Endemic diseases are continually occurring all across the globe at any given moment in time. The term 'Endemic disease' is used to describe a disease which is prevalent in a particular area and is maintained in the specific population without the need for input from external sources. These diseases are constantly present in their particular community but occur at a low frequency. Examples of endemic viruses seen in varying parts of the world include Influenza, Hepatitis A, Norovirus and the West Nile virus. There are several endemic viruses which are transmitted through arthropod vectors. Of these arthropod spread diseases the invasive West Nile Virus has become an endemic threat over the past ten years to many areas of the United States. Since its introduction into the United States in 1999 the virus has rapidly extended across the country and was first identified in Georgia in 2001. Spread via infectious mosquitoes, West Nile can cause a human infection which can show a range from mild or no symptoms to fatal encephalitis. Understanding the structure, life cycle and public impact of this virus can help populations take preventative measures to protect against further outbreaks along with helping scientists lead to developments of successful vaccines and treatments against the disease.
The West Nile virus, or WNV, is considered an arbovirus which is classified within the Flaviviridae family. 'Arbovirus' is an acronym used to identify viruses which are specifically spread through arthropod vectors. Viruses within this group belong to several different families and Baltimore classification groups. The Flaviviridae family, which includes WNV, is classified in the Baltimore class of group IV. This group includes positive-sense single stranded RNA viruses. Positive sense ssRNA viruses are unique because they are similar to mRNA, therefore having the ability to be immediately translated upon entry into the host cell. Other families within this group include Astroviridae, Caliciviridae, Coronaviridae, Picornaviridae and Togaviridae. All geneses grouped within the family of Flaviviruses tend to share common shapes, sizes, symmetry and appearance. West Nile is grouped within the genus of Flavivirus Japanese Encephalitis Antigenic Complex. Classified within this genus are viruses which are known to cause encephalitis including Alfuy, Cacipacore, Murray Valley, and Stratford virus, among several others. Two lineages of WNV have been identified, type I and type II. All infections resulting in human disease have fallen under type I. Lineage I is found in North America, Africa, Asia and Australia while Lineage II has only been identified in sub-saharan Africa and Madagascar. WNV is found to be a small, enveloped icosahedral virus with the capsid being contained within a lipid bi-layer membrane which is derived from its host cell. Similar to many other enveloped viruses the immature WNV particle has surface projections, or spikes, which are formed by trimers of the protein M-E heterodimers. Mature infectious west Nile particles contain protein E-E homodimers on their surfaces, therefore creating a much smoother appearance. Three structural proteins can be found on the WNV particle, M, E and C. C is a capsid protein found within the nucleocapsid. Proteins M (membrane) and E (envelope) are surface proteins which are important during the binding of the virus to the host cell. The 11-kb genome has been found to encode 7 different nonstructural proteins which are necessary for the RNA genome replication of the virus. These 7 proteins include NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5. A single polyprotein is used to derive both these structural and nonstructural proteins.
In order for a successful life cycle of the west Nile virus replication must be able to take place in both the vertebrate host as well as the arthropod vector. WNV is a +ssRNA virus meaning its replication strategy is extremely effective, an important factor in considering the widespread success and distribution of the disease throughout the world. +ssRNA viruses have the characteristic in which the virus particle can function as mRNA directly upon recognition by the host cellular machinery. The sequenced genome of WNV contains only one open reading frame and both ends of the virus contain un-translated regions which are thought to be important in the replication process. Upon attachment to an unknown host receptor site, entry of the virus is achieved through an endocytotic process which is clathrin-mediated. After entry a conformational change occurs in the surface proteins due to a response to a drop in pH. This change exposes the hydrophobic domain of the protein which then proceeds to be inserted into the lysosome membrane causing fusion between the virus and host cell. The nucleocapsid is then deposited into the cytoplasm of the cell and replication can begin. A unique characteristic about the replication of WNV is the synthesis of only a single polyprotein is processed into both the proteins and the membrane. One end of this polyprotein contains the 3 viral structural components while the remainder of the strand forms the 7 nonstructural proteins. Translation occurs at the ER and envelope protein products are transported into the ER lumen while the remaining products are sent to the cytoplasm. Once polymerase and helicase are produced replication can begin in the cytoplasm. As synthesis of the new RNA strands occur, the capsid proteins are associated with the nucleic acids and result in the formation of a new nucleocapsid. The nucleocapsid associates itself with the membrane of the ER followed by the completed assembled virion budding through the membrane into the lumen. Exit of the host cell occurs through a secretory pathway mediated by surface proteins. Transmission of this virus between its known reservoir, vector and incidental host is quite dynamic. Birds have been found to be the reservoir of the disease and can only spread infection to vertebrate hosts such as humans or horses through a bite from an infected mosquito. Mosquito's acquire the disease by feeding on an infected bird. The disease is then allowed to circulate throughout the blood until finally settling in the salivary glands of the insect. When an infected mosquito feeds on a human or horse the disease can be transmitted through the arthropod saliva resulting in the possibility of disease. Humans and horses are a dead end for the virus as it cannot be transmitted directly from human to human. However, one case has documented a trans-placental transmission and evidence of transmission through transfusions and organ transplants have been identified. There is also no evidence of bird to human transmission through either direct contact or ingestion of infected meat. Transmission is only successful through an arthropod vector.
The pathogenesis, host immune response and patterns of clinical features of the west Nile virus is still undergoing extensive research in order to better understand its development. It is thought only a single amino acid change in the WNV structure enabled the virus to rapidly mutate and allow spread over a large geographical area. Once infection from the virus-laden saliva of a diseased mosquito has occurred, the viral particles move through the body to infect several different cells. Fibroblasts, vascular endothelial cells, and reticuloendothelial system cells are prominent areas in which infection may manifest. Two specific genes are being researched as primary areas for WNV infection-the CCR5 and OAS genes. With the onset of the disease the host will develop viremia, which in many cases can progress to a CNS infection such as encephalitis. It is thought the primary target of WNV is the medulla because of its characteristic to develop persistent brain infection in older or immune suppressed individuals. Increased cytopathic effects have been observed in infections of brain glioma cells. These effects occur within 24 hours post infection and tend to show a high level of viral yield. Observations in several cases have shown that during these encephalitis infections scattered microglial nodulas and destroyed spinal anterior cells can be noted. Although detailed immune response is not yet fully understood it is thought the WNV can induce upregulation of genes controlling apoptosis and those present in increased amounts can result in neurodegenerative diseases. Down regulation of mitochondria and genes belonging to the energy synthesis pathways has also been observed. Immunosupression along with increase in age is thought to increase the chance of severe illness. Symptoms among infected individuals can develop between 3-14 days and can vary in severity. Many will experience no symptoms or only a slight fever accompanied with headache and body ache. Neurological damage is generally only seen in the elderly and will either cause permanent brain trauma or death.
Although West Nile is a widespread endemic disease no successful treatment for the illness has yet been created. Supportive care for the infected is currently the only treatment provided. Unfortunately this care will not lessen the severity of the disease in the patient but will provide one with symptom relief. Relief is often aimed at decreasing fevers and brain swelling, fluid and nutrition support to avoid dehydration, ventilator support, and bed rest. Medicine such as acetaminophen is often taken to relieve any pain. Prevention of the disease is minimal as well. Only vaccines for horses are currently available but none thus far have been approved for use on any other pet mammals, birds or humans. Preventative treatment includes increased mosquito control plans. These arthropods can be avoided by eliminating standing water, use of insect repellent, insect strips, reducing outdoor time during periods of high mosquito activity, shielding your body by wearing lightweight long sleeved clothing during summer months, and maintaining building screens to prevent mosquito entry. Prognosis after infection is generally pretty good. Only a very small amount of infected individuals actually develop severe neurological symptoms resulting in fatality or long term brain trauma. With bed rest and good supportive care the majority of infected individuals will recover with no long term effects.
Since the increased amount of West Nile cases across the globe the public health concern of infection has seen an increase over the past few years. Although a large percentage of fatal cases observed were seen in underdeveloped countries, such as Africa, more industrialized areas, such as the United States and Europe, have reported only a low percentage of severe illnesses. The difference in the intensity between these two regions is due primarily to the influence of the rate of mosquito exposure to the population. Incidences of the disease can also be related to seasonal changes and weather patterns. Warm, wet climates found in regions with poor sanitation are going to be more susceptible to outbreaks because the rate of exposure to possible infected mosquitoes is higher than the rate of exposure in cold, dry climates. People of all ages can contract WNV but the most severe cases seem to be concentrated in those of the elderly population. Infection through organ donations, blood transfusions, and vertical transmission through mother and child have all been reported but in small numbers.
It is important to understand and have up to date knowledge of endemic diseases found among populations where you live. By understanding risk factors, treatment options and preventative measures available one can decrease their risk of being exposed to one of these viruses. West Nile Virus is a worldwide endemic problem. Regions all throughout the globe have been cautioned by the presence of this possible fatal disease that only limited knowledge of has been discovered. Although there is currently no vaccine or treatment and very little understanding of the pathogenesis of the virus in general, precautions can still be taken to limit possible exposure to infected vectors. By understanding how the disease is transmitted and knowing the methods of avoiding contact with mosquitoes, the risk of becoming infected with West Nile is miniscule. If underdeveloped countries could learn to take preventative precautions similar to those seen in populations within Europe and North America, the overall presence of this disease could eventually disappear. Increased protection against mosquitoes in those areas of high fatality percentages will lead to a decrease in these numbers and overall aid in stopping the continuation of this endemic disease.
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