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  1. 1. DENGUE FEVER Dr.T.V.Rao MD Professor of Microbiology
  2. 2. Arboviruses <ul><li>The Arboviruses are also called as Arthropod borne viruses, represent an ecological grounding of viruses with complex transmission cycles involving Arthropods </li></ul><ul><li>These viruses have diverse physical and chemical properties and are classified in several virus families. </li></ul><ul><li>Dengue infection is caused by Arboviruses </li></ul>
  3. 3. History Dengue <ul><li>This disease was first described 1780, and the virus was isolated by Sabin 1944. Dengue virus infection is the most common arthropod-borne disease worldwide with an increasing incidence in the tropical regions of Asia, Africa, and Central and South America. There are four serotypes of the virus. All are transmitted by mosquitoes, which are not affected by the disease, although an infected mosquito may infect others (not via man). </li></ul>
  4. 4. Current Trends <ul><li>In the 1980s, DHF began a second expansion into Asia when Sri Lanka, India, and the Maldives Islands had their first major DHF epidemics; Pakistan first reported an epidemic of dengue fever in 1994. The epidemics in Sri Lanka and India were associated with multiple dengue virus serotypes, but DEN-3 was predominant and was genetically distinct from DEN-3 viruses previously isolated from infected persons in those countries. </li></ul>
  5. 5. Prevalence of Dengue Infection
  6. 6. Dengue Infection and Implications <ul><li>Dengue virus (DENV) infects 50 million (WHO) to 100 million (NIH) people annually. Forty percent of the world’s population, predominately in the tropics and sub-tropics, is at risk for contracting  dengue virus. DENV infection can cause dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and death. </li></ul>
  7. 7. Dengue Mosquito traanmitted Viral Infection
  8. 8. What causes Dengue <ul><li>Dengue (DF) and dengue hemorrhagic fever (DHF) are caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus . Infection with one of these serotypes provides immunity to only that serotype for life, </li></ul>
  9. 9. Aedes aegypti – Vector <ul><li>Aedes aegypti , a domestic, day-biting mosquito that prefers to feed on humans, is the most common Aedes species. Infections produce a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease. Other species of Aedes can also transmit. </li></ul>
  10. 10. Dengue Virus – A Flavivirius <ul><li>Flavivirius are spherical and 40- 60 mm in diameter. </li></ul><ul><li>Genome – Positive sense, single sense RNA,11kb in size </li></ul><ul><li>Genome – RNA infectious </li></ul><ul><li>Enveloped virus </li></ul><ul><li>Three structural polypeptides two are glycosylated </li></ul><ul><li>Replication in cytoplasam </li></ul>
  11. 11. How Mosquitos spread the infection <ul><li>The disease starts during the rainy season, when vector Mosquito Aedes aegypti is abundant </li></ul><ul><li>The Aedes breeds in the tropical or semitropical climates in water holding receptacles or in plants close to human dwellings </li></ul><ul><li>A female Aedes acquires the infection feeding upon a viremic human. </li></ul><ul><li>After a period of 8 – 14 days mosquitoes are infective and remain infective for life. ( 1- 3 ) months. </li></ul>
  12. 12. Dengue - Endemics <ul><li>Persons living in a dengue-endemic area can have more than one dengue infection during their lifetime. DF and DHF are primarily diseases of tropical and sub tropical areas, and the four different dengue serotypes are maintained in a cycle that involves humans and the Aedes mosquito. </li></ul>
  13. 13. Clinical Manifestations <ul><li>Any or few of the following events can occur. </li></ul><ul><li>Fever, </li></ul><ul><li>Severe head ache </li></ul><ul><li>Muscle and joint pains </li></ul><ul><li>Nausea, vomiting, </li></ul><ul><li>Eye pain </li></ul>
  14. 14. How Dengue Infection starts and manifests <ul><li>Incubation period 4 – 7 days ( 3 – 14 days) </li></ul><ul><li>Fever may start with, Malise,chills,head ache </li></ul><ul><li>Soon leads to severe back ache, joint pains, muscular pain, pain in the eye ball. </li></ul><ul><li>Temperature may persist for 3 -5 days. </li></ul><ul><li>On some occasions once again raises in about 5 – 8 days ( Saddle back fever ) </li></ul><ul><li>Myalgia may be severe with deep bone pain </li></ul><ul><li>( Break bone fever ) characteristic of the Disease </li></ul><ul><li>On majority of the occasions a self limited condition, </li></ul><ul><li>Subside on its own </li></ul><ul><li>Death is a rare event . </li></ul>
  15. 15. Dengue with Rashes
  16. 16. Dengue Hemorrhagic Fever <ul><li>Common in children. </li></ul><ul><li>In children passively acquired contributed by the maternal antibodies transferred to the fetus. </li></ul><ul><li>In other ( Adults ) the presence of antibodies due to previous infection with different serotype </li></ul><ul><li>Initially presents like classical Dengue infection </li></ul><ul><li>But patients condition abruptly worsens, an important cause of morbidity and mortality in Dengue </li></ul>
  17. 17. Risk factor for DHF <ul><li>Important risk factors for DHF include the strain of the infecting virus, as well as the age, and especially the prior dengue infection history of the patient </li></ul>
  18. 18. Dengue Hemorrhagic Syndrome <ul><li>Chateresied by shock and hemoconcentration </li></ul><ul><li>Contributed by circustantial evidence suggests secondary infection with Dengue type 2 following type 1 infection in the past. </li></ul>
  19. 19. Pathogenesis <ul><li>Presence of existing Dengue antibody, associated with fresh viral infection with new serotype complexes and forms within few days of the second dengue infection. </li></ul><ul><li>Non neutralizing enhancing antibodies promote infection of higher number of Mononuclear cells. </li></ul>
  20. 20. Dengue hemorraghigic Syndrome <ul><li>DHS is caused due to release of, </li></ul><ul><li>1 Release of cytokines </li></ul><ul><li>2 Vasoactive mediators. </li></ul><ul><li>3 Procoagulants </li></ul><ul><li>Manifest with disseminated intravascular coagulation </li></ul>
  21. 21. Risk of Hemorrhagic Fever <ul><li>The risk of hemorrhagic fever syndrome is about 0.2% during the first attack </li></ul><ul><li>The second attack with different serotype increases the risk to ten fold </li></ul><ul><li>The fatality rate with dengue hemorrhagic fever can reach 15% but proper medical care and symptomatic mangement can reduce mortality to less than 1% </li></ul><ul><li>On few occasions patients condition abruptly worsens into Dengue shock syndrome, a more severe form of disease characterized by shock and hemoconcentration. </li></ul>
  22. 22. Diagnosis <ul><li>In resource rich establishments </li></ul><ul><li>1 Reverse transcriptase polymerase chain reaction methods help rapid identification </li></ul><ul><li>2 Isolation of virus is difficult </li></ul><ul><li>3 The current favored approach is inoculation of mosquito cell line with patient serum coupled with nucleic acid assay to identify a recovered virus. </li></ul>
  23. 23. Dengue Serology <ul><li>The serology is limited with cross reactivity of IgG antibodies to heterologus Flavivirius antigens </li></ul><ul><li>Most commonly used methods are </li></ul><ul><li>Viral protein specific capture IgM or IgG by ELISA </li></ul><ul><li>IgM antibodies develop within few days of illness </li></ul><ul><li>Neutralizing anti Hemagglutination inhibiting antibodies appear within a week after onset of Dengue fever </li></ul>
  24. 24. Importance of paired sample testing in Serology <ul><li>Testing one sample for serum and reporting a negative test is fallacious </li></ul><ul><li>Analysis of paired acute and convalescent sera to show significant rise in antibody titer is the most reliable evidence of an active dengue infection . </li></ul>
  25. 25. Newer Diagnostic Methods RT - PCR <ul><li>RT PCR is a highly sensitive tool in Diagnosis, with established high sensitivity in Diagnosis in Puzzles </li></ul><ul><li>Developing world lacks resources to implement and utilize the Scientific advances </li></ul>
  26. 26. Immunology Dengue <ul><li>Four serotypes exist distinguished by Molecular basis and Nt tests </li></ul><ul><li>Infection confers life long immunity </li></ul><ul><li>But cross protection between serotypes is of short duration. </li></ul><ul><li>Reinfection with different serotype after primary attack is more dangerous causes Dengue hemorrhagic fever. </li></ul>
  27. 27. Treatment <ul><li>No Anti viral therapy available </li></ul><ul><li>Symptomatic management in Majority of cases </li></ul><ul><li>Dengue Hemorrhagic fever to be treated with suitable fluid replacement </li></ul><ul><li>No Vaccine available, difficult in view of four serotypes. </li></ul>
  28. 28. Control of Dengue <ul><li>Control of Mosquito breeding places. </li></ul><ul><li>Anti mosquito measures </li></ul><ul><li>Use of Insecticides. </li></ul><ul><li>Screened windows and doors can reduce exposure to vectors. </li></ul>
  29. 29. Epidemiology - Dengue <ul><li>Dengue virus are distributed world wide in tropical regions. </li></ul><ul><li>Where the Aedes vectors exist, are endemic areas </li></ul><ul><li>Changing and increasing incidences are associated with rapid urban population growth, over crowding and lax mosquito control measures </li></ul>
  30. 30. Dengue a Reemerging Infection <ul><li>Dengue in 2005 identified as the most important mosquito borne viral disease </li></ul><ul><li>An estimated 50 million or more cases occur annually worldwide </li></ul><ul><li>400,000 cases of dengue hemorrhagic fever. </li></ul><ul><li>Asian counties report major cases of childhood deaths </li></ul>
  31. 31. Avoiding Mosquito bites remain only way to prevent Dengue
  32. 32. Created for Training Medical and Health Care Workers in Developing World Dr.T.V.Rao MD Email [email_address]