Microbiology
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Viral Hemorrhagic Fever
• Severe multisystem syndrome
• Damage to overall vascular system
• Symptoms often accompanied by hemorrhage
− Rarely life threatening in itself
− Includes conjunctivitis, petechia, echymosis
Viral Hemorrhagic Fever
• Viruses of four distinct families: Arenaviruses,
Filoviruses, Bunyaviruses, Flaviviruses.
• RNA viruses: Enveloped in lipid coating
• Survival dependent on an animal or insect host, for the
natural reservoir
Classification
Arenaviridae
• Junin virus
• Machupo virus
• Guanarito virus
• Lassa virus
• Sabia virus
Microbiology
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Arenaviridae History
• First isolated in 1933
• 1958: Junin virus - Argentina
− First to cause hemorrhagic fever
− Argentine hemorrhagic fever
• 1963: Machupo virus – Bolivia
− Bolivian hemorrhagic fever
• 1969: Lassa virus – Nigeria
− Lassa fever
Arenaviruses
• Enveloped helical –ve ssRNA viruses
• virions 80-150nm in diameter
• genome consists of 2 pieces of ssRNA.
• 7-8 nm spikes protrude from the envelope.
Members of arenaviruses include Lassa fever, Junin
and Macupo viruses
Arenaviridae Transmission
• Virus transmission and amplification occurs in rodents
• Shed virus through urine, feces, and other excreta
• Human infection
− Contact with excreta
− Contaminated materials
− Aerosol transmission
• Person-to-person transmission by infected body fluids.
Arenaviridae Epidemiology
• Africa
− Lassa
• South America
− Junin, Machupo, Guanarito, and Sabia
• Contact with rodent excreta
• Case fatality: 5 – 35%
• Explosive nosicomial outbreaks with Lassa and Machupo
Lassa fever virus particles budding from
the surface of an infected cell.
Microbiology
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Arenaviridae in Humans
• Incubation period: 10–14 days
• Fever and malaise: 2–4 days
• Hemorrhagic stage: Hemorrhage, leukopenia, thrombocytopenia, Neurologic signs.
Bunyaviridae
• Rift Valley Fever virus
• Crimean-Congo Hemorrhagic Fever virus
• Hantavirus
Bunyaviridae History
• 1930: Rift Valley Fever – Egypt
− Epizootic in sheep
• 1940s: CCHF - Crimean peninsula
− Hemorrhagic fever in agricultural workers
• 1951: Hantavirus – Korea
− Hemorrhagic fever in UN troops
• 5 genera with over 350 viruses
Bunyaviridae Transmission
• Arthropod vector
− Exception – Hantaviruses
• RVF – Aedes mosquito
• CCHF – Ixodid tick
• Hantavirus – Rodents
• Less common
− Aerosol
− Exposure to infected animal tissue
Microbiology
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Bunyaviridae Epidemiology
• RVF - Africa and Arabian Peninsula
− 1% case fatality rate
• CCHF - Africa, Eastern Europe, Asia
− 30% case fatality rate
• Hantavirus - North and South America, Eastern Europe, and Eastern Asia
− 1-50% case fatality rate
Bunyaviridae Humans
• RVF
− Incubation period – 2-5 days
− 0.5% - Hemorrhagic Fever
• CCHF
− Incubation period –2-9 days
− Hemorrhagic Fever - 3–6 days
• Hantavirus
− Incubation period – 7–21 days
− HPS and HFRS
CRIMEAN-CONGO HEMORRHAGIC FEVER
Caused by Nairovirus
Etiology
• Family Bunyaviridae
• Genus Nairovirus
• Virus Crimean-Congo HF - RNA virus
• Virions have the spherical form of 92-96 nm in diameter.
• The virus is opened in 1945 by M.P.Chumakovym in the Crimea.
Microbiology
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Epidemiology
> Humans become infected by being bitten by ticks, principally of the genus Hyalomma,
or by crushing ticks, often while working with domestic animals or livestock.
Clinical symptoms
> The incubation period for CCHF is about 2-9 days. The incubation period following
contact with infected blood or tissues is usually 5 to 6 days, with a documented
maximum of 13 days.
There are 2 stages in current of disease:
> Initial stage
> The heat period
Initial stage
fever and chills 3-12 days after tick exposure,
headache,
myalgia, arthralgia,
lumbar and abdominal pain,
nausea and vomiting,
delirium, and prostration.
Sore throat, conjunctivitis, jaundice, photophobia, and various sensory and mood
alterations may develop.
Microbiology
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The heat period
petechial rash
,
hemorrhagic diathesis,
large ecchymoses,
bleeding from
needle puncture sites, and hemorrhage from multiple other sources.
bleeding from nasal,
gastric, intestinal, uterine and renal membranes.
Fatal cases are associated with
extensive hemorrhage, coma, and shock.
Death is usually due to shock, blood loss or
intercurrent infection.
Hantaviruses
• Forms a separate genus in the Bunyavirus family.
• Unlike under bunyaviridae, its transmission does not
involve an arthropod vector.
• Enveloped helical -ve ssRNA virus.
• Virions 98nm in diameter with a characteristic square
grid-like structure.
• Genome consists of three RNA segments: L, M, and S.
Rodent Carriers of Hantaviruses
Stripped field mouse (Apodemus Agrarius) Bank Vole (Clethrionomys Glareolus) Deer mouse (Peromyscus Maniculatus) Rat (Rattus)
Clinical Features of Hantavirus Disease (HFRS)
Classically, hantavirus disease consists of 5 distinct phases.
Febrile phase - abrupt onset of a severe flu-like illness with a erythematous rash after an
incubation period of 2-3 days.
Hypotensive phase - begins at day 5 of illness
Oliguric phase - begins at day 9 of illness. The patient may develop acute renal failure
and shock. Haemorrhages are usually confined to petechiae.
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The majority of deaths occur during the hypotensive and oliguric phases
Diuretic phase - this occurs between days 12-14 .
Convalescent phase - this may require up to 4 months
Hantavirus Pulmonary Syndrome (HPS)
• In common with classical HVD, HPS has a similar febrile phase.
• However, the damage to the capillaries occur predominantly in the lungs rather than
the kidney.
• Shock and cardiac complications may lead to death.
The majority of HPS cases are caused by the Sin Nombre virus
Bunyaviridae Animals
• RVF
− Abortion – 100%
− Mortality rate
▪ >90% in young
▪ 5-60% in older animals
• CCHF
− Unapparent infection in livestock
• Hantaviruses
− Unapparent infection in rodents
Filoviridae
• Marburg virus
• Ebola virus
Filoviridae History
• 1967: Marburg virus
− European laboratory workers
• 1976: Ebola virus
− Ebola Zaire
− Ebola Sudan
• 1989 and 1992: Ebola Reston
− USA and Italy
− Imported macaques from Philippines
• 1994: Ebola Côte d'Ivoire
Microbiology
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Filoviridae Transmission
• Reservoir is UNKNOWN: Bats implicated with Marburg
• Intimate contact
• Nosicomial transmission
− Reuse of needles and syringes
− Exposure to infectious tissues, excretions, and hospital wastes
• Aerosol transmission: Primates
Filoviridae Epidemiology
• Marburg – Africa
− Case fatality – 23-33%
• Ebola - Sudan, Zaire and Côte d'Ivoire – Africa
− Case fatality – 53-88%
• Ebola – Reston – Philippines
• Pattern of disease is UNKOWN
Filoviridae Humans
• Most severe hemorrhagic fever
• Incubation period: 4–10 days
• Abrupt onset
− Fever, chills, malaise, and myalgia
• Hemorrhage and DIC
Death around day 7
–11
Filoviridae Animals
• Hemorrhagic fever
− Same clinical course as humans
• Ebola Reston
− High primate mortality - ~82%
Flaviviridae
• Dengue virus
• Yellow Fever virus
• Omsk Hemorrhagic Fever virus
• Kyassnur Forest Disease virus
Microbiology
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Flaviviridae History
• 1648 : Yellow Fever described
• 17
th
–20
th
century: Yellow Fever and Dengue outbreaks
• 1927: Yellow Fever virus isolated
• 1943: Dengue virus isolated
• 1947: Omsk Hemorrhagic Fever
virus isolated
• 1957: Kyasanur Forest virus isolated
Flaviviridae Transmission
• Arthropod vector
• Yellow Fever and Dengue viruses
− Aedes aegypti
− Sylvatic cycle
− Urban cycle
• Kyassanur Forest Virus
− Ixodid tick
• Omsk Hemorrhagic Fever virus: Muskrat urine, feces, or blood
Transmission Cycles
Man-Arthropod-Man Cycle
Animal-Arthropod-Man Cycle
Microbiology
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Flaviviridae Epidemiology
• Yellow Fever Virus – Africa and Americas
− Case fatality rate – varies
• Dengue Virus – Asia, Africa, Australia, and Americas
− Case fatality rate – 1-10%
• Kyasanur Forest virus – India
− Case fatality rate – 3–5%
• Omsk Hemorrhagic Fever virus –
Europe
− Case fatlity rate – 0.5–3%
Disease in Humans
Clinical Symptoms
• Differ slightly depending on virus
• Initial symptoms Marked fever, Fatigue, Dizziness,
Muscle aches, Exhaustion
• More severe
− Bleeding under skin
▪ Petechiae, echymoses, conjunctivitis
− Bleeding in internal organs
− Bleeding from orifices
− Blood loss rarely cause of death
Microbiology
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Diagnosis
• Specimens must be sent to
− reference lab.
− Medical Research Institute of Infectious Disease .
▪ Serology
▪ PCR
▪ Viral isolation
− Electron microscopy
Treatment
• Supportive treatment
• Ribavirin
− Effective in some individuals
− Arenaviridae and Bunyaviridae only
• Convalescent-phase plasma
− Argentine HF, Bolivian HF and Ebola
• Strict isolation of affected patients is required
• Report to health authorities
Prevention and Control
• Avoid contact with host species
− Rodents
• Control rodent populations
• Discourage rodents from entering or living in human populations
• Safe clean up of rodent nests and droppings
− Insects
• Use insect repellents
• Proper clothing and bed nets
• Window screens and other barriers to insects
• Vaccine available for Yellow fever
• Experimental vaccines under study
− Argentine HF, Rift Valley Fever, Hantavirus and Dengue HF
• If human case occurs
− Decrease person-to-person transmission
Microbiology
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Isolation of infected individuals
• Protective clothing
− Disposable gowns, gloves, masks and shoe covers, protective eyewear
when splashing might occur, or if patient is disoriented or uncooperative
• WHO and CDC developed manual
− “Infection Control for Viral Hemorrhagic Fevers In the African Health Care
Setting”
Protective equipment worn by a nurse during Ebola outbreak in Zaire
• Anyone suspected of having a VHF must use a chemical toilet
• Disinfect and dispose of instruments
− Use a 0.5% solution of sodium hypochlorite (1:10 dilution of bleach)
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