MIKROBIOLOGI

VIRUS 2 :
Rodent Borne
Viruses

MIKROBIOLOGI

BLOK HEMATOIMUNOLOGI
TUJUAN PEMBELAJARAN :

– Mampu menjelaskan mengenai : morfologi, daur hidup virus dan

manifestasi klinis:
Rodent-borne viruses (hantavirus infections, Lassa fever, and South
American hemorrhagic fevers, hantavirus pulmonary syndrome and
Colorado tick fever, African hemorrhagic fevers—Marburg and Ebola)
Overview :

– The zoonotic rodent-borne hemorrhagic fevers include Asian

(eg, Hantaan and Seoul viruses), South American (eg, Junin and
Machupo viruses), and African (Lassa virus) fevers.
– Hantaviruses also cause a hantavirus pulmonary syndrome in the
Americas (eg, Sin Nombre virus).
– The natural reservoirs of Marburg and Ebola viruses (African
hemorrhagic fever) are not known but are suspected to be rodents
or bats.
– Causative agents are classified as bunyaviruses, arenaviruses,
and filoviruses.
BUNYAVIRUS
DISEASES
 BUNYAVIRUS DISEASES

– Hantaviruses are classified in the Hantavirus genus of the Bunyaviridae family.

– The viruses are found worldwide and cause two serious and often fatal human
diseases: hemorrhagic fever with renal syndrome and hantavirus pulmonary
syndrome.
– The virus infections in rodents are lifelong and without deleterious effects.
– Transmission among rodents seems to occur horizontally, and transmission
to humans occurs by inhaling aerosols of rodent excreta (urine, feces,
saliva).
– The presence of hantavirus-associated diseases is determined by the geographic
distribution of the rodent reservoirs.
 Hemorrhagic Fever with
Renal Syndrome
– is an acute viral infection that causes an interstitial nephritis that can lead to
acute renal insufficiency and renal failure in severe forms of the disease.
– Hantaan and Dobrava viruses cause the severe disease that occurs in Asia
(particularly China, Russia, and Korea) and in Europe (primarily in the Balkans).
– Generalized hemorrhage and shock may occur, with a casefatality rate of 5–
15%.
– In a mild clinical form, called nephropathia epidemica, which is caused by Puumala
virus.
– HFRS is treated using supportive therapy.
– Prevention depends on rodent control and protection from exposure to rodent
droppings and contaminated material.
 Hantavirus Pulmonary
Syndrome
– In 1993, an outbreak of severe respiratory illness occurred in the United States, now
designated the hantavirus pulmonary syndrome (HPS).
– This agent was the first hantavirus recognized to cause disease in North America and
the first to cause primarily an adult respiratory distress syndrome.
– Since that time, numerous hantaviruses have been detected in rodents in North,
Central, and South America.
 Hantavirus Pulmonary
Syndrome
– Infections with hantaviruses are not common, and subclinical infections appear to be
unusual, particularly with Sin Nombre virus.
– HPS is generally severe, with reported mortality rates of 30% or greater.
– The disease begins with fever, headache, and myalgia followed by rapidly progressive
pulmonary edema, often leading to severe respiratory compromise.
– There are no signs of hemorrhage.
– Pathogenesis of HPS involves the functional impairment of vascular endothelium.
– Person to- person transmission of hantaviruses seldom occurs, although it has been observed
during outbreaks of HPS caused by Andes virus.
ARENAVIRUS
DISEASES
 ARENAVIRUS DISEASES

– Arenaviruses are divided into Old World viruses (eg, Lassa virus) and New World
viruses.
– Arenaviruses establish chronic infections in rodents.
– Humans are infected when they come in contact with rodent excreta.
– Some viruses cause severe hemorrhagic fever.
– Several arenaviruses are known to infect the fetus and may cause fetal death in
humans.
 Lassa Fever

– Lassa virus is highly virulent—the mortality rate is about 15% for patients
hospitalized with Lassa fever.
– Overall, about 1% of Lassa virus infections are fatal.
– The incubation period for Lassa fever is 1–3 weeks from time of exposure.
– The disease can involve many organ systems, although symptoms may vary in the
individual patient.
– Onset is gradual, with fever, vomiting, and back and chest pain.
– The disease is characterized by very high fever, mouth ulcers, severe muscle aches,
skin rash with hemorrhages, pneumonia, and heart and kidney damage.
– Deafness is a common complication, affecting about 25% of patients during recovery;
hearing loss is often permanent.
– Lassa virus infections cause fetal death in more than 75% of pregnant women.
– During the third trimester, maternal mortality is increased (30%), and fetal
mortality is very high (>90%).
– Diagnosis usually involves detection of IgM and IgG antibodies by ELISA.
– Immunohistochemistry can be used to detect viral antigens in postmortem
tissue specimens.
– Viral sequences can be detected using RT-PCR assays in research laboratories.
– The antiviral drug ribavirin is the drug of choice for Lassa fever and is
most effective if given early in the disease process.
– No vaccine exists, although a vaccinia virus recombinant that
expresses the glycoprotein gene of Lassa virus is able to induce
protective immunity both in guinea pigs and in monkeys.
 South American
Hemorrhagic Fevers
– Junin hemorrhagic fever (Argentine hemorrhagic fever)
– The disease has a marked seasonal variation, and the infection occurs almost exclusively
among workers in maize and wheat fields who are exposed to the reservoir rodent,
Calomys musculinus.
– An effective live-attenuated Junin virus vaccine is used to vaccinate high-risk
individuals in South America.
South American
Hemorrhagic Fevers
– Guanarito virus (the agent of Venezuelan hemorrhagic fever)
was identified in 1990; it has a mortality rate of about 33%.
– Sabia virus was isolated in 1990 from a fatal case of hemorrhagic
fever in Brazil.
– Both Guanarito virus and Sabia virus induce a clinical disease
resembling that of Argentine hemorrhagic fever and probably have
similar mortality rates.
FILOVIRUS DISEASES
 Classification and Properties of
Filoviruses
– Filoviruses are pleomorphic particles, appearing as long filamentous threads or as odd-
shaped forms 80 nm in diameter.
– Unit-length particles are from 665 nm (Marburg) to 805 nm (Ebola).
– The two known filoviruses (Marburg virus and Ebola virus) are antigenically distinct and
are classified in separate genera.
– The four subtypes of Ebola virus (Zaire, Sudan, Reston, Ivory Coast) differ from one
another by up to 40% at the nucleotide level but share some common epitopes
– Filoviruses are highly virulent and require maximum containment
facilities (Biosafety Level 4) for laboratory work.
– Filovirus infectivity is destroyed by heating for 30 minutes at 60°C, by
ultraviolet and γ-irradiation, by lipid solvents, and by bleach and
phenolic disinfectants.
– The natural hosts and vectors, if any, are unknown but are suspected
to be bats or possibly rodents.
 African Hemorrhagic Fevers
(Marburg and Ebola Viruses)
– Marburg and Ebola viruses are highly virulent in humans and nonhuman
primates, with infections usually ending in death.
– The incubation period is 3–9 days for Marburg disease and 2–21 days for Ebola.
– They cause similar acute diseases characterized by fever, headache, sore throat,
and muscle pain followed by abdominal pain, vomiting, diarrhea, and rash, with
both internal and external bleeding, often leading to shock and death.
– Very high titers of virus are present in many tissues, including the liver, spleen,
lungs, and kidneys, and in blood and other fluids.
– These viruses have the highest mortality rates (25–90%) of all the viral
hemorrhagic fevers
– Marburg virus disease was recognized in 1967 among laboratory
workers exposed to tissues of African green monkeys (Cercopithecus
aethiops) imported into Germany and Yugoslavia.
– Transmission from patients to medical personnel occurred, with high
mortality rates.
– Antibody surveys have indicated that the virus is present in East
Africa and causes infection in monkeys and humans.
– Ebola virus was discovered in 1976 when two severe epidemics of
hemorrhagic fever occurred in Sudan and Zaire (now the Democratic
Republic of the Congo).
– These subtypes of Ebola virus (Zaire, Sudan) are highly virulent.
– The mean time to death from the onset of symptoms is 7–8 days.
– There are no specific antiviral therapies available.
– Treatment is directed at maintaining renal function and electrolyte
balance and combating hemorrhage and shock.
– There is no vaccine, but candidate vaccines are under development.
Summary
Summary

• Arboviruses and rodent-borne viruses have complex transmission cycles

involving arthropods or rodents. These viruses are classified in several
different virus families (Arena-, Bunya-, Flavi-, Reo-, and Togaviridae).

• Arbovirus diseases fall into three general categories: fevers (usually

benign), encephalitides, and hemorrhagic fevers. The latter two categories
can be fatal.

• Major mosquito-borne diseases are yellow fever, dengue, Japanese B

encephalitis, West Nile fever, and eastern equine encephalitis.
• All alphaviruses, in the Togaviridae family, are antigenically
related; all flaviviruses are antigenically related.

• Inapparent infections are common with the viral encephalitis

viruses and neuroinvasion seldom occurs.

• Humans are accidental hosts of arbovirus infections and are

not essential for the viral life cycles.
• Dengue is distributed worldwide in tropical regions and is probably
the most important mosquito-borne viral disease of humans.

• Dengue fever is a self-limited disease, but dengue hemorrhagic fever

and dengue shock syndrome are severe and potentially fatal.

• Dengue hemorrhagic fever occurs with secondary infections in the

presence of preexisting antibody from a primary infection by a
different viral serotype.
•Japanese B encephalitis often leaves serious sequelae, but yellow fever infections
have none.

•Major rodent-borne viral diseases are hantavirus infections, Lassa fever, and South
American hemorrhagic fevers. The reservoir hosts for African hemorrhagic fevers,
Marburg and Ebola, are suspected to be bats or possibly rodents.

•Rodent-borne hemorrhagic fevers are caused by bunyaviruses (hantaviruses) and

arenaviruses (Lassa fever).
• Lassa virus is distributed in West Africa. About 1% of Lassa virus
infections are fatal. Infections often cause fetal death.

• Marburg and Ebola viruses (classified as filoviruses) are found in East

Africa and are highly virulent in humans, with infections frequently
ending in death.

• Prevention of many arbovirus infections involves protection against

mosquito or tick bites, mosquito control, wearing of protective
clothing, use of repellent chemicals, or avoidance of infested areas.
Reference :

Jawetz, Melnick, & Adelberg’s Lippincott’s Illustrated Reviews:

Medical Microbiology Microbiology