Arbovirus part 2


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Arbovirus part 2

  1. 1. Dr.T.V.Rao MD Dr.T.V.Rao MD 1 Arboviruses Arthropod-Borne Viruses Part 2
  2. 2. Arthropod-borne Viruses Arboviruses belong to three families 1. Togaviruses e.g. EEE, WEE, and VEE 2. Bunyaviruses e.g. Sandfly Fever, Rift Valley Fever, Crimean-Congo Haemorrhagic Fever 3. Flavivirus e.g. Yellow Fever, Dengue, Japanese Encephalitis Dr.T.V.Rao MD 2
  3. 3. DENGUE FEVER Dr.T.V.Rao MD 3
  4. 4. Arboviruses • The Arbovirus are also called as Arthropod borne viruses, represent an ecological grounding of viruses with complex transmission cycles involving Arthropods • These viruses have diverse physical and chemical properties and are classified in several virus families.Dr.T.V.Rao MD 4
  5. 5. History - Dengue • 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. Dr.T.V.Rao MD 5
  6. 6. Over view of Dengue • With more than one-third of the world’s population living in areas at risk for transmission, dengue infection is a leading cause of illness and death in the tropics and subtropics. As many as 100 million people are infected yearly. Dengue is caused by any one of four related viruses transmitted by mosquitoes Dr.T.V.Rao MD 6
  7. 7. Dengue • Dengue is the biggest Arbovirus problem in the world today with over 2 million cases per year. Dengue is found in SE Asia, Africa and the Caribbean and S America. • Flavivirus, 4 serotypes, transmitted by Aedes mosquitoes which reside in water-filled containers. • Human infections arise from a human-mosquitoe- human cycle Dr.T.V.Rao MD 7
  8. 8. Current Trends • 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.. Dr.T.V.Rao MD 8
  9. 9. Distribution of Dengue Dr.T.V.Rao MD 9
  10. 10. Dengue Infection and Implications • Dengue virus (DENV) infects 50 million (WHO) to 100 million (NIH) people annually.. DENV infection can cause dengue fever, dengue haemorrhagic fever, dengue shock syndrome, and death. Dr.T.V.Rao MD 10
  11. 11. Dengue Mosquito transmitted Viral Infection Dr.T.V.Rao MD 11
  12. 12. What causes Dengue • Dengue (DF) and dengue haemorrhagic fever (DHF) are caused by one of four closely related, but antigenic ally 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, Dr.T.V.Rao MD 12
  13. 13. Aedes aegypti – Vector • Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans, is the most common Aedes species. Other species of Aedes can also transmit. Dr.T.V.Rao MD 13
  14. 14. Dengue Virus – A Flavivirus • Flavivirus are spherical and 40- 60 mm in diameter. Genome – Positive sense, single sense RNA,11kb in size Genome – RNA infectious Enveloped virus Dr.T.V.Rao MD 14
  15. 15. How Mosquitos spread the infection • The disease starts during the rainy season, when vector Mosquito Aedes aegypti is abundant • The Aedes breeds in the tropical or semitropical climates in water holding receptacles or in plants close to human dwellings Dr.T.V.Rao MD 15
  16. 16. Cycle of Infection Continues • A female Aedes acquires the infection feeding upon a viremic human. • After a period of 8 – 14 days mosquitoes are infective and remain infective for life. ( 1- 3 ) months. Dr.T.V.Rao MD 16
  17. 17. Pathogenesis • Presence of existing Dengue antibody, associated with fresh viral infection with new serotype complexes and forms within few days of the second dengue infection. • Non neutralizing enhancing antibodies promote infection of higher number of Mononuclear cells. Dr.T.V.Rao MD 17
  18. 18. Immunology Dengue • Four serotypes exist distinguished by Molecular basis and Nt tests • Infection confers life long immunity • But cross protection between serotypes is of short duration. • Reinfection with different serotype after primary attack is more dangerous causes Dengue hemorrhagic fever. Dr.T.V.Rao MD 18
  19. 19. Clinical Manifestations • Any or few of the following events can occur. • Fever, • Severe head ache • Muscle and joint pains • Nausea, vomiting, • Eye pain Dr.T.V.Rao MD 19
  20. 20. How Dengue Infection starts and manifests • Incubation period 4 – 7 days ( 3 – 14 days) • Fever may start with, Malise,chills,head ache • Soon leads to severe back ache, joint pains, muscular pain, pain in the eye ball. • Temperature may persist for 3 -5 days. • Myalgia may be severe with deep bone pain ( Break bone fever ) characteristic of the Disease Dr.T.V.Rao MD 20
  21. 21. Dr.T.V.Rao MD 21
  22. 22. Dengue with Rashes Dr.T.V.Rao MD 22
  23. 23. Dengue Hemorrhagic Fever • DHF was first recognized in the 1950s during the dengue epidemics in the Philippines and Thailand. Today emerging DHF cases are causing increased dengue epidemics in the Americas, and in Asia, where all four dengue viruses are endemic, DHF has become a leading cause of hospitalization and death among children in several countries. ( WHO ) Dr.T.V.Rao MD 23
  24. 24. Dengue Hemorrhagic Fever • Common in children. • In children passively acquired contributed by the maternal antibodies transferred to the fetus. • In other ( Adults ) the presence of antibodies due to previous infection with different serotype • Initially presents like classical Dengue infection • But patients condition abruptly worsens, an important cause of morbidity and mortality in Dengue Dr.T.V.Rao MD 24
  25. 25. Basic Understanding of Dengue Hemorrhagic Fever • Dengue Hemorrhagic Fever is a probable case of dengue and • hemorrhagic tendency evidenced by one or more of the following: • Ø Positive tourniquet test • Ø Petechial, ecchymosis or purpura • Ø Bleeding from mucosa (mostly epistaxis or bleeding from • gums), injection sites or other sites • Ø Haematemesis or melena Dr.T.V.Rao MD 25
  26. 26. How to do a Tourniquet test • The tourniquet test is performed by inflating a blood pressure cuff to a point mid-way between the systolic and diastolic pressures for five minutes. A test is considered positive when 10 or more petechiae per 2.5 cm2 (1 inch) are observed. In DHF, the test usually gives a definite positive result (i.e. >20 petechiae). Dr.T.V.Rao MD 26
  27. 27. What Happens in Dengue Hemorrhagic Fever • Thrombocytopenia (platelets 100,000/ or less) and Ø Evidence of plasma leakage due to increased capillary permeability manifested by one or more of the following: • – A >20% rise in hematocrit for age and sex • – A >20% drop in hematocrit following treatment with • fluids as compared to baseline • – Signs of plasma leakage (pleural effusion, ascites or • hypoproteinaemia). Dr.T.V.Rao MD 27
  28. 28. Risk factor for DHF • 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 Dr.T.V.Rao MD 28
  29. 29. Dengue Hemorrhagic Syndrome • Chateresied by shock and hemoconcentration • Contributed by circumstantial evidence suggests secondary infection with Dengue type 2 following type 1 infection in the past.Dr.T.V.Rao MD 29
  30. 30. Dengue hemorraghigic Syndrome • DHS is caused due to release of, 1 Release of cytokines 2 Vasoactive mediators. 3 Procoagulants Manifest with disseminated intravascular coagulation Dr.T.V.Rao MD 30
  31. 31. Diagnosis In resource rich establishments 1 Reverse transcriptase polymerase chain reaction methods help rapid identification 2 Isolation of virus is difficult 3 The current favored approach is inoculation of mosquito cell line with patient serum coupled with nucleic acid assay to identify a recovered virus. Dr.T.V.Rao MD 31
  32. 32. Dengue Serology • The serology is limited with cross reactivity of IgG antibodies to heterologous Flavivirus antigens • Most commonly used methods are Viral protein specific capture IgM or IgG by ELISA IgM antibodies develop within few days of illness Neutralizing anti Haemagglutination inhibiting antibodies appear within a week after onset of Dengue feverDr.T.V.Rao MD 32
  33. 33. Importance of paired sample testing in Serology • Testing one sample for serum and reporting a negative test is fallacious • Analysis of paired acute and convalescent sera to show significant rise in antibody titer is the most reliable evidence of an active dengue infection. Dr.T.V.Rao MD 33
  34. 34. Newer Diagnostic Methods RT - PCR • RT PCR is a highly sensitive tool in Diagnosis, with established high sensitivity in Diagnosis in Puzzles • Developing world lacks resources to implement and utilize the Scientific advances Dr.T.V.Rao MD 34
  35. 35. Treatment • No Anti viral therapy available • Symptomatic management in Majority of cases • Dengue Hemorrhagic fever to be treated with suitable fluid replacement • No Vaccine available, difficult in view of four serotypes. Dr.T.V.Rao MD 35
  36. 36. Control of Dengue • Control of Mosquito breeding places. • Anti mosquito measures • Use of Insecticides. • Screened windows and doors can reduce exposure to vectors. Dr.T.V.Rao MD 36
  37. 37. Epidemiology - Dengue • Dengue virus are distributed world wide in tropical regions. • Where the Aedes vectors exist, are endemic areas • Changing and increasing incidences are associated with rapid urban population growth, over crowding and lax mosquito control measures Dr.T.V.Rao MD 37
  38. 38. Viral Hemorrhagic Fevers Dr.T.V.Rao MD 38
  39. 39. Viral Haemorrhagic Fevers • Acute infection: fever, myalgia, malaise; progression to prostration • Small vessel involvement: increased permeability, cellular damage • Multisystem compromise (varies with pathogen) • Hemorrhage may be small in volume (indicates small vessel involvement, thrombocytopenia) • Poor prognosis associated with: shock, encephalopathy, extensive hemorrhage Dr.T.V.Rao MD 39
  40. 40. Viral Hemorrhagic Fevers • Diverse group of illnesses caused by RNA viruses from 4 families: – Arenaviridae, Bunyaviridae, Filoviridae, Flaviridae – Differ by geographic occurrence and vector/reservoir – Share certain clinical and pathogenic features • Potential for aerosol dissemination, with human infection via respiratory route (except dengue) • Target organ: vascular bed • Mortality 0.5 - 90%, depending on agent Dr.T.V.Rao MD 40
  41. 41. Viral Hemorrhagic Fever viruses • Filoviruses Ebola Hemorrhagic fever (EHF) Marburg virus • Arena viruses Lassa fever “New World Arena viruses” • Bunyaviruses Rift Valley fever (RVF) Crimean Congo Hemorrhagic fever (CCHF) Dr.T.V.Rao MD 41
  42. 42. Viral Hemorrhagic Fevers • Category A agents – Filo viruses – Arena viruses • Category C agents – Hantaviruses – Tick-borne hemorrhagic fever viruses – Yellow fever Dr.T.V.Rao MD 42
  43. 43. Viral Hemorrhagic Fevers Transmission • Zoonotic diseases – Rodents and arthropods main reservoir – Humans infected via bite of infected arthropod, inhalation of rodent excreta, or contact with infected animal carcasses • Person-to-person transmission possible with several agents – Primarily via blood or bodily fluid exposure – Rare instances of airborne transmission with arenaviruses and filoviruses • Rift Valley fever has potential to infect domestic animals following a biological attack Dr.T.V.Rao MD 43
  44. 44. Viral Hemorrhagic Fevers Clinical Presentation • Clinical manifestations nonspecific, vary by agent • Incubation period 2-21 days, depending on agent • Onset typically abrupt with filoviruses, flaviviruses, and Rift Valley fever • Onset more insidious with arenaviruses Dr.T.V.Rao MD 44
  45. 45. Viral Hemorrhagic Fevers Initial Symptoms – High fever – Headache – Malaise – Weakness – Exhaustion – Dizziness – Muscle aches – Joint pain – Nausea – Non-bloody diarrhea Prodromal illness lasting < 1 week may include: Dr.T.V.Rao MD 45
  46. 46. VHF Surveillance: Clinical Identification of Suspected Cases • Clinical criteria: – Temperature 101 F(38.3 C) for <3 weeks – Severe illness and no predisposing factors for hemorrhagic manifestations – 2 or more of the following: • Hemorrhagic or purple rash • Epistaxis • Hematemesis • Hemoptysis • Blood in stools • Other hemorrhagic symptoms • No established alternative diagnosis JAMA 2002;287 Adapted from WHO Dr.T.V.Rao MD 46
  47. 47. Viral Hemorrhagic Fevers Treatment • Supportive care • Correct coagulopathies as needed • No antiplatelet drugs or IM injections • Investigational treatments, available under protocol: – Ribavirin x 10 days for Arenaviridae and Bunyaviridae – Convalescent plasma w/in 8d of onset for AHF Dr.T.V.Rao MD 47
  48. 48. Viral Hemorrhagic Fevers Management of Exposed Persons • Medical surveillance for all potentially exposed persons, close contacts, and high-risk contacts (i.e., mucous membrane or percutaneous exposure) x 21 days – Report hemorrhagic symptoms (slide 47) – Record fever 2x/day • Report temperatures 101 F(38.3 C)  Initiate presumptive ribavirin therapy • Percutaneous/mucocutaneous exposure to blood or body fluids of infected: – Wash thoroughly with soap and water, irrigate mucous membranes with water or saline Dr.T.V.Rao MD 48
  49. 49. Viral Hemorrhagic Fevers Infection Control • Airborne & contact precautions for health care, environmental, and laboratory workers • Negative pressure room, if available – 6-12 air changes/hour – Exhausted outdoors or through HEPA filter • Personal protective equipment – Double gloves – Impermeable gowns, leg and shoe coverings – Face shields and eye protection – N-95 mask or PAPR Dr.T.V.Rao MD 49
  50. 50. Tick Borne Hemorrhagic Fevers • Kyasanur Forest Disease, • ( Karnataka India ) • Like Russian Spring Summer Encephalitis, • Present with Fever, Headache, Conjunctivitis, Myalgia, Severe prostration, Dr.T.V.Rao MD 50
  51. 51. Viral Hemorrhagic Fevers Summary of Key Points • A thorough travel and exposure history is key to distinguishing naturally occurring from intentional viral hemorrhagic fever cases. • Viral hemorrhagic fevers can be transmitted via exposure to blood and bodily fluids. Dr.T.V.Rao MD 51
  52. 52. Pathogenesis. • Enters through the bite of Insect vector, • Multiply in RES. • Target the organ CNS Encephalitis, Liver Yellow fever, Capillary endothelium in Hemorrhagic fevers. Dr.T.V.Rao MD 52
  53. 53. Rodent Borne Hemorrhagic Fevers, •Hanta Virus, Produces pulmonary infections in USA •Belong to Bunya Virus – Hanta Viruses Dr.T.V.Rao MD 53
  54. 54. Hanta Viruses, • Human disease Hemorrhagic fever with renal syndrome • Hanta virus pulmonary syndrome. • Spread by inhalation of Aerosols of Rodent Excreta, • Renal Involvement and failure • Lead to Hemorrhagic shock, Korea • Spread by Rats carried in ships, Dr.T.V.Rao MD 54
  55. 55. Dr.T.V.Rao MD 55
  56. 56. Laboratory Diagnosis •Detection of viral nucleic acid, •Grown in culture lines, •PCR, Dr.T.V.Rao MD 56
  57. 57. Filoviruses, African Hemorrhagic Fevers. • Most important Diseases are • Marburg and Ebola. • The nature of Viruses are 80 nm Filamentous threads, • Produce Internal and external Bleeding. Dr.T.V.Rao MD 57
  58. 58. Filoviruses. Marburg • Marburg 1967 African Green Monkey, • Bat – Rodent – Host Human. • East Africa Monkey – Humans. Dr.T.V.Rao MD 58
  59. 59. Filoviruses - Ebola • Incubation 2-21 days • Carries 80% mortality. • Barrier Nursing Most essential. • ELISA test • Culturing Hazardous. • RT-PCR • Transporting and carrying Primates is Hazardous Dr.T.V.Rao MD 59
  60. 60. 1979, 2004 4,0002,000 kilometers 0 DRCDRCDRCDRCDRCDRCDRCDRCDRC (formerlyZaire)(formerlyZaire)(formerlyZaire)(formerlyZaire)(formerlyZaire)(formerlyZaire)(formerlyZaire)(formerlyZaire)(formerlyZaire) GabonGabonGabonGabonGabonGabonGabonGabonGabon South AfricaSouth AfricaSouth AfricaSouth AfricaSouth AfricaSouth AfricaSouth AfricaSouth AfricaSouth Africa UgandaUgandaUgandaUgandaUgandaUgandaUgandaUgandaUganda SudanSudanSudanSudanSudanSudanSudanSudanSudan Ivory CoastIvory CoastIvory CoastIvory CoastIvory CoastIvory CoastIvory CoastIvory CoastIvory Coast 1994 1994, 1996, 1996 1976, 1995 1996* 2000 1976, 1979, 200 4 *Doctor returning from Gabon Ebola Outbreaks Congo 2003 Dr.T.V.Rao MD 60
  61. 61. Dr.T.V.Rao MD 61
  62. 62. Bunya viruses • Rift Valley fever • Crimean Congo hemorrhagic fever Dr.T.V.Rao MD 62
  63. 63. Rift Valley Fever • Disease of sheep and cattle • Humans: Asymptomatic- to-mild • Rare VHF, encephalitis, retiniti s
  64. 64. Rift Valley Fever • Mosquito-borne (Aedes spp.) vertical transmission in mosquitos • Transmission: – Animal contact (birthing or blood) – Laboratory aerosol • Mortality 1% overall • Therapy: Ribavirin? • Live-attenuated vaccine (MP-12) undergoing trials Dr.T.V.Rao MD 64
  65. 65. Rift Valley Fever: Clinical features • 3-7 day incubation, 3-5 day duration • Asymptomatic or mild illness • Fever, myalgia, weakness, weight loss • Photophobia, conjunctivitis • Encephalitis • <5% hemorrhagic fever • 1-10% vision loss (retinal hemorrhage, vasculitis) Dr.T.V.Rao MD 65
  66. 66. CRIMEAN CONGO HEMORRHAGIC FEVER (CCHF) • Extensive geographic distribution (Africa, Balkans, and western Asia) • Transmission: – Tick-borne (Hyalomma spp.) – Contact with animal blood or products – Person-to-person transmission by contact with infectious body fluids – Laboratory worker transmission documented • Mortality 15-40% • Therapy: RibavirinDr.T.V.Rao MD 66
  67. 67. CCHF: Pathogenesis • Viremia present throughout disease • IFA becomes positive in patients destined to survive days 4- 6, often simultaneously with Viremia • Recovery may be due to CMI or neutralizing antibodies • Patients that die usually still Viremia • Virus grows in macrophages and other cells • DIC often present • Poor prognosis signaled by early elevated AST and clotting Dr.T.V.Rao MD 67
  68. 68. CCHF: Clinical features • 4-12 day incubation after tick exposure • 2-7day incubation after direct contact with infected fluids • Abrupt onset fever, chills, myalgia, severe headache • Malaise, GI symptoms, anorexia • Leukopenia, thrombocytopenia, hemoconcentration, pro teinuria, elevated AST • Hemorrhages may be profuse (hematomas, ecchymoses) Dr.T.V.Rao MD 68
  69. 69. PREVENTION OF CCHF • DEET repellents for skin • Permethrin repellents for clothing – (0.5% permethrin should be applied to clothing ONLY) • Check for and remove ticks at least twice daily. • If a tick attaches, do not injure or rupture the tick. Remove ticks by grasping mouthparts at the skin surface using forceps and apply steady traction. Dr.T.V.Rao MD 69
  70. 70. Guanarito (Venezuelan Hemorrhagic Fever) • Venezuela, central plains • Rodent borne (Zygodontomys brevicauda) • Person-to-person transmission not documented • Mortality 20-30% • Therapy: Ribavirin(?)Dr.T.V.Rao MD 70
  71. 71. South American Hemorrhagic Fevers: Clinical features • 1-2 week incubation • Gradual onset fever, malaise, myalgias, anorexia • Headache, abdominal pain, nausea, vomiting, orthostasis • Petechiae (axillae, palate), gingival hemorrhage • Neurologic signs (hyporeflexia, tremor, lethargy, hyperesthesia) • Leukopenia, thrombocytopenia, proteinuria Dr.T.V.Rao MD 71
  72. 72. South American Hemorrhagic Fevers: Clinical features • 70% Recovery in 7-8 days without sequelae, prolonged fatigue and weakness common. • Severe disease – Severe hemorrhage – Delerium, coma, convulsions – Combined hemorrhagic/neurologic disease • High mortality Dr.T.V.Rao MD 72
  73. 73. • Rule out or treat febrile illnesses: malaria, rickettsia, leptospirosis, typhoid, dysentery • Early hospitalization • Distant medical evacuation associated with high mortality • Cautious sedation and analgesia • Careful hydration • Pressors, cardiotonic drugs • Support of coagulation system VHF: Supportive therapy Dr.T.V.Rao MD 73
  74. 74. Ribavirin • Guanosine nucleoside analog: blocks viral replication by inhibiting IMP dehydrogenase • Licensed for treatment of RSV and HCV • Potential adverse effects: • Dose dependent reversible anemia • Pancreatitis • Teratogen in rodents Dr.T.V.Rao MD 74
  75. 75. • Programme Created by Dr.T.V.Rao MD for Medical Students in the Developing World • Email • Dr.T.V.Rao MD 75