Diagnosis history and pathology of Dengue virus

Diagnosis history and pathology of Dengue virus

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  DENGUE VIRUS BY NEHARAWAT
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  Dengue virus  Dengueis the most common mosquito-borne arboviral illness caused by dengue virus. The name dengue is derived from a Swahili word ki-dinga-pepo. In 1780, Rauss coined the term “break-bone fever” based on description of symptoms reported by patients during Philadelphia epidemics of probably dengue fever. The possible outbreak of dengue fever epidemics were documented sporadically every 10–30 years until World War II. Subsequently, after World War II the dengue fever spread and became worldwide. The first epidemic of dengue hemorrhagic fever was described in 1963 in Manila. In 1979–1980, the first reported outbreak of dengue fever occurred simultaneously in Asia, Africa, and North America.
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  Morphology  Dengue virusis a small, spherical, and enveloped virus. It is a flavivirus having a cubic symmetry and measures 40–50 nm in diameter. It is a single-stranded RNA virus of 11 kb size. It has an icosahedral nucleocapsid and is covered by a lipid envelope. The virus is inactivated by diethyl ether and bile salts, such as sodium deoxycholate
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  Viral replication:  Thereplication cycle is similar to that of other flaviviruses, such as yellow fever virus.
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  Antigenic and genomicproperties  Dengue virus has four distinct closely related serotypes: dengue 1 (DEN-1), dengue 2 (DEN- 2), dengue 3 (DEN-3), and dengue 4 (DEN-4). The speciation was done by Albert Sabbin in 1944. Each serotype is known to have several different genotypes.
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  Pathogenesis and immunity Humans acquire infection and become infected with the virus by the bite of Aedes mosquito vector. The leakage of plasma caused by increased capillary permeability is the major pathophysiological abnormality that occurs in dengue hemorrhagic fever and dengue shock syndrome. Bleeding, which is most important manifestation in patients with dengue hemorrhagic fever, is caused due to capillary fragility and thrombocytopenia, and it manifests by various ways ranging from petechial skin hemorrhages to life-threatening gastrointestinal bleeding.
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   In thesame patient on reinfection with another serotype of dengue virus, the virus antibody complexes are formed within a few days of second dengue infection. This results in an increase in viral entry and replication of a higher number of mononuclear cells followed by the release of cytokines, vasoactive mediators, and few coagulants. This phenomenon is called antibody- dependent enhancement and is responsible primarily for the disseminated intravascular coagulation seen in the patients with dengue hemorrhagic fever. In addition, certain dengue strains particularly of dengue 2 are being considered to be more virulent. This is because more epidemics of dengue hemorrhagic fever have been associated with dengue 2 than with other serotypes.
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  Host immunity  Infectionwith dengue virus confers lifelong immunity. The immunity is serotype specific. Infection by one serotype does not confer protection against other serotypes. The infection with dengue virus of different serotypes may cause a more severe disease, such as dengue hemorrhagic fever. Although dengue and yellow fever viruses are antigenically related, infection with dengue virus does not result in significant cross-immunity against yellow fever virus.
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  Clinical syndromes  Thedengue virus causes classic dengue or break-bone fever characterized by fever, muscle and joint pain, lymphadenopathy, and rash. In addition, it also causes dengue hemorrhagic fever, i.e., a much more severe disease than classic dengue fever with a high fatality rate.
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   Classic denguefever: The incubation period varies from 2 to 7 days. The onset of the disease is sudden, which begins as influenza-like illness manifesting as fever, malaise, cough, and headache. The fever, which may be as high as 41°C, typically begins on the third day and lasts for 5–7 days. The fever is typically biphasic, coinciding with the absence of virus in the blood. A maculopapular rash usually appears on third or fourth day of the illness. The rash lasts for 1–5 days, fading with desquamation. Severe pain in muscles and deep bone pain and joint pain (break-bone fever) are characteristic. Enlarged lymph nodes and leukopenia are also seen. Classic dengue fever is a self-limiting disease. It is rarely fatal and has few sequelae and complications. The convalescent phase may last for 2 weeks
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  Dengue hemorrhagic fever Dengue hemorrhagic fever is a most severe manifestation of the disease. The initial classic phase of dengue hemorrhagic fever is similar to that of dengue fever and other febrile viral illnesses. But, subsequently, the condition of the patient suddenly worsens with shock and hemorrhage, especially into the gastrointestinal tract and skin. The hemorrhagic manifestations include bleeding from nose or gums, melena, and hematemesis. This condition shows a high fatality rate as high as 10%. It occurs in children with passively acquired maternal antibodies. It may also occur in a person previously infected with a different serotype of the virus, showing non-neutralizing heterologous antibodies in the serum
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  Dengue shock syndrome It is the most severe form of the disease caused by dengue virus. This is most commonly seen in untreated cases of dengue hemorrhagic fever. The common symptoms include abdominal pain, vomiting, and restlessness and finally, the patient may die of circulatory failure and shock. When treated, dengue hemorrhagic fever has a mortality rate of 5%; if left untreated, the condition has a mortality rate as high as 50%.
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  Epidemiology  Dengue virusis distributed worldwide. Dengue hemorrhagic fever is primarily a disease of children and a leading cause of death in Southeast Asia.  Geographical distribution: An estimated 3 billion people living in approximately 110 countries worldwide are at a risk of dengue infection. Every year, approximately 100 million people are infected with dengue worldwide. Dengue hemorrhagic fever occurs in approximately 2.51 lakhs of affected person.
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   Reservoir, source,and transmission of infection: Humans are reservoirs of the infection. The human host serves as source of viral amplification. Humans are infectious to mosquitoes during viremia for 3–5 days. The infection is transmitted by bite of A. aegypti mosquitoes. After feeding, the virus shows an extrinsic incubation period of 10–14 days in the mosquito, before the mosquito becomes infectious. The mosquitoes are vectors as well as sources of viral amplification. A. aegypti are small and highly domesticated mosquitoes, which breed on artificial water sources, and they prefer to bite humans typically at the back of the neck and at the ankles.
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  Laboratory diagnosis  Specimens:Blood collected during first 3–5 days of illness is useful for isolation of virus, and serum is useful for serological tests.  Isolation of the virus: Diagnosis of dengue is confirmed by isolation of virus from blood during first 3–5 days of illness. The virus can be isolated in various cell cultures.  Serodiagnosis: Serodiagnosis of dengue fever is based on the demonstration of IgM immunoglobulin in a single serum sample or rise in IgG antibodies in paired serum specimens. The IgM capture ELISA (MacELISA) is the most widely used test for demonstration of IgM antibody in the serum. Neutralization test, hemagglutination inhibition, and IgG ELISA are the other serological tests used for diagnosis of the condition.
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  Molecular Diagnosis  RT-PCRis being used for genomic detection of dengue virus in the clinical specimen.
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  Treatment and Prevention No specific antiviral treatment is available to treat dengue infection. No vaccine is available for prevention of dengue infection.  The preventive measures are based mostly on mosquito- control activities. These include the use of insecticides and clearing the stagnant water and artificial collections of water that serve as breeding ground for the mosquitoes.  Personal control measures include wearing good protective clothings and use of mosquito nets, mosquito repellants, etc.