1969: First recognized case in Nigerian village of Lassa

ARENAVIRUS o
o Highly virulent – 15% mortality rate; 1% fatal
o Active in western African countries between Senegal and
Republic of Congo
o Incubation period: 1-3 weeks
o Involve many organ systems
o Onset is gradual, w/ fever, vomiting, back and chest pain
o Very high fever, mouth ulcers, severe muscle aches, skin rash
w/ hemorrhages, pneumonia, heart and kidney damage
o Deafness – common complication; often permanent
o Can cause fetal death in more than 75% of pregnant woman
3rd trimester – maternal mortality 30%
fetal mortality >90%
o Diagnosis:
ELISA - detection of IgM and IgG antibodies
Immunohistochemistry – detect viral antigens in postmortem
tissue specimens
RT-PCR – detect viral sequences
o Principal rodent reservoir: house rat (Mastomys natalensis)
o Transmission: human-to-human
o Family: Arenaviridae
o Antiviral drug: Ribavirin – most effective if given early
o Typified pleomorphic particles
o No vaccine
o Segmented RNA genome
o Vaccinia virus recombinant – expresses glycoprotein of Lassa
o Envelope w/ large, club-shaped peplomers
virus is able to induce protective immunity both in guinea pigs
o 50-300 nm (mean, 110-130 nm)
and monkeys
o Two single-stranded RNA w/ unusual ambisense genetic
organization LUJO HEMORRHAGIC FEVER VIRUSES
o 29 spherical, enveloped RNA virus o 2008: 1st identified as a cause of hemorrhagic fever in South
o T-shaped glycoprotein spikes 7-10 nm long surrounding the Africa
surface membrane of virion o Source of infection: unknown
o Divided into: Old World viruses and New World viruses o Treatment: Ribavirin
• Group A – Pichinde virus o Primary host: rodents
• Group B – Human pathogenic viruses (Machupo virus)
• Group C SOUTH AMERICAN HEMORRHAGIC FEVERS
Whitewater Arroyo virus – recombinants between New o Members of Tacaribe complex
World lineages A and B o Rodent reservoir: cricetid
o Establish chronic infections in rodents ➢ Junin hemorrhagic fever (Argentine hemorrhagic fever) –
o Transmission: contact w/ rodent excreta, aerosols, milk, saliva, major public health problem in agricultural areas of
urine Argentina
o Replication: host ribosomes - 1958 – 1980: 18,000 cases w/ 10-15% mortality rate in
untreated patients
- Marked seasonal variation almost exclusively among
workers in maize and wheat fields
- Reservoir rodent: Calomys musculinus
- Produces both humoral and cell-mediated
immunodepression; deaths caused by inability to initiate
cell-mediated immune response
- Treatment: administration of convalescent human plasma
during 1st week of illness
- May develop a self-limited neurologic syndrome 3-6
weeks later
- Prevention: Live attenuated Junin virus vaccine

LASSA FEVER
 ➢ Machupo hemorrhagic fever (Bolivian hemorrhagic fever) –
1st outbreak in Bolivia in 1962
- Host: Calomys callosus
- Prevention: rodent control program
➢ Guanarito virus – agent of Venezuelan hemorrhagic fever
- Identified in 1990; mortality rate of 33%
- Its emergence was tied to clearance of forest land for
small farm use
- Induce a clinical disease resembling that of Argentine
hemorrhagic fever
➢ Sabia virus – isolated in 1990 in Brazil
- Induce a clinical disease resembling that of Argentine
hemorrhagic fever

LYMPHOCYTIC CHORIOMENINGITIS VIRUS (LCM)

o Discovered in 1933 and widespread in Europe and Americas
o Natural vector: wild house mouse, Mus musculus
o Endemic in mice but can also infect other rodents
o May chronically infect mouse or hamster colonies and may
infect pet rodents
o Occasionally transmitted to humans, presumably via mouse
droppings
o In humans: an acute disease manifested by aseptic meningtits
or mild systemic influenza-like illness
o Rarely is there a severe encephalomy-elitis or fatal systemic
disease in healthy people
o Infections are subclinical
o Incubation period: 1-2 weeks
o Illness period: 1-3 weeks
o Can be serious w/ impaired immune systems
o Can be transmitted from mother to fetus; infection of fetus in
early infection can lead to serious defects (hydrocephalus,
blindness, fetal death)
o Diagnosis:
Serologic Tests: ELISA – detect IgM and IgG antibodies
Immunohistochemical staining of tissues – viral antigens
RT-PCR – viral nucleic acid
Viral culture – Vero cells
o Immune response may be protective or deleterious in LCM
virus-infected mice
T cells – control infection but may induce immune-mediated
disease
o Mice infected as adults – may develop rapidly fatal disease
cause by T cell-mediated inflammatory response in brain
o Congenitally or neonatally infected mice – do not become
acutely ill but carry a lifelong persistent infection
BUNYAVIRUS
o 1st detected in Bunyamwera, Uganda
o RNA virus consisting of 3 single-stranded RNA segments
enclosed in helical nucleocapsid that is surrounded by lipid
envelope
o Spherical particles measuring 80-120 nm contain single-
stranded, negative-sense or ambisense, triple-segmented RNA
genome 11-19 kb in total size
o Envelope: has 2 glycoproteins
o Unique feature of this family of viruses is their tripartite genome
o Provides a mechanism for genetic reassortment in nature
o Large, diverse group of viruses (300 total members w/ 12
human pathogens)
o Transmitted by mosquitoes (arboviruses); transovarial
transmission occurs in some mosquitoes; some are transmitted
by sandflies
o Sensitive to inactivation by heat, detergents, formaldehyde, low
pH; some are hemagglutinating
o California serogroup (CAL) – most important human pathogens
in US; includes California encephalitis and Lacrosse viruses
(LAC)
o Belongs to Hantavirus genus are not arboviruses
o Transmission: exposure (inhalation) to aerosolized rodent
excreta
o Rodents develop a chronic infection that results in shedding of
virus in saliva, feces, and urine
o Disruption of these animal excreta by vacuuming, sweeping, or
shaking rugs aerosolizes infected particles, which are then
inhaled
Bunyavirus Encephalitis Viruses
o California encephalitis virus complex – comprises 14
antigenically related viruses in Orthobunyavirus genus
➢ La Crosse virus – significant human pathogen in US
- Major cause of encephalitis and aseptic meningitis in
children, particularly in upper Midwest
- Most occur between July and September in children <16
- Transmitted by various woodland mosquitoes, Aedes
triseriatus
 - Principal vertebrate host: small mammals (squirrels,
chipmunks, rabbits)
- Human infection is tangential
- Overwintering can occur in eggs of mosquito vector
- Virus is transmitted transovarially; adult mosquitoes
develop from infected eggs can transmit virus by bite
- Onset is abrupt, typically w/ severe headache, fever,
some cases vomiting and convulsions
- Illness period: 10-14 days
- Neurologic sequelae are rare
- Diagnosis:
Serology: HI, ELISA, neutralization tests – acute and
convalescent specimens
Sandfly Fever Virus (Phlebotomus virus)
o mild, insect-borne disease
o occurs in countries bordering Mediterranean Sea and Russia,
Iran, Pakistan, India, Panama, Brazil, Trinidad
o caused by Phlebovirus genus
o transmitted by female sandfly, Phlebotomus papatasii, midge
only a few mm in size
o prevalent all year in the tropics
o transovarial transmission
o common to childhood in endemic areas
o bite results in small itching papules on skin that persist for up
to 5 days
o begins abruptly after an incubation period of 3-6 days
o found in blood briefly near time of onset of symptoms:
headache, malaise, nausea, fever, photophobia, stiffness of
neck and back, abdominal pain, leukopenia
o all patients recover
o no specific treatment
o Sandflies – most common just above the ground; small and
can pass through ordinary screens and mosquito nets; feed at
night
o Prevention: use of insect repellents during night and residual
insecticides around living quarters
Rift Valley Fever Virus
o Phlebovirus genus
o Mosquito-borne zoonotic virus pathogenic primarily for
domestic livestock
o Humans are secondarily infected during course of epizootics in
domesticated animals
o Infection occur among lab workers
o Epizootics occur periodically after heavy rains that allow
hatches of primary vector and reservoir: Aedes species
mosquitoes
o Viremia in animals lead to infection of other vectors w/
collateral transmission to humans
o Transmission: contact w/ infected animal blood or body fluids
o Usually mild and febrile illness that is short lived
o Recovery: almost always complete
o Complications: retinitis, encephalitis, hemorrhagic fever
o Permanent loss of vision may occur
o Exists in most countries of sub-Saharan Africa;
1977 – spread to Egypt where it caused enormous losses of
sheep and cattle and thousands of human
1987 – large outbreak in West Africa
1997 – outbreak in East Africa
2000 – 1st documented spread of Rift Valley fever virus outside
Africa, Yemen and Saudi Arabia
Severe Fever w/ Thrombocytopenia Syndrome
o Discovered in 2010 as cause of severe fever w/
thrombocytopenia syndrome in northeast and central China
o Present w/ fever, thrombocytopenia, leukopenia, elevated liver
enzymes
o Transmitted by ticks but can pass from person to person
o Humans are rarely seropositive but domesticated animals are
often seropositive, including sheep, cattle, pigs, dogs,
chickens, goats
o Diagnosis:
Serology Using highly conserved regions of three L,M and S
PCR genome segments
Heartland Virus
o Novel Phlebovirus in bunyavirus family discovered in Missouri
in 2012
o Presents: fever, fatigue, anorexia, nausea, or diarrhea,
leukopenia, thrombocytopenia, and elevated liver enzymes
o Vector: Lone Star ticks (not yet sure)
Hemorrhagic Fever w/ Renal Syndrome (HFRS)
o Acute viral infection that causes interstitial nephritis that lead to
acute renal insufficiency and renal failure in several forms of
disease
o Hantaan and Dobrava virus – cause severe disease that
occurs in Asia (China, Russia, Korea) and Europe (Balkans)
o Generalized hemorrhage and shock may occur
Type Virus Area affected
Moderate form Seoul virus Eurasia
Mild form (Nephropathia Puumala virus Scandinavia
epidemica)
o Host: Urban rats
o Occurred in persons whose occupations place them in contact w/
rats
o Treatment: supportive therapy
o Prevention: depends on rodent control and protection from
exposure to rodent droppings and contaminated material
Hantavirus Pulmonary Syndrome (HPS)
o 1993: outbreak of severe respiratory illness in US
o Found to caused by novel hantavirus (Sin Nombre virus) – 1st
recognized to cause disease in N. America and 1st to cause
primarily an adult respiratory distress
o Primary rodent reservoir: deer mouse (Peromyscus
maniculatus) – widely spread
o New York virus, Black Creek Canal virus and Bayou virus –
also cause HPS in US
o Andres virus – causative hantavirus in Argentina and Chile
 o Choclo virus – identified in Panama
o Not common, w/ relatively fewer subclinical infections
o Sin Nombre Virus - generally severe, w/ reported mortality
rates of 30% or greater
o Begins w/ fever, headache, myalgia followed by rapidly
progressive pulmonary edema, leading to severe respiratory
compromise, no signs of hemorrhage
o Hentaviral antigens – detected in endothelial cells and
macrophages in lung, heart, spleen, lymph nodes
o Pathogenesis: functional impairment of vascular endothelium
o Person-to-person transmission seldom occurs
o Laboratory diagnosis:
RT-PCR – detect viral nucleic acid
Immunohistochemistry – detect viral antigens in fixed tissues
Recombinant proteins - detection of specific antibodies
ELISA test – detect IgM to diagnose acute infections;
4fold rise in IgG antibody titer between acute and
convalescent sera is diagnostic
Isolation of hantavirus – difficult and requires use of
containment facilities
o Treatment: maintenance of adequate oxygenation and support
of hemodynamic functioning
o Antiviral drug: Ribavirin
o Prevention: rodent control and avoidance of contact w/ rodents
and rodent droppings; care to avoid inhaling aerosolized dried
excreta when cleaning rodent-infested structures
FILOVIRUS
o Most pathogenic of hemorrhagic fever viruses
o filo – threadlike, referring to virus’s long, filamentous structural
morphology seen w/ EM
o pleomorphic, enveloped, nonsegmented, single-stranded,
negative sense RNA viruses, 19kb, contains 7 genes
o filamentous morphology appears in many forms or
configurations under EM such as number “6”,”U”, or circular
o unit length particles are from 665 (Marburg) to 805 nm (Ebola)
o 4 subtypes of Ebola virus: Zaire, Sudan, Reston, Ivory Coast
differ from one another by up to 40% at nucleotide level but
share some common epitopes
o Subtypes appear stable over time
o Highly virulent and require maximum containment facilities
(BioSafety Level 4) for laboratory work
o Infectivity is destroyed by heating for 30 minutes at 60OC by
ultraviolet and -irradiation, by lipid solvents, and by bleach
and phenolic disinfectants
o Natural host: African fruit bats
African Hemorrhagic Fevers (Marburg and Ebola Viruses)
o Highly virulent in humans and nonhuman primates, w/
infections usually ending in death
o Incubation period: 3-9 days for Marburg disease
2-21 days for Ebola
o Cause similar acute diseases characterized by fever,
headache, sore throat, and muscle pain followed by abdominal
pain, vomiting, diarrhea, rash w/ both internal and external
bleeding, leading to shock and death
o Have tropism for cells of macrophage system, dendritic cells,
interstitial fibroblasts, and endothelial cells
o Very high titers of virus are present in liver, spleen, lungs,
kidneys, blood and other fluids
o Have the highest mortality rates (25-90%) of all viral
hemorrhagic fevers
➢ Marburg virus disease – recognized in 1967 among
laboratory workers exposed to tissues of African green
monkeys (Cercopithecus aethiops) imported into Germany
and Yugoslavia
- Transmission: patient to medical personnel occurred w/
high mortality rates
- Present in East Africa and causes infection in monkeys
and humans
- Can infect guinea pigs, mice, hamsters, monkey
- Documented in Kenya, South Africa, Democratic Republic
of the Congo, Angola
➢ Ebola virus – discovered in 1976 when two severe
epidemics of hemorrhagic fever occurred in Sudan and Zaire
- Outbreaks involved more than 500 cases and at least 400
deaths caused by clinical hemorrhagic fever
- Hospital staff became infected through close and
prolonged contact w/ patients, their blood, or their excreta
- Subtypes (Zaire, Sudan) are highly virulent
- Mean time to death from onset of symptoms is 7-8 days
- Outbreaks:
Uganda – 2000
Republic of the Congo – 1995, 2001, 2002, 2003
Gabon – 1994, 1996, 1997, 2002
South Africa – 1996
Sudan – 2004
- Epidemics often stopped by institution of barrier nursing
methods and training of hospital personnel, along w/ strict
quarantine measures
 - Western Africa (2014) – largest known Ebola outbreak
o Filovirus infections appear to be immunosuppressive
o Antibodies appear as patients recover that are detectable by
ELISA
o Diagnosis:
ELISA – detect viral antigens in serum; rapid screening test of
human samples
RT-PCR – used on clinical specimens
Culture in cell lines – uses fresh virus isolates (Vero and MA-
104 monkey cell lines)
o Tests can be conducted under suitable biologic containment
conditions
o Reservoir host: fruit bat (probable); unknown
o Highly communicable to human contacts
o Transmission: direct contact w/ blood or body fluids
o Outbreaks are associated w/ intro of virus into community by
one infected person followed by dissemination by person-to-
person spread
o Prevention: extreme care must be taken w/ infected blood,
secretions, tissues, wastes; no specific antiviral therapies; no
vaccine
o Treatment: direct at maintaining renal function and electrolyte
balance and combating hemorrhage and shock