Dengue: A Survey Report

 

Pooja Yadav, Ayush Victor, Dr. V M Berlin Grace, Dr. C. Vani

Department of Biotechnology, School of Agriculture and Biosciences, Karunya University, Coimbatore 641114

*Corresponding Author E-mail: topoojayadavp@gmail.com, ayushvictor12@gmail.com, vani@karunya.edu, geneexpressionbrca1@gmail.com

 

Abstract:

Dengue is a viral disease that is endemic in more than 100 countries especially in the South East Asia and Western Pacific regions. The rapid growth in population and sudden climatic changes has contributed to the increase. The World Health Organization has classified dengue into three types: dengue fever, dengue hemorrhagic fever and dengue shock syndrome.Annually, around 50-100 million people living in subtropical countries are infected by dengue. Symptoms occur usually 3 to 14 days after spread by Aedes [Aedes aegypti] mosquitoes and consist of fever, headache, vomiting, pains and aches in muscle and joints and a typical rash. The symptoms last for 2 to 7 days. A novel vaccine for dengue fever has been approved in three countries, but is not yet commercially available. Dengue fever is caused by flavi virus which belongs toFlaviviridae family. flavi virus is a positive single stranded RNA virus which enter inside thecell by receptor-mediated endocytosis andfuse their membrane with that of the endosome. The virus genome then enters into cytoplasm and forms immature virions that enter into exocytotic pathway of cell and perform proteolysis.

 

KEY WORDS: Dengue, Survey Report

 

1. INTRODUCTION:

1.1 Dengue:

In recent years, dengue has become a worldwide public health problem and is alsoan important emerging disease in the tropical and sub-tropical regions. Dengue is endemic around 100 countries in which South East Asia and Western pacific regions are heavily infected by it. The rapid rise in population and sudden climatic changes has also contributed to an increase of dengue fever throughout the world. The World Health Organization has classified dengue into three types: dengue fever, dengue hemorrhagic fever and dengue shock syndrome. Annually, around 50-100 million people living in subtropical countries are infected by dengue fever. The hallmark of dengue hemorrhagic fever that differentiates it from dengue fever is not hemorrhagic. Dengue hemorrhagic fever causes an increased vascular permeability leading to capillary leak syndrome, according to the World Health Organization.

 

Dengue fever is a mosquito-bornetropical diseaseand iscaused by the Dengue virus. Fever, head ache, aches in the muscle and joints, vomiting, a typical rash, etc., and occurs 3 to 14 days after the bite of the infected mosquito. The symptoms remain for 2 days to a week. Prevention of dengue can be done by reducing mosquito habitat and limiting exposure to mosquito bites. It includes getting rid of or covering any stagnant water and wearing clothes that covers the whole body respectively. A vaccine that is not yet commercially available has been used in some countries.

 

The viral disease like many of the other viral diseases can cause lowering of white blood cells and platelets. Most of the time disease is mild but sever disease can lead to death in about ten to twenty thousand of the 50 to 528 million who are infected all over the World. In 2009 World Health Organization classified the disease into severe group with significant bleed and multiple organ dysfunction. In 1997 it was then classified by Nam et. al into undifferentiated fever, dengue fever, and dengue - haemorrhagic fever.

 

 

FIG NO: 1 Symptoms of Dengue Fever

 

1.2 Dengue virus:

 

 

FIG 2: Structure offlavi virus (Source: Swiss institute of Bioinformatics)

 

Dengue fever is caused by flavi virus which belongs to flaviviridae family. This dengue virus is divided into four major types: which are den-1,den-2,den-3, den-4 respectively. It isenveloped, spherical shape and is 50 nm in diameter. Mature virions contain two virus-encoded membrane proteins M and E respectively, whereas immature virions contain a membrane protein precursor. Theflavi virus is a positive single standed RNA virus and its genome contains three structural genes and seven non-structural genes. It gets transmitted from one human to another through mosquito bites. The genome of flavivirusis about 11000 bases that codes for three structural proteins (capsid protein C, membrane protein M, envelope protein E) and seven non-structural proteins (ns1, ns2a, ns2b, ns3, ns4a, ns4b, ns5). It also has short non-coding regions on both the 5' and 3' ends. The envelope protein, found on the viral surface is important for the initial attachment of the viral particle to the human cell (Larsen CP.et.al.2015).

 

1.3Replication of Flavivirus:

Flavivirus enters cell by receptor-mediated endocytosis and fuse their membrane with that of the endosome. The acidic pH of this compartment triggers an irreversible conformational change in the viral fusion protein E (a class II viral fusion protein) that drives the fusion of the viral membrane with the endosomal membrane, resulting in the release of the viral genome into the cytoplasm.


The assembly of flavivirus takes place inside endoplasmic reticulum (ER) leading to the formation of immature virions which are transported through the exocytotic pathway of the cell. Virus maturation occurs in trans-Golgi network (TGN) and involves the proteolytic processing of the precursor-to-membraneprotein (PrM).We investigate and define individual steps of the existing models of membrane fusion and assembly using infectious flavivirus c-DNA clones and structure-based experimental approaches.One should have an in-depth knowledge about complex molecular mechanisms of these processes as they are crucial for understanding virus infection of the host cells. This will be important for the specific design of antiviral agents against flavi virus which are not yet available. (Larsen CP.et.al.2015)

 

 

Fig NO:3 Entry of flavi virus into Human Cell

 

1.3.1 Steps involved in mechanism of entry of flavi virus into human cell

1.      Attachment of the viral envelope protein E to host receptors mediates internalization into the host cell by clathrin-mediated endocytosis, or by apoptotic mimicry.

2.      Fusion of virus membrane with host endosomal membrane. RNA genome is released into the cytoplasm.

3.      The positive-sense genomic ss-RNA is translated into a poly-protein, which is cleaved into all structural and non-structural proteins (to yield the replication proteins).

4.      A ds-RNA genome is generated from the genomic ss-RNA at the surface of the endoplasmic reticulum

5.      The ds-RNA genome is transcribed or replicated thereby providing viral m-RNA or new ss-RNA genomes.

6.      Virus assembly occurs at the endoplasmic reticulum. The virion buds via the host escrtcomplexes at the endoplasmic reticulum, is transported to the Golgi apparatus.

7.      The PRM protein is cleaved in the Golgi, thereby maturing the virion which is fusion competent.

8.      Release of new virions by exocytosis.

 

1.4 Dengue vectors:

 

 

Fig NO:4 Aedesaegypti Mosquito                                     Fig NO: 5 Aedesaegypti Larvae

 

Aedesaegyptimosquito is a vectorresponsible for transmitting several tropical fevers. Only the female mosquito bites for blood as itneeds to mature her eggs. To find a host, these mosquitoes are attracted to chemical compounds emitted by mammals. The compounds include ammonia, carbon dioxide, lactic acid, and octenol.

 

Agricultural research service studied in detail the chemical structure of Octenol to find out more about this attraction attracting the mosquito to its host.

 

It was found out that the mosquito has a preference for "right-handed" (dextrorotatory) octenol molecules.The yellow fever mosquito can also contribute in spreading of reticulum cell sarcoma among Syrian hamsters. TheAedesaegypti mosquitoes most commonly feed at dusk and dawn, indoors, in shady areas, or when the weather is cloudy. They can bite and spread infection all year long and at any time of the day.These mosquitoes prefer to breed in areas of stagnant water, such as flower vases, uncovered barrels, buckets, and discarded tires. But the most dangerous areas for its breeding are wet shower floors and toilet tanks, as they allow the mosquitos to breed in the residence. Research has also shown that certain chemicals emanating from bacteria in water containers stimulate the female mosquitoes to lay their eggs.

 

Wang et. al., showed that appropriate balance of specific fatty acids and bacteria that are necessary for degradation of organic matter like leaves are required for the mosquitoes to lay the eggs.

 

 

Fig No.6: life cycle of Aedesaegypti.

 

Symptoms:

Dengue virus causes self-resolving dengue fever in majority of the cases which are characterized by severe body ache, retro-orbital pain, headache and at times rash, abdominal pain and nausea.

 

In 2009 WHO again classified Dengue into those with and without warning signs and sever Dengue. The warning signs include abdominal pain, vomiting, bleed from mucosal surface, increase in intracranial tension and significantly decreased platelet count.

 

Clinical significance:

Currently there is no specific anti-viral medication available for treating dengue. The treatment of dengue fever is symptomatic and supportive in nature. Bed rest and mild analgesic-antipyretic therapy are often helpful in relieving lethargy, malaise, and fever associated with the disease. Acetaminophen (Paracetamol) is recommended for the treatment of pain and fever. Aspirin, other salicylates, and non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided.

 

Patients with dengue hemorrhagic fever or dengue shock syndrome may require intravenous volume replacement. Also Plasma volume expander can be used in patients who do not respond to isotonic fluids (Suzanne Moore Shepherd, 2017; MedScape).

Research gap:

Although a lot of research has been developed to treat dengue fever and dengue hemorrhagic fever but, the outcomes led no benefits. Till dateno profound drug has been isolated or no such vaccine has been found. This has become a major area of research. Presently, much survey, and control programs aredonethat is clear about dengue epidemiology and there much less awareness about dengue prevention and control. Dengue virus antigen has been developed that are non-structural protein (NS1, NS2, NS3, NS4 and NS5) which plays a major role in diagnostic and research for the dengue fever and dengue hemorrhagic fever. This artificially synthesized dengue virus antigen binds with dengue virus envelope and capsid protein, which helps in diagnostic of dengue fever.

 

CONCLUSION:

The literature reports from various texts and recent studies on dengue shows that there is a rapid increase in reported number of cases every year. There should also be an integrated vector management for control of mosquitoes. Use of larval fishes will also be helpful. A greater in-depth research and awareness regarding it is to be encouraged among population in the world by which this problem can be overcome and prevented. All medical professionals should be given special training at CHC and PHC level for clinical management of the reported cases.

 

ACKNOWLEDGEMENT:

I acknowledge my sincere thanks to Dr. C Vani, Assistant professor, Department of Biotechnology, School of Agriculture and Biosciences for her kind support and encouragement.

 

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Received on 21.04.2018       Modified on 25.04.2018

Accepted on 30.04.2018      ©A&V Publications All right reserved

Research J. Science and Tech. 2018; 10(4):279-284.

DOI: 10.5958/2349-2988.2018.00039.6