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        Dr Sampurna Roy MD

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Dengue the most prevalent arthropod-borne viral (Arborvirus) disease of humans caused by  four  serotypes of dengue virus (DENV 1-4) of the genus Flavivirus.

It is transmitted to man by mosquito  Aedes aegypti. It is common in tropical and subtropical countries, especially in coastal areas. (World distribution of dengue viruses and their mosquito vector, Aedes aegypti : CDC)

Source: Man is infective to mosquito and mosquito transmits the disease to man.

Clinical presentation:

Clinically, symptoms start 6 days after of infection as malaise and headache, followed by sudden onset of fever, intense backache and generalized pains, mainly in the orbital and periarticular areas. After an afebrile interval of 24 to 48 hours, there is recurrence of fever for a day or two (‘saddleback fever’). There may be skin rash and lymphadenopathy.

In persons, previously exposed to Dengue virus, antiviral antibodies may enhance the uptake of virus into host cells and cause disseminated intravascular coagulation, shock and death (hemorrhagic dengue).

Pathological features:

Biopsy studies of the rash seen in nonfatal dengue fever show a lymphocytic vasculitis in the dermis.

In cases of fatal dengue hemorrhagic fever the gross findings are petechial hemorrhages in the skin and hemorrhagic effusions in the pleural, pericardial and abdominal cavities. Hemorrhage and congestion are seen in many organs. Histopathological examination show hemorrhage, perivascular edema and focal necrosis but no vasculitic or endothelial lesions. It is believed that most of the morphologic abnormalities seen result from disseminated intravascular coagulation and shock.

Visit: Chikungunya virus infection; click here

Differential diagnosis : Includes malaria , typhoid fever, leptospirosis,  West Nile virus infection, measles , rubella, acute human immunodeficiency virus conversion disease, Epstein–Barr virus infection, viral hemorrhagic fevers, rickettsial diseases, early severe acute respiratory syndrome (SARS), and any other disease that can manifest in the acute phase as an undifferentiated febrile syndrome.

Diagnosis:  A confirmed diagnosis is established by culture of the virus, polymerase-chain-reaction (PCR) tests, or serologic assays.

The diagnosis of dengue hemorrhagic fever is made on the basis of the following triad of symptoms and signs:  Hemorrhagic manifestations; a platelet count of less than 100,000 per cubic millimeter; and objective evidence of plasma leakage, shown either by fluctuation of packed-cell volume (greater than 20 percent during the course of the illness) or by clinical signs of plasma leakage, such as pleural effusion, ascites, or hypoproteinemia. Hemorrhagic manifestations without capillary leakage do not constitute dengue hemorrhagic fever.

Dengue (WHO)

Abstracts:

Coagulopathy in dengue infection and the role of interleukin-6. Acta Med Indones. 2006 Apr-Jun;38(2):105-8.

Dengue Fever in malaria endemic areas.J Coll Physicians Surg Pak. 2006 May;16(5):340-2.

Clinical case report: Dengue hemorrhagic fever in a patient with acquired immunodeficiency syndrome.Am J Trop Med Hyg. 2006 May;74(5):905-7

Dengue hemorrhagic fever patients with acute abdomen: clinical experience of 14 cases.Am J Trop Med Hyg. 2006 May;74(5):901-4.

Serotype-specific differences in clinical manifestations of dengue.Am J Trop Med Hyg. 2006 Mar;74(3):449-56

Neurological manifestations of dengue virus infection.J Neurol Sci. 2006 May 15;244(1-2):117-22. Epub 2006 Mar 9.

Pathologic study of a fatal case of dengue-3 virus infection in Rio de Janeiro, Brazil.Braz J Infect Dis. 2005 Aug;9(4):341-7. Epub 2005 Nov 1

Hepatosplanchnic circulatory dysfunction in acute hepatic infection: the case of dengue hemorrhagic fever. Shock. 2005 Nov;24(5):407-11

Dengue in travelers.N Engl J Med. 2005 Sep 1;353(9):924-32.

Dengue and dengue hemorrhagic fever.Clin Microbiol Rev. 1998 Jul;11 (3) :480-96

The global pandemic of dengue/dengue haemorrhagic fever: current status and prospects for the future. Ann Acad Med Singapore. 1998 Mar;27(2):227-34.

                    

2006 - October 7th:    With one more person dying on Saturday , dengue has claimed 46 lives in the country as 84 fresh cases were reported taking the number of patients to over 3,300 in at least14 states.

Of the states affected by the mosquito-borne disease, Delhi has reported the maximum number of 19 deaths as 82 persons were admitted to hospitals since last night taking the total number of cases in the national capital to 825.

Official reports said the number of dengue cases reported from Kerala so far were 713,  Gujarat 411,  Rajasthan 326,  West Bengal 314,  Tamil Nadu 306,  Maharashtra 228,  Andhra Pradesh 90,  Uttar Pradesh 79,  Karnataka 59 and  Haryana 50. Other affected states include Bihar, Uttaranchal and Punjab.

Dengue outbreak in India kills 38, infects thousands. 05 Oct 2006:  Read more....

Dengue Outbreak Kills 14 in India - NEW DELHI, Oct. 3, 2006 :  Read more...

Dengue fever outbreak overwhelms Delhi hospitals - October 3, 2006:  Read more...

Abstracts:

Serodiagnosis of dengue during an outbreak at a tertiary care hospital in Delhi. Indian J Med Res. 2005 Jan;121(1):36-8.

Experience in adult population in dengue outbreak in Delhi.J Assoc Physicians India. 1998 Mar;46(3):273-6

The 1996 outbreak of dengue hemorrhagic fever in Delhi, India.Southeast Asian J Trop Med Public Health. 1998 Sep;29(3):503-6.

An epidemic of dengue hemorrhagic fever and dengue shock syndrome in children in Delhi. Indian Pediatr. 1998 Aug;35(8):727-32.

Dengue haemorrhagic fever in children in the 1996 Delhi epidemic.Trans R Soc Trop Med Hyg. 1999 May-Jun;93(3):294-8.

Dengue haemorrhagic fever in adults: a prospective study of 110 cases.Trop Doct. 1999 Jan;29(1):27-30.

The first major outbreak of dengue hemorrhagic fever in Delhi, India.Emerg Infect Dis. 1999 Jul-Aug;5(4):589-90.

The 2003 outbreak of Dengue fever in Delhi, India.Southeast Asian J Trop Med Public Health. 2005 Sep;36(5):1174-8.
Dengue fever: from disease to vaccination. Med Trop (Mars). 2009 Aug;69(4):333-4.

Dengue is a tropical disease affecting 110 countries throughout the world and placing over 3 billion people at risk of infection. According the World Health Organization 70 to 500 million persons are infected every year including 2 million who develop hemorrhagic form and 20,000 who die. Children are at highest risk for death. Due to the absence of specialized laboratories in most endemic regions and to the lack of specifici clinical presentation, the incidence of dengue and its economic costs are certainly underestimated. Dengue iscaused by an arbovirus belonging to the Flavivirus genus of the family Flaviviridae. There are four dengue virus serotypes and no cross protection between them. The disease is transmitted through the bites of mosquitoes belonging to the Aedes genus, mainly Aedes aegypti. However A. albopictus has played an important role in the spread of the disease and other species may be involved in specific locations (e.g., A. polynesiensis in the South Pacific). There is no specific treatment for dengue. Management of severe forms depends on symptomatic treatment of hemorrhagic complications and hypovolemic shock. Prevention requires control of vector mosquitoes that is difficult to implement and maintain. Dengue is a major emerging infectious disease with a heavy impact on public health. The high human and economic costs as well as the absence of specific preventive measures underscore the need to develop a vaccine. However finding and distributing such a vaccine to populations at risk is hampered by numerous obstacles. The most notable challenges standing in the way of development of a candidate vaccine are as follows: absence of an animal model, which has important implications for the preclinical development strategy; need to develop a live attenuated vaccine; existence of 4 antigenically distinct serotypes with the resulting risk of competition between vaccine strains; immunologic risks related to antibody-dependent enhancement that has been hypothesized to be the cause of severe forms of the illness; absence of a well defined correlate of protection and preexisting vaccine, which will require the organization of large-scale pre-clinical trials to demonstrate the efficacy of the virus; complexity associated with industrial production of a tetravalent vaccine. Development and production of a safe and reliable vaccine are only the first steps to ensuring protection of the populations at risk, It twill also be necessary to identify and take into account a variety of geographic, economic, regulatory, and logistic factors: The epidemiological profile of dengue is variable. For example the age at which the likelihood of developing the disease is highest is not the same in Asia and Latin America. Vaccination programs must be tailored to regional and national epidemiological specificities. Introduction of dengue vaccination in the national immunization programs must take into account the special features of each country without jeopardizing the existing vaccines already in use. The need for an additional visit can represent a hardship both economically and logistically. Alternative funding will be needed to finance vaccination programs in some countries located in endemic zones, Long-term phase 4 effectiveness and tolerance field studies must be planned in collaboration with national authorities. All these challenges and obstacles have been taken into account in the development of Sanofi Pasteur's live attenuated tetravalent vaccine. Research for development of a dengue vaccine began during the 1990s. Clinical studies with the most promising tetravalent vaccine were started in the 2000s. A trial carried out in adults in the United States has shown that administration of three doses of the tetravalent candidate vaccine was 100% successful in inducing an antibody response capable of neutralizing all four dengue virus serotypes. Phase II clinical trials are now under way in children and adults in Mexico, Peru, and the Philippines. The first efficacy trial in children began in Thailand in February 2009. The purpose is to evaluate the efficacy of the tetravalent dengue vaccine in children. The study is being conducted in the Ratchaburi province in collaboration with the University of Mahidol and the Thai Ministry of Health as well as the Pediatric Dengue Vaccine Initiative (PDVI). This efficacy trial will be an important step for successful development of a live attenuated tetravalent vaccine.

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