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7/29/2019 Arthropod and Rodent- Borne Viruses
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ARTHROPOD ANDRODENT- BORNE
VIRUSES
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ARTHROPOD-BORNEVIRUSES(ARBOVIRUSES)
Blood-sucking Arthropods (Vectors)
Multiply in tissues of vector
Some Major Arboviruses:
Yellow feverDengue
West Nile Fever
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100 are known pathogenic to humans
Zoonotic (except urban yellow fever and dengue)
3 syndromes:
1. Fevers of undifferentiated type with or without a
maculopapular rash and benign
2. Encephalitis(inflammation of brain)
3. Hemorrhagic fevers (usually sever and fatal)
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ARBOVIRUSES
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TOGAVIRUS Genus Alphavirus Spherical
70 nm diameter
42 capsomeres (nucleocapsid )
Genome: 11-12kb positive-sense, single stranded
RNA
Enveloped
3 or 4 major structural
polypeptides (2 glycosylated) Assembly:budding through
host cell membranes
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FLAVIVIRIDAE Genus Flavivirus Spherical
40-60 nm diameter
Genome: 11kb,Single -
stranded , positive-senseRNA (INFECTIOUS!)
Enveloped
3 structural polypeptides,(2 glycosylated)
Assembly:withinendoplasmic reticulum
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TRANSCRIPTION
Genomic Length
Precursorproteins for viral
replication
Elaborated by posttranslational cleavage
Subgenomic (26S)
Encodesstructural
proteins
ALPHAVIRUS
Replication: CytoplasmMature : By Budding Nucleocapsids
Plasma Membrane
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FLAVIVIRUSREPLICATION
Replication: Cytoplasm
Particle Assembly: intracellular vesicles
Viral Replication
Cleaved by Viral andHost protease
Large PrecursorProtein
Genome-length mRNA
Viral Proteins(structuraland non structural)
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Cross-section inimmunotechniques
(antigenically related)
HI,ELISA,IF test
define 8 serogroupsID specific virus: Nttests
Antigenicallyrelated
Nt test : ID 8
complexes
ANTIGENIC
Alphavirus Flavivirus
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PATHOGENESIS
myeloid and lymphoid cells or vascular
endothelium
CNS (depends on ability of virus)
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FLAVIVIRUS LIFE CYCLE
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CLINICAL FINDINGSIncubation: 4 to 21 days
Inapparent infections (common)
Mild flu-like illness & encephalitisSudden onset of severe headache, chills and fever, nausea and
vomiting, generalized pain, and malaise.
Drowsiness and stuporous (24-48 hrs.)
Severe: mental confusion, tremors, convulsions and coma
4-10 days (fever)
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LABORATORY DIAGNOSISDirect Detection & RecoverySpecimens:
blood (early infection), CSF, tissue specimen
Common cell lines: Vero, BHK, HeLa, & MRC-5
Mosquito Cell Lines
Intracerebral inoculation of suckling mice or
hamstersAppropriate biosafety precautions!
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SEROLOGYNeutralizing & hemagglutination-inhibiting antibodies
HI test (simplest diagnostic test)
ELISA (most sensitive)Serum
1st sample (after onset)
2nd sample (2-3 weeks later)
Cross reactivity must be considered! (Alphavirus &Flavivirus )
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Immunity
-permanent after single infection
-immunity may be modified prior exposure to another same
group of viruses
Epidemiology
Eastern equine Encephalitis
Most severe (hisghest case-fatality rate)
Culex tarsalisand birds
St. Louis Encephalitis10,000 cases and 1000 deaths (N.America)
Presence of infected mosquitoes
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West Nile Fever
Flavivirus (member of Japanes B encephalitis )
Europe, Middle East, Africa, Soviet Union, Southwest
Asia, and United States
Infected bird, mosquito, or human
Organ transplantation, blood transfusion, in utero &
breast feeding
Viremia, acute, mild, febrile disease withlymphadenopathy and rash, transitory meningeal
involvement.
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.
T I C K B O R N E F L AV I V I RU S A N D
M O S Q U I T O - B O R N E F L AV I V I R U S C Y C L E
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TREATMENT AND
CONTROL
No specific treatment
Arthropod control (effective method)
spray insecticides
repellents
Vaccines developed (for horses only)
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YELLOW FEVER
Flaviviridae Family
Mosquito-borne
Local lymph nodes, spleen, & heart,(degenerative
changes)
liver and kidney(necrotic lesion) ,
bone marrow
myocardium(shock) [days]
Blood(early onset)
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CLINICAL MANIFESTATIONS:
Incubation: 3-6 days
Fever, chills, headache, dizziness, myalgia, &
backache & Nausea, vomiting, and bradycardia
Most patient recover (15% progresses)
Severe: fever, jaundice, renal failure, & hemorrhage;
vomiting Mortalit y rate: high
Death: 710 days illness
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LABORATORY DIAGNOSIS
Virus Detection/Isolation
Blood ( first 4 days), tissue specimen(immunochemistry),postmortem tissue(intracerebral inoculation of mice), cell lines
Viral antigen/nucleic acid
ELISA or PCR
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IgM (1st week)
ELISA (presumptive)
Fourfold or greaterrise of titer(confirmation)
Immunity
Neutralizingantibodies (completeprotection)
NO antiviral drug therapy
Vaccination (most effective
treatment)17D strain and virulent
Asibi strain (vaccine)
Good antibody response
(95%)
SEROLOGY
Treatment, Prevention,
Control
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TRANSMISSION CYCLE
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DENGUE
Breakbone fever
Mosquito-borne (Aedes aegypti & Aedes
albopictus)
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CLINICAL
MANIFESTATIONS
4-7 days ( range 3-14 days)
Onset fever (2-7 days), malaise, chills, & haedache
Pain in back, joints, muscles, eyeballs
saddleback form
Rash (3rd or 4th day ) lasts up to 1-5 days
Enlargement of lymph nodesMild febrile illness
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Dengue hemorrhagic fever/dengue shock syndrome
Increased vascular permeability with plasma leakage
Pre-existing dengue antibody
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LABORATORY DIAGNOSIS
Reverse transcriptase-PCR-based methods(rapid ID) serum
Inoculation of mosquito cell line with px serum with
nucleic acid
E/M viral protein-specific capture IgM or IgG ELISA
HI test
Rise in antibody titer (reliable)
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Nt test and molecular-based assays (4 serotypes
)Infection (lifelongprotection)
Reinfection of virus
of different serotype(dengue hemorrhagicfever)
NO antiviral drug
NO vaccines (difficult todevelop)
DHF: fluid replacementtherapy
control: breeding places& insecticides
Immunity Treatment or Control
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BUNYAVIRIDAE
Spherical
50-300 nm
Genome: double-segmented, negative sense and ambisense, single-stranded RNA, 10-14 kb
Enveloped
3 or 4 major structural polypeptides, 2 gycosylated
Replication: cytoplasm
Assembly: budding through host cell membranes
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BUNYAVIRIDAE
transovarial transmission :Woodland
mosquito(Aedes triseriatus) & sandfliesHosts: squirrels,chipmunks, & rabbits
Inactivated:
heat, detergents, formaldehyde, andlow pH
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Genus Phlebovirus
Bordering
Mediterranean sea
Female sandfly(Phlebotomus papatasii)
Small (pass throughnets) and feeds at night
Incubation: 3-6 days
SANDFLY FEVER
small, itching papules (5days)
Headache, malaise, nausea,fever, photophobia, stiffnessof neck & back, abdominalpain, and leukopenia.
NO specific treatment
Insect repellents at nightand insecticides
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RIFT VALLEY FEVER
Phlebovirusgenus
Sub-Saharan AfricaZoonotic (human secondarily infected)
Humans: mild, febrile illness, short-lived,and high chance of recovery (1% died)
Complications: retinitis, encephalitis, &hemorrhagic fever
FEVER
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FEVER
Mountain fever or tick fever
Genus Coltivirus(tick)
mild, febrile disease without rash
4-6 incubation daysSudden fever and myalgia
Headache, muscle & joint pain, lethargy, and
nausea & vomitingSelf-limited
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RODENT-BORNE VIRUSES
Intra-species or interspecies
Rodents or bats (reservoir)Contact with body fluids or excretions
Examples:
Lassa Fever
Hantavirus infectionsSouth American hemorrhagic fevers
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BUNYAVIRUSGenus Hantavirus (Hantaviruses)
HFRS and HPS
Transmissions: inhaling aerosols rodent
excreta (urine,feces,saliva)
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HEMORRHAGIC FEVER WITH
RENAL SYNDROME (HFRS)
Hantaan Virus (Apodemus agrarius) and Dobravavirus
Acute viral infectionInterstitial nephritis, acute renal insufficiency andrenal failure (severe form)
Nephropathia epidemica (Puumala virus)
Treatment: supportive therapy
Prevention: rodent control
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HANTAVIRUS PULMONARY
SYNDROME (HPS)
Novel hantavirus (Sin Nombre virus)
Severe (>30%)
Reservoir: deer mouse (Peromyscus maniculatus)
New York Virus, Black Creek Canal virus & Bayou
virus(U.S.A)
Andes virus (Argentina and Chile)
Choclo virus (Panama)
MANIFESTATIONS:
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MANIFESTATIONS:
Fever, headache, and myalgia
Progressive pulmonary edema, severe respiratory
compromise
No hemorrhage
Hantaviral Ag: endothelial cells and macrophages in
heart, lung, spleen, and lymph nodes
Pathogenesis: impairment of vascular endothelium
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LABORATORY
DIAGNOSIS:
Detection of viral nucleic acid (reverse transcriptase-PCR)
Immunohistochemistry of viral Ag ( fixed tissues)
Detection of specific Ab (recombinant proteins)
ELISA (IgM)
Fourfold rise in titer (IgG) [diagnostic]
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THERAPY
Maintain adequate oxygenation of hemodynamic functioning
Ribavirin (HPS)
Prevention:
rodent control
Avoid inhalation of aerosolized dried excreta
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ARENAVIRUS
Spherical
50-30nmGenome: double-segmented,negative sense andambisense; single stranded RNA; 10-14kb
Virion has transcriptase4 major polypeptides
Enveloped
Replication: cytoplasm
Assembly: incorporate ribosomes and budfrom plasma membrane
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ARENAVIRUS
Old world and New world viruses
NW: Grp. A (Pichinde virus)
Grp. B (Machupo Virus)
Chronic infections (rodents)
Aerosols, Milk, saliva, and urine
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LASSA FEVER
Highly virulent
Rodent Reservoir: house rat (Mastomys natalensis)
Incubation: 1-3 weeks
High fever, mouth ulcers, severe muscle aches, skinrashes with hemorrhages, pneumonia, and heart &
kidney damage; deafnessFetal death
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Transmission: human-to-human contact
Laboratory Diagnosis:
ELISA (IgG and IgM)
Immunochemistry
Reverse transcriptase-PCRTreatment: Ribavirin (antiviral)
Control/prevention:
Rodent control
Standard precautions(hospital)
Avaoid contact contaminated body fluids and blood
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SOUTH AMERICAN
HEMORRHAGIC FEVERS
Tacaribe complex
Junin hemorrhagic fever (Argentine hemorrhagic fever )
Calomys musculinus(rodent)
Machupo hemorrhagic fever
Calomys callosus
Venezuelan hemorrhagic fever
Guanarito virus
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Wild house mouse (Mus
musculus)
Via mouse droppings
acute disease
Aspetic meningitis or mild
systemic inlfuenza-like illness
Subclinical infections
Serology diagnosis: ELISA
(IgM & IgG Ab)
Immunochemistry
Viral culture (Viro cells)
Reverse transcriptase-PCR
(viral nucleic acid)
LYMPHOCYTIC
CHORIOMENINGITIS
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AREANAVIRUS LIFE CYCLE
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FILOVIRIDAE Long filaments, 80 nm (varying length)
Marburg 665nm
Ebola 805nm
Genome:
negative-sense,
Non-segmented
single-stranded RNA ;19kb
7 genes
Enveloped(glycoprotein)
encoded in two reading frames
transcriptional editing
Virions released by budding (plasma membrane)
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Replication: cytoplasm
Assembly: budding from plasma membrane
Marburg and Ebola (antigenically seperate)
4 subtypes of EbolaZaire
Sudan
Reston
Ivory Coast
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HIGHLY VIRULENT! (Biosafety Level 4)
Destroyed by
heating (30 mins.) at 60oC
Ultraviolet
Gamma-radiation
Lipid solvents
Bleach
Phenolic disinfectants
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AFRICAN HEMORRHAGIC
FEVERS
Marburg and Ebola viruses
Incubation: 3-9 days (Marburg); 2-21 days (Ebola)
Fever, headache, sore throat, muscle pain
Abdominal pain, vomiting, diarrhea (death)
Tropism for cells
Very high titers in tissues
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Marburg virus
1967lab. Workers exposed to tissues of African green monkeys
(Cercopithecus aethiops)
Patients to medical personnel transmissions
Ebola Virus
1976close, prolonged contact with patients, blood and excreta
-subtypes: Zaire and Sudan (Virulent!)
2008- pigs (Philippines)
Ebola Reston Virus
5 individuals developed Ab, but healthy.
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LABORATORY DIAGNOSIS:
ELISA for viral antigens (serum)
Reverse transcriptase-PCR (clinical specimens) Fresh Virus isolates (Vero and MA-104)
Under maximum biologic containment
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Reservoir
Rodent or Bat
Human (accidental)
Human to Human (direct contact)
PREVENTION:
Isolation facilities
Strict barrier techniques
Therapy
NO antiviral therapy
Maintaining renal function &
electrolyte balance
No vaccine