Dengue Virus Hemorrhagic Fever Biology Essay


Dengue virus is a ssRNA virus of viral family Flaviviridae, and it is the causative agent of dengue fever and dengue hemorrhagic fever. Dengue fever is caused by a family of viruses that is transmitted to humans by mosquito bites and is characterized by a sudden high fever following muscle aches, swollen lymph nodes, rash and vomiting. Presently, dengue virus is thought to be one of the most common causes of arthropod borne disease in the world (craven 626).

Up until now, four serologically distinguishable type of dengue strain has been identified. If a person is infected with one strain of the virus, the antibodies produced during the time of infection do not protect them from infection with another serotype of dengue virus. Instead, infection with one serotype makes them more susceptible to the severe form of the infection called dengue hemorrhagic fever. The virus is endemic throughout tropical and subtropical areas of the world. Due to the increasing number of cases every year and the ability of the virus to cause fatal diseases such as dengue hemorrhagic fever and shock syndrome, the virus is considered to be an emerging global health threat. Also, there are no vaccines or specific anti viral medications available for the prevention and treatment of the dengue virus (Craven 625). As a result, the virus is getting transmitted easily from endemic areas to the non endemic areas and very large number of population throughout the world is at high risk of developing dengue infections. To better understand how the infection process starts and how it is transmitted, the paper will focus on the virus structure, life cycle, the type of disease they cause and about available treatments.

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Dengue virus is a type of arbovirus with ssRNA (+). Based on the virus morphology, genome and the type of disease they cause dengue viruses are classified as Baltimore class 4 RNA virus. Baltimore classification is an international system of grouping virus into one of seven families based on the viral genome, mode of replication and their strandedness etc. Baltimore classification system is very useful in that when viruses are placed in a group based on their genome, within the same group they all will behave in a similar fashion so the situation will be favorable for conducting further research on them as well as predict their behaviors (Parilla 2010). Dengue virus poses a 25-30 nm long icosahedral capsid which contains single stranded positive sense RNA molecule with a length of approximately 10,700 nucleotides. The genome is enclosed in a nucleocapsid and consists of one large open reading frame. Nucleocapsid is composed of single capsid protein and surrounded by glycosylated envelope protein and nonglycosylated membrane protein. Single long poly protein from viral mRNA gets translated and later on develops in to three virion structural proteins and seven nonstructural proteins (Kronen). The genome is organized in such a way that structural proteins are located at the 5' end and nonstructural proteins are located at the 3'end of the genome (Olson et al 391). The three major structural protein of dengue virus are the core nucleocapsid protein C, and the envelope glycoproteins M and E. Envelope glycoprotein E's receptors help the virus to attach to the host cells and help the virus to fuse its envelope with endosomal membrane. Protein M is formed by proteolytic cleavage of precursor protein pre-M and its function is associated with glycoprotein E. without the glycoprotein M, the glycoprotein E is inactive and unresponsive to low PH (Helenius 651).

Capsid protein C is a dimeric alpha helices protein, its interaction with RNA is very crucial toward production of viable virus particle. The protein also has potential function in viral RNA replication. Besides protein C, the gene for protein C is thought to play an important role in viral RNA replication and translation (Modis et al 6986) . As there are four different strains of dengue viruses are present, the molecular weight of large envelope glycoprotein varies. The template strand RNA inside the capsid is used to make proteins directly and, mRNA is capped at the 5' end but does not have the poly A tail at the 3' end to protect it from degradation. An important aspect of dengue viruses' replication and encapsidation is that they have non coding sequences at the extreme 5' and 3' ends. The complement of the 5' end is similar to 3' terminal sequence of the plus strand, serving as the recognition sites for the viral replicase to start the RNA synthesis.

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Dengue virus can replicate in both mammal and insects and, they can survive for long period of time within the host. Also, the virus can survive inside the mosquito egg until it's hatched. Dengue virus has an urban life cycle, where the virus is transmitted from mosquito to human and from human to mosquito. The virus attaches to the host cell using viral envelope glycoprotein receptor E. cellular receptor that is involved in attachment is still unknown. Following attachment to the cellular receptor, virus enters the host cell by receptor mediated endocytosis. The vesicle becomes endosomic vesicle as it becomes more acidic and this causes a conformational change in the envelope protein E. Dengue virus stability is greatest at PH 8, but it gets inactivated at low PH (Craven 625). The virus membrane fuses with endosome membrane and releases its nucleocapsid in the cytoplasm and nucleocapsid uncoats releasing the viral RNA.Viral RNA gets translated into a long piece of polyprotein within the cytoplasm. After translation, RNA replication starts and a progeny positive strand is made following the negative strand using viral RNA dependant RNA polymerase. Newly formed RNA interacts with protein C to form the capsid. The capsid is transferred to Golgi, and secretory vesicle where it acquires the envelope; from there mature virus particle is released at the cell surface through exocytosis (Parilla 2010).

Dengue virus infection is one of the most common arthropod borne diseases throughout the world with higher incidence in the tropical areas of Asia, Africa, North and South America. Dengue virus is most common in areas where there is inadequate water supply, poor sanitation and bad waste management. These situations create perfect breeding environment for principle dengue virus vector mosquito Aedes Aegypti. The virus is transmitted to humans by the bite of infected mosquito. The mosquito is usually infected by feeding on the blood of an infected person and the incubation time for the virus within mosquito is about eight days. Once the virus enters a mosquito, it replicates in the virus midgut and then moves to the mosquito's salivary gland where it continues to replicate. Infected mosquito then feeds on to the human and transmits the virus. Once the virus enters the human body, it moves to organs such as liver, lymph nodes and spleen. Incubation time for the virus within a human is approximately four to eight days. The virus is then released to the bloodstream of the host and the symptoms of dengue fever starts to appear ( dengue entomology 2009)

Symptoms of dengue fever vary depending on the age, sex and whether the infection is at first exposure or a reinfection. The usual symptoms of dengue fever includes sudden onset of fever, swollen lymph nodes, severe muscle and joint pain, headache and a skin rash that appears few days after the onset of the fever. Most of the symptoms of the dengue fever disappear within ten days but it might take up to a month for complete recovery. Even though, dengue fever is a relatively mild disease in most people but in some people it can develop into sever dengue hemorrhagic fever or dengue shock syndrome (Craven 628). Dengue hemorrhagic fever (DHF) is most common in children under the age of fifteen and usually occurs in two stages. The first stage of disease is similar to that of dengue fever with high fever, malaise, headache plus respiratory and intestinal problems such as coughing, vomiting, and abdominal pain. After two to five days of the infection, the patient's condition worsens and patient becomes irritable, restless and starts bleeding from all most all parts of the body even with small bruises followed by a shock like state which might cause death. As a result, the patient may develop increased vascular permeability and abnormal homeostasis which can result into hypotension and in severe cases hypovolemic shock. Abnormal homeostasis causes plasma leakage and patients may develop gastrointestinal bleeding which causes abdominal pain. When blood vessels run out of clotting factors, severe bleeding starts and the damaged vessels become unable to supply the blood flow and oxygen to the body's tissue which causes failure of body's main organs such as heart and kidney ( Dengue fever 2010).

During DHF, there is an increased macrophage infection because macrophages containing the virus antigen will be attacked by effector lymphocyte and the body produces more antibodies to fight the infection. A person infected with dengue for the first time will develop a primary serologic response to the infection serotype; on the other hand, patient reinfected with different serotype will develop a secondary serologic response characterized by very high titers of all four dengue serotypes. DHF usually develops in people who was previously infected with another serotype of dengue virus because during the reinfection period , the person's immune system will be overreacting and the symptoms will worsen (Craven 628).

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Some of the physical signs and tests such as enlarged liver, red eyes, skin rash, platelet count, coagulation studies and serologic studies may help identifying DHF.

Like most viral infections, dengue fever must run its course. For uncomplicated dengue fever, treatments are mainly targeted to lower the fever and body pain associated with it. To prevent dehydration, enough fluids and complete rest should be taken. For the fever and headache, acetaminophen is preferred but aspirin and nonsteroidal anti inflammatory drugs should be avoided as they can trigger gastritis and provoke bleeding. Like Dengue fever, dengue hemorrhagic fever does not have any specific medications; the treatment is supportive. Patient who has gastrointestinal bleeding, their vital signs should be monitored frequently and intravascular homeostasis should be maintained. For management of DHF/DSS, one of the major problem to be corrected is the leakage of plasma into the extravascular space. Plasma loss should be replaced with isotonic saline solutions and once the vital sign of the patient improves, intravenous volume replacement should be continued. Patients in shock must be treated with oxygen and may require treatment with fresh whole blood, fresh frozen plasma or platelet concentrations (Craven 631). Currently there is no vaccine available for the prevention of dengue virus; however, experimental vaccines are under development. For the prevention of dengue virus it is important to avoid coming in contact with mosquitoes and wear long pants and sleeves when going outdoor. Exposed skins should be protected from mosquito bite using insect repellent. To prevent the spread of mosquito in endemic areas, all the breeding source of the mosquito should be destroyed including artificial containers, used tires, flower vase and ant traps etc. Also, using aerosol house spray and vaporizing mosquito spray works great in minimizing contact with vector mosquito. As, there are no vaccine and specific medications are not available for the prevention and treatment of dengue virus, it is very important that we protect ourselves from the virus carrying mosquito, using the appropriate prevention strategies. Also, anyone that shows the symptom of dengue fever or Dengue hemorrhagic fever needs to get medical assistance as soon as possible because if DHF is not managed well it can lead to death. Dengue virus is endemic in both tropical and subtropical areas of the world. Emerging cases of dengue viral infection is increasing every year and this places the dengue virus among one of the important arboviral infection. Every year about 50 -100 million case of dengue fever and 500,000 cases of dengue hemorrhagic are reported and out of the reported cases about 24,000 people die of dengue hemorrhagic fever( Cdc web)

Widespread transmission levels are affected mainly by the amount of susceptible person in the population and the size of infected vector population. About 40 percent of the world's populations are living in areas endemic with dengue. The most endemic areas are south and Southeast Asia, Africa, central and South America and the Caribbean. Dengue is more common in children under the age of fifteen than in adults. Currently, dengue hemorrhagic fever is reported to be one of the major of cause of hospitalization and death of children in many countries of Southeastern Asia (Craven 625).

In the endemic areas of southeast Asia, dengue infection appears mostly in young children is because most of the adult from the same area have been infected with different serotype of dengue virus before they reached adulthood. On the other hand, in the Caribbean region, older children and adults are more often reported to the hospital with dengue infection and, there was no reported difference to susceptibility of dengue infection (Craven 626).

Some of the factors that make a person more susceptible to the virus is that if the person is living or traveling in the dengue endemic area and if the person have been infected with a dengue virus before. Prior infection with dengue virus makes a person more susceptible to the severe form of the infection, especially children. Having antibodies from previous dengue infection increases a person's chance of developing dengue hemorrhagic fever in case of a reinfection. Also,traveling between dengue endemic and non endemic area aids in spread of the dengue virus.

The increased incidence of dengue virus infection every year is affecting the society as well as the economy. According to the world health organization (WHO), there is approximately 50 million dengue infections worldwide every year and, 2.5 billion people are at risk of developing dengue infection. The disease is now endemic in about 100 countries including Africa, Americas and Asia. Due to the increased traveling, even the non endemic countries are at high risk of dengue virus transmission. Hence, high risk of transmission of dengue is limiting the trade, travel, export and import within countries.

Dengue virus is a positive stranded, enveloped RNA virus of viral family Flaviviridae. Dengue virus genome includes three positive structural proteins and seven non structural proteins.the major envelope proteins E helps in viral attachment to cell surface. Dengue virus causes dengue fever and dengue hemorrhagic fever. Symptoms of dengue fever is mild whereas symptoms of dengue hemorrhagic fever is severe and can lead to shock which will cause plasma leakage, collapse of the major body organs such as kidney, heart and, liver etc. For such severe conditions there is no specific medication available and the treatments are supportive. For the prevention of the disease, its best to avoid coming in contact with mosquito as the virus is transmitted by infected mosquito bites. Also, the vaccine for dengue virus is under development. By educating general public about dengue virus and its prevention strategies, we can be able to stop the spread of the disease and save many lives.