Arthropod & Rodent-borne

Viruses
TOGAVIRUS
TOGAVIRUS: Classification
Group IV: ssRNA positive-sense viruses
Family: Togaviridae
Genera: Alphavirus
Chikungunya, Eastern, Western, and Venezuelan Equine
Encephalitis viruses, Mayaro, O’Nyong-nyong, Ross River,
Semliki Forest, Sindbis viruses, etc.

Rubivirus
Rubella virus

Arterivirus
CHIKUNGUNYA VIRUS
TOGAVIRUS: Viral Structure

65-70 nm in diameter
Spherical, icosahedral
Capsid: t=4 icosahedral
asymmetry made of 240
monomers
Envelope: 80 spikes, each spike
are trimer of E1/E2 proteins
TOGAVIRUS: Genomic Structure
9.7-11.8 kb in size
Monopartite, linear
ssRNA-positive genome
Capped at 5’ end
Polyadenylated at 3’ end
CHIKUNGUNYA VIRUS: Structure
CHIKUNGUNYA VIRUS: Structure
 CHIKUNGUNYA VIRUS: Epidemiology

Reemergence First documented

First isolated in
outbreak in the
Tanzania in Kenya
Americas

1952 2004 2013

1960s 2007

Periodic outbreaks in Localized outbreak in

Asia and Africa north-eastern Italy
CHIKUNGUNYA VIRUS: Epidemiology

1986 - First reported cases

2011 - Outbreaks in Cagayan de
Oro and Davao
2013 - State of calamity in
Ilocos Norte
CHIKUNGUNYA VIRUS: Transmission
CHIKUNGUNYA VIRUS: Pathogenesis
CHIKUNGUNYA VIRUS: Clinical Manifestations & Complications
CHIKUNGUNYA VIRUS: Clinical Manifestations & Complications
CHIKUNGUNYA VIRUS: Laboratory Diagnosis & Identification
CHIKUNGUNYA VIRUS: Laboratory Diagnosis & Identification
CHIKUNGUNYA VIRUS: Treatment, Prevention & Control
Flavivirus
CLASSIFICATION
❖ Flavivirus: ❖ In the genus Flavivirus there
➢ Class: Flasuviricetes are 70 defined species:
➢ Order: ➢ sorted by vectors.
Amarillovirales
➢ Family: Flaviviridae
➢ Genus: Flavivirus
CLASSIFICATION
CLASSIFICATION
 FLAVIVIRUS: DENGUE
❖ Dengue: ❖ “Breakbone Fever”
➢ Group: Group IV ❖ Characterized by:
((+)ssRNA) ➢ fever, severe headache, muscle and
➢ Order: Unassigned joint pain, nausea and vomiting, eye
➢ Family: Flaviviridae pain, and rash.
➢ Genus: Flavivirus ➢ 4 serotypes
➢ Species: Dengue Virus ■ DENV-1
■ DENV-2
■ DENV-3
■ DENV-4
DENGUE: VIRAL STRUCTURE
❖ Flavivirus virions:
➢ 50-80 nm in diameter
➢ Consist of 3 structural proteins
➢ The E protein is the major
protein of the virus.
DENGUE: GENOME STRUCTURE
EPIDEMIOLOGY
❖ Dengue viruses are distributed worldwide in tropical
regions. Most subtropical and tropical regions around
the world where Aedes vectors exist are endemic
areas.
❖ In the past 20 years, epidemic dengue has emerged
as a problem in the Americas.
❖ Dengue is common in more than 100 countries
around the world. 40% of the world’s population,
about 3 billion people, live in areas with a risk of
dengue.
❖ In Philippines:
➢ Negros Occidental, Iloilo, Aklan, Antique,
Capiz, Bacolod City, and Guimaras.
➢ Peak: May to November
➢ Incidence rate: 178 episodes per 100,000
population
➢ Fatality rate: approx. 0. 44%
PATHOGENESIS
❖ Mode of Transmission
➢ transmitted to humans through the bites
of infective female Aedes mosquitoes
➢ Mother to child
❖ Incubation Period
➢ 4-10 days
❖ Symptoms last:
➢ 2-7 days
VIRAL REPLICATION
VIRAL REPLICATION
VIRAL REPLICATION
VIRAL REPLICATION
VIRAL REPLICATION
VIRAL REPLICATION
VIRAL REPLICATION
DENGUE: CLINICAL MANIFESTATIONS
❖ Symptoms:
➢ Mild or Severe
➢ typically last 2–7 days.
❖ The most common symptom of dengue is fever with any of
the following:
➢ Nausea, vomiting
➢ Rash
➢ Aches and pains (eye pain, typically behind the eyes, muscle,
joint, or bone pain)
➢ Any warning sign
❖ Watch for signs and symptoms of severe dengue. Warning
signs usually begin in the 24–48 hours after your fever has
gone away.
DENGUE: LABORATORY DIAGNOSIS
❖ Reverse transcriptase PCR (RT-PCR)-based methods
➢ rapid identification and serotyping of dengue virus
❖ Cross-reactive flaviviruses
❖ Nucleic acid amplification tests (NAATs)
➢ preferred method of laboratory
❖ Serologic diagnosis
➢ IgM antibody testing
■ Additional infections
■ Plaque Reduction Neutralization Tests (PRNTs)
 TREATMENT, PREVENTION, AND CONTROL
❖ There is no antiviral drug therapy
❖ Dengue hemorrhagic fever can be treated by fluid replacement therapy.
❖ There is no vaccine, but candidate vaccines are under development.
➢ limited

❖ Control:
➢ elimination of breeding places
➢ use of insecticides
➢ screened windows and doors
➢ using repellents and wearing protective
clothing.
FILOVIRUS

37
FILOVIRUS: CLASSIFICATION
▸ Kingdom: Orthornavirae
▸ Phylum: Negarnaviricota
▸ Class: Monjiviricetes
▸ Order: Mononegavirales
▸ Family: Filoviridae
▸ Genus: Ebola, Cueva,
and Marburg

38
FILOVIRUS: STRUCTURE
▸ Viral Particle: PLEOMORPHIC
▸ Diameter: 80 nm in diameter × >10,000
nm
▸ Envelope: LIPID FATTY MEMBRANE
▸ Appearance: LONG FILAMENTOUS
THREADS OR ODD-SHAPED FORMS
▸ Genome: NEGATIVE-SENSE,
NONSEGMENTED, SINGLE-STRANDED
RNA
39
FILOVIRUS: EBOLA

40
EBOLAVIRUS: STRUCTURE
▸ Approximately 805 nm in length
▸ Has viral spikes
▸ Has six species: Zaire, Sudan,
Taï Forest, Bundibugyo, Reston,
and Bombali
▸ Only four viruses are known to
cause disease in humans

41
EBOLAVIRUS: EPIDEMIOLOGY
▸ Mostly seen in several
African countries
▸ Discovered in 1976
▸ The largest known
Ebola Outbreak –
Western Africa in
2014-2016
42
 EBOLAVIRUS: PATHOGENESIS

▸ Has tropism for:

Macrophage
System, Dendritic
Cells, Interstitial
Fibroblasts, and
Endothelial Cells

43
 EBOLAVIRUS: CLINICAL COMPLICATIONS AND MANIFESTATIONS
COMPLICATIONS & S/S
MANIFESTATION ▸ Fever
▸ Aches and pains
▸ Hemorrhagic fever ▸ Weakness and fatigue
▸ Incubation Period: 2-21 ▸ Gastrointestinal
symptoms
days
▸ Abdominal pain
▸ Typically progresses from
▸ Unexplained
dry symptoms to wet
hemorrhaging, bleeding or
symptoms
bruising
▸ Leads to shock and death
44
EBOLAVIRUS: LAB DIAGNOSIS AND IDENTIFICATION
▸ Detected in the blood after
onset of symptoms
▸ Biosafety Level 4
▸ Detectable by ELISA –
rapid screening test
▸ PCR – diagnostic method
▸ Can be cultured in cells
45
EBOLAVIRUS: TREATMENT, PREVENTION AND CONTROL
PREVENTION AND CONTROL
TREATMENT
▸ Use of isolation facilities
▸ Inmazeb ▸ Strict barrier nursing
▸ Ebanga techniques
▸ Extreme care must be
taken with infected
fluids
▸ Vaccine

46
FILOVIRUS:
MARBURG

47
FILOVIRUS: CLASSIFICATION
▸ Kingdom: Orthornavirae
▸ Phylum: Negarnaviricota
▸ Class: Monjiviricetes
▸ Order: Mononegavirales
▸ Family: Filoviridae
▸ Genus: Ebola, Cueva,
and Marburg
48
FILOVIRUS: STRUCTURE
▸ Viral Particle: PLEOMORPHIC
▸ Diameter: 80 nm in diameter × 10,000
nm
▸ Envelope: LIPID FATTY MEMBRANE
▸ Appearance: LONG FILAMENTOUS
THREADS OR ODD-SHAPED FORMS
▸ Genome: NEGATIVE-SENSE,
NONSEGMENTED, SINGLE-STRANDED
RNA
49
MARBURG VIRUS: STRUCTURE

Approximately 665 nm in length

Shaded areas (coding regions)

White areas (noncoding
sequences)
MARBURG VIRUS: EPIDEMIOLOGY
Mostly seen in several
first recognized in African countries
1967 Kenya
South Africa
Democratic Republic of
cases of this
the Congo
disease are rare
Angola

51
MARBURG VIRUS: OUTBREAK

Democratic United States and

South Africa
Republic of Congo Netherlands ex Uganda

1975 1998-2000
1967 1980 2004-2005 2008 2014
Germany and Kenya Angola Uganda
Yugoslavia
MARBURG VIRUS: PATHOGENESIS
How Marburg virus first transmits
from its animal host to humans?

UNKNOWN!

RESERVOIR HOST
African Fruit Bat
Rousettus aegyptiacus (CDC)
53
 MARBURG VIRUS: PATHOGENESIS

Transmission may occur in

several ways:
▸ Direct contact to droplets
▸ Contact with equipment
and other objects

The spread of virus occurred in close environments and direct contacts.

Filoviruses have a tropism for cells of the macrophage system, dendritic cells,
interstitial fibroblasts, and endothelial cells.
54
MARBURG VIRUS: MANIFESTATION AND COMPLICATIONS
Signs and symptoms
Highly Virulent Fever Abdominal pain
Headache
Vomiting
Incubation period: Diarrhea Sore throat
➔ 3-9 days (Jawetz) Rash
➔ 5-10 days (CDC)
➔Internal and
External bleeding
MORTALITY RATE ➔Multi-organ
(25-90%) dysfunction
➔Shock
➔Death
EBOLAVIRUS: LAB DIAGNOSIS AND IDENTIFICATION

Marbug virus can be detected by Can be cultured in cell lines such

● ELISA as
● RT-PCR ● Vero
● IgM-capture ELISA ● MA-104 monkey
● IgG-capture ELISA (after recovery)

56
MARBURG VIRUS: TREATMENT, PREVENTION AND
CONTROL
TREATMENT PREVENTION AND CONTROL

➔No specific No organized prevention

treatment or and control activities
antiviral therapies ➔Isolation facilities
➔Experimental ➔Increasing awareness
vaccine is ➔Wearing of PPE
present ➔Improving the use of
diagnostic tools
57
BUNYAVIRUS

58
 BUNYAVIRUS: Classification
ARthropod BOrne Viruses
FIVE GENERA: ▸ Nairovirus
▸ Orthobunyavirus ▸ Phlebovirus
▸ Hantavirus ▸ Orthobunyavirus
▸ Nairovirus
▸ Tospovirus
▸ Phlebovirus
▸ Tospovirus ROdent BOrne Viruses
▸ Hantavirus
59
BUNYAVIRUS: Structure

▸ Viral Particle: Spherical

▸ Diameter: 80-120 nm
▸ Segments: Tripartite
▸ Genome: Negative-sense ssRNA
▸ Virion: Transcriptase
▸ Envelope: Lipid membrane
▸ Assembly: Budding into golgi
60
 BUNYAVIRUS: Epidemiology

Diseases occur when

humans or animals are in
contact with infected
vertebrates or when fed on
by infected arthropods in
specific geographic areas.

Bunyamwera, Uganda

61
HANTAVIRUS:
Epidemiology

1993, United States

SIN NOMBRE VIRUS

62
 Crimean-Congo
Rift Valley La Crosse Virus Hemorrhagic Hantaan virus Sin Nombre Virus
Fever Virus Fever Virus (Old World) (New World)

PLACE 1ST East Africa La Crosse, Crimean peninsula Early 1950’s, Four corner areas of
DETECTED; Wisconsin, USA Hantaan River US
DISTRIBUTION (Asia)

DISEASE Rift Valley Fever California Crimean-Congo Korean Hantavirus Pulmonary

(RVF) Encephalitis (CE) Hemorrhagic Fever Hemorrhagic Fever Syndrome (HPS)
(CCHF) Virus (KHF)

RESERVOIR Bats Chipmunks, foxes, Cattle, goats, birds, Rodents Rodents

squirrels, and ticks
woodchucks

VECTOR Mosquitoes Mosquitoes Ticks No arthropod vector No arthropod vector

(not arbovirus) (not arbovirus)

63
 BUNYAVIRUS: PATHOGENESIS

VECTOR
MODES OF TRANSMISSION
through exposure (inhalation)
to aerosolized mouse urine,
Saliva and feces.

PERSON TO PERSON
Apodemus agrarius
TRANSMISSION: RARE
(STRIPED FIELD MOUSE)

64
 LCAPILLARY
LEAK

LUNGS KIDNEYS

Incubation Period: ACUTE

1-2 weeks PULMONARY
EDEMA
PRE-RENAL
AZOTEMIA
TUBULOINTERSTITIAL
NEPHRITIS

65
Is the Disease Fatal?
Yes. It has a mortality Hemorrhagic Fever with Renal
rate of 5-15%. Syndrome (HFRS)
BUNYAVIRUS: Clinical Manifestation and Complication
INITIAL SIGNS AND SYMPTOMS LATER SIGNS AND SYMPTOMS
▸ Headache ▸ Low blood pressure
▸ Fever ▸ Acute shock
▸ Chills, nausea, and blurred vision ▸ Vascular leakage
▸ Body aches ▸ Acute kidney failure (severe
▸ Flushing of the face, fluid overload)
inflammation or redness of the
eyes, or a rash.

66
 Crimean-Congo
Rift Valley La Crosse Virus Hemorrhagic Hantaan Virus Sin Nombre Virus
Fever Virus Fever Virus

MODE OF Arthropod transmits the virus when feeding Through exposure (inhalation) to
TRANSMISSION on the blood of vertebrate hosts, including humans aerosolized mouse urine, saliva and feces.

TARGET ORGANS Brain, liver Vascular Peritoneal cavity, kidneys, thoracic

endothelium, cavity, kidneys, or lungs
liver

CAUSES Encephalitis, Encephalitis CCHF fever Hemorrhagic Hantavirus

hepatitis fever with renal Pulmonary
syndrome (HFRS) Syndrome (HPS)

MORTALITY RATE Approximately 300,000 persons About 30% of 5-15% 50%

1% of humans annually patients die
infected with RVF
die

67
BUNYAVIRUS: Laboratory Diagnosis
ELISA -method of choice
- IgM or IgG antibodies
Immunohistochemistry
- Viral Antigen
RT-PCR
- Amplifiable viral RNA sequences
68
BUNYAVIRUS: Treatment, Prevention and Control
TREATMENT
▸ Supportive
▸ Ribavirin
▸ No vaccine!!!

PREVENTION AND CONTROL

▸ Rodent control
▸ Protection from exposure to rodent droppings
and contaminated material
69
ARENAVIRUS

70
ARENAVIRUS: Classification
OLD WORLD NEW WORLD

▸ Lymphocytic ▸ Tacaribe
Choriomeningitis ▸ Junin
▸ Lassa ▸ Machupo
▸ Mopeia ▸ Cupixi
▸ Mobala ▸ Parana
▸ Ippy ▸ Tamiami
▸ Merino Walk ▸ Pichinde
▸ Menekre ▸ Whitewater Arroyo
▸ Gbagroube ▸ Guanarito
▸ Morogoro ▸ Catarina
▸ Kodoko ▸ Chapare 71
ARENAVIRUS/LASSA VIRUS: Structure
Viral Particle: Pleomorphic and Spherical
Diameter: 110-130 nm
Envelope: Lipid Membrane
Appearance: Grainy/Sandy
Genome: ssRNA
Virion: Budding from host cell
72
 LASSA VIRUS: Epidemiology

1969

73
15% Mortality
Rate
>5000 deaths

Hospitalized
74
LASSA VIRUS: PATHOGENESIS
VECTOR MODES OF TRANSMISSION
MOUSE to HUMAN: through
contact with excreta, inhalation of
urine, ingestion of contaminated
food

HUMAN to HUMAN: through

Mastomys natalensis body fluid
(HOUSE RAT) 75
 Targets:
▸ Liver (Hepatocellular
Necrosis)
▸ Endothelium (Capillary
Lesion)

which LEADS TO
GP-1: Binding to Receptor HEMORRHAGE
GP-2: Cell Membrane Attachment
https://microbewiki.kenyon.edu/index.php/Lassa_virus 76
1-3 weeks
Incubation Period and it involves many ORGAN
SYSTEM

77
LASSA VIRUS: Clinical Manifestation and Complication
Signs and Symptoms
▸ Fever
▸ Vomiting
▸ Back and chest pain
▸ SKIN RASH WITH HEMORRHAGE
Complications
▸ Deafness (permanent)
78
LASSA VIRUS: Laboratory Diagnosis
ELISA
- IgM and IgG antibodies
Immunohistochemistry
- Viral Antigen (Post-mortem)
RT-PCR
- Viral Sequence
79
LASSA VIRUS: Treatment, Prevention, and Control
Treatment Prevention and Control
▸ Ribavarin (antiviral ▸ Rodent Control
drug) Measures
▸ NO VACCINE!

80
 “

THANK YOU
81