Effects of Pathogen-Vector Interactions on the Transmission of Dengue Virus: Difference between revisions

From MicrobeWiki, the student-edited microbiology resource
No edit summary
Line 1: Line 1:
===Effects of Pathogen-Vector Interactions on the Transmission of Dengue Virus===
{{Curated}}
{{Viral Biorealm Family}}
<br>
<br>
==Dengue Virus==
==Types of DENV strains==
[[File:Micrograph of dengue virus.jpg‎|240px|thumb|right|Figure 1. Electron micrograph of dengue virus (DENV).[1]]]
<br>
<br>
<br> Group IV: ss(+)RNA virus
There are multiple ways to classifications DENV srains depending on the context.Dengue viruses maintaining transmission mostly between nonhuman primates and forest dwelling <I>Aedes aegypti</I> are considered sylvatic. It was once thought that sylvatic strains were less virulent than epidemic or endemic strains of DENV. Some believed sylvatic strains lacked the potential to cause virulent epidemics because cases of sylvatic dengue fever are rare when compared to overall incidence of of dengue fever. As it turns out, sylvatic strains share the same pathogenic potential as strains found in urban areas. There are reported cases  dengue hemorrhagic fever from infection with sylvatic DENV. The destruction of forest areas where sylvatic strains of DENV are maintained  has not even lead to a decrease in outbreaks of sylvatic DENV in West Africa [18].
<br> Family: <i>Flaviviridae</i>
<br> Genus: <i>Flavivirus</i>
<br>
[[File:Aedes aegypti.jpg‎|400px|thumb|right|Figure 2. Main vector of dengue virus, <I>Aedes aegypti</I> or the Asian tiger mosquito.[2]]]
<br>
Dengue virus (DENV) is the causative agent of both classical dengue fever, and the more severe manifestations; dengue hemorrhage fever (DHF) and dengue shock syndrome (DSS)[4]. It is most commonly transmitted by the mosquito vector <I>Aedes aegypti</I> as seen in figure 2, but can be transmitted by other members of the genus <I>Aedes</I> including <I>Aedes albopictus</I>[5]. There are four different serotypes of dengue virus (DENV 1-4). Infection with one serotype affords life-long immunity to that serotype but only partial (heterologous) immunity to other serotypes for a short period of time post-infection. After initial protective immunity the risk of developing DHF or DSS upon reinfection strain from a different serotype increases.
<br><br>
<br><br>
This increased risk for  severe dengue is the result of antibody-dependent enhancement of viral infection. Host heterotypic non-neutralizing antibodies from previous DENV infection bind DENV virions. After recent DENV infection there are enough antibodies to neutralize any new dengue viruses but overtime the number of neutralizing antibodies drops. At some point there are so few enough antibodies left that upon reinfection with a new strain the anitbodies can bind but not nuetralize the virus. The constant region of the antibody can go on to bind a FcγR receptor on the surface of a number of different types of immune cells.Normally, when a pathogen-antibody complex binds to a FcγR receptor a cytoxic or phagocytoic response initiated by the immunne cell. DENV somehow avoids this response and instead binds its host cell surface receptor with unbound E protiens and infects the cell as seen in figure 3.
Epidemic and endemic DENV strains infect and replicate within humans and domesticated <I>Aedes</I> species [9].  
<br>
The distinction between epidemic and endemic dengue has become hazy as epidemic strains of DENV have become endemic in tropical urban slums. In areas where there is poor sanitation, free standing water, high population density, and constant human traffic allow continuous  transmission of the virus (Figure 1)[4,8]. Epidemic strains of DENV are best transmitted by <I>Aedes ageypti</I> mosquitoes but can be transmitted less efficiently by other <I>Aedes</I> species and cause[19]. Epidemic strains can also produce large fast moving epidemics if a number of factors create high density vectors populations in close proximity to high density host populations [20].
[[File:AD enhancement figure.jpg‎|600px|thumb|center|Figure 3. Antibody-dependent enhancement of DENV infection, adapted from Takada and Kawaoka, 2003. [3]]]
<br>
The FcγR receptors are effect in controlling other pathogens but DENV has evolved to exploit this pathway. The FcγR receptor is not needed for DENV entry but does increase infectivity DENV and allows the virus display cell tropisms not seen in primary DENV infection. With more cells infected more viroins are produced leading to higher levels of viremia in the blood which is correlated with increased risk for DHF and DSS.
increase infectivity of the virus in immune cells by increasing overall viral load within the patient. Higher levels of viremia are associated with incresed the risk of DHF and DSS [3,?]
<br><br>
<br><br>
Within serotypes dengue viruses are organized by genotypes, subtypes, clades, variants, groups and finally strains [3]. The large number of dengue strains in the world combined with only partial crossover immunity to other strains makes concurrent (multi-strain) infections or reoccurring dengue infections possible (just like repeated bouts of the flu), especially in areas with high prevalence of DENV.
?????????Innvassive species are defined as newer genotypes and strains not previously seen in a particular area or geographic region. They tend to cause large epidemics because the population in that area does not have homologous immunity to the virus. Noninvasive species are strains that have been present for some time and continue to be tranmissted to new susceptible hosts in the area. They can be thought of more as endemic strains. Invassive species can be more virulent than noninvassice strains but this is dependent on host population susceptibility which depends on what other strains of DENV are circulating at the time. Superinfection of the same vector can decrease overall titers of both infecting strains (asymmetric competitive suppression) and if the innvassive strain is less competitive/virulent than existing dengue strains in may not be able to colonize that geographic area (asymmetric as well as selection for dengue).
<br><br>
<br><br>
Dengue viruses are now endemic in many tropical parts of the world putting about a third of the world’s population at risk of infection. There are estimated to be over one hundred million new infections per year and rising [5,6]. Rising rates of infection are the result of reduced multiple factors that affect vector population and range. vector control in areas that need it most has been cutback and global warming has expanded vector ranges to areas previously DENV free. Milder winters at higher latitudes are allowing adult and larvae mosquitoes to survive longer into the fall and return earlier in the spring allowing the DENV transmission cycle to continue throughout a greater part of the year than in the past. DENV is becoming a threat to industrialized nations once thought to be too far away from the tropics for Dengue fever to be a threat. In the U.S. the number of indigenous dengue cases is rising. In Brownsville Texas, 25% of the residents who had never traveled outside the united states had antibodies indicating prior exposure to a strain of DENV that had to have been maintaining a transmisssion cycle in that are for quite some time [6,7].
[[DENVsuperinfection.jpg|400px|thumb|center|Figure ?. Simplified epidemiological triad for dengue virus transmission. Note the number of factors that influence DENV replication in mosquito vector.]]
<br><br>
<br><br>
The severity of dengue infection also continues to increase. The ratio of dengue DHF and DSS cases to classical dengue fever have increased dramatically over the past sixty years. It has become the leading cause of hospitalization and death in children in several endemic countries [7].
Two of the most common types of genotypes mentioned in the literature are America and Southeast Asian. They are commonly compared because of known differences in virulence genotype which allows researchers to look for differences in replication, infectivty and other factors that may explain why certain strains of DENV are worse than others. American genotypes tend to be less virulent as well as less competitive than Southeast Asian strains (selection for dengue viruses in humans and mosquitoes). In both mosquitoe and human dendritic cells Southeast Asian genotypes have higher rates of replication than American genotypes resulting in higher viral titers in humans….uhhhh
<br>
 
==Dengue Shock Syndrome and Dengue Hemorrhagic  Fever==
[[File:Dengue_hemorragic_fever.jpg‎|400px|thumb|right|Figure 4. Ecchymosis (bleeding under the skin) associated with dengue hemorrhage fever.[6]]]
Although classical dengue fever is not usually fatal it has very high morbidity; its alternate name is break-bone fever because of the severe joint pain during infection. DENV infection is most common in infants, young children, and adults. Classical dengue fever manifests as a mild to high fever with red rash, debilitating headaches, muscle and joint pain.
<br><br>
<br><br>
The more severe manifestations of the disease are dengue hemorrhage fever and dengue shock syndrome. Young children and those with antibodies from previous DENV infection are most at risk for these complications because of antibody-dependent enhancement of infection[5].
[[File:Viral output DCs.jpg|400px|thumb|center|Figure ?. Virus output for American and Southeast Asian genotypes in various dendritic cell donors. 7 American genotype strains and 12 Southeast Asian genotypes. Viral output was defined as the number of genome equivalents in the supernatant of the culture (number of virions that budded out of the host cell) divided by the number of host cells in culture.]]
<br><br>
<br><br>
Dengue shock syndrome results from DENV infection of the endothelial cells lining the blood vessel [17]. When these cells become damaged the integrity of the blood vessels is compromised and plasma leaks out, causing a host of systemic problems including edema and hypotenstion. The swelling of tissue because plasma escaping the circulatory system (edema) causes abdominal pain. Hypotension is a drop in blood pressure that results from a drop in total blood volume from plasma loss. Edema and hypotension both impede proper circulaton.Oxygen and nutrients stop reaching the body's tissues possibly leading to shock and death [6].
Southeast Asian genotypes also outcompete American genotypes when coninfecting mosquito hosts by replicating and disseminating to the salivary glands faster.
<br><br>
<br><br>
Dengue hemorrhage fever occurs when normal blood coagulation is disrupted by infection. Fever, emesis (vomiting), and hemorrhaging (bleeding) are all symptoms common to this type of dengue infection[5]. The results of internal hemorrhaging are visible on the skin in the form of tiny red spots (petechiae) or sometimes patches under the skin (ecchymosis)as seen in figure 4. As well as bloody stool (feces) and bleeding from the gums and nose (Figure 3)[5]. Mortality from these complications can be up to 14% without proper care [4].
[[File:Table2coinfection.jpg|400px|thumb|center|Figure ?. explain from selection for dengue strains. Etc..[DHF has link]]
<br><br>
<br><br>
Unfortunately there are no anti-viral drugs for DENV infection. The only treatment is supportive care in the form of fluid replacement and pain management [5]. With no licensed vaccine, disruption of the vector-host transmission cycle is the only form of disease control.
[[File:Beware_of_bite.jpg|600px|thumb|right|Figure 5. Beware of the Bite; poster warning residents to avoid mosquito bites in areas with high prevalence of dengue fever.[11]]]
<br><br>
Controlling the transmission of dengue virus is simple but labor-intensive and costly. In the past heavy pesticides such as DDT were used to wipe out mosquito populations, but this has fallen out of favor as the environmental toxicity of pesticides has come to light [7]. Nowadays, active disease control centers around public health campaigns that urge citizens to get rid of standing water in and around their homes and seek treatment if they have dengue fever-like symptoms. Use of insect repellents to is also encouraged as to reduce risk of mosquito bite, as inferred in figure 5.
Current DENV education campaigns and vector control programs are not as cost-effective as other public programs and this has led to a decrease in government funding over the years in areas that need it most. In an attempt to make vector control programs more efficient, researchers are trying to understand the complexities of dengue virus replication in mosquito vectors. Coinfection of the mosquito vector with multiple DENV strains or the bacterium <I>Wolbachia</I> and interactions between DENV and the vector’s immune system all modulate viral replication within the vector.The replication kinetics of DENV in the vector-host have  because of its overreaching effects on the epidemiology of the disease [5].With a better understanding of how each of these factors affects the overall viral load and rate of viral replication with in the vector, it will be possible to come up with better strategies for vector transmission control and prevention as well as the mitigation  of future DENV epidemics (figure DENV triangle).
[[File:Dengue epidemiology triangle.jpg|900px|thumb|center|Figure ?. Simplified epidemiological triad for dengue virus transmission. Note the number of factors that influence DENV replication in mosquito vector.]]
<br>

Revision as of 16:41, 7 December 2010


Types of DENV strains


There are multiple ways to classifications DENV srains depending on the context.Dengue viruses maintaining transmission mostly between nonhuman primates and forest dwelling Aedes aegypti are considered sylvatic. It was once thought that sylvatic strains were less virulent than epidemic or endemic strains of DENV. Some believed sylvatic strains lacked the potential to cause virulent epidemics because cases of sylvatic dengue fever are rare when compared to overall incidence of of dengue fever. As it turns out, sylvatic strains share the same pathogenic potential as strains found in urban areas. There are reported cases dengue hemorrhagic fever from infection with sylvatic DENV. The destruction of forest areas where sylvatic strains of DENV are maintained has not even lead to a decrease in outbreaks of sylvatic DENV in West Africa [18].

Epidemic and endemic DENV strains infect and replicate within humans and domesticated Aedes species [9]. The distinction between epidemic and endemic dengue has become hazy as epidemic strains of DENV have become endemic in tropical urban slums. In areas where there is poor sanitation, free standing water, high population density, and constant human traffic allow continuous transmission of the virus (Figure 1)[4,8]. Epidemic strains of DENV are best transmitted by Aedes ageypti mosquitoes but can be transmitted less efficiently by other Aedes species and cause[19]. Epidemic strains can also produce large fast moving epidemics if a number of factors create high density vectors populations in close proximity to high density host populations [20].

?????????Innvassive species are defined as newer genotypes and strains not previously seen in a particular area or geographic region. They tend to cause large epidemics because the population in that area does not have homologous immunity to the virus. Noninvasive species are strains that have been present for some time and continue to be tranmissted to new susceptible hosts in the area. They can be thought of more as endemic strains. Invassive species can be more virulent than noninvassice strains but this is dependent on host population susceptibility which depends on what other strains of DENV are circulating at the time. Superinfection of the same vector can decrease overall titers of both infecting strains (asymmetric competitive suppression) and if the innvassive strain is less competitive/virulent than existing dengue strains in may not be able to colonize that geographic area (asymmetric as well as selection for dengue).

400px|thumb|center|Figure ?. Simplified epidemiological triad for dengue virus transmission. Note the number of factors that influence DENV replication in mosquito vector.

Two of the most common types of genotypes mentioned in the literature are America and Southeast Asian. They are commonly compared because of known differences in virulence genotype which allows researchers to look for differences in replication, infectivty and other factors that may explain why certain strains of DENV are worse than others. American genotypes tend to be less virulent as well as less competitive than Southeast Asian strains (selection for dengue viruses in humans and mosquitoes). In both mosquitoe and human dendritic cells Southeast Asian genotypes have higher rates of replication than American genotypes resulting in higher viral titers in humans….uhhhh

Figure ?. Virus output for American and Southeast Asian genotypes in various dendritic cell donors. 7 American genotype strains and 12 Southeast Asian genotypes. Viral output was defined as the number of genome equivalents in the supernatant of the culture (number of virions that budded out of the host cell) divided by the number of host cells in culture.



Southeast Asian genotypes also outcompete American genotypes when coninfecting mosquito hosts by replicating and disseminating to the salivary glands faster.

File:Table2coinfection.jpg
Figure ?. explain from selection for dengue strains. Etc..[DHF has link



Retrieved from "https://microbewiki.kenyon.edu/index.php?title=Effects_of_Pathogen-Vector_Interactions_on_the_Transmission_of_Dengue_Virus&oldid=56354"