VIRAL HEMORRHAGIC FEVERS

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VIRAL HEMORRHAGIC FEVERS

• Hantavirus Pulmonary Syndrome
• Hemorrhagic Fever with Renal Syndrome
• Marburg Hemorrhagic Fever
• Ebola Hemorrhagic Fever
• Rift Valley Fever
• Crimean-Congo Hemorrhagic Fever
• Lassa Fever

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VIRAL HEMORRHAGIC FEVERS

• General information applying to all VHFs
• cause severe, multisystem disorder
• zoonotic
• RNA viruses with lipid envelope
• worldwide distribution (all agents combined)

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Ebola hemorrhagic fever

• Epidemiology
• Occurrence Africa (Congo, Ivory Coast, Sudan)
  not known to be native to other continents
• Agent four strains, only one that causes
  disease in non-human primates but not humans
  (Ebola-Reston)
• Frequency rare, typically occurring in sporadic
  outbreaks, the largest (gt300) in two different
  outbreaks in Zaire (1976 and 1995)

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Ebola hemorrhagic fever

• Epidemiology
• Reservoir Unknown
• Transmission
• humans are incidental hosts
• index case usually someone in contact with
  infected animal
• subsequent transmission by
• direct contact with infected patient
• contact with contaminated objects
• nosocomial transmission
• airborne not documented although can occur with
  Ebola-Reston

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Ebola hemorrhagic fever

• Clinical features
• Incubation period 2-21 days
• Initial symptoms
• severe, often fatal, with majority manifesting
  with
• high fever
• headache
• myalgia
• fatigue
• diarrhea
• additional symptoms in some patients include
• sore throat, rash, bloody vomiting and diarrhea

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Ebola hemorrhagic fever

• Clinical features
• Symptoms within one week
• most will experience
• chest pain
• shock
• death
• additional symptoms in some patients include
• blindness, hemorrhaging
• Case fatality rate 50-90

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Ebola hemorrhagic fever

• Diagnosis
• ELISA (IgG and antigen-capture)
• PCR
• virus isolation
• later in disease course of after recovery, both
  IgG and IgM testing may be performed

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Ebola hemorrhagic fever

• Treatment
• none specific, similar as with Lassa fever
• Prevention/control
• early recognition in health-care facilities
• proper infection-control practices
• protective clothing
• avoid sexual intercourse until semen is negative
  (at least 3 months post-recovery)

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Marburg hemorrhagic fever

• Epidemiology
• Agent a filovirus related to Ebola
• Occurrence even though outbreaks occur
  sporadically in different locations (first in a
  laboratory in Marburg, Germany), agent is
  indigenous to Africa, especially Uganda, Kenya,
  and Zimbabwe
• Frequency rare, limited to sporadic outbreaks
  as with Ebola

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Marburg hemorrhagic fever

• Epidemiology
• Reservoir unknown, although first cases came
  from exposure to African green monkeys
• Transmission
• animal to human transmission unknown
• spread to others by direct contact as with other
  VHFs

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Marburg hemorrhagic fever

• Clinical features
• Incubation period 5-10 days
• Initial symptoms
• fever
• headache
• chills
• myalgia

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Marburg hemorrhagic fever

• Clinical features
• Severe symptoms beginning five days after onset
• maculopapular rash
• vomiting
• chest pain
• sore throat
• cramping and diarrhea
• jaundice
• pancreatitis
• liver failure, shock, delirium, hemorrhage,
  multi-organ dysfuntion
• Case fatality 25

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Marburg hemorrhagic fever

• Diagnosis
• Same as with other VHFs
• Treatment
• Similar to other VHFs
• plasma products critical
• Prevention
• Similar to other VHFs

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Lassa Fever

• Epidemiology
• Occurrence West Africa (Nigeria, Guinea,
  Liberia, Sierra Leone)
• Frequency
• Up to 300,000 cases annually (very crude
  estimates)
• in certain regions, may account for up to 16 of
  all hospitalizations
• Reservoir
• Mastomys huberti and M. erythroleucus called
  multimammate rat

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Lassa Fever

• Epidemiology
• Transmission virus shed in urine and droppings
  of reservoir host
• direct contact
• contaminated objects through cut, abrasions
• ingestion of contaminated food or ingestion of
  infected rat (food source in some areas)

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Lassa Fever

• Epidemiology
• Transmission
• airborne inhalation of contaminated aerosols
• person to person contact with body fluids or
  aerosolized particles from coughing patient
• nosocomial transmission from contaminated
  equipment

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Lassa Fever

• Clinical features
• Incubation period 6-21 days
• Acute viral illness with gradual onset of
• headache
• fever (persistent or intermittent with spikes)
• general malaise
• myalgia
• sore throat (pharyngeal inflammation/exudation)
• vomiting/diarrhea
• chest/abdominal pain

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Lassa Fever

• Clinical features
• more severe cases
• hypotension
• shock
• pleural effusion
• hemorrhage
• encephalopathy and seizures
• albuminuria/hemoconcentration
• neutrophilia later in course of disease
• thrombocytopenia

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Lassa Fever

• Clinical features
• alopecia and ataxia during recovery
• more severe cases my develop deafness (25), with
  not all returning to normal function
• Case fatality rate
• 15 among those hospitalized
• up gt 90 fetal loss (spontaneous abortion) if
  infection occurs during pregnancy

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Lassa Fever

• Diagnosis
• clinical diagnosis based on signs/symptoms
  difficult
• serologic
• ELISA for detection of IgM, IgG, antigen
• Immunohistochemistry post-mortem
• PCR for detection of virus (primarily a research
  tool)

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Lassa Fever

• Treatment
• Ribavirin (Virazole)
• most effective early (within first week of
  disease)
• IV - after initial loading dose, give high dose
  (15 mg/kg) q6h for 4 days, then 8 mg/kg q8h for 6
  days
• supportive treatment
• maintenance of fluid/electrolyte balance
• oxygenation
• monitor BP, maintain normotensive state

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Lassa Fever

• Prevention
• avoid contact with rodents
• avoid eating rodents
• rodent-proof food and environment
• rodent control by trapping
• isolation of patients while symptomatic
• protective clothing, proper sterilization and
  infection control procedures while caring for
  patients

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Rift Valley Fever

• Agent phlebovirus, first detected in early
  1900s
• Occurrence

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Rift Valley Fever

• Epidemiology
• Reservoir livestock (primarily sheep and
  cattle)
• Vector
• mosquitoes (Aedes) which can be infected
  transovarially
• possibly other biting insects
• Transmission
• vector-borne
• direct contact with fluids from infected animals
• aerosol transmission in laboratory has been
  documented
• generally occurs after heavy rainfall and flooding

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Rift Valley Fever

• Clinical features
• Incubation period 3-7 days
• Symptoms
• asymptomatic to very mild (fever, liver
  abnormalities)
• hemorrhagic fever
• shock, hemorrhage
• encephalitis
• ocular disease, particularly retinitis, with up
  to 10with some permanent vision loss
• Case fatality ratio 1 in humans, higher in
  animals, causing up to 100 abortions in infected
  pregnant cattle and sheep

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Rift Valley Fever

• Treatment
• ribavarin has shown some promise in animal
  studies
• interferon, immune modulators, and
  convalscent-phase plasma may also help
• Prevention and control
• protection against mosquitoes
• avoid direct contact with tissues of infected
  animals

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Crimean-Congo Hemorrhagic Fever

• Agent Nairovirus (bunyaviradae)
• related to Hazara virus in ticks in Pakistan and
  Nairobi sheep virus
• Initial recognition of disease and origin
• 1944-45 USSR troops helping with harvest in
  Western Crimea later realized similar disease
  known throughout Central Asian republics and
  areas bordering Black and Caspian Seas
• 1956 Congo virus isolated from child in Zaire
• 1969 experimental evidence concluded that the
  two were identical

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Crimean-Congo Hemorrhagic Fever

• Epidemiology
• Occurrence
• widespread in Africa and Asia
• may be more virulent in Asia
• Frequency rare, occurs as isolated case or small
  sporadic outbreak
• Reservoir wild and domestic mammals and their
  ticks (Hyalomma spp.) - bont ticks
• Transmission by bite of tick or occassionally
  by direct contact with infected blood via broken
  skin

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Crimean-Congo Hemorrhagic Fever

• Clinical features
• Incubation period 2-7 days
• Symptoms
• Acute
• high fever
• mylagia
• headache
• vomiting
• epigastric pain
• diarrhea

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Crimean-Congo Hemorrhagic Fever

• Clinical features
• Symptoms some patients recover within 7 days
  75 develop hemorrhagic illness in 3-5 days
• petechial rash in throat with hematomesis
• epistaxis
• conjunctival injection and hemorrhage
• marked neutrophilia despite high viremia
• painful hepatomegaly
• disseminated intravascular coagulopathy
• recovery within 20 days many die by 9th day

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Crimean-Congo Hemorrhagic Fever

• Clinical features
• Diagnosis
• ELISA IgM detectable after first 5-7 days
  significant rise in IgG detected after 10 days
• PCR for detection of viral nucleic acid
• virus culture in monkey kidney (VERO) cells
• Treatment
• may respond to ribavarin
• intensive supportive management early in disease
  is critical to survival
• Case fatality ratio lt20

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Crimean-Congo Hemorrhagic Fever

• Prevention and Control
• Tick control, especially on farm animals
• Use of tick repellents
• Infection control in hospital