual through a mosquito bite.
Another method of transmission that contributed to its spread throughout the United States was blood transfusions and organ transplants. There have been cases in which it took only weeks after receiving contaminated blood products or organs to exhibit signs and symptoms of meningeal encephalitis.1,5 Due to this occurrence, there have been stricter restrictions and tests that must be passed in order to be eligible to donate blood or organs.
Systemic manifestations of West Nile virus can range anywhere from being completely asymptomatic to contracting meningoencephalitis. From the time that the patient gets bitten by an infected mosquito, the incubation period ranges from 2-14 days until the patient to show mild symptoms.1,3,5 Despite having the virus, approximately 80% of individuals that contract the virus exhibit are asymptomatic.5 Mild symptoms include flu-like symptoms such as ‘fever, headache, and myalgia, often accompanied by gastrointestinal symptoms’ which only last for about a week.1 In addition, patients produce a non-specific macupapular rash which self resolves after a week without skin peeling. According the CDC, even after recovering from West Nile fever, patients have reported to experience long term effects such as weakness and fatigue. In more serious cases, the number of reported patients that exhibit neurological diseases, more than half of them acquired encephalitis or meningoencephalitis.1 These particular patients manifest mild flu-like symptoms (similar to that of West Nile fever) as well as brain dysfunction leading to paralysis or a coma. Observing different patient encounters from Dr. Chan, it is evident that those that had more serious symptoms were of older age or were diagnosed with another systemic complication such as diabetes.
Currently, there is no FDA approved vaccination for West Nile virus but only supportive therapy to relieve their symptoms. It is vital of patients to be admitted to the hospital for observation if they exhibit clinical neurological symptoms in order to prevent and monitor possible cerebral edema or respiratory failure. Even though there is currently no FDA approved treatments for treating West Nile, there are a number of medications that are being experimented with including ribavirin, which is a purine and pyrimidine analogue and interferon alpha. The concept behind ribavirin is that in high concentrations, it can have the ability to inhibit the replication process within the cytoplasm.1 Studies have led scientist to believe that interferon alpha has the ability to inhibit virus cells from infecting the spinal cord. The most effective way of inhibiting the spread of the virus is by controlling the mosquito population as well as eradicating infected birds. It is also recommended to use insect repellent that contains DEET in order to prevent the transmission of the virus from infected mosquito bites.
West Nile is transmitted and circulated through the blood stream, ultimately leading to the development of ophthalmic manifestations. The most common ocular finding of the virus is chorioretinitis. A dilated fundus exam will reveal chorioretinal lesions that present in an organized linear fashion and are typically found bilaterally, but there are some cases of monocular presentations.3 The chorioretinal lesions, also referred to as “target lesions,” are described as deep and whitish in color typically 200 to 1200 microns in size. These are usually found in the posterior pole and periphery and can be associated with vitreal inflammation. West Nile increases the patient’s chance of developing uveitis (vitritis and iritis) in the presence and absence of chorioretinitis. If the patient shows severe neurological symptoms, such as encephalitis, an increase in intracranial pressure may lead to optic neuritis and optic nerve papilledema. The systemic inflammation throughout body affects the vascular system, potentially causing retinal vasculitis causing ischemia within the eye, significantly decreasing the patient’s visual acuity.
A cure for West Nile virus does not exist, however there are a number of treatments that are available to maintain the health and function of the eye. Since ocular manifestations are usually present in patients with severe systemic symptoms, ocular findings are not the priority for treatment. In order to reduce edema and inflammation, intravitreal bevacizumab has been used in order to treat intraocular presentations of the virus. A number of these ocular findings are self resolving once the underlying systemic condition is controlled.
A majority of the manifestations of the West Nile virus are non-specific, making it extremely difficult to diagnose clinically. Due to its difficulty to diagnose, it is extremely important to obtain a good case history. It is important to note if they have been sick recently following a mosquito bite and if they exhibit any neurological discrepancies. Being aware and educated of areas in your community will also help narrow down your differential diagnosis. If there is any clinical evidence of West Nile virus, the gold standard for diagnosis is an enzyme-linked immunosorbent assay (ELISA) which detects levels of WNV-specific IgM within the blood or CSF.3 According the CDC, if the ELISA test results positive for the specific IgM for West Nile within the CSF, this confirms the diagnosis.3 A CBC serology test may show positive results of anemia, lymphopenia, and thrombocytopenia, all of which is evidence that there is an infection present within the body.5 A brain MRI is helpful in determining the current condition of the meninges and brain function, however, this method is more used for prognosis instead of diagnosis. The presence of ocular manifestations may lead to the differential of West Nile, however, serum and CSF sample testing are the primary method of diagnosing this presence of the virus.