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
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
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
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
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
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
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
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
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
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
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
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