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FILOVIRIDAE

 Marburg Virus
 Ebola virus
o Genome: (-) sense, nonsegmented, single-stranded RNA
o Size: 19kb
o 7 polypeptides
o Enveloped
o Replication: Cytoplasm
o Assembly: budding from plasma membrane
FLAVIVIRIDAE
 Flavivirus (Japanese B Encephalitis)
o Shape: Spherical
o Diameter: 40-60nm
o Genome: (+) sense, single-stranded RNA (infectious)
o Size: 11kb
o 3 structural polypeptides; 2 glycosylated
o Enveloped
o Replication: Cytoplasm
o Assembly: within endoplasmic reticulum
 Hepatitis C has NO ARTHROPOD VECTOR and is NOT AN ARBOVIRUS
TOGAVIRIDAE
 Alphavirus (Chikungunya)
o Shape: Spherical
o Diameter: 70nm
o Nucleocapsid: 42 capsomeres
o Genome: (+) sense, single-stranded RNA
o Size: 11-12kb
o 3 or 4 major structural polypeptides; 2 glycosylated
o Enveloped
o Replication: Cytoplasm
o Assembly: budding through host cell membranes
 Antigenically related
 Inactivated by acid pH, heat, lipid solvents, detergents, bleach, phenol, 70% alcohol, and formaldehyde
 MOST possess hemagglutinating ability
 Rubella virus has NO ARTHROPOD VECTOR and is NOT AN ARBOVIRUS
 Replicase & transcriptase – needed for viral RNA replication
CLINICAL FINDINGS (Encephalitides)
 Incubation period: between 4-21 days
 Sudden onset
 Fever lasts 4-10 days
LABORATORY DIAGNOSIS
 Appears in blood only in EARLY INFECTION (before onset of symptoms)
 Can be found in CSF and tissue specimens
 Alphaviruses and flaviviruses are usually unable to grow in common cell lines, such as:
o Vero
o BHK
o HeLa
o MBC
 Mosquito cell lines are useful
 Intracerebral inoculation of suckling mice or hamster may also be used
 Antigen detection and PCR assays are used for direct detection of viral RNA
IMMUNITY
 Believed to be permanent after a single infection
 Humoral antibody and cellular immune responses are important
EPIDEMIOLOGY
 Most infections are ASYMPTOMATIC
 Most cases occur in summer months when arthropods are most active
ANTIGENIC PROPERTIES
 HI, ELISA, and IMMUNOFLUORESCENCE TESTS define 8 antigenic complexes or serogroups of
alphaviruses
 Neutralization test – identification of a specific virus
PATHOGENESIS AND PATHOLOGY
 MYELOID and LYMPHOID CELLS or VASCULAR ENDOTHELIUM – where primary viral
multiplication occurs
 Multiplication in the CNS depends on the ability of the virus to pass the blood-brain barrier to infect
nerve cells
Japanese B Encephalitis Virus
 Leading cause of viral encephalitis in Asia
 50,000 cases in China, Japan, Korea, and Indian subcontinent
 10,000 deaths among children and elderly adults
 30% mortality rate
 50% survival rate but left with neurologic and psychiatric sequelae
 300:1 – ratio of asymptomatic to symptomatic infections
 Host: Swine (important)
o Mosquito-bird-mosquito cycle also occurs
o Mosquitos remain infected for life
o ONLY female mosquitoes feed on blood and can transmit the virus more than once
o Mosquito’s midgut: site of primary viral multiplication
 Treatment: none
 Vaccine: Available in Asia
o Inactivated Vero cell culture-derived vaccine (US, 2009)
Chikungunya Virus
 Mosquito-borne alphavirus
 Semliki Forest antigenic complex
 Reemerged in Kenya in 2004 after an absence of several decades and subsequently caused massive
outbreaks of infection in India, southeastern Asia, and the Indian Ocean region
 Outbreak in Italy 2007
 Cases reported from returning travelers in US
 Established in Carribean region in 2013 and spread rapidly
 Resembles a dengue fever, rash, and severe joint pain
 Asymptomatic infections are rare
 Vaccine: not available
Dengue
 Also known as breakbone fever
 Caused by flavivirus
 Characterized by:
o Fever
o Severe headache
o Muscle and joint pain
o Nausea
o Vomiting
o Eye pain
o Rash
 Occur in severe forms:
o Dengue hemorrhagic fever
o Dengue shock syndrome

CLINICAL FINDINGS
 Disease begins 4-7 days after an infective mosquito bite
 Onset of fever may be sudden
 Prodromal symptoms: malaise, chills, and headache
 Back, joint, and muscle pain then develops
 Fever lasts from 2 to 7 days (peak viral load)
 Myalgia and deep bone pain (breakbone fever) are characteristic
 Enlarged lymphnodes
 Severe syndrome (DHF and DSS) may occur in children with passively acquired (maternal antibody)
infection
o Key pathological feature: increased vascular permeability with plasma leakage
LAB DIAGNOSIS
 RT-PCR – rapid identification and serotyping of dengue virus in acute-phase serum
 Isolation of virus is difficult
 Serologic diagnosis: cross-reactivity of IgG antibodies to heterologous flavivirus antigen
o ELISA and HI
EPIDEMIOLOGY
 Distributed worldwide in tropical regions where Aedes vectors exist
 2008 – most important mosquito-borne viral disease affecting humans
 A. aegypti - primary vector for dengue in the Western Hemisphere
 WW2 was responsible for the spread of dengue from SE Asia throughout the Pacific region
 Only type 2 dengue was present in America for years
 1977 – dengue type 1 was detected in the Western Hemisphere
 1981 – dengue type 4
 1994 – dengue type 3
 2005 – first case of dengue hemorrhagic fever in US 2005
 A. albopictus – mosquito of Asian origin, was discovered in Texas (1985)
o Replaced A. aegypti which cannot overwinter in the northern states
TREATMENT AND CONTROL
 No antiviral drug therapy
 Fluid replacement therapy – DHF
 No vaccine
 Control: antimosquito measures
o Elimination of breeding places
o Use of insecticides
o Screened windows and doors
FILOVIRUSES
 Pleomorphic particles
 Appear as long filamentous threads or as an odd-shaped forms 80nm in diameter
 Highly virulent and require maximum containment facilities (Biosafety level 4)
 Destroyed by:
o heating for 30 minutes @ 60C
o ultraviolet and gamma-radiation
o lipid solvents
o bleach and phenolic disinfectants
 Natural hosts and vectors are suspected to be African fruit bats
Marburg virus and Ebola virus
 Incubation period: 3 to 9 days (Marburg); 2-21 days (Ebola)
 Characterized by fever, headache, sore throat, and muscle plain followed by abdominal pain, vomiting,
diarrhea, and rash with external and internal bleeding
 Tropism: cells in macrophage system, dendritic cells, interstitial fibroblasts, endothelial cells
 Possess the highest mortality rates (25-90%) among all the viral hemorrhagic fevers
 Reservoir host: fruit bats
 Accidental host: humans
 Natural reservoirs are still unknown
Marburg virus
 Recognized in 1967
 Laboratory workers exposed to tissues of African green monkeys (Cercopithecus aethiops)
 Outbreaks documented in:
o Kenya
o South Africa
o Democratic Republic of Congo
o Angola
 Can infect guinea pigs, mice, hamsters, monkeys

Ebola Virus
 Discovered in 1976 when two severe epidemics of hemorrhagic fever occurred in Sudan and Zaire (now
Democratic Republic of Congo)
 More than 500 cases and at least 400 deaths during outbreaks
 Hospital staff became infected through close and prolonged contact with patients and their blood
 Zaire and Sudan subtypes are highly virulent
 Mean time to death (7-8 days)
 Western Africa 2014 – largest known Ebola outbreak
 September 30, 2014 – first confirmed case by CDC of travel-associated case of Ebola in US

Lab Diagnosis
 Infections appear to be immunosuppressive
 Fatal cases show impaired humoral immune responses
 Filovirus antibodies are detectable by ELISA
 Viral antigens in serum – ELISA (rapid screening test)
 RT-PCR – clinical specimens
 Culture: Vero and MA-104 monkey cell lines

Treatment, Prevention, and Control


 No control activities because natural reservoirs are still unknown
 Use of isolation facilities in hospital settings remains the most effective means of controlling Ebola
disease outbreaks
 Strict barrier nursing techniques should be implemented
 No specific antiviral therapies available
 Maintaining renal function and electrolyte balance and combating hemorrhage and shock
 No vaccine
ADDITIONAL INFO (Research)
Japanese Encephalitis Virus
 Also known as Arbovirus B
 Japanese B Encephalitis or Mosquito-borne encephalitis
 Vector: Culex tritaeniorhynchus

Zika Virus
 February 2017 (Philippines)
 Asymptomatic
 Characterized by
o Myalgia (muscle pain)
o Joint paint
o Retro orbital pain
 Associated with Guillan-Barre syndrome

Ebola
 Zaire and Sudan Ebola virus – responsible subtype for Africa Outbreak (2014-2016)
 Reston Ebola virus – subtype found in Philippines (2015)
o From monkeys, does not cause disease to humans
 First outbreak in US (1989) among laboratory monkeys

Chikungunya
 Name came from Kimakonde language of Tanzania and Mozambique meaning “to become contorted”
 Outbreak in Indang, Cavite (September 2016)
 Vector may be A. aegypti or A. albopictus
 Characterized by severe muscle and joint pain