Download Arboviruses

Chair of Microbiology, Virology, and Immunology
Arboviruses
The arthropod-borne viruses, or arboviruses, are a
group of infectious agents that are transmitted by bloodsucking arthropods from one vertebrate host to another.
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.
There are more than 500 arboviruses, grouped according to
their antigenic relationships.
Current taxonomic status of some arboviruses
Current
Taxonomic
Classification
Arbovirus Members
Togaviridae
Aura, Chikungunya, eastern equine encephalitis, Getah,
Genus Alphavirus Maygro, Mucambo, Ndumu, O'Nyong-nyong, Ross River,
Semliki Forest, Sindbis, Venezuelan and Western equine
encephalitis
Flaviviridae
Genus Flavivirus
Dengue, Israel turkey meningoencephalitis, Japanese B
encephalitis, Kunjin, Kyasanur Forest disease, Murray Valley
encephalitis, Ntaya. Omsk hemorrhagic fever, Powassan,
St. Louis encephalitis, tick-borne encephalitis, Uganda S,
Wesselsbron, West Nile fever, yellow fever,
Bunyaviridae
Genus
Bunyavirus
Bunyamwera, Bwamba, C, California, Capim, Guama,
Koongol, Patois, Simbu, and Tete;
Genus Uukuniemi Uukuniemi, Anopheles A, Anopheles B, Bakau, CrimeanCongo hemorrhagic fever, Kaisodi, Mapputta, Nairobi sheep
disease, Phlebotomus fever, and Turlock; 8 unassigned
viruses
Current taxonomic status of some arboviruses
Current Taxonomic
Classification
Arbovirus Members
Reoviridae
Genus Orbivirus
African horse sickness, bluetongue, and Colorado tick
fever viruses
Rhabdoviridae
Genus Vesiculovirus
Cocal, Hart Park, Kern Canyon, and vesicular stomatitis
viruses
Arenaviridae
Genus Arenavirus
Junin, Lassa, Machupo, and Pichinde viruses
Nodaviridae
Nodamura virus
Diseases produced by the arboviruses may be divided
into 3 clinical syndromes:
 fevers of an undifferentiated type with or without a
maculopapular rash and usually benign;
 encephalitis, often with a high case fatality rate;
 hemorrhagic fevers, also frequently severe and fatal.
These categories are somewhat arbitrary, and some
arboviruses may be associated with more than one syndrome,
eg, dengue.
Togaviridae
Genera:
 Alphavirus (typical virus – Sindbis virus)
 Rubivirus
 Pestivirus
Togaviruses general properties
Small viruses, (+) ssRNA, linear, м.w. 4,0 МD, Icosahedral
symmetry, envelope, virus-specific polypeptides, some of them –
glycoproteins. unstable at room temperature, stable at —70 °C, and
rapidly inactivated by ether or by 1:1000 sodium deoxycholate. This
property separates them easily from enteroviruses
Alphavirus
There are 30 alphaviruses, 13 of them can infect human
Virus structure
Virions are spherical, 60-70 nm in diameter,
icosahedral nucleocapsid enclosed in a lipidprotein envelope.
Alphavirus RNA is a single 42S strand of
approximately 4x106 daltons Virion RNA is
positive sense: it can function intracellularly as
mRNA, and the RNA alone has been shown
experimentally to be infectious.
The single capsid protein (C protein)
Two envelope viral glycoproteins (E1 and E2)
of molecular weights of 48,000 to 52,000
daltons.
A small third protein (E3) of molecular weight
10,000 to 12,000 daltons remains virionassociated in Semliki Forest virus but is
dispatched as a soluble protein in most other
alphaviruses.
On the virion surface, E1 and E2 are
closely paired, and together form
trimers that appear as "spikes" in an
orderly array.
The viruses infect many cell lines, embryonated eggs,
mice, birds, bats, mules, horses, and other animals.
In susceptible vertebrate hosts, primary virus multiplication occurs
either in myeloid and lymphoid cells or in vascular endothelium.
Multiplication in the central nervous system depends on the ability of
the virus to pass the blood-brain barrier and to infect nerve cells.
In natural infection of birds and mammals (and in experimental
parenteral injection of the virus into animals), an inapparent infection
develops in a majority. However, for several days there is viremia,
and arthropod vectors acquire the virus by sucking blood during this
period—the first step in its dissemination to other hosts.
Principal medically important alphaviruses
Virus
Antigenic
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
Principal medically important alphaviruses
Virus
Antigenic
Clinical
Syndrome
Vector
Host
Distribution
Chikunguny (CHIK)
Febrile
Africa
illness, rash,
arthralgia
Mosquito
Primates,
humans
India, Southeast
Asia
O’nyong-nyong
(ONN)
Febrile
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
Classification and Antigenic Types
Classification is based upon antigenic relationships.
Viruses have been grouped into seven antigenic
complexes. Typical species in four medically important
antigenic complexes are:
 Venezuelan equine encephalitis,
 Eastern equine encephalitis,
 Western equine encephalitis,
 Semliki Forest viruses.
Multiplication. Alphaviruses attach to
cells via interactions between E2 and
cellular receptors. Entry is thought to take
place in mildly acidic endosomal vacuoles
where glycoprotein spikes undergo
conformational rearrangements and an
acid-dependent fusion event (principally a
function of E1) delivers genomic RNA to
the cell cytoplasm. Viral replication
occurs in the cytoplasm. Initial translation
of virion RNA produces a polyprotein that
is proteolytically cleaved into an RNA
polymerase.
Transcription of the virion RNA
through a negative-strand RNA
intermediate produces a 26S
positive-strand mRNA (short)
which encodes only the structural
proteins,
as well as additional 42S RNA
(long), which is incorporated into
progeny virions.
Translation from the 26S mRNA
(which represents the 3' one-third of
genomic
RNA)
produces
a
polyprotein
that
is
cleaved
proteolytically into three proteins: C,
PE2, and E1; PE2 is subsequently
cleaved into E2 and E3.
Envelope proteins formed by
posttranslational
cleavage
are
glycosylated and translocated to the
plasma membrane.
Virion formation occurs by budding of
preformed icosahedral nucleocapsids
through regionsof the plasma
membrane containing E1 and E2
glycoproteins
Pathogenesis and Clinical Manifestations. Human illness
caused by alphaviruses is exemplified by agents that produce three
markedly different disease patterns.
 Chikungunya virus is the prototype for those causing an acute (3to 7-day) febrile illness with malaise, rash, severe arthralgias, and
sometimes arthritis.
 O'nyong'nyong, Mayaro, and
Ross River viruses, which are
closely related (antigenically) to
chikungunya virus, cause similar
or identical clinical
manifestations;
 Sindbis viruses cause similar
but milder diseases known as
Ockelbo (in Sweden), Pogosta
(Finland), or Karelian fever
(Russia).
Epidemiology. Diseases are maintained in natural ecologic cycles
involving birds and, principally, bird-feeding mosquitoes such as Culex,
Aedes. Eastern equine encephalitis (EEE) virus is enzootic in fresh
water swamps in the eastern United States; it causes sporadic equine
and rare human cases. Small human outbreaks may occur.
Alphavirus transmission
Virus abbreviations:
Chik, chickungunya; RR,
Ross River; May, Mayaro;
ONN, O'nyong-nyong;
SIN, Sindbis; EEE,
eastern equine
encephalitis; VEE,
Venezuelan equine
encephalitis.
Host Defenses
 Differences in susceptibility between individuals and species
are not easily ascribed to specific immune responses, and a
variety of non-specific defense mechanisms may be important.
 Alphaviruses are efficient inducers of interferon, the production
of which probably plays a role in modulating or resolving
infections.
 Antibodies are important in disease recovery and resistance.
The appearance of neutralizing antibodies in serum coincides
with viral clearance, and immune serum can diminish or prevent
alphavirus infection.
 Although their precise roles are not clearly established, T-cell
responses are also demonstrable and may contribute
substantially to immunity.
Diagnosis
Blood, cerebrospinal fluid examination, section material, blood
serum to include viral cultures, is critical in differentiating
bacterial from viral infections, and infectious from noninfectious
etiologies.
Laboratory diagnosis can be established by isolating virus from
the blood during the viremic phase or by antibody determination.
 Express-methods: IRHAT, IFT, ELISA
 Virological diagnosis: inoculation of laboratory animals (into
the brain) – suckling mice, cell cultures, embryotaned eggs.
Identificarion: plaques formation, CPE, HIT, CFT, NT
Serology: paired sera (NT, CFT, HIT, IHAT, ELISA)
Control
Control of alphavirus diseases is based on surveillance of disease and
virologic activity in natural hosts and, when necessary, on control
measures directed at reducing populations of vector mosquitoes. These
measures include:
 control of larvae and adult mosquitoes, sometimes by using ultra-lowvolume aerial spray techniques; in some areas, insecticide resistance (for
example, resistant C tarsalis) is a major limitation to effective control.
 Inactivated vaccines are used to protect laboratory workers from
eastern, western, and Venezuelan equine encephalitis viruses. An
effective live attenuated Venezuelan equine encephalitis vaccine has
been employed extensively in equines as an epidemic control measure,
and a similar vaccine is used to protect laboratory workers.
 A live attenuated chikungunya vaccine has proven safe and
immunogenic in investigational human trials.
Rubellaviruses
Rubella (German measles) is a common mild disease
characterized by a rash. It affects children and adolescents
worldwide and can also affect young adults. When rubella virus
infects susceptible women early in pregnancy, it may be
transmitted to the fetus and may cause birth defects. Therefore,
accurate diagnosis is critical in pregnancy.
Structure
Rubella virus is a spherical
40- to 80-nm, positive-sense,
single-stranded RNA virus
consisting of an electrondense 30- to 35-nm core
surrounded by a lipoprotein
envelope. The RNA has a
molecular weight of about 3
X 10-6. It has 2 structural
proteins: major and minor.
The virus particles are
generally spherical with spiky
hemagglutinin-containing
surface projections. It has
haemolytic and
neuraminidaze activities too.
Classification and Antigenic Types
Rubella virus is the single member of the genus Rubivirus in the family
Togaviridae. It is serologically distinct from other members of the
Togaviridae, and, unlike most other togaviruses, is not known to be
transmitted by an arthropod. Only one genetically stable serotype of
rubella virus has been identified.
Cultivation
The virus reproducts in primary cell
cultures of human embryo and continious
cell lines. It produses CPE as other
Togaviruses.
Reproduction (slowly!) is in cytoplasm.
Eosinophilic inclusions are formed.
We can detect the viruuses in the cells by
interferention test – additional infection of
cell culture with ЕСНО-11 viruses.
CPE
Epidemiology
Humans are the only
reservoir of rubella virus.
known
Incubation period - 16-18 days.
Mechanism of transmission:
 postnatal
person-to-person
transmission occurring via direct or
droplet contact with the respiratory
secretions of infected persons,
 contact (formites),
 transplacental
Although
the
early
events
surrounding
infection
are
incompletely characterized, the
virus almost certainly multiplies in
cells of the respiratory tract, extends
to local lymph nodes, and then
undergoes viremic spread to target
organs.
Clinical Manifestations
Postnatal rubella is often asymptomatic but may result in a generally mild,
self-limited illness characterized by rash, lymphadenopathy, and low-grade
fever. As is the case for many viral diseases, adults often experience more
severe symptoms than do children. In addition, adolescents and adults may
experience a typical mild prodrome that is not seen in infected children; this
occurs 1 to 5 days before the rash and characterized by headache, malaise,
and fever.
Abnormalities Associated with Congenital Rubella Syndrome
Type of defects
Examples
Ocular defects
Cataracts
Microphthalmia
Glaucoma
Retinitis
Heart defects
Patent ductus arteriosus
Atrial septal defect
Ventricular septal defect
Peripheral pulmonic artery stenosis
Hearing impairment
Sensorineural deafness
Abnormalities Associated with Congenital Rubella Syndrome
Type of defects
Examples
Central nervous system
Mental retardation
Meningoencephalitis
Progressive rubella panencephalitis (rare)
Microcephaly
Other
Growth retardation
Radiolucent borne disease
Hepatosplenomegaly
Hemathologic abnormalities:
Thrombocytopenia, purpura
Pneumonitis
Endocrine dysfunction:
Insulin dependent diabetes mellitus,
thyroididtis
Catarata
Rash
Glaucoma
Host Defenses
Postnatal infection rapidly induces a specific immune response
which provides lifelong protection against the natural disease.
Neutralizing and hemagglutination-inhibiting antibodies appear
shortly after the onset of rash and reach maximum levels in 1 to 4
weeks. Specific antibodies persist after infection. Cell-mediated
immunity also develops in convalescence and can be detected for
years following infection.
Diagnosis
Serologic studies:
 detection of IgM and/or fourfold antibody rises);
 presence of specific IgM antibodies indicates recent rubella infection;
Specific IgG antibodies in healthy individuals demonstrate immunity to rubella;
Antibodies are detectible by a variety of methods including:
 neutralization test (seldom used because of its complexity and expense),
 hemagglutination inhibition,
 ELISA,
 indirect immunofluorescent immunoassay.
Virologic studies:
Virus can be readily recovered in cell cultures from respiratory tract secretions
and, in infants with congenital infection, from urine, cerebrospinal fluid, and
blood. Presence of virus in inoculated cultures can be recognized by viral
interference or immunoperoxidase staining assays. Because virus isolation
procedures are costly and require a relatively sophisticated virologic laboratory,
they are seldom used except for the diagnosis of congenital rubella.
Test-system for Rubella diagnosis
Prophylaxis
Live attenuated vaccines are used for vaccination of girls 12-15
months of old, revaccination – in 12-14 years of old.
ЕRЕVAX (rubella), Belgium
 RUDIVAX (rubella), France
 PRIORIX (rubella, measles,mumps), Belgium
 TRIMOVAX (rubella, measles, mumps), France
 MMR (rubella, measles, mumps), USA

Immunoglobulin has been used in attempts to prevent rubella
in pregnant women exposed to the virus.
Flaviviruses
Classification and Antigenic Types
Classification within the genus is based upon antigenic
relationships and genetic relationships are becoming
increasingly important in classification. Viruses have
been grouped into several antigenic complexes typified,
for example, by dissimilar viruses:
 dengue,
 tick-borne encephalitis,
 St. Louis encephalitis,
 yellow fever viruses
Flaviviruses
Flavivirus virions are spherical, 50 nm in diameter, and consist of a nucleoprotein
capsid enclosed in a lipid envelope. The RNA is a single 40S positive-sense
strand.
The virion has a single capsid protein (C) that is approximately 13,000 daltons.
The envelope consists of a lipid bilayer, a single envelope protein (E) of 51,00059,000 daltons, and a small nonglycosylated protein (M) of approximately 8,500
daltons. Only E, which is glycosylated in most flaviviruses, is clearly demonstrable
on the virion surface.
Antigenic properties
In nucleocapsid there is one group-specific protein.
Envelope glycoprotein has haemagglutinating properties.
Surface proteins provide type-specific properties.
Flavivirus
Tick borne encephalitis virus
Multiplication. The mechanism by which
flaviviruses enter cells probably involves an
interaction between the E protein and
cellular receptors, followed by a postattachment fusion event that occurs in
acidic intracytoplasmic vacuoles. Naked
genomic RNA is infectious if introduced into
the cytoplasm. The genomic RNA is
capped but not polyadenylated; it serves
as mRNA for all proteins. Structural
proteins are encoded at the 5' end of the
genome, and nonstructural proteins (e.g.,
NS-1
and
RNA-dependent
RNA
polymerase) are encoded in the 3' twothirds. Complementary (negative-sense)
RNA, made from genomic RNA, serves as
a template to generate genomic RNA.
Replication occurs in the cytoplasm.
Virions are formed in perinuclear regions of the cytoplasm in association
with Golgi or smooth membranes. Virions appear within cytoplasmic
vacuoles and appear to exit the cell as vacuoles fuse with the plasma
membrane. Unlike alphaviruses, no evidence of budding has been seen in
flavivirus-infected cells, and the mechanisms of virion assembly and
release remain obscure.
Morphogenesis
of flaviviruses
Pathogenesis and Clinical Manifestations
Flaviviruses vary widely in their pathogenic potential and
mechanisms for producing human disease. It is useful to
consider them in three major categories: those associated
primarily with:
 the encephalitis
encephalitis),
syndrome
(prototype:
St.
 fever-arthralgia-rash (prototype: dengue fever),
 hemorrhagic fever (prototype: yellow fever).
Louis
Principal medically important flaviviruses
Virus
Antigenic Clinical
Syndrome
Vector
Host
Distribution
Dengue (DEN) Febrile illness, rash,
hemorrhagic fever,
shock syndrome
Mosquito
Humans
Tropics,
worldwide
Yellow fever
(YF)
Hemorrhagic fever,
hepatitis
Mosquito
Primates,
humans
Africa, South
America
St. Louis
encephalitis
(SLE)
Encephalitis
Mosquito
Birds
Americas
Japanese
encephalitis
(JE)
Encephalitis
Mosquito
West Nile
Febrile illness
Mosquito
Pigs, birds India, China,
Japan, SouthEast Asia
Birds
Africa, Middle
East, Europe
Principal medically important flaviviruses
Virus
Antigenic Clinical
Syndrome
Vector
Host
Distribution
Tick-borne
encephalitis (TBE)
Encephalitis
Tick
Rodent
Europa, Asia
Omsk hemorrhagic
fever
Hemorrhagic fever
Tick
Muskrats
Siberia
Kyasanur Forest
disease (KFD)
Hemorrhagic fever
Tick
Rodents
India
primates
Epidemiology. The flaviviruses constitute a highly diverse genus, and their
ecology is similarly varied and complex. Only the basic concepts are considered
here. The mosquito-borne encephalitis viruses (St. Louis encephalitis, Japanese
encephalitis, Murray Valley encephalitis, and West Nile viruses) exist primarily as
viruses of birds and are transmitted by Culex mosquitoes that feed readily on birds.
Flavivirus transmission. Virus abbreviations: DEN, dengue; KFD, Kyasanur Forest
Disease; OMSK, Omsk hemorrhagic fever; WN, West Nile, YF, yellow fever; SLE, St.
Louis encephalitis; JE, Japanese encephalitis; POW, Powssan, RSSE, Russian springsummer encephalitis; MVE, Murray Valley encephalitis; ROC, Rocio.
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.
Pathogenesis of flaviviruses.
The tick-borne flaviviruses are
maintained by tick-mammal cycles
and by transovarian transmission in
ticks.
Humans are infected with this
subgroup of flavivirus through the
bite of infected ticks, and thousands
of cases may occur annually in the
region of the Eurasian continent
between central Europe and western
Siberia.
A closely-related virus transmitted by
Ixodes ticks, termed Powassan virus,
produces sporadic cases of
encephalitis in the eastern parts of
Canada and the U.S.
In most human infections with St. Louis encephalitis
(SLE) and Japanese encephalitis (JE) viruses, there
is either no apparent disease or a nonspecific febrile
illness with headache.
Clinical manifestations of encephalitis due to SLE, JE,
or Murray Valley encephalitis (MVE) virus begin as
fever, headache, and stiff neck, and progress to an
altered level of consciousness and focal neurologic
deficits (e.g., tremors, pathologic reflexes, cranial
nerve palsies, nystagmus, ataxia). Paralysis is more
commonly seen with JE and MVE.
Structure of the Yellow Fever Virus
 Spherical viruses
 Capsid, Membrane protein, and
Envelope protein
 Capsid (C protein)
 Structural Protein
 Houses the RNA and the viral
RNA polymerase
 Membrane protein (prM/M)
 Helps the capsid pass through the
cell membrane.
 Nonstructural proteins (NS)
 Nonstructural protein 1 (NS1) is a
glycosylated protein found on an
infected cell’s surface and is
involved in viral assembly and
release. This protein induces
protective antibodies.
 Nonstructural protein 5 is a viral
RNA polymerase.
History
 Carlos Finlay
 Cuban physician and
scientist.
 Pioneered the early research
on YF.
 Hypothesized that YF was
spread by mosquitoes.
 Walter Reed
 Appointed by the government
to head the Yellow Fever
Commission.
Geography
Out of Africa
Mosquito larvae carried in ship’s water barrels spread the virus to the
Americas: A new cycle in South American monkeys
Transmission of Yellow Fever
 Three types of transmission
to humans:
 Sylatic or jungle YF
 Intermediate YF
 Urban YF
 Vertical and Horizontal
Transmission
 Vertical transmission is
mosquito to mosquito.
 Horizontal transmission
is when an infected
mosquito bites a noninfected human or
monkey.
Mosquitoes (Aedes spp. in Africa, and Haemagogus spp. in South America)
There are 2 kinds of yellow fever

One is jungle fever that is spread from monkeys
to people by mosquitoes.
 The other kind is found in urban areas and are
spread from person to person by mosquitoes
Early symptoms of Yellow Fever
Yellow fever is usually mild but in some cases can be life threatening.
 Acute phase
 Fever
 Muscle pains (prominent
backaches)
 Headaches
 Shivers
 Nausea, vomiting
 These symptoms are also
closely related to the flu
and common cold.
 Usually recover in 3-4
days
Deadly symptoms of Yellow Fever
After a brief recovery period 15% of yellow fever victims go into
toxic phase that leads to
 Toxic phase
 Fever
 Jaundice
 Yellowish color develops in the patients
face and eyes
 This gives Yellow fever its name
 Complains of abdominal pain with
vomiting.
 Bleeding can occur from the mouth, nose,
eyes and/or stomach.
 Once this happens, blood appears in the
vomit and faeces.
 Kidney function deteriorates; this can
range from abnormal protein levels in the
urine (albuminuria) to complete kidney
failure with no urine production (anuria).
 Half of the patients in the "toxic phase"
die within 10-14 days. The remainder
recover without significant organ damage.
Is yellow fever curable or preventable?


This disease is caused by Yellow Fever virus that can not be cured.
But it can be prevented by a yellow fever vaccination.
YF17D vacccine
 Is given attenuated to the patient.
 Once given to the patient there is approximately 95% immunity from YF
for about ten years.
 Risks
There are not have not been many problems related with the YF17D
vaccine
 People who are at risk are:
 Infants under 12 months
 Immunocompromised
People who have had this disease develop a life long immunity. So it
can't recur
Denge fever virus
Dengue viruses


SS-RNA arbovirus (Flavivirus)
4 serotypes (DEN-1, 2, 3, 4)







Based on envelop glycoprotein
DEN-1 and 3 are more closely
related
DEN-4 less closely related to others
Virulent variants (genotypes) within
serotype
Infection with any serotype
confers specific lifelong immunity
Transient cross-protection to
other serotypes
Any serotype can cause severe /
fatal disease
Dengue Fever





Dengue viruses – 4
flavours cause it
It is transmitted by a
mosquito- the Aedes
aegypti
It is generally an
animal virus
Man is accidentally
infected
Other vertebrates are
the reservoirs
Dengue Fever spread
Prevalent from centuries
Highly prevalent now
How is Dengue Spread ?
Dengue is spread when the female Aedes
aegypti mosquito bites an infected person, it
sucks up the blood with the virus and passes
this virus onto the next person she bites for
more blood. In this way the mosquito
becomes a carrier of the dengue virus. We
call these carriers of disease and illness
“vectors”
Pathogenic Pathway
Dengue Hemorrhagic Fever
Mosquito bite  virus injected into blood
 Virus replicates in lymphocytes
 Fever, myalgia, arthralgia, rash
 Slow recovery
 Immunity to the virus (Serotype)
Mosquito bite
 Second serotype injected into blood
 Enhanced replication, severe disease,
hemorrhage, cardiovascular shock
What do we experience ?







2–7 days after the mosquito had its dinner on us we
may develop
Sudden onset of fever, chills, headache
Back pain with severe muscle and joint pains
Pain behind the eyes and on moving the eyes
Nick name - Break bone fever- pains so severe
Red patches or spots on the skin
Mild nose bleeds
This is the ordinary classical
Non dangerous form!
Dengue Presentations
Like any other viral fever- not clear cut
 Dengue Fever with Muscle pains this is
classical presentation in 90% cases
 Dengue Fever with bleeding in 7%
 Dengue – the dangerous form in 3%

What is the end result?
Complete recovery is the rule
 Severe weakness many persist for
days after the fever leaves us

many
Skin bleeds
Dengue – The bleeding form
Blood vessels are affected
 There is severe oozing into tissues
 Bleeding into all possible parts of body
 Blood clotting mechanism is disrupted
 Blood pressure falls and many end in collapse
and death
 In the best centers 5% of this type of Dengue
will reach their forefathers

Bleeding into the eye
Large bleed into skin
Bleeding spots in skin
Normal
Dengue
Child with severe form of Dengue
Oxygen
IV Fluids
Special Care
See the tubes every
where
Frightening, isn’t it?
What are the tests needed?
 Routine
blood test
 Tests to check the clotting process
 Special tests to identify the Dengue or its foot
marks in our blood
 Urine to check protein leak
Special Test (ELISA)
ELISA Plate
IgM-capture ELISA
Can we protect ourselves?
There is no vaccine available as yet
 But we can prevent the disease by preventing
ourselves from mosquito bite

Bunyaviridae
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.
There are 300 viruses in 5 genera:
- Bunyavirus
- Phlebovirus
-- Nairovirus
- Uukuvirus
- Chantavirus
Bunyaviruses
are
spherical,
enveloped particles 90 to 100 nm in
diameter. They contain singlestranded RNA, which, with the
nucleoprotein,
forms
three
nucleocapsid
segments.
The
segments are large (L), medium (M),
and small (S) helical, circular
structures. The RNA has a total
molecular weight of 5 X 106. The
nucleocapsid is surrounded by a lipidcontaining envelope. Surface spikes
are composed of two glycoproteins
that confer properties of neutralization
of infectivity and hemagglutination of
red blood cells.
Bunyaviridae
Human diseases Caused by Viruses of the Family Bunyaviridae
Genus and Group
Virus
Disease
Vector
Distribution
Bunyavirus
Anopheles A
Tacaiuma
Fever
Mosquito
South America
Bunyamwera
Bunyamwera
Fever
Mosquito
Africa
Germiston
Fever
Bwamba
Bwamba
Fever, Rash
Mosquito
Africa
C
Apeu
Fever
Mosquito
South America
California
California
encephalitis
Encepha-litis
Mosquito
Snowshoe hare
Encephalitis
Mosquito
North America,
Asia
Tahyna
Fever
Mosquito
Europe
Shuni
Fever
Mosquito
Africa, Asia
Simbu
Africa
North America
Human diseases Caused by Viruses of the Family Bunyaviridae
Genus and
Virus
Disease
Vector
Distribution
Group
Phlebovirus
Phlebovirus
fever
Alenquer
Fever
Unknown
South America
Naples
Fever
Sand fly
Europe, Asia, Africa
Rift Valley
Fever
Fever, encephalitis,
hemorrhagic fever,
blindness
Mosquito
Africa
Sicilian
Fever
Sand fly
Europe, Africa, Asia
Nairovirus
CrimeanCongo
Nairobi
sheep
disease
CrimeanCongo
hemorrhagic
fever
Hemorrhagic fever
Tick
Nairobi
sheep
disease
Fever
Tick
Africa, Asia
Africa, Asia
Human diseases Caused by Viruses of the Family Bunyaviridae
Genus and Group
Virus
Disease
Vector
Distribution
Hantavirus
Hataan
Hantaan
HFRS
Rodent
Asia
Puumala
HFRS
Rodent
Asia
Sequl
HFRS
Rodent
Asia, Europe
Genus unassigned
Bangui
Fever, rash
Unknown
Africa
Bhanja
Fever,
encephalitis
Tick
Africa,
Europa, Asia
Issk-kul
Fever
Tick
Asia
Kasokero
Fever
Unknown
Africa
Nyando
Fever
Mosquito
Africa
Tataguine
Fever
Mosquito
Africa
Wanowrie
Fever,
hemorrhage
Tick
Middle East,
Asia
Multiplication. Replication occurs in the cytoplasm. The host RNA
sequence in some representative viruses primes viral mRNA synthesis.
In most bunyaviruses the genome is antisense. In some phleboviruses,
the small RNA segment is ambisense (i.e., one portion is viral
complementary in sense and the other portion is viral in sense). Genetic
reassortment can occur during infection because the RNA is segmented.
Virus particles bud into the Golgi cisternae and are liberated from the cell
by plasma membrane disruption and by fusion of intracellular vacuoles
with the plasma membrane.
Pathogenesis. Except for members of the genus Hantavirus, bunyaviruses replicate
in arthropods. The gut of the vector is infected initially, and after a few days or weeks the
virus appears in the saliva; the arthropod then remains infective for life but is not ill. When
the vector takes a blood meal, the infective saliva enters the small capillaries or lymphatics
of the human or other vertebrate host.
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.
Clinics of Hataan virus infection
Bunyaviruses
Rift Valley fever
 Crimean Congo
hemorrhagic fever

Distribution of Rift Valley Fever (RVF) Virus
(Countries with outbreak of RVF, periodic isolations of virus, or
serologic evidence of RVF 1910-1999)
Rift Valley Fever  Disease of sheep and cattle


Humans: Asymptomatic-to-mild
Rare VHF, encephalitis, retinitis

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

1997-1998 East Africa Outbreak





478 deaths
115 VHF deaths
9% IgM+
~89,000 cases
70% animal loss
Rift Valley Fever: Clinical features

3-7 day incubation, 3-5 day duration

Asymptomatic or mild illness
Fever, myalgia, weakness,
weightloss
Photophobia, conjunctivitis





Encephalitis
<5% hemorrhagic fever
1-10% vision loss (retinal
hemorrhage, vasculitis)
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: Ribavirin
Distribution of CCHF virus
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,
proteinuria, elevated AST
Hemorrhages may be profuse (hematomas, ecchymoses)
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 viremic

Virus grows in macrophages and other cells

DIC often present

Poor prognosis signaled by early elevated AST and clotting
CCHF: Slaughterhouses

Sheep and cattle
become viremic without
disease

Blood and fresh tissues
infective by contact

Possibility of
establishing
transmission of CCHF
in holding pens by
Hyalomma or other tick
vectors
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.
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