Arbovirus part 2

1. Dr.T.V.Rao MD
Dr.T.V.Rao MD 1
Arboviruses
Arthropod-Borne Viruses
Part 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. DENGUE FEVER
Dr.T.V.Rao MD 3

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. 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. 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. 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. 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. Distribution of Dengue
Dr.T.V.Rao MD 9

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. Dengue
Mosquito transmitted Viral Infection
Dr.T.V.Rao MD 11

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. 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. 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. 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. 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. 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. 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. 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. 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. Dr.T.V.Rao MD 21

22. Dengue with Rashes
Dr.T.V.Rao MD 22

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. 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. 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. 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. What Happens in Dengue
Hemorrhagic Fever
• Thrombocytopenia (platelets 100,000/cu.mm 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Viral Hemorrhagic Fevers
Dr.T.V.Rao MD 38

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Rodent Borne Hemorrhagic
Fevers,
•Hanta Virus, Produces
pulmonary infections in
USA
•Belong to Bunya Virus –
Hanta Viruses
Dr.T.V.Rao MD 53

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. Dr.T.V.Rao MD 55

56. Laboratory Diagnosis
•Detection of viral nucleic
acid,
•Grown in culture lines,
•PCR,
Dr.T.V.Rao MD 56

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. Filoviruses. Marburg
• Marburg 1967 African Green
Monkey,
• Bat – Rodent – Host Human.
• East Africa Monkey – Humans.
Dr.T.V.Rao MD 58

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. 1979, 2004
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Dr.T.V.Rao MD 60

61. Dr.T.V.Rao MD 61

62. Bunya viruses
• Rift Valley fever
• Crimean Congo
hemorrhagic
fever
Dr.T.V.Rao MD 62

63. Rift Valley Fever
• Disease of sheep and
cattle
• Humans: Asymptomatic-
to-mild
• Rare
VHF, encephalitis, retiniti
s

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. 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. 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. 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. 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. 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. 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. 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. 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. • 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. 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. • Programme Created by Dr.T.V.Rao
MD for Medical Students in the
Developing World
• Email
• doctortvrao@gmail.com
Dr.T.V.Rao MD 75