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This week I am introducing another arbovirus: West Nile virus. If you remember from the series on dengue fever, an arbovirus is an arthropod-borne virus. The relevant arthropod for West Nile virus (WNV) is once again a mosquito, and the virus is once again a Flavivirus. Wondering where the name Flavivirus comes from? Well, flavus is Latin for yellow. The Flaviviruses are named after the virus that causes yellow fever, which is also, of course, a Flavivirus. Yellow fever, when it presents as clinically severe, can cause jaundice due to liver damage. And, thus we get the name yellow fever, whose "yellow" virus name was subsequently shared with all the Flaviviruses (though not all Flaviviruses cause jaundice).
So, West Nile virus. This is a single-stranded RNA virus that is transmitted, generally, though not exclusively, by the bite of Culex mosquitoes. This is a new genus of mosquito we have not discussed before, but some of the unique aspects of its ecology will be described below. Here is a look at the virus:
There are two major lineages of this virus, though a few others do exist. Lineage 1 has a wide range across the Middle East, parts of Africa, eastern Europe, North America, and Australia. Lineage 2 viruses are present in sub-Saharan Africa and Madagascar. The Lineage 1 viruses are associated with the greatest pathogenicity in humans, whereas the Lineage 2 viruses typically are asymptomatic or are associated with mild disease in humans. The spread of WNV into the western hemisphere, which began in New York in 1999, is due to Lineage 1.
The virus was first identified in 1937 in the West Nile district of Uganda, but during this time was considered a minor concern because it was typically asymptomatic, occasionally causing minor illness in humans.
However, in subsequent decades WNV began to be identified with more far reaching sporadic outbreaks of mortality in horses and encephalitis in humans in South Africa, India, the Middle East, and Europe. This map from the Center for Disease Control and Prevention (CDC) shows the global distribution of WNV in 2000 in blue. Notice New York newly represented here:
The sporadic nature of WNV across this large geographic region in the eastern hemisphere has been consistent over much of its epidemiologic history there, and continues in this way today. On the other hand, the pattern of virus spread has been quite dramatic in North America. Annual epidemics occurred in increasing areas of geographic space, moving from east to west with chronological time, since it's introduction in 1999. This sequence of CDC maps shows the westward spreading distribution of WNV in the US:
This series of maps shows quite dramatically the rapid spread of WNV across the US, which is in contrast to the pattern in Africa, the Middle East, and Europe where localized sporadic activity following favorable conditions has been the norm.
What could have led to this dramatic difference in the spread of the virus in these two distinct geographic regions? We also have to ask, IS there a difference, or was the western hemisphere simply comprised of entirely naive populations, such that the spread in North America appears more dramatic? Or can differences in pattern emergence be attributed to differences in surveillance?
Let's first look more specifically at who and what the virus infects, the disease it can cause, and the vector ecology that is important to transmission.
Birds serve as the primary hosts for WNV. While humans and horses are commonly infected, the avian hosts are able to maintain levels of viremia high enough to infect new mosquito vectors. Humans and horses can become infected and develop disease, but their viremia is generally too low to infect new mosquitoes so they are "dead end hosts" for the virus. Therefore, birds are the reservoir for WNV. Moreover, both migratory and non-migratory birds can serve as hosts for WNV, with the former obviously creating the potential for wide geographic distribution of the virus as long as a suitable vector is also present across the migratory landscape.
In humans, infection with WNV is most often asymptomatic. The low viremia established in humans following infection may be related to this low pathogenicity, however this is uncertain. Nevertheless, aymptommatic infection in humans is not a concern for future transmission of the virus because, as mentioned earlier, the viremia is too low to infect biting mosquitoes. Among infected individuals that do demonstrate symptoms, the presentation is typically a flu-like illness with fever, headache, myalgia, and sometimes diarrhea and vomitting. Most of these patients will recover in 7 to 10 days. However, about 1 person of every 150 infected will develop severe neuroinvasive disease. This condition can be classified into three, non-mutually exclusive, syndromes: encephalitis, meningitis, and acute flaccid paralysis. The highest neurologic complications and the greatest mortality are associated with the occurrence of encephalitis, which is an inflammation of the brain. Encephalitic complications can include headache, drowsiness, mental confusion, loss of memory, and convulsions. This map based on CDC surveillance illustrates the incidence of WNV neuroinvasive disease in 2010:
There is a very important risk factor associated with increased risk for severe WNV infection: AGE. This graph published by the CDC's Morbidity and Mortality Weekly Report in July of 2010 demonstrates this relationship nicely:
This week I am introducing another arbovirus: West Nile virus. If you remember from the series on dengue fever, an arbovirus is an arthropod-borne virus. The relevant arthropod for West Nile virus (WNV) is once again a mosquito, and the virus is once again a Flavivirus. Wondering where the name Flavivirus comes from? Well, flavus is Latin for yellow. The Flaviviruses are named after the virus that causes yellow fever, which is also, of course, a Flavivirus. Yellow fever, when it presents as clinically severe, can cause jaundice due to liver damage. And, thus we get the name yellow fever, whose "yellow" virus name was subsequently shared with all the Flaviviruses (though not all Flaviviruses cause jaundice).
So, West Nile virus. This is a single-stranded RNA virus that is transmitted, generally, though not exclusively, by the bite of Culex mosquitoes. This is a new genus of mosquito we have not discussed before, but some of the unique aspects of its ecology will be described below. Here is a look at the virus:
There are two major lineages of this virus, though a few others do exist. Lineage 1 has a wide range across the Middle East, parts of Africa, eastern Europe, North America, and Australia. Lineage 2 viruses are present in sub-Saharan Africa and Madagascar. The Lineage 1 viruses are associated with the greatest pathogenicity in humans, whereas the Lineage 2 viruses typically are asymptomatic or are associated with mild disease in humans. The spread of WNV into the western hemisphere, which began in New York in 1999, is due to Lineage 1.
The virus was first identified in 1937 in the West Nile district of Uganda, but during this time was considered a minor concern because it was typically asymptomatic, occasionally causing minor illness in humans.
However, in subsequent decades WNV began to be identified with more far reaching sporadic outbreaks of mortality in horses and encephalitis in humans in South Africa, India, the Middle East, and Europe. This map from the Center for Disease Control and Prevention (CDC) shows the global distribution of WNV in 2000 in blue. Notice New York newly represented here:
The sporadic nature of WNV across this large geographic region in the eastern hemisphere has been consistent over much of its epidemiologic history there, and continues in this way today. On the other hand, the pattern of virus spread has been quite dramatic in North America. Annual epidemics occurred in increasing areas of geographic space, moving from east to west with chronological time, since it's introduction in 1999. This sequence of CDC maps shows the westward spreading distribution of WNV in the US:
1999
2000
2001
2002
2003
2004
2005
2006
This series of maps shows quite dramatically the rapid spread of WNV across the US, which is in contrast to the pattern in Africa, the Middle East, and Europe where localized sporadic activity following favorable conditions has been the norm.
What could have led to this dramatic difference in the spread of the virus in these two distinct geographic regions? We also have to ask, IS there a difference, or was the western hemisphere simply comprised of entirely naive populations, such that the spread in North America appears more dramatic? Or can differences in pattern emergence be attributed to differences in surveillance?
Let's first look more specifically at who and what the virus infects, the disease it can cause, and the vector ecology that is important to transmission.
Birds serve as the primary hosts for WNV. While humans and horses are commonly infected, the avian hosts are able to maintain levels of viremia high enough to infect new mosquito vectors. Humans and horses can become infected and develop disease, but their viremia is generally too low to infect new mosquitoes so they are "dead end hosts" for the virus. Therefore, birds are the reservoir for WNV. Moreover, both migratory and non-migratory birds can serve as hosts for WNV, with the former obviously creating the potential for wide geographic distribution of the virus as long as a suitable vector is also present across the migratory landscape.
In humans, infection with WNV is most often asymptomatic. The low viremia established in humans following infection may be related to this low pathogenicity, however this is uncertain. Nevertheless, aymptommatic infection in humans is not a concern for future transmission of the virus because, as mentioned earlier, the viremia is too low to infect biting mosquitoes. Among infected individuals that do demonstrate symptoms, the presentation is typically a flu-like illness with fever, headache, myalgia, and sometimes diarrhea and vomitting. Most of these patients will recover in 7 to 10 days. However, about 1 person of every 150 infected will develop severe neuroinvasive disease. This condition can be classified into three, non-mutually exclusive, syndromes: encephalitis, meningitis, and acute flaccid paralysis. The highest neurologic complications and the greatest mortality are associated with the occurrence of encephalitis, which is an inflammation of the brain. Encephalitic complications can include headache, drowsiness, mental confusion, loss of memory, and convulsions. This map based on CDC surveillance illustrates the incidence of WNV neuroinvasive disease in 2010:
There is a very important risk factor associated with increased risk for severe WNV infection: AGE. This graph published by the CDC's Morbidity and Mortality Weekly Report in July of 2010 demonstrates this relationship nicely:
Number of incident cases of neuroinvasive disease per 100,000 population in 2009
Back to the vector. It's another mosquito. Mosquitoes do not serve as the exclusive vectors for WNV, but they are, by far, the most important for bird, and, likewise, human transmission. The genus of primary importance for WNV transmission is Culex, and the important species are Culex pipiens in the eastern United States and Culex tarsalis in the west.
Culex mosquito taking a blood meal
Culex mosquitoes seek out dirty water for oviposition, and lay their eggs on the water's surface in the form of an egg raft. With respect to ovipositioning, Culex mosquitoes are not dissimilar from the Aedes mosquitoes in that they both seek out water rich in decayed nutrients (i.e. dirty) for their developing larvae. However, Culex mosquitoes bite primarily at night, and also during the dusky times of dawn and sunset, whereas Aedes mosquitoes bite throughout the day. Both mosquito genera are well adapted to anthropogenic settings and therefore do well in urban areas in and around human habitation.
Culex life cycle
Another difference between Culex and Aedes mosquitoes is their host preference. While Aedes mosquitoes prefer humans, the Culex species are ornithophilic, meaning they prefer bird species. This has two important implications for their ability to act as a vector in human disease. First, if appropriate and sufficient bird populations are available, these mosquitoes will seek their blood meals primarily from the birds, meaning they will have less contact with humans and thus less opportunity to transmit the virus to this secondary host. Second, since birds serve as the reservoir for WNV, the virus is amplified in birds thus providing a consistent source of reinfection to mosquitoes, who can subsequently reinfect other birds, or humans.
Alameda County Vector Control Services
Ok, we've talked about the West Nile virus, the disease it can cause, and the mosquito vector that can transmit it. There is still a critical element that is essential to the etiology of this disease: the environment, and more specifically, the weather.
As described so far, the virus needs two things to maintain itself in host populations: birds and mosquitoes. The reservoir and the vector, respectively. There are other arthropod vectors that can transmit WNV, but mosquitoes are the most important for maintaining the virus, so we limit this discussion to the mosquito vector. So, birds and mosquitoes. As you would, perhaps, expect, both the reservoir and the vector are highly attuned to particular ecologies. One universal necessity to both birds and mosquitoes is water. Water is essential for both to maintain healthy populations. However, birds and mosquitoes utilize water for different purposes, and when water and temperature interact, ecologies can change, resulting in a change in each's ability to maintain its populations. For example, during periods of increased heat combined with decreased precipitation, drought can ensue. This kind of interaction between temperature and precipitation can disturb bird ecology such that birds are forced to leave the area to find better water sources in different geographic landscapes. At the same time, as water sources are dried up, they become more concentrated with organic matter, i.e. more polluted, which is favorable to the culicine mosquitoes. In addition, these mosquitoes can often find suitable water conditions in and around human habitation even during times of drought. Therefore, drought conditions can reduce the the availability of preferred bird species, while at the same time maintain mosquito populations as long as the drought is not so extensive as to eliminate all water sources entirely. If mosquitoes are able to maintain their populations in a local geographic region while the birds are not, then the mosquitoes will be forced to find alternative hosts for their blood meals. Thus, humans and horses can become targets and subsequently acquire WNV infection.
There are a number of studies in the WNV literature that have shown that dry times in temperate regions lead to increased occurrence of WNV infection in humans. However, there are also studies showing positive associations between increased precipitation and the subsequent occurrence of infection. However this direct relationship is typically shown when precipitation is considered in combination with increased temperature. So the sensitivities of birds may be to precipitation, or they may be to temperature. Likely there is an important interaction between the two that is involved in bird ecology and which determines bird species' localized geography from one season to the next. Nevertheless, there is strong evidence to suggest the spatial movement of birds, and specifically the ability of bird species favored by Culex mosquitoes to exploit a particular localized ecological niche from season to season, plays an important role in human incidence of WNV infection from season to season. Accomplished parasitologist and medical ecologist, Dickson Despommier, has written extensively on the balance between birds and mosquitoes acting in the etiology and epidemiology of WNV. He has an excellent presentation at here.
The situation as it has evolved in the United States is interesting. From 1999 through 2006 the virus was able to move farther west with each season. This pattern of movement is due to a complete causal mechanism, all the components of which we do not yet understand. Nevertheless, there are some factors that are likely components in this causal mechanism. The movement of birds is a distinct phenomenon that has undoubtedly played a role. As described above, the changing distribution of bird species according to variation in weather can leave alternate host populations, such as humans, more available. In addition, migratory birds can play an important role in moving WNV across large distances simply by way of their natural seasonal trajectories across geographic space. There is also the possibility of westward mosquito migration. Culex mosquitoes are capable of traveling up to a kilometer per day making them additional potential disseminators of WNV across a shifting landscape.
While WNV was introduced into the northeastern US, the current annual epidemic peaks are occurring in the drier western climates of the US, which is consistent with what we discussed above about the scarcity of favored bird species in such conditions:
The arid west and southwest are more likely to experience regular periods of diminished precipitation, which could lead to a settled equilibrium of endemicity in this region of the country.
WNV persistence in the southwest may also be affected by the mortgage crisis during the last few years, which has left very many homes foreclosed, and containers (and pools) abandoned to collect rainwater. Indeed, a study published by the CDC in Emerging Infectious Diseases examined this relationship in Kern County, California, finding that these pools naturally served as excellent egg sites for Culex mosquitoes leading to an increase in WNV cases nearly three times what would normally be expected. Nevertheless, while these localized conditions may be contributing to WNV incidence in a short period of time, it is unlikely that this will be a major factor in the long-term establishment of WNV in the US. Climate factors, and climate change, are much more likely to play a role as temperatures increase, and we continue to experience wild fluctuations in levels of precipitation. These will undoubtedly affect bird ecology, mosquito ecology, and human ecology, and will therefore affect the disease ecology of WNV.