ARTHROPOD AND RODENT- BORNE VIRUSES

ARTHROPOD-BORNE VIRUSES (ARBOVIRUSES )

Blood-sucking Arthropods (Vectors) Multiply in tissues of vector Some Major Arboviruses: Yellow fever Dengue West Nile Fever

 100 are known pathogenic to humans Zoonotic (except urban yellow fever and dengue) 3 syndromes: 1. 2. 3. Fevers of undifferentiated type with or without a maculopapular rash and benign Encephalitis(inflammation of brain) Hemorrhagic fevers (usually sever and fatal)

ARBOVIRUSES

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

FLAVIVIRIDAE
Genus Flavivirus Spherical 40-60 nm diameter Genome: 11kb,Single stranded , positive-sense RNA (INFECTIOUS!) Enveloped 3 structural polypeptides, (2 glycosylated) Assembly: within endoplasmic reticulum

A L P H AV I RU S
Genomic Length

TRANSCRIPTION

Subgenomic (26S)

Precursor proteins for viral replication

Encodes structural proteins

Elaborated by posttranslational cleavage

Replication: Cytoplasm Mature : By Budding Nucleocapsids Plasma Membrane

Viral Replication

Genomelength mRNA

Large Precursor Protein Cleaved by Viral and Host protease

FLAVIVIRUS REPLICATION

Viral Proteins(structural and non structural)

Replication: Cytoplasm
Particle Assembly: intracellular vesicles

ANTIGENIC
Alphavirus
Cross-section in immunotechniques (antigenically related) HI,ELISA,IF test define 8 serogroups ID specific virus: Nt tests

Flavivirus
Antigenically related Nt test : ID 8 complexes

PATHOGENESIS
myeloid and lymphoid cells or vascular endothelium CNS (depends on ability of virus)

FLAVIVIRUS LIFE CYCLE

CLINICAL FINDINGS
Incubation: 4 to 21 days Inapparent infections (common) Mild flu-like illness & encephalitis Sudden 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)

LABORATORY DIAGNOSIS
Direct Detection & Recovery

Specimens: blood (early infection), CSF, tissue specimen Common cell lines: Vero, BHK, HeLa, & MRC-5 Mosquito Cell Lines Intracerebral inoculation of suckling mice or hamsters Appropriate biosafety precautions!

SEROLOGY
Neutralizing & 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 )

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 tarsalis and birds St. Louis Encephalitis

10,000 cases and 1000 deaths (N.America)

Presence of infected mosquitoes

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 with lymphadenopathy and rash, transitory meningeal involvement.

T I C K B O R N E F L AV I V I R U 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

TREATMENT AND CONTROL

No specific treatment Arthropod control (effective method) spray insecticides repellents

Vaccines developed (for horses only)

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)

CLINICAL MANIFES TATIONS :

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: 7 10 days illness

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

SEROLOGY
IgM (1st week) ELISA (presumptive) Fourfold or greater rise of titer (confirmation) Immunity Neutralizing antibodies (complete protection)

Treatment, Prevention, Control NO antiviral drug therapy Vaccination (most effective treatment) 17D strain and virulent Asibi strain (vaccine) Good antibody response (95%)

TRANSMISSION CYCLE

DENGUE
Breakbone fever Mosquito-borne (Aedes aegypti & Aedes albopictus )

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 nodes Mild febrile illness

 Dengue hemorrhagic fever/dengue shock syndrome Increased vascular permeability with plasma leakage Pre-existing dengue antibody

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)

Immunity
Nt test and molecularbased assays (4 serotypes ) Infection (lifelong protection) Reinfection of virus of different serotype (dengue hemorrhagic fever)

Treatment or Control NO antiviral drug NO vaccines (difficult to develop) DHF: fluid replacement therapy control: breeding places & insecticides

BUNYAVIRIDAE
Spherical 50-300 nm Genome: double-segmented, negative sense and ambisense, singlestranded RNA, 10-14 kb Enveloped 3 or 4 major structural polypeptides, 2 gycosylated Replication: cytoplasm Assembly: budding through host cell membranes

BUNYAVIRIDAE
transovarial transmission :Woodland mosquito(Aedes triseriatus) & sandflies Hosts: squirrels,chipmunks, & rabbits Inactivated: heat, detergents, formaldehyde, and low pH

SANDFLY FEVER
Genus Phlebovirus Bordering Mediterranean sea Female sandfly (Phlebotomus papatasii) Small (pass through nets) and feeds at night Incubation: 3-6 days
small, itching papules (5 days) Headache, malaise, nausea, fever, photophobia, stiffness of neck & back, abdominal pain, and leukopenia. NO specific treatment Insect repellents at night and insecticides

RIFT VALLEY FEVER

Phlebovirus genus Sub-Saharan Africa Zoonotic (human secondarily infected) Humans: mild, febrile illness, short-lived, and high chance of recovery (1% died) Complications: retinitis, encephalitis, & hemorrhagic fever

COLORADO TICK FEVER Mountain fever or tick fever Genus Coltivirus (tick) mild, febrile disease without rash 4-6 incubation days Sudden fever and myalgia Headache, muscle & joint pain, lethargy, and nausea & vomiting Self-limited

RODENT-BORNE VIRUSES
Intra-species or interspecies Rodents or bats (reservoir) Contact with body fluids or excretions Examples: Lassa Fever Hantavirus infections South American hemorrhagic fevers

BUNYAVIRUS
Genus Hantavirus (Hantaviruses)
HFRS and HPS Transmissions: inhaling aerosols rodent excreta (urine,feces,saliva)

HEMORRHAGI C FEVER WI TH RENAL SYNDROME (HFRS)

Hantaan Virus (Apodemus agrarius) and Dobrava virus Acute viral infection Interstitial nephritis, acute renal insufficiency and renal failure (severe form) Nephropathia epidemica (Puumala virus) Treatment: supportive therapy Prevention: rodent control

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:
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

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]

THERAPY
Maintain adequate oxygenation of hemodynamic functioning Ribavirin (HPS)

Prevention:
rodent control Avoid inhalation of aerosolized dried excreta

Spherical ARENAVIRUS 50-30nm Genome: double-segmented,negative sense and ambisense; single stranded RNA; 10-14kb Virion has transcriptase 4 major polypeptides Enveloped Replication: cytoplasm Assembly: incorporate ribosomes and bud from plasma membrane

ARENAVIRUS
Old world and New world viruses NW: Grp. A (Pichinde virus) Grp. B (Machupo Virus) Chronic infections (rodents)

Aerosols, Milk, saliva, and urine

LASSA FEVER
Highly virulent Rodent Reservoir: house rat (Mastomys natalensis) Incubation: 1-3 weeks High fever, mouth ulcers, severe muscle aches, skin rashes with hemorrhages, pneumonia, and heart & kidney damage; deafness Fetal death

Transmission: human-to-human contact Laboratory Diagnosis:

ELISA (IgG and IgM)

Immunochemistry Reverse transcriptase-PCR

Treatment: Ribavirin (antiviral)

Control/prevention: Rodent control

Standard precautions(hospital)
Avaoid contact contaminated body fluids and blood

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

LYMPHOCYTIC CHORIOMENINGITIS
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)

AREANAVIRUS LIFE CYCLE

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)

Replication: cytoplasm Assembly: budding from plasma membrane

Marburg and Ebola (antigenically seperate)

4 subtypes of Ebola

Zaire
Sudan Reston Ivory Coast

 HIGHLY VIRULENT! (Biosafety Level 4) Destroyed by heating (30 mins.) at 60oC Ultraviolet Gamma-radiation Lipid solvents Bleach Phenolic disinfectants

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

Marburg virus 1967 lab. Workers exposed to tissues of African green monkeys (Cercopithecus aethiops) Patients to medical personnel transmissions Ebola Virus 1976 close, prolonged contact with patients, blood and excreta -subtypes: Zaire and Sudan (Virulent!) 2008- pigs (Philippines)

Ebola Reston Virus

5 individuals developed Ab, but healthy.

LABORATORY DIAGNOSIS:
ELISA for viral antigens (serum) Reverse transcriptase-PCR (clinical specimens) Fresh Virus isolates (Vero and MA-104) Under maximum biologic containment

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