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In Somalia, a mosquito bite that results in diseases and infections are very common. One of the mosquito-borne infections that occur often in Somalia results from Dengue Virus. The Dengue virus is an arbovirus that is transmitted to humans and non-human primates by the mosquito Aedes aegypti. The Dengue virus is a mosquito-borne infection that makes millions of people living in the tropical and sub-tropical region at risk for developing the virus and its severe symptoms. It is endemic in more than 100 countries throughout the world, therefore, making it a global concern. The dengue virus is an RNA virus that has four different serotypes. The four dengue serotypes each have the ability to cause disease, the fact its many serotypes makes treatment and vaccine development difficult because the vaccine needs to be effective against all serotypes in order to have immunity against the Dengue virus. The dengue virus topics that will be discussed are the following: the classification & structure of the virus, the life cycle, the disease, the treatment, and the public health impact of the virus. (http://www.who.int/mediacentre/factsheets/fs117/en/index.html)
The Dengue virus is classified as a Baltimore class 4 and positive ssRNA virus. The virus is in the Family Flaviviridae, the Genus Flavivirus (Virology lecture). The virus structure is an enveloped virus about 50nm; it has M protein, E protein, and capsid protein with11kb genome around it. The Dengue virus has two types of proteins structural and nonstructural. The structural proteins are the (capsid) C protein, the (membrane) M protein, and the (envelope) E protein. The Capsid protein is involved in packaging the viral genome into the nucleocapsid. The M protein is a glycoprotein that is cleaved during particle maturation and is expressed as prM. The E protein is a glycoprotein that has the receptor-binding site and fusion peptide. The non structural proteins consist of the following: NS1, NS2A, NS2B, NS3, NS4A, 2K, NS4B, and NS5. The NS1, NS2A, NS4A, 2K, and NS4B proteins might have a role in the replication of RNA, but for the most part their function is unknown. The protein NS2B functions as a cofactor for Serine Protease. The protein NS3 functions in Serine Protease as well as RNA helicase. The protein NS5 is involved with RNA dependent RNA polymerase (http://www.ncbi.nlm.nih.gov/genomes/VirusVariation/dengue_help.html).
The reproduction strategy of Dengue Virus is to have the female Aedes mosquito transmit the virus to the human via a bite, and then the infected person has the virus circulating throughout their blood for about 2-7days, resulting in a fever and the other symptoms associated with Dengue virus. The mosquito acquires Dengue from feeding on the blood of an infected person during the incubation period it then develops the ability to transmit the virus for the rest of its life (http://www.who.int/mediacentre/factsheets/fs117/en/index.html). The lifecycle of the Dengue virus starts with the enveloped virus attaching to receptors with the E protein. The virus then enters via endocytosis. The uncoating step takes place when the low pH cause fusion, which then proceeds to the release of genomic RNA into the cytoplasm. The RNA is then translated into a polyprotein that develops into mature structural protein (capsid, membrane, and envelope) and non-structural (NS) proteins. The replication step occurs when a (-) strand is made by the RNA dependent RNA polymerase (http://www.ncbi.nlm.nih.gov/genomes/VirusVariation/dengue_help.htm). The Assembly step occurs when prM associates with E Protein along with C protein inside the membrane, and then encapsidation/envelope formation occur. Then during egress the prM is cleaved by furin and then exocytosis occurs (Virology lecture). The cell tropism for Dengue virus in an autopsy and In Vitro studies show that the immune system, the liver, and the endothelial cells lining the blood vessel have a role in the pathogenesis of Dengue Hemorrhagic fever or Dengue Shock syndrome (Martina, Koraka, and Osterhaus).The immune system plays a role because when the mosquito bites, the virus is not only injected into the bloodstream but also on the skin surface, which results in an infection in the epidermal dendritic cells and keratinocytes. The virus then travels to the lymph nodes and is distributed throughout the lymphatic system resulting in a primary viremia, and for the monocytes, the myeloid dendritic cell, the spleen, and the liver macrophages to become infected (Martina, Koraka, and Osterhaus). The liver is generally involved in Dengue infections, because there might be a connection between the enzyme level in the liver and the blood patterns during an infection. The endothelial cells in a person infected with Dengue have varying activation arrangements in different tissues (Martina, Koraka, and Osterhaus).
The pathogenesis of Dengue virus is that it causes Dengue fever, Dengue Hemorrhagic fever (DHF), or Dengue shock syndrome (DSS). The Dengue virus has four different serotypes. The four serotypes are the following: DEN-1, DEN-2, DEN-3, and DEN-4. When an infection occurs the antibodies produced are serotype-specific to the one that caused the primary infection. An infection with one serotype of Dengue virus does not provide immunity against the other serotypes (Tolle, A. Michael). When another infection with a dengue serotype that is different from the first infection occurs, the antibodies that are present are not able to neutralize the new serotype, so they form antibody-virus complex. The complexes then bind to the receptor on the mononuclear cells to improve "dengue virus uptake, replication in macrophages, and to release vasoactive mediators" this method is called the antibody-dependent enhancement (Tolle, A. Michael). The antibody -dependent enhancement leads to the hemorrhage and vascular permeability and is responsible for severe dengue like Dengue Hemorrhagic fever and Dengue Shock Syndrome. The symptoms vary among the types of Dengue infection. The symptoms for Dengue fever are the following: headache, rash, myalgia, arthralgia, retro-orbital pain, hemorrhagic manifestation, and leucopenia. (Tolle, A. Michael). The symptoms for the Dengue Hemorrhagic fever are the following: fever/acute fever for 2-7days, petechiae, ecchymosis, bleeding from mucosa, hematemesis, and plasma leakage (Tolle, A. Michael). The symptoms for the Dengue Shock Syndrome are the following: rapid and weak pulse, narrow pulse pressure, hypertension, cold, clammy skin, and restlessness (Tolle, A. Michael). The long-term consequences of Dengue virus varies, because it depends on the infected person. In dengue fever, the younger children may get a rash and fever, whereas the older person may get a fever and more of the pain-related symptoms. The dengue fever infections usually clears and do not result in further complications or death. In Dengue Hemorrhagic fever, the symptoms can eventually clear after the fever clears or there can cause complications like, an enlarged liver, convulsions, failure of circulatory, a state of shock, or death (http://www.who.int/mediacentre/factsheets/fs117/en/index.html).
In a dengue virus infection, the immune system may have a role in the pathogenesis of virus rather than clearing the viral infection by the immune system. For example the complement system is a part of the innate immunity and it's first in helping to clear the pathogens before the adaptive immunity. The investigators observed that when plasma leakage takes place, the complement components like C3a and C5a were reduced in people with Dengue Shock Syndrome, therefore, the complement activation help in the pathogenesis of Dengue (Martina, Koraka, and Osterhaus). The role of CD8 T-cells is not entirely understood, but it is believed that it helps with clearing infection and immunopathogenesis. The reason why T-cells have such different response is because the memory T-cell can provide immunity to serotypes that it already have a primary infection with and cause pathogenesis in the serotypes that the person does not have immunity against (Martina, Koraka, and Osterhaus).
The Dengue virus does not have an exact method of treatment or a vaccine currently to protect against Dengue, but there are vaccines in development. There are two vaccines that are being tested on human subjects in areas where the virus is endemic. The reason why the development of the vaccine is taking a lot longer than other mosquito-borne diseases are the following: "There are four different dengue serotypes capable of causing disease and the vaccine must be able to provide immunity against all the serotypes, the behavior of the virus and the way it works with the immune system is not quite understood, and the lab does not have animal models to test the vaccines and their immune responses" (http://www.who.int/mediacentre/factsheets/fs117/en/index.html).
The prognosis for the Dengue virus is that the symptoms associated with the virus such as fever, hemorrhagic manifestations, and headache will continue because there is no actual treatment available for those that are infected, unless they identify the symptoms early. The Dengue fever may be treated with antipyretics, analgesics, and supportive care to clear the infection (Tolle, A. Michael). In severe dengue the Prognosis depends on the early recognition and immediate treatment of shock, and when careful the risk for mortality is greatly reduced (Tolle, A. Michael). The preventative methods for Dengue infections is mosquito control such as not allowing Aedes aegypti breeding grounds in sitting water, old infrastructure, tires, and cans. Some other preventative methods are using insect repellant (DEET), wearing long clothing, and having bed nets (Virology lecture).
The Dengue virus demographic for infection is people living in tropical and sub-tropical areas are at risk and endemic countries like in Africa, Americas, Eastern Mediterranean, South-east Asia, and Western Pacific. A very large portion of those infected with Dengue Hemorrhagic fever are children. The factors that make the populations susceptible to the virus and for it to spread is the fact that dengue has four different serotypes and their vectors. Some dengue types are more virulent than other, for example South-east Asia was first known to have high virulent types of dengue (Tolle, A. Michael). The rise in mosquito coming into contact with people also makes populations more susceptible because the mosquitoes have breeding sites near the homes in sitting water and waste that is not properly contained. These factors contribute in making dengue virus a continuously growing global issue (http://www.who.int/mediacentre/factsheets/fs117/en/index.html).
The Dengue Virus is one of the many mosquito-borne diseases that affect millions around the world. In order for the Dengue virus to be understood the classification & structure, the life cycle, the disease, the treatment, and the public health impact of virus needed to be described in detail. In order for Dengue virus to be under control an effective vaccine that has immunity against all serotypes of dengue need to be made, and the Global initiative to inform and rid the endemic countries of conditions suitable for mosquitoes to breed needs to continue like the World Health organization and CDC.