Spreading Awareness by the AMCA: One Mosquito Bite Can Change a Life Forever

https://youtu.be/CBP_sDCMwr4

One Mosquito Bite Can Change a Life Forever [Motion Picture]. (2014). United States: American Mosquito Control Association.

The American Mosquito Control Association (AMCA) created the short documentary video above as part of their “I’m One” Outreach Program. This program is aimed at encouraging individuals to proactively find opportunities to prevent the spread of mosquito-borne diseases in their community and draw attention to the threat of West Nile Virus in particular. Ultimately, the AMCA’s mission is to spread the message about the necessity for mosquito control, protection, and prevention.

This video is very powerful to watch and does a great job of helping the public better understand West Nile Virus, its threats, and what individuals can do to prevent risk of infection. The video starts off by giving statistics on the number of mosquito born illnesses reported in the year of 2012 in the United States, which is over 5,600. 286 of these cases were fatal according to the video; these statistics really send a message that mosquito bites can be more than just a pesky itch and cause serious, life threatening diseases. One of the most impactful aspects of the video are the personal stories shared by individuals who have suffered from West Nile Virus and experienced the devastating side effects of the more severe forms of the disease. One of the individuals infected was an older man that was a surgeon, and another was a middle-aged man that had lived a very healthy and active lifestyle prior to becoming infected. Both of these individuals shared their experiences with the abrupt onset of neuroinvasive diseases that lead to muscle weakness, paralysis, and excruciating pain. The two men shared how the recovery process was incredibly difficult and slow; one had to take off work for more than 7 months and the was hospitalized for an entire year. These stories highlight the dangerous complications from WNV and also emphasize the long-term consequences of the disease. The individuals in the video, who have since recovered from WNV, talk about the lifelong persistent impairments they suffer from to this day. They both had to relearn how to walk, and continue to experience fatigue, muscle weakness, and difficulties with physical control of their movements. One of the men can longer longer run and requires support for mobility through walking. Another story shared in the video is by a woman who lost tragically lost her young child to West Nile Virus. Her child began to show symptoms and passed away 6 days later. This particular story emphasized the possibility for mosquito-borne illnesses like West Nile Virus to be virulent and deadly. The woman also mentioned the large medical expenses that attributed to medical treatments; her statements were supported by the men who said they had to face incredible medical expenses as a result of their long hospital stays and continual physical therapy and rehabilitation.

Overall this video did a good job of highlighting the nature of this virus; primarily, the video stressed that this virus can happen to anyone and everyone is susceptible and at risk. The stories featured people of very different demographics, including a young girl, an older man, and a middle aged man that all were infected with WNV. I think that this aspect of the video helps to combat people’s notions that this situation will not happen to them. In addition, the video highlights the far-reaching impacts of WNV on not only an individual’s health, but also the economy and their families for the rest of their lives. The video also mentioned the importance of taking prevention measures in the community to control mosquito populations and discourage breeding in the area.

While I believe this video is very effective in raising awareness of the potential serious consequences of mosquito-borne illnesses, I think it would have been beneficial for the video to talk about more ways people can contribute to mosquito surveillance in their community. Surveillance is an important part of keeping track on the spread of WNV and reporting dead birds or other animals to surveillance agencies can be crucial indicators of impending outbreaks of the virus in communities. The video also does not mention individuals who are at higher risk for the more serious aspects of the disease and who should be especially care, including young children, immunocompromised individuals, and especially elderly persons over the age of 70. I also believe that it would be helpful to not only touch upon the severe neuroinvasive cases of the disease, but to inform the public about the fact that about 80% of infected people are asymptomatic and the majority of symptomatic individuals display signs of West Nile Fever. I believe it is important for people to know that they may have WNV or experience WNF without even knowing it because of febrile-like symptoms of the illness. This is important because this would make individuals more aware of the role they could play in accurate surveillance of incidence reports of the disease. If the video provided information on the more vague symptoms of WNV and also emphasized the issue of underreporting and inaccurate surveillance of WNV cases, people would be more likely to address this issue by obtaining diagnosis for their symptoms and reporting their cases to the CDC. This type of awareness would also stress to the public the gravity of the risk and the widespread nature of mosquito-borne illnesses due to their ease of transmissibility.

Despite these small additions I would make to the documentary, I really encourage you to share this informative video with your friends and family to help spread awareness about West Nile Virus! The more educated people are about the risks and how WNV could directly impact them, the more likely they will be to learn more about ways they can help to prevent the spread of the virus and protect themselves, as well as their community.

For more information about preventing mosquito-borne diseases like West Nile Virus, you can visit the American Mosquito Control Association’s website (where the video is originally from):

http://www.mosquito.org

Studies on West Nile Virus Treatment

As we have previously discussed, there is no specific or effective treatment for West Nile Virus at this time. WNV is treated medically through supportive care that can help manage pain and other symptoms. This is a particularly concerning obstacle for the more serious forms of West Nile Virus, such as the West Nile neuroinvasive diseases, which can result in severe and life-threatening symptoms. Lack of specific treatment options to target West Nile Virus contributes to morbidity and mortality rates, and increases the risk of infected people suffering through extensive recovery periods and persistent side-effects post recovery. There is currently a lot of scientific research being done to better understand the pathology of West Nile Virus. This research aims to better understand how West Nile Virus causes and maintains infections inside humans, in hopes of figuring out what antiviral medications would best target the virus and its mechanisms of infection.

One scientific study published in 2014 made important contributions to this field of research by improving our current understanding of how West Nile Virus and other flaviviruses are able to evade host immune responses in humans. This breakthrough study found evidence to support the belief that West Nile Virus evades host immune responses by preventing interferon production and signaling in infected cells. Not only that, the results of the study suggested that a specific human protein plays a vital role in preventing and combating WNV infection, and found a way to hamper the spread of WNV virions by re-targeting this protein to the endoplasmic reticulum during WNV replication.

This experimental study focused on the human MxA protein, which is induced by interferon production and localizes in the cytoplasm of cells. Previous studies have shown that MxA proteins have the ability to self-assemble into highly ordered oligomers and prevent active replication and infection of invading viral cells (Hoenen et al., 2014). Studies have also suggested that MxA’s antiviral properties had to do with their ability to oligomerize into ring-like structures that form around viral nucleocapsids and inhibit their replicative function  (Hoenen et al., 2014). To study the effects of MxA protein in viral WNV cells, researchers used laboratory methods to express the human MxA protein into a WNV replicon, and then transfected the replicon into a WNV packaging cell line. Replicons were transfected using in vitro transcription and electroporation techniques. Subsequently, the researchers analyzed supernatants by performing titer tests to determine the concentrations of WNV particles in the solution. Concentrations of viral particles were performed using plaque assays. Interestingly, analysis showed that the titers recovered from the transfected WNV cell line were significantly lower than titers recovered from WNV replicons that were not transfected with human MxA protein  (Hoenen et al., 2014). This lead the researchers to believe that human MxA protein may indeed play a role in inhibiting WNV cell replication.

Figure 1. Graph A displays data suggesting that the WNV particle concentrations (in infectious particles/mL) were lower for WNV cells transfected with human MxA protein than for regular WNV cells (Hoenen et al., 2014).

To study how human MxA protein might inhibit WNV cell replication, researchers also performed immunofluorescence analysis of the WNV cells transfected with human MxA protein. These immunofluorescence analysis involved cryofixation, preparations of cryosections, and immunolabeling with appropriate antibodies and proteins. Images were then developed by contrasting these immunolabeled mediums were viewed under a transmission electron microscope. The researchers looked at the effects of MxA protein on structural characteristics of the viral cells. After finding that MxA proteins aggregated in the cytoplasm of cells, they conducted more immunofluorescence tests and confocal microscopy investigations that looked at how MxA protein aggregates affected the distribution of viral proteins that comprised the West Nile Virus envelope. This investigated the claim that antiviral proteins like MxA inhibited West Nile Virus infection by disrupting the flavivirus envelope and thereby inhibiting replication abilities (Hoenen et al., 2014).The results of immunofluorescence assays showed that WNV cells that were transfected with human MxA protein, exhibited re-distribution of viral envelope proteins. The distribution of these proteins was also different from that of normal WNV cells, whose envelope proteins were locally diffused within the cytoplasm and nucleolus (Hoenen et al., 2014). Further analysis of viral envelope proteins in MxA transfected WNV cells was conducted using electron tomography. Electron tomography showed that aggregation of human MxA protein within WNV cells resembled organized bundles of hollow tubes located adjacent to membranes and vesicles involved in WNV replication. These results suggest that the co-localization of human MxA protein with viral replication structures may interfere with the ability of viral capsid proteins to assemble during the replication process; this could result in restricted production of infectious viral particles by WNV (Hoenen et al., 2014).

Researchers also wanted to better understand the antiviral properties of human MxA protein on WNV, so they cloned WNV cells and genetically transfected them with different genetically altered versions of human MxA protein. One type of human MxA protein that was MxA protein that contained a genetically altered targeting sequence that signaled for the protein to be retained in the endoplasmic reticulum (ER). Immunofluorescence assay showed that the during replication, transfected WNV cells exhibited localization of protein disulfide isomerase(PDI)-positive ER membranes in the ER with MxA (Hoenen et al., 2014). PDI-positive membranes have previously shown to play a role in WNV replication and assembly; localization of these membranes in the ER would therefore inhibit viral production  (Hoenen et al., 2014). These results were significant because they suggested that human MxA protein could directing MxA protein to appropriate cellular locations would allow it to target its antiviral mechanisms to normally inaccessible viral components. The results of this study contribute greatly to the field of WNV research by providing evidence of promising antiviral effects of human MxA protein on West Nile Virus. Not only does the data suggest MxA has intrinsic abilities to inhibit viral particles, but it also suggests that MxA can also have antiviral effects on WNV when targeted to specific regions like the ER (Hoenen et al., 2014). In addition, the inhibition of viral particle production as a result of localization of viral replicative components to specific regions of the ER, implies that these are regions that flaviviruses might assemble within infected host cells.

Figure 2. Panels A and B reveal the presence of oligomerization of hollow tubes by human MxA protein in WNV cells and shows their location adjacent to viral membranes and vesicles related to replication. Panels C and D show the localization of MxA protein oligomer bundles near the rough ER. Panels E and F show the co-localization of MxA proteins with WNV virals in the ER together (Hoenen et al., 2014).

There are a number of additional research experiments that could be conducted in the future to follow up on the discoveries made by this 2014 study. First and foremost, it would be beneficial for this study to be replicated to verify the antiviral properties of human MxA protein on WNV or on different strains of WNV. It would also be beneficial to conduct similar studies using different interferon-induced human proteins to see if they may also have antiviral properties. Further studies that test different hypotheses on how human MxA proteins inhibit the production of new WNV particles would also be helpful in understanding what viral mechanisms should be targeted by antiviral compounds. One of the important questions to investigate asks whether or not human MxA protein has the potential for application as antiviral therapy for West Nile Virus. In order for a potential antiviral therapy to be developed, it would be important for future research how to stimulate interferon-induced production of human MxA proteins in the presence of WNV infection. At the same time, it would be valuable for researchers to begin studies on how human MxA proteins of people with WNV could be re-targeted to cells in certain regions of the body like the ER.

Hoenen, A., Gillespie, L., Morgan, G., van der Heide, P., Khromykh, Al, & Mackenzie, J. (2014). The West Nile virus assembly process evades the conserved antiviral mechanism of the interferon-induced MxA protein. Virology, 448, 104-116. doi: 10.1016/j.virol.2013.10.005

Treatment and Prevention of West Nile Virus

If you read my last post, you have probably been made aware that the most common way humans are infected by West Nile Virus is by mosquitoes. It is important to note, however, that a very small number of people have acquired West Nile Virus through other routes. These modes have included blood transfusions containing WNV, organ transplants from infected individuals, exposure in laboratory settings, and from an infected mother to her baby during pregnancy, delivery, or breastfeeding. You cannot, however, acquire West Nile Virus from casual contact with an infected human or animal. You also will not become infected from handling infected birds (dead or alive), but it is best to still avoid bare-hand contact. You also won’t acquire WNV from consuming birds or animals that carried the virus.

Mosquitoes are the main mode of transmission for West Nile Virus and although 60 species have been known to carry the virus, there are 3 main species of mosquitoes that primarily influence its spread. The primary species differ by region within the United States and include the Culex pipiens in the north, Culex quinquefaciatus in the south, and Culex Tarsalis in the west.

Centers for Disease Control, 2015

How do these mosquitoes become infected with West Nile Virus? Where does the virus come from originally? The natural host of the virus is birds. Birds are considered an amplifying host for the virus because within birds, WNV is able to easily enter the bloodstream and spread throughout the body. Consequently, birds carry a high concentration of WNV in their blood and are great for transmitting the virus. In addition, most ill birds can be infectious while still being able to fly around happily. Mosquitoes become infected when they feed on infected birds, and these infected mosquitoes proceed to go on and infect even more birds. This increased number of infected birds leads to even more mosquitoes becoming infected; this transmission cycle continues through the spring and summer months. By the middle of the summer, there are huge numbers of infected mosquitos so that humans and other animals become at risk for WNV from being bitten by these mosquitoes. Humans and horses are considered “dead-end” hosts for West Nile Virus because they become, but are not able to create huge amounts of virus in their blood. This makes it hard for us to infect other mosquitoes when they bite us.

© COPYRIGHT 2015 SUTTER-YUBA VECTOR CONTROL DISTRICT

In the United States, West Nile Virus is most prevalent in the late summer months into early fall because by this time a considerable number of mosquitoes have been infected. In addition, warmer weather plays a role in increasing incidence of WNV because heat shortens the incubation period of the virus in mosquitoes. Therefore, in temperate regions of the world, WNV occurs primarily in late summer to early fall, while tropical climates can experience incidences of WNV all year. As of June 16th, 2015, CDC surveillance of WNV activity in the U.S. has shown that the virus has been most active in southern states, including Kansas, New MExico, Oklahoma, and Texas. In 2014 in the U.S., California, Arizona, North Dakota, South Dakota, Nebraska, and Louisiana showed the greatest incidences of West Nile neuroinvasive disease (greater than 1 per 100,000 population). In 2014, the CDC report also seemed to suggest that the East Coast region of the United States had lower rates of incidence of WNV than the Midwest and Southern regions of the country.

In the last blog post, you were also introduced to the history of West Nile Virus, as well as its many consequences on infected humans. You may now be wondering what your risk is for acquiring the disease this summer. Who is at risk for acquiring West Nile Virus? The truth is that since WNV is most commonly transmitted to humans through mosquito bites, anyone that lives in an area where the virus is present in mosquitoes is at risk for being infected. As discussed in the previous post, however, the people who have the greatest risk of being infected are older and immunocompromised individuals. These individuals are not only at greater risk for acquiring the disease, but are also at greater risk for suffering from serious complications of the disease. The main factors that put someone greater risk for developing the more serious form of WNV, West Nile neuroinvasive disease, are also age and immunosuppression; the biggest factor seems to be old age. The incidence rate for neuroinvasive disease among infected individuals increases significantly with age and are greatest for the elderly who are 70 years of age or older (Sejvar, 2003).

WNV Incidence Rate by Age Group by Centers for Disease Control for 2010

The unfortunate thing is that to date, there is no licensed vaccine for use in humans to prevent West Nile Virus infections (Fillette et al., 2012). There is also no specific treatment or antiviral medication for WNV in humans and the only available care is supportive treatment to combat or relieve symptoms. For the more mild symptoms, over-the-counter pain medications can be given for fevers and headaches associated with the virus. The more severe cases of WNV, such as the neuroinvasive diseases, may require further support in the form of hospitalization for intravenous fluids and monitoring (Fillette et al., 2012). Patients that develop WNE usually have to be hospitalized and monitored because they have the potential to develop elevated intracranial pressure or dangerous seizures. For both WNE and WNP, hospitalization and close monitoring by nurses is recommended in case the patient goes into respiratory failure and require ventilator support.

The current lack of a antiviral medicines or vaccinations for WNV make prevention an especially important endeavour for this virus. Prevention of the spread of WNV by mosquitoes is crucial at both the personal level and community level (Fillette et al., 2012). To protect yourself and your family from being infected with WNV, it is important to avoid to implement strategies to avoid your exposure to mosquitoes and risk of being bitten. You can decrease your risk of getting mosquito bites by using mosquito nets and insect repellent, in addition to wearing light coloured clothing, long sleeves, pants, and socks (Fillette et al., 2012). Preventing mosquitoes from entering your home is also helpful for reducing your exposure to infected mosquitoes; to protect your home you can use screen on windows and doors, and turning up the air conditioning to make conditions less desirable for mosquitoes. Eliminating mosquito breeding grounds is also important; mosquitoes can breed in less than 1 inch of water, so it is important to empty standing water around your home (Fillette et al., 2012).

One important aspect of preventing West Nile Virus in the U.S. involves enhanced surveillance to help us more effectively detect the presence of WNV in an area and quickly implement preventative measures that would keep the virus from spreading. Surveillance should monitor the incidence of infection in birds, mosquitoes, and humans. Recognizing the presence of disease in animals like horses and birds is  crucial because it can give us vital clues that a human outbreak will occur in the future (Fillette et al., 2012). There is a vaccine available for horses, so utilizing these vaccines and preventing the transmission of WNV to horses is also important in pretending the spread of the virus. According to the Centers for Disease Control (CDC), the most effective method of preventing the transmission and spread of WNV is through reducing human exposure through mosquito control (Fillette et al., 2012). Implementation and establishment of a larger number of well-equipped state and local health departments focused on mosquito control are currently underway.

Current prevention measures rely heavily on local measures, such as community mosquito control programs (Sejvar, 2003). These programs focus on identifying local mosquito species playing roles in WNV transmission, and implementing active control measures through water management, chemicals, and biological control strategies (Fillette et al., 2012). While it is noted that surveillance of WNV incidence in many different species is helps us understanding disease spread, research has shown that the best way to recognize and halt an outbreak is by frequently monitoring the vector index for WNV. The vector index is the product of the mosquito population size, and the estimated rate of WNV infection in local mosquito populations.  A study analyzing a 2012 outbreak in Dallas, has supported the theory that monitoring mosquito cases of disease and vector index, rather than human cases, was an effective means of predicting future epidemics and allowing early intervention. Through statistical models, the study showed that Dallas public health officials could have prevented 100 cases and 12 deaths if they had monitored the vector index and intervened as soon as the vector index hit the crucial threshold level indicating an epidemic was coming (Fillette et al., 2012).

In addition to frequent monitoring of infected mosquito populations, community mosquito control programs often aim to eliminate mosquito larval habitats and apply insecticides to areas with mosquito larvae or larger densities of infected mosquitoes. Control measures, such as spraying pesticides to kill infected mosquitoes, has been proven to stop further spread of outbreaks in the past. For instance, New York City, New Jersey, and Connecticut were able to successfully stop further spread of the 1999 disease outbreak in this way (Fillette et al., 2012). You can play a role in supporting your community mosquito control programs by helping to report dead birds to local authorities. Reporting dead birds to state and local health departments is crucial for effective monitoring of WNV in your area. These birds need to be tested for the virus and can serve as indicators that West Nile Virus is circulating in a specific area. Helping spread awareness of the importance of these personal preventative measures is another way you can help protect yourself and the community from West Nile Virus outbreaks.

Are we doing a good job of preventing  outbreaks of West Nile Virus in the United States right now and do I think we have a reliable plan in place? Yes and no. I do believe that we are taking necessary steps to develop an effective plan of controlling mosquitoes and transmission of West Nile Virus. There is ongoing surveillance in place to measure the incidences of disease and to help us better understand patterns of how WNV spreads. We have also improved diagnostic techniques that allow us to accurately report WNV and make unequivocal diagnoses of the virus. These are all important steps in the right direction, but I still think that we have a ways to go in terms of efficiently and effectively regulating mosquito transmission and human exposure to WNV. In my opinion, one of the things that needs to be improved is public outreach that educates communities about the disease, how they are transmitted, and how to prevent and reduce risk of exposure. I also think that it would be helpful for more local health infrastructures to be put in place at the state and local levels to address prevention and control of vector-borne diseases. No only should these organizations be in place for surveillance, but I think these agencies need to have access to proper training and equipment that would render them capable of responding to West Nile outbreaks. Since birds migrate and influence the spread of disease at more than just a local level, I believe we could also improve coordination and data exchange between agencies at the local, state, and federal levels. Cooperation and teamwork would give all of these public health agencies a clearer picture of the patterns of WNV transmission around the nation as a whole. Greater cooperation among branches of surveillance, including vector control, agriculture, and wildlife departments, would also help health officials develop more efficient and effective strategies to prevent disease transmission in a variety of hosts. By confronting the issue of transmission from many different angles among many different hosts, I believe we would be most effective in cutting off modes of viral spread.

In addition to improved surveillance measures, I feel that it would be beneficial for researchers to continue in their quest for understanding the mechanisms that allow West Nile Virus to infect and spread so quickly. A better understanding of the virus persistence mechanisms, mosquito behavior, viral pathogenesis, and vector relationships, may enable us to come up with antiviral therapy specifically for WNV. Specifically, understanding the mechanisms that allow WNV to surpass the blood-brain barrier and cause neuroinvasive disease in individuals is important. If we are able to inhibit these mechanisms and decrease the more severe forms of disease from occurring, we would be able to decrease the number of WNV-related fatalities. Development of a vaccine for humans against WNV should also be a research priority, since it would prevent the possibility of outbreaks and eventually provide herd immunity.

References

Filette, M., Ulbert, S., Diamond, M., & Sanders, M. (2012) Recent progress in West Nile Virus diagnosis and vaccination. Vet Res, 43(1), 16

Sejvar, J. (2003). West Nile Virus: A historical Overview. Oschner Journal, 5(3), 6-10

History, Etiology, and Symptoms of West Nile Virus

Ah, summertime. Sunny skies, warm weather...some would argue that it’s the best time of the year. However, the arrival of the summer season also brings along with some pesky guests--mosquitos. We are all familiar with these arthropods that bite us and leave us with red, itchy bumps on our skin. While mosquito bites are usually annoying and harmless, mosquitoes can also carry certain diseases that can be transmitted to other hosts through these bites. Some of these diseases, called arboviruses, can be passed to humans; one of these diseases is West Nile Virus.

Back in 1937, a woman from Uganda became the first documented case of West Nile Virus infection. Prior to 1999, West Nile Virus (WNV) was recognized in Africa, the Middle East, Asia, and some European countries. WNV appeared in North America in 1999, when there was an outbreak of the disease in New York City; it has since spread rapidly throughout the United States, as well as parts of Canada and Mexico (Primer, 2002). The U.S. Centers for Disease Control (CDC) has reported more than 30,000 human cases of West Nile Virus since 1999; outbreaks happen every summer and have occurred in at least 48 states (Primer, 2002). In the United States alone, there was a reported 5,674 cases of West Nile Virus in 2012 and 2,469 reported cases in 2013. These statistics do not include the mild cases of West Nile Viruses that have gone unreported; consequently, West Nile Virus is considered to be the most widespread disease in the flavivirus genus it belongs to. The flavivirus name comes from one of the major diseases classified within this genus: Yellow Fever Virus. In Latin, “flavus” means yellow.  

States reporting epizootic activity and human infection of West Nile Virus from 1999-2001 (Petersen & Marfin, 2002)

So what exactly is West Nile Virus and how is it characterized? West Nile Virus is a plus-sense, single stranded RNA virus that belongs to the Japanese Encephalitis Antigenic Complex of the Flaviviridae family. West Nile Virus has been detected in humans, more than 100 species of birds, as well as other mammals including horses, dogs, and cats. This blog will primarily focus on West Nile Virus and its relationship to humans.

The typical incubation period, or period between exposure to the infection and appearance of symptoms, is typically between 1-6 days although it can be as long as up to 14 days. However, the majority of people infected with West Nile Virus (approximately 80%) do not show any clinical symptoms (Madden, 2003). About 20-30% of infected people develop West Nile Fever and experience mild symptoms, and less than 1% of infected people develop West Nile neuroinvasive disease in the form of West Nile Encephalitis, Meningitis, Poliomyelitis, or Acute Flaccid Paralysis (Madden, 2003).  Around 10% of these cases of West Nile neuroinvasive disease end up being fatal; both the morbidity and mortality rate is higher for individuals older than 50 years of age.

Shives, 2012

For the fortunate middle 20-30% of infected people who develop West Nile Fever, the symptoms are usually so mild that less than 1% of these people actually go to a doctor and are diagnosed. West Nile Fever usually presents as an acute disease, and infected people experience abrupt onset of fever, headache, fatigue, and muscle pain (Madden, 2003). The first symptoms are vague and can also  involve a skin rash on the chest, stomach, and back. Other symptoms of West Nile Fever include nausea, vomiting, diarrhea, and other body aches or joint pains. A person that develops West Nile Fever is expected to make a full recovery, although they might experience some fatigue or weakness for weeks or even months (Madden, 2003). It is safe to say that if you were going to be infected with West Nile Virus and develop clinical symptoms, you would want to develop West Nile Fever as opposed to a neuroinvasive form of the disease.

1 out of 150 people infected with West Nile Virus will experience the severe symptoms of West Nile neuroinvasive disease. Neurological symptoms are exacerbated for individuals that have certain pre-existing medical conditions, including cancer, diabetes, hypertension, and kidney disease. The mortality rate for West Nile neuroinvasive disease is about 10%, and those who do survive are in for a difficult recovery; recovery take several weeks to several months, and some people may experience permanent neurologic effects (Lim et al., 2011). When a person is infected with West Nile Virus, the virus multiplies within the person’s bloodstream. Research suggests that the virus first infects the body’s epidermal and dendritic cells, before migrating to regional lymph nodes for replication (Lim et al., 2011). The virus then spreads throughout the body to other organs, including the kidney and spleen, and continues to replicate. Normally, a blood-brain barrier exists to protect the brain and spinal cord from infection; when the blood-brain barrier (BBB) does its job, the infected person will likely develop no symptoms or West Nile Fever (Lim et al., 2011). In rarer cases, in which the virus is able to cross the BBB, West Nile neuroinvasive disease occurs. This small percentage of people that develop a West Nile neuroinvasive disease experience severe symptoms related to West Nile Meningitis (WNM) or West Nile Encephalitis (WNE).

West Nile Meningitis involves inflammation of the membranes surrounding the brain and spinal cord. Symptoms of WNM involve abrupt onset of fever and severe headaches, as well as gastrointestinal symptoms like nausea, vomiting, and diarrhea (Lim et al., 2011). Dehydration and severity of symptoms sometimes requires hospitalization for pain management. Other serious symptoms include nuchal rigidity, or the inability to flex the neck forward, Kernig’s and Brudzinski’s signs, and sensitivity to light and sounds (Lim et al., 2011). Kernig’s signs involve bending of the thigh at awkward angles, painful extensions of the knee, and body spasms. Brudzinski’s signs include involuntary movements of the leg such as flexion and lifting. This type of West Nile neuroinvasive disease usually has a favorable outcome and infected people recover, although persistent headaches, fatigues, and body aches can remain. West Nile Poliomyelitis (WNP) and Acute Flaccid Paralysis (AFP) are also neuroinvasive forms of West Nile Virus characterized by limb and muscle weakness or paralysis. Some individuals with WNP make full recoveries, while others experience persistent limb weakness or pain (Lim et al., 2011). In severe cases of WNP, infected people can suffer from respiratory failure due to respiratory muscle disruption by the virus. Recovery from the severe forms of WNP are more difficult and are associated with high rates of mortality; those that do survive usually need intensive hospital care for many months.

West Nile Encephalitis, or inflammation of the brain, is the more serious of West Nile neuroinvasive diseases and is most commonly seen in individuals over the age of 55 and immunocompromised individuals (Lim et al., 2011). Symptoms of WNE can range from being mild and involving self-limited states of confusion, to causing severe brain damage, malfunctioning, coma, and death (Lim et al., 2011). Common symptoms of WNE include tremors in the upper extremities, involuntary jerks of the upper extremities and facial muscles, Parkinson’s disease-like decreases in facial expressions, and difficulty with balance and overall body movement. People suffering from WNE can also experience depression, anxiety, and apathy (Lim et al., 2011). The prognosis for WNE varies and depends on the individual, the mortality rate is higher for immunocompromised and older people, and some people also are observed to make full recoveries.

Average annual incidence of West Nile virus neuroinvasive disease by age group and clinical syndrome in the U.S. 2008 by the Centers for Disease Control, 2010

Diagnosing West Nile Virus relies on both clinical symptoms, as well as laboratory tests that can isolate the virus or detect WNV-specific antibodies in a person’s blood or cerebrospinal fluid (CSF) (Sejvar, 2014). Most commonly, antibody testing is used to detect immunoglobulin WNV antibodies, which are detectable from 3-90 days after onset of illness, in blood or CSF. Detection of antibodies can be done through enzyme-linked immunosorbent assays, known as ELISA assays, that measure the concentration of antibodies (Sejvar, 2014). Plaque reduction neutralization tests (PRNTs) are also used to diagnose WNV infections, such as West Nile Meningitis, to detect changes in the amount of WNV-specific antibodies and white blood cells in a person’s blood or CSF. A fourfold or greater change in these antibodies suggests the presence of infection. Methods of isolating West Nile Virus RNA in tissues, blood, or CSF are also used to confirm infection. These methods include viral cultures or reverse transcriptase-polymerase chain reactions (RT-PCR), and immunohistochemistry analyses (Sejvar, 2014).

One of the positive consequences of contracting West Nile Virus is that these antibodies and T-lymphocyte white blood cells produced to fight the infection will stay in your body for a long time. These antibodies and white blood cells will protect you from future infections of the virus and it is currently assumed that you have lifelong immunity after contracting WNV once; however, this immunity does decrease as time since the infection passes. As you can see, West Nile Virus is no joke--it can have mild consequences or cause life-threatening illnesses. If you live in an area where West Nile Virus has been documented in mosquitoes, I hope that you remember the importance of staying protected from mosquitoes this summer. Not only will this protect you from those pesky, itchy mosquito bites, but it could also save your life. The next blog posts will talk more about how to protect yourself from West Nile Virus and prevent its spread, as well as how the disease is transmitted and leads to seasonal outbreaks.

References

Hoenen, A., Gillespie, L., Morgan, G., van der Heide, P., Khromykh, Al, & Mackenzie, J. (2014). The West Nile virus assembly process evades the conserved antiviral mechanism of the interferon-induced MxA protein. Virology, 448, 104-116. doi: 10.1016/j.virol.2013.10.005

Lim, S., Koraka, P., Osterhaus, A., & Martina, B. (2011). West Nile Virus: Immunity and Pathogenesis. Viruses, 3(6), 811-828

Petersen, L., & Marfin, A. (2002). West Nile Virus: A Primer for the Clinician. Annals of Internal Medicine, 137(3), 173-179. doi: 10.736/0003-4819137-3-200208060-00009

Sejvar, J. (2014). Clinical Manifestations and Outcomes of West Nile Virus Infection. Viruses, 6(2), 606-623