arthropod and rodent- borne viruses

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


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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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

arthropod and rodent- borne viruses

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