Arboviruses are viruses that can be transmitted to humans by arthropod vectors such as mosquitoes and ticks. There are approximately 80 known arboviruses that cause human disease. They are classified into families including Togaviridae, Flaviviridae, Bunyaviridae, Reoviridae, and Rhabdoviridae. Some important arboviruses prevalent in India include Chikungunya virus, Dengue virus, Japanese encephalitis virus, Kyasanur forest disease virus, and Sindbis virus. These viruses are transmitted between vertebrate hosts and arthropod vectors in natural cycles and can cause diseases ranging from fever and rash to hemorrhagic

1. Arboviruses
Dr. Pendru Raghunath Reddy

2. Arthropod-borne viruses (arboviruses) are viruses that can
be transmitted to man by arthropod vectors
The WHO definition
Viruses that are maintained in nature principally, or to an
important extent, through biological transmission between
susceptible vertebrate host by hematophagous arthropods or
through transovarian and possibly venereal transmission in
arthropods”

3.  They can multiply in the tissues of the arthropod without evidence of
disease or damage
 The vector acquires a lifelong infection through the ingestion of blood
from a viremic vertebrate
 All arboviruses have an RNA genome, and most have a
lipid-containing envelope and consequently are inactivated by
ether or sodium deoxycholate
 Inclusion in this group is based on ecological and epidemiological
considerations and hence it contains viruses of diverse physical
and chemical properties
 Though taxonomically unacceptable, the name “arbovirus” is a
useful biological concept

4. Classification
 Togaviridae
Genus Alphavirus
 Flaviviridae
Genus Flavivirus
 Bunyaviridae
Genus Bunyavirus
 Reoviridae
Genus Orbivirus
 Rhabdoviridae Genus Vesiculovirus
 Orthomyxoviridae
Approximately 80 arboviruses known to cause human disease

5. Arboviruses prevalent in India
Virus
Reservoir
Vector
Disease
Chikungunya
Monkeys
Mosquito
Chikungunya fever
Dengue
Monkeys,
Man
Mosquito
Dengue
haemorrhagic fever
Japanese B
encephalitis
Wild birds,
pigs
Mosquito
Encephalitis
Kyasanur forest
disease
Forest birds,
animals
Tick
Haemorrhagic fever
Sindbis
-
Mosquito
Sindbis fever

6. General properties
The arboviruses share some common biological properties
1. All members produce fatal encephalitis in suckling mice after
intracerebral inoculation
2. They possess haemagglutinin and agglutinate erythrocytes of goose
or day-old chicks
3. They can be grown in tissue cultures of primary cells like chick
embryo fibroblasts or continuous cell lines like vero, and in cultures
of appropriate insect tissues
4. They may also be isolated in the yolk sac or CAM of chick embryo
5. In general, arboviruses are readily inactivated at room temperature
and by bile salts, ether and other lipid solvents

7. Arthropod Vectors
Mosquitoes
Japanese encephalitis, dengue, yellow fever, Rift valley fever
St. Louis encephalitis, EEE, WEE, VEE etc
Ticks
Crimean-Congo haemorrhagic fever, Kyasanur forest disease
and various tick-borne encephalitis etc.
Sandflies
Sicilian sandfly fever

8. Examples of Arthropod Vectors
Aedes aegyti
Culex Mosquito
Ixodid Ticks
Phlebotomine Sandfly

9. Animal Reservoirs
In many cases, the actual reservoir is not known. The
following animals are implicated as reservoirs
Birds
encephalitis,
Japanese
B
encephalitis,
St
Louis
EEE, WEE
Pigs
Japanese B encephalitis
Monkeys
Yellow Fever
Rodents
VEE, Russian Spring-Summer encephalitis

10. Pathogenesis
When an infected vector bites a suitable host, the virus
is injected into the capillary circulation
Virus comes in contact with susceptible target cells such as
endothelial cells of capillaries, monocytes, macrophages
and cells of RES
After replication in endothelial cells and RE cells, a
secondary viraemia usually results leading to infection of
target organs such as brain, skin, musculature and liver,
depending on the tissue tropism
The virus reaches the brain by infecting small blood vessels
of the brain or choroid plexus

11. Diseases Caused
Fever with or without rash - this is usually a non-specific illness
resembling a number of other viral illnesses such as influenza,
rubella, and enterovirus infections. The patients may go on to
develop encephalitis or haemorrhagic fever
Encephalitis - e.g. EEE, WEE, St Louis encephalitis, Japanese B
encephalitis
Haemorrhagic fever - e.g. yellow fever, dengue, Crimean-Congo
haemorrhagic fever
All arbovirus infections occur with varying degree of severity,
subclinical infections being common

12. Structure of Alphaviruses

13. Principal medically important alphaviruses
Virus
Clinical
Syndrome
Vector
Host
Distribution
Eastern
equine
encephalitis
Encephalitis
(EEE)
Mosquito
Birds
Americas
Western
equine
encephalitis
Encephalitis
(WEE)
Mosquito
Birds
North
America
Venezuelan
equine
encephalitis
Febrile
illness,
encephalitis
(VEE)
Mosquito
Rodents,
horses
Americas

14. Virus
Clinical
Syndrome
Vector
Host
Distribution
Febrile
illness, rash,
arthralgia
Mosquito
humans
Africa,
India,
Southeast
Asia
O’nyongFebrile
nyong (ONN) illness, rash,
arthralgia
Mosquito
Primates
Africa
Sindbis (SIN)
Febrile
illness, rash,
arthralgia
Mosquito
Birds
Nothern
Europe,
Africa, Asia,
Australia
Semliki
Forest
Febrile
illness, rare
encephalitis
Mosquito
Birds
Africa
Chikungunya
(CHIK)

15. Chikungunya virus
 The virus is transmitted by Aedes aegypti
 Full-blown disease is most common in adults
 Incubation period - 2-3 days
 The disease is chracterised by fever, crippling joint pains,
lymphadenopathy, conjunctivitis and rash
 Migratory polyarthritis mainly affects the small joints of the hands
and wrists
 The fever is typically biphasic with a period of remission after
1-6 days

16.  A maculopapular rash is common and most intense on the trunk
and limbs that may desquamate
 Haemorrhagic manifestations are seen in some patients
 Chickungunya is the native word for the disease in which the
patient lies ‘doubled up’ due to severe joint pains
 The virus first appeared in India in 1963 when it caused extensive
epidemics in calcutta, Madras and other areas
 There is no animal reservoir for the virus
 No vaccine is available

17. Structure of Flaviviruses

18. Principal medically important flaviviruses
Virus
Clinical
Syndrome
Vector
Host
Distribution
Dengue
(DEN)
Febrile
illness, rash,
hemorrhagic
fever, shock
syndrome
Mosquito
Humans
Tropics,
worldwide
Yellow fever Hemorrhagic
fever,
(YF)
hepatitis
Mosquito
Primates,
humans
Africa, South
America
Birds
Americas
St. Louis
encephalitis
(SLE)
Encephalitis Mosquito

19. Principal medically important flaviviruses
Virus
Clinical
Syndrome
Vector
Host
Distribution
Japanese
encephalitis
(JE)
Encephalitis
Mosquito
Pigs, birds
India, China,
Japan,
South-East
Asia
West Nile
Febrile
illness
Mosquito
Birds
Africa, Middle
East, Europe
Tick-borne
encephalitis
(TBE)
Encephalitis
Tick
Rodent
Europa, Asia

20. Principal medically important flaviviruses
Virus
Clinical
Syndrome
Vector
Host
Distribution
Omsk
hemorrhagic
fever
Hemorrhagic
fever
Tick
Muskrats
Siberia
Kyasanur
Forest disease
(KFD)
Hemorrhagic
fever
Tick
Rodents
India

21. Human infection with both mosquito-borne and tick-borne
flaviviruses is initiated by deposition of virus through the skin via
the saliva of an infected arthropod (Fig).
Figure. Pathogenesis of flaviviruses.

22. Japanese B encephalitis
First discovered and originally restricted to Japan. Now large
scale epidemics occur in China, India and other parts of Asia
The virus was named Japanese B encephalitis virus to distinguish
it from Japanese A encephalitis virus
Transmitted by Culex tritaeniorhynchus mosquitoes
The virus is maintained in nature in a transmission cycle involving
mosquitoes, birds (reservoirs) and pigs (amplifier hosts)
Herons act as reservoir host and pigs as amplifier hosts

23. Clinical features
 Most human infections are subclinical: the inapparent to clinical
cases is 500-1000:1
 Incubation period: 5-15 days
 The course of the disease in man may be divided into three stages
1.Prodromal stage
2.Acute encephalitic stage
3.Late stage and sequelae

24. Prodromal stage
The onset of illness is usually acute and symptoms include fever,
headache and vomiting
Acute encephalitic stage
 After 1-6 days, signs of encephalitis characterised by neck rigidity,
convulsions, altered sensorium and coma appear
Late stage and sequelae
 Convalescence may be prolonged and residual neurological deficits
may not be uncommon
 Case fatality rate varies between 20-40%, but it may reach 58% and
over in some epidemics
 Residual neurological damage may persist in about 50% of survivors

25.  The disease is usually diagnosed by serology
 No specific therapy is available
Prevention
Preventive measures include mosquito control and establishment
of piggeries away from residential areas
 A formalin inactivated mouse brain vaccine using the Nakayama
strain has been employed for human immunisation
 A live attenuated vaccine prepared in hamster kidney cell line
is also available

26. Yellow fever

27. Yellow Fever
 Yellow
fever is a mosquito-borne
accompanied by hepatic necrosis
acute
febrile
illness
 It occurs mainly in tropical Africa and Latin America
 It does not exist in India
 The name has been derived from ‘yellow quarantine flag’ used
by the ships during 17th century to warn the presence, on board
of this infection
 Yellow fever occurs in 2 major forms: urban and jungle (sylvatic)
cycle

28.  In the urban cycle, man serves both as reservoir and as definitive
host, the virus being transmitted by Aedes aegypti mosquito
 In the forest or sylvatic cycle, wild monkeys act as reservoirs and
several species of forest mosquitos are vectors. Human cases occur
only when humans trespass into the forest or when monkeys raid
villages

29. Pathogenesis
After introduction into the skin by the mosquito-bite, the
virus multiplies locally and spreads to the local lymphnodes
where it multiplies
From the lymphnodes, it enters the circulating blood. The
virus starts appearing in blood 3-6 days after the bite of
infected mosquito and viraemia lasts for 4-5 days
From blood, the virus becomes localised in the liver,
spleen, kidney, bonemarrow and myocardium, where
it may persist for days
The lesions of yellow fever are due to the localization and
propagation of the virus in a particular organs

30. Clinical features
 After an incubation period of 3-6 days, patient develops fever with
chills, headache, myalgia and vomiting
 Most cases are mild in nature, especially in the endemic areas, in
whom the disease may present as undifferentiated fever without
jaundice
 The pulse is usually slow despite a high temperature
 In 15-20% of cases, the disease progresses to a more serious form
with jaundice, albuminuria, renal failure and haemorrhagic
manifestations and the patient may die of hepatic and renal failure

31. Laboratory diagnosis
Diagnosis is usually clinical; laboratory diagnosis is
made for confirmation
1.Detection of viral antigen
2.Isolation of virus
3.Postmortem diagnosis
4.Serology

32. Detection of viral antigen
Viral antigen or nucleic acid can be detected in tissue
specimen using ELISA, PCR, and immunohistochemistry
Isolation of virus
Virus can be isolated from blood in the first 4 days after
onset or from postmortem tissue by intracerebral inoculation
of mice or inoculating cell lines

33. Postmortem diagnosis
Can be made histologically
There is severe midzonal degeneration, necrosis and
acidophilic inclusion bodies seen in the liver
Serology
During first week of illness, IgM antibody can be
detected by ELISA

34. Prophylaxis
 There is no antiviral drug against yellow fever
The control of urban yellow fever can be achieved by eradicating
the vector mosquito
 Two vaccines have been developed for human use
1. The french neurotropic vaccine (Dakar) produced from infected
mouse brain
2. 17D vaccine developed by Theiler in 1937 by passaging the Asibi
strain serially in mouse embryo and whole chick embryo tissues
and then in chick embryo tissue from which the central nervous
tissue has been removed

35. Dengue Virus

36. Dengue
The word dengue is derived from the Swahili Ki denga pepo
meaning a sudden seizure by a demon
Dengue fever is clinically similar to the illness caused by the
chikungunya and O’nyong-nyong viruses
Dengue virus is widely distributed in the Caribbean region,
south east asia
In India first outbreak of dengue was recorded in 1812
In New Delhi, outbreaks of dengue fever reported in
1967,1970,1982, &1996

37. Distribution of Dengue

38. Morphology of Dengue 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

39.  Three viral proteins are associated with virions
 The E (envelope), M (membrane) and C (capsid) proteins

40. The E protein is the major surface protein of the viral particle and
mediates virus-cell membrane fusion. Antibodies that neutralize
virus infectivity usually recognize this protein and mutations in E
can affect virulence
 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

41. Etiology types
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
All 4 types of dengue viruses are present in India, more than one
type of dengue virus has been occasionally recovered from a
patient
Subsequent infection with other serotypes may result in a severe
illness i. e., dengue haemorrhagic fever or dengue shock
syndrome
Some genetic variants within each serotype appear to be more
virulent or have greater epidemic potential

42. The most common epidemic vector of dengue in the world is the
Aedes aegypti mosquito. It can be identified by the white bands or
scale patterns on its legs and thorax.

43. Aedes aegypti
• Dengue transmitted by infected female mosquito
• Primarily a daytime feeder
• Lives around human habitation
• Lays eggs and produces larvae preferentially in artificial containers

44. Pathogenesis
1.The virus is inoculated into
humans with the mosquito
saliva
2.The virus localizes and
replicates in various organs,
for example, local lymph
nodes, liver, spleen and the
thymus
3.The virus is then released
from these tissues into the
blood
4.Via the blood, the virus
spreads throughout the body
to infect other lymphatic
tissues and organs, which is
accompanied by symptoms

45. 5.The mosquito ingests blood containing the virus
6.The virus replicates in the mosquito midgut, the ovaries, nerve
tissue and fat body. It then escapes into the body cavity, and later
infects the salivary glands
7.The virus replicates in the salivary glands and when the
mosquito bites another human, the cycle continues

46. Clinical features
The disease may occur in two forms
1. Classical dengue fever (break-bone fever)
2. Dengue in more serious forms with haemorrhagic manifestations
(DHF/DSS)

47. Classical dengue fever
 This usually affects older children and adults
 It has relatively benign course with fever, headache, retrobulbar
pain, conjunctival infection, pain in muscles and bones,
lymphadenopathy and maculopapular rash
 The fever is typically biphasic (saddle back)
 Incubation period is 5 – 8 days
 A maculopapular rash generally appears on 3rd or 4th day
 The febrile illness lasts for about 10 days after which recovery is
generally complete. It is rarely fatal

48. Other manifestations
 Dengue may also occur in more serious forms, with haemorrhagic
manifestations or with shock
 DHF/DSS remains mostly confined among children of 5 -10 years
age group in area where multiple dengue viruses cause disease
 It appers to be hyperimmune response
 On reinfection with a different serotype of dengue virus, antibody
formed against the first virus reacts with the second serotype virus
forming immune complexes (virus-antibody complex)

49.  In
DHF/DSS, initial symptoms are like those of dengue fever but
associated with haemorrhagic rash, thrombocytopenia and shock
 The moratality rate is 5 -10 %
 The disease is more often found in epidemic form in Thailand, South
-East Asia and India where dengue serotypes are regularly present
 All four types of dengue virus are present in India

50. Clinical Case Definition for Dengue Fever
Classical Dengue fever or Break bone fever is an acute febrile viral
disease frequently presenting with headaches, bone or joint pain,
muscular pains,rash,and leucopenia
Clinical Case Definition for Dengue Hemorrhagic Fever
4 Necessary Criteria:
1. Fever, or recent history of acute fever
2. Hemorrhagic manifestations
3. Low platelet count (100,000/mm3 or less)
4. Objective evidence of “leaky capillaries:”
• elevated hematocrit (20% or more over baseline)
• low albumin
• pleural or other effusions

51. Clinical Case Definition for Dengue Shock Syndrome
 4 criteria for DHF
+
 Evidence of circulatory failure manifested indirectly by all of the
following
•Rapid and weak pulse
•Narrow
pulse
pressure
hypotension for age
(<
20
mm
•Cold, clammy skin and altered mental status
•Frank shock is direct evidence of circulatory failure
Hg)
OR

52. Hemorrhagic Manifestations of Dengue
•Skin
petechiae, purpura, ecchymoses
hemorrhages:
•Gingival bleeding
•Nasal bleeding
•Gastrointestinal
Hematemesis, melena, hematochezia
•Hematuria
•Increased menstrual flow
bleeding:

53. Laboratory diagnosis
Specimens
1) For antibody detection – serum
2) For antigen detection – serum
3) For isolation of virus and PCR
a) Serum
b) Plasma
c) Whole blood (washed buffy coat)
d) Autopsy tissues
e) Mosquitoes collected in nature

54. Haematological diagnosis
 Thrombocytopenia (1,00,000 cells or less per mm3)
 Haemoconcentration (> 20 % rise in haematocrit)
Microbiological diagnosis
Isolation of virus is difficult hence serology plays a major role in
diagnosis
1. Detection of antibody
 Demonstration of IgM antibody in serum provides early diagnosis
 IgM antibody appears 5 days after onset of symptoms and persists
for one to three months
 Detection of four fold rise in IgG titre in paired sera taken at an
interval of ten days or more is confirmatory

55. 2. Detection of NS1 antigen
 Immunochromatographic test is available for detection of NS1 antigen
(nonstructural protein 1)
 It is a rapid test and detects antigen on the first day of fever
3. Isolation of virus
 Virus isolation can be done by inoculating clinical specimen into
mosquitoes, mosquitoes cell lines (C6/36 or AP-61 cells) or
suckling mice
4. PCR
 Viral RNA can be detected in clinical specimens by RT-PCR

56. Dengue fever Management
There is no specific antiviral treatment
The management is essentially supportive and symptomatic
The key to success is frequent monitoring and changing
strategies depending on clinical and laboratory evaluations
Bed rest is advisable during the acute febrile phase
Antipyretics or cold sponging should be used to keep the body
temperature < 400C
Analgesics and mild sedation may be required to control pain

57. Prophylaxis
 Control measures include elimination of mosquitoes
 No effective vaccine is available
 In order to avoid the DHF/DSS in immunised persons, a live
attenuated vaccine containing all four dengue serotypes is under
clinical trials

58. Tick-borne Flaviviruses
1.Tick-borne encephalitis viruses
a) Russian spring-summer encephalitis
b) Powassan virus
2. Tick-borne haemorrhagic fevers
a) Kyasanur Forest Disease (KFD)
b) Omsk haemorrhagic fever

59. Kyasanur Forest Disease (KFD)
 Febrile disease associated with hemorrhages that appeared in
Kyasanur Forest of Karnataka in 1957 as a fatal epizootic affecting
monkeys, along with a severe prostrating illness in some of the
villagers in the area
 Antigenically related to the RSSE virus
 Birds and small mammals are believed to be the reservoirs of the
virus
 Virus is transmitted by bite of tick (Haemaphysalis spinigera)
 Ticks may also act as the reservoir hosts as virus is transmitted
transovarially in them
 Monkeys act as amplifier hosts

60. Clinical features
 Incubation period varies from 3 – 7 days
 Patient develops fever of sudden onset with headache, vomiting,
conjunctivitis, myalgia and severe prostration
 Some patients also develop haemorrhages into the skin, mucosa,
alimentary canal, chest cavity and also in viscera
 Epistaxis may occur in some cases
 Case fatality is about 5 %

61. Control
 Control of ticks
 The population at risk should be vaccinated with killed KFD vaccine
 Personnel protection – protection of individuals by adequate clothing
and insect repellents

62. Bunyaviridae is a family of arthropod-borne or rodent-borne,
spherical, enveloped RNA viruses. Bunyaviruses are
responsible for a number of febrile diseases in humans and
other vertebrates. They have either a rodent host or an
arthropod vector and a vertebrate host

63. Human diseases Caused by Viruses
of the Family Bunyaviridae
Genus and
Group
Virus
Disease
Vector
Distributi
on
Bunyavirus
Bunyamwera Bunyamwera
Bwamba
Bwamba
California
California
encephalitis
Simbu
Shuni
Fever
Mosquito
Africa
Fever , Mosquito
Rash
Africa
Encep Mosquito North
ha-litis
America
Fever
Mosquito
Africa,
Asia

64. Human diseases Caused by Viruses of the Family
Bunyaviridae
Genus and
Group
Virus
Disease
Vector
Distribution
Phlebovirus
Phlebotomus
fever
Fever
Sand fly
Europe,
Africa, Asia
Naples
Rift Valley
Fever
Sicilian
Fever
Sand fly
Europe, Asia,
Africa
Rift
Valley
Fever
Fever,
encephalitis,
hemorrhagic
fever,
blindness
Mosquito
Africa

65. Human diseases Caused by Viruses of the
Family Bunyaviridae
Genus and
Group
Virus
Disease
Vector
Distribution
Tick
Africa, Asia
Tick
Africa, Asia
Nairovirus
CrimeanCongo
Nairobi
sheep
disease
Crimean- Hemorrhagic
Congo
fever
hemorrhagi
c fever
Nairobi
sheep
disease
Fever

66. Human diseases Caused by Viruses of the
Family Bunyaviridae
Genus and
Group
Virus
Disease
Reservoir Distribution
host
Hantavirus
Hanntavirus
Hantaan
HFPS
(hantavirus
pulmonary
syndrome),
HFRS
Rodent
Asia
Puumala
HFPS,
HFRS
Rodent
Asia
Seoul
HFPS,
HFRS
Rodent
Asia, Europe

67. Human diseases Caused by Viruses of the Family
Bunyaviridae
Genus and
Group
Virus
Disease
Vector
Distribution
Genus unassigned
Bangui
Fever, rash
Unknown
Africa
Bhanja
Fever,
encephalitis
Tick
Africa,
Europa, Asia
Issk-kul
Kasokero
Fever
Fever
Tick
Unknown
Asia
Africa
Nyando
Tataguine
Fever
Fever
Mosquito
Mosquito
Africa
Africa
Wanowri
Fever,
hemorrhage
Tick
Middle East,
Asia

68. FIGURE.
Pathogenesis of bunyavirus infections. Humans are
dead-end hosts of most bunyaviruses; however, the blood of
Crimean-Congo hemorrhagic fever patients may be highly
infectious

69. Signs of Crimean-Congo Hemorrhagic Fever

70. Laboratory diagnosis of arboviruses
Specimens
Blood, CSF, brain tissue may be used for isolation of virus
1. Virus isolation
a) Suckling mice
Specimens are inoculated intracerebrally into suckling mice
The animal develops fatal encephalitis
Most sensitive method for isolation of arboviruses

71. b) Tissue culture
 Vero, BHK-21 and mosquito cell lines are inoculated with specimens
 Growth of virus in cell cultures is identified by immunofluorescence,
haemagglutination inhibition, CFT, ELISA or neutralisation tests
2. Serology
 Usually used to make a diagnosis of arbovirus infections
3. Direct detection tests
 Methods for detection of antigen and nucleic acids are available

72. Prevention of arbovirus infections
Surveillance - of disease and vector populations
Control of vector - pesticides, elimination of breeding grounds
Personal protection - screening of houses, bed nets, insect
repellants. When possible, wear protective clothing while outdoors
Vaccination - available for a number of arboviral infections e.g.
Yellow fever, Japanese encephalitis, Russian tick-borne
encephalitis

73. Treatment of arbovirus infections
No specific therapy
Arboviral encephalitis treated by hospitalization, intravenous fluids,
respiratory support, prevention of secondary infections, and good
nursing care