Dengue

1. Dengue • Professor.Shivaprasad

5. Dengue • The word dengue is derived from African word denga: meaning fever with hemorrhage . • Is caused by virus transmitted of bites of mosquito aedes.

6. DEFINITION • Dengue Fever is a benign syndrome caused by several arthropod – borne viruses, is characterized by biphasic fever, Myalgia, or Arthralgia, rash, Leukopenia and lymphadenopathy.

7. History • Over the last two hundred years dengue was known to the physician as a self limiting benign febrile condition. • The first outbreak that resembles a disease now recognized as dengue fever was that described by Benjamn Rush in Philadelphia, Pennsylvania in 1780. • Epidemics probably due to dengue were common from the eighteenth to the twentieth centuries among the inhabitants of the Atlantic coast of the United States.

8. History • Dengue viruses almost certainly were the cause of the 5 and 7 day fevers that occurred among European Colonists in Tropical Asia. • In 1905 Aedes Aeggpti was identified as a dengue vector by Bancroft Ashburn and C raig.

9. History • When Dengue viruses were isolated in the laboratory mice in 1943 and 1944, the modern era of dengue research began. • In the beginning only two different dengue viruses named dengue virus type I and II. • During most of the previrologic era, dengue viruses were thought to be the cause of a generally benign self limited febrile exanthema.

10. History • In 1956 Philippine hemorrhage fever was associated with dengue when types 3 and 4 were recovered. • It now has become endemic through out tropical Asia since 1967 the term dengue hemorrhagic fever and DSS have come in to general use.

11. Problem statement • Dengue fever is the most common arthropod borne viral disease. • Dengue fever is one of the most important emerging disease of the tropical and sub tropical regions, affecting urban and pre urban areas. • The geographical distribution of the disease has greatly expanded and the number of cases has increased dramatically in the past 30 Years

12. Problem statement • The increase of Dengue and DHF is due to uncontrolled population growth and urbanization with out appropriate water management, to the global spread of dengue in a travel and trade and to erosion of vector control programme. • By 1997 most of the countries have experienced large out breaks of the disease, currently DF / DHF is endemic in Bangladesh , India, Indonesia, Maldives, Srilanka, Thailand approximately 1.3 billion people are leaving in endemic areas ;

13. Problem statementIndia • Dengue / DHF is widely prevelent in India and all the 4 serotype are found. There has been a decline in dengue incidence after 1996. • However during 2001 out breaks have been reported from Rajasthan (1433 cases and 33 deaths), Tamilnadu (761 cases and 8 deaths), Karnataka (161 cases) Gujarath (46 cases)

14. ETIOLOGY VIRUS • Dengue virion are spherical particles approximately 50 nm in diameter. • contains a single plus strand of RNA. Surrounded by a lipid bilayer. • Mature virions are composed of 6% RNA, 9% carbohydrate, and 17% lipid. • Because of the lipid envelope, flavviviruses are readily inactivated by organic solvents and detergents.

15. ETIOLOGYVIRUS

16. ETIOLOGY VIRUS • Three viral proteins are associated with virions. • The E (envelop), M (membrane) and C (capsid) proteins.

17. VIRUS • The E protein is the major surface protein of the viral particle probably interacts with viral receptors, and mediates virus-cell membrane fusion. • Antibodies that neutralize virus infectivity usually recognize this protein and mutations in E can affect virulence.

18. VIRUS • M protein is a small proteolytic fragment which is important for maturation of the virus into an infectious form. • C protein is a component nucleocapsid.

19. EtiologyTypes • Four distinct antigenically related serotypes ( 1to 4) of dengue virus of the family flaviviridae are etiologically responsible. • Infection in human by one serotypes produces life long immunity against re-infection by the same serotype. • subsequent infection with other serotypes may result in a severe illness ie., DHF or DSS

20. EtiologyDengue like fever • Three other arthropod born viruses cause similar febrile diseases with rash. • Chikungunya, Onyong-nyong and West Nile Fever

22. EtiologyDengue like fever • Dengue like diseases may also occur in epidemics. • Epidemiological features depends on the vector and their geographic distribution.

23. EtiologyDengue like fever • Chikungunya Virus is wide spread in the most areas of the world. In Asia A Aegypti is the principal vector. In South East Asia dengue and Chikungunya outbreaks occurs concurrently • Outbreaks of onyong-nyong and West Nile Fever usually involve villages or small towns in contrast to the urban outbreaks of dengue and chikungunya.

24. EPIDOMIOLOGY • Dengue outbreaks in urban areas infested with A.aegypti may be explosive upto 70-80% of population may be involved. • During epidemic most disease occur in older children and adults because A.aegypti has a limited range spread, epidemic occurs mainly through viremic human beings and follows the main lines of transportation . • Where dengue is endemic children and susceptible foreigners may be the only persons to acquire overt disease adults having become immune.

25. EPIDOMIOLOGY Vector • Dengue viruses are transmitted by mosquitoes of the stegomyia family. • Acdes aegypti a day time biting mosquito is the principal vector and all 4 types of virus have been recovered from it.

27. Vector • Aedes mosquitoes (Tiger mosquito): distinguished by white stripes on black body. • Important members aedes family:A. aegypty, A.vittatus and A. albopictus. • They are most abundent during rainy season.

28. Vector • Lays egg singly, and eggs are cigar shaped. • Female mosquito acts as vector. • They do not fly over long distance- <100mts(110yards), this factor facilitates its eradication.

29. Transmission • In most tropical areas A-aegypti is highly urbanized. • They breed in fresh water like water stored for drinking or bathing and in rain water collected in any container. • Dengue viruses have also been recovered from Aedes- Albopictus.

30. Transmission • Outbreaks in the Pacific area have been attributed to several other Aedes species. • These species breed in water trapped in vegetation.

31. Pathogenesis • In experimental studies of dengue virus infection in rhesus monkeys, after subcutaneous inoculation, virus was disseminated rapidly to regional lymph nodes and then to lymphatic tissue through out the body.

32. Pathogenesis • Early in the viremic period virus could be recovered only from lymphonodes. • 2-3 days later there will be evidence of dissemination of skin and other tissues • Virus was recovred from skin, lymphonodes and several leukocyte –rich tissues for up to 3 days after termination of Viremia.

33. Pathogenesis • The number of sites of virus recovery greater as the infection progresses. Intra cellular infection is terminated abruptly 2-3 days after viremia ceases. • Animals infected with dengue virus type, 1,3 & 4 and then infected with dengue virus type 2 circulated virus at higher titer than when the strain was inoculated on to susceptible animals.

34. Pathogenesis • Epidemiological , Clinical and virologic studies of DHF / DSS in humans have shown a significant association between severe illness and infection in presence of circulating dengue antibody. • If tissue culture or suckling mice are used for virus recovery, dengue virus almost invariably is absent in tissues at the time of death. Tissue suspension contain large qualities of dengue neutralizing substances.

35. Pathogenesis Prospective study of dengue virus infection in Thai children: • DHF / DSS occurred in children who were circulating enhancing antibodies from a previous single dengue virus infection. But did not occur in children whose first infection left them with low levels of cross reactive Dengue virus type-2 neutralizing antibodies at the time of second dengue virus infections.

36. Pathogenesis • In vitro studies of dengue virus type-2 demonstrated enhanced growth in cultures of human mononuclear phagocytes that were supplemented with very small qualities of dengue antibodies. • It has been proposed that the number of infected mono nuclear phagocytes in individuals with naturally or passively acquired antibody may exceed that in non immune individuals.

37. Pathogenesis • Increase production of infected cells may contribute to shock, possibly through the release of cytokines, themselves the products of the immune elimination of virus infected, mononuclear phagocytes through cell mediated mechanisms.

38. Pathogenesis • It is thought that the reduced risk to DHF / DSS of protein – calorie malnourished children is consistent with hypothesis that a competent immune elimination system generates the cytokines that produce DHF / DSS.

39. Pathogenesis • Early in the acute stage of secondary dengue virus infection, there is rapid activation of the complement system. • During shock : Blood levels of C1q, C3, C4, C5, C6, C7, C8 and C3 proactivator are depressed. C3 catabolic rates elevated. The blood clotting and fibrinolytic system are activated.

40. Pathogenesis Recent studies suggest a role for tumor necrosis factor and interferon gamma. As yet neither the mediator of vascular permiability nor complete mechanism of bleeding has been identified.

41. Pathogenesis • Capillary damage allows fluid electrolytes, protein, and in some instances red blood cell to leak in to intra vascular spaces. This internal redistribution of fluid together with deficit due to fasting, thirsting and vomiting results in hemo concentration, hypovolemia, increased cardiac work, tissue hypoxia, metabolic acidosis and hyponatremia.

42. Pathogenesis • A mild degree of DIC plus liver damage and thrombocytopenia Could contribute additively to produce haemorrhage.

43. Pathology • Pathologic examination there usually are no gross or microscopic lesions found that might account for death. • In rare instances death may be due to gastro intestinal or intra cranial hemorrhages. • Haemorrhages are seen in: Upper GI tract intra ventricular septum of heart, on the pericardium. And on the subserosal surfaces of major viscera.

44. Pathology • Focal hemorrhages occasionally seen in the lungs, liver, adrenals, sub arachniod space. • The liver is usually is enlarged often with fatty changes. • Yellow watery at times blood tinged effusions are present in serous cavities in about ¾ of patient and retro peritoneal tissues are markedly edematous.

45. PathologyMicroscopy • Perivascular edema in the soft tissues and wide spread of diapedesis of RBC. • There may be maturational arrest of megakaryocytes in the bone marrow and increased numbers of them are seen in capillaries of lungs, in renal grlomeruli and in sinusoids of the liver and spleen.

46. PathologyMicroscopy • Proliferation of lymphoid and plasma cytoid cells, lymphocytolysis and lymphophagocytosis occurs in the spleen and lymphonodes. • In the spleen malpighian corpuscle germinal centres are necrotic there is a depletion of lymphocytes in the thymus.

47. PathologyMicroscopy • Liver: there are varying degrees of Falty metamorphosis, Focal midzonal necrosis Hyperplasia of the Kupffer Cells. Non nucleated cells with vacuolated acidophilic cytoplasm resembling councilmanbodies are seen in the sinusoids.

48. PathologyMicroscopy • Kidney:There is a mild proliferative glamerulo nephritis . • Skin: Biopsies of the rash reveal swelling and minimal necrosis of endothelial cells. Subcutaneous deposits of fibrinogen and in a few cases dengue antigen in extra vascular mononuclear cells and on blood vessel walls.

49. DengueClassification • Dengue fever • Dengue hemorrhagic fever • Dengue shock syndrome

50. Classification Dengue fever • Dengue fever is an acute febnile viral illness presenting with Headache, bone (Back break fever), or joint (chikungunya or o-nyony-nyong) and muscular pains, rash and leucopenia caused by arthropod borne viruses.