Viral Hemorrhagic Fevers

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Viral Hemorrhagic Fevers
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Objectives

• Describe the natural geographic distribution of
  VHF and scenarios suggestive of bioterrorism
• Describe the clinical manifestations of VHF in
  general
• List exposure classification of contact for cases
  of VHF
• Describe infection control precautions for
  personnel caring for patients with VHF
• List therapeutic options for patients with VHF

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Case Presentation

• 38 yo business man returned from West Africa via
  London, ill for 3 days
• new onset fever
• chills
• severe sore throat
• diarrhea
• back pain
• PE T103.6 BP 90/60, alert
• Skin with diffuse ecchymosis and a maculopapular
  rash on the extremities

MMWR 200453(38)891-897
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Differential Diagnosis

• Fever in a traveler
• Malaria
• Typhoid fever
• Other Differential Diagnoses
• Meningococcemia
• Rickettsial infection
• Leptospirosis
• Acute leukemia
• Idiopathic or thrombotic thrombocytopenic purpura

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Hospital Course

• Hospital Day 4
• Despite empiric antibiotics including
  antimalarials, pt develops acute respiratory
  distress syndrome (ARDS)
• Required intubation

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Differential Diagnosis

• Fever in a traveler
• Malaria
• Typhoid fever
• Yellow fever
• Lassa fever

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Hospital Course

• Hospital Day 4
• Despite empiric antibiotics including
  antimalarials, pt develops ARDS
• Required intubation
• Hospital Day 5
• Local and state health departments notified
• Investigational new drug (IND) protocol to
  administer IV ribavirin
• Patient died before administration of any drug

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Diagnosis

• Clinical and post-mortem specimens sent to CDC
• Lassa virus confirmed
• Serum antigen detection
• Immunohistochemical staining liver tissue
• Virus isolation in cell culture
• RT-PCR sequencing of virus

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FAMILY/GEOGRAPHY AGENT CASE-FATALITY
Filoviridae Sub-saharan Africa Ebola Marburg 50-75 25
Arenaviridae West Africa (Lassa) South America, California (Whitewater) Old World Lassa New World Junin, Machupo, Guanarito Sabia, Whitewater arroyo Lassa1-2 (up to 25 in hospitalized pts) 30 for New World
Bunyaviridae Sub-saharan Africa Egypt, Yemen SW US (Hantavirus) Phlebovirus Rift Valley Nairovirus Crimean Congo Hantavirus Sin Nombre Rift Valley lt1 overall 50 in hemorrhagic
Flaviviridae Sub-saharan Africa Central Asia Yellow fever Dengue Omsk Kyasanur Yellow Fever 5-7 overall 50 in hemorrhagic
www.cidrap.umn.edu/index.html accessed 2/4/05
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Epidemiology

• Incubation period
• 2 days to 3 weeks for most VHF
• Lassa fever 21 days
• Endemic regions
• Sub-saharan Africa
• Lassa fever causes 100-300,000 infections and
  5,000 deaths each year
• 20 imported cases reported worldwide
• Human to human transmission has occured
• South America

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Why do VHFs make good Bioweapons?

• Disseminate through aerosols
• Low infectious dose
• High morbidity and mortality
• Cause fear and panic in the public
• No effective vaccine
• Available and can be produced in large quantity
• Research on weaponization has been conducted

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Clinical Presentation

• Initial
• High grade fever, headache, myalgias, fatigue,
  abdominal pain
• Advanced disease
• Bleeding
• Maculopapular rash
• Exudative Pharyngitis (Lassa)
• Meningoencephalitis
• Jaundice

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Transmission

• Direct contact with blood/body fluids/cadavers
• Aerosol spray (droplet v. airborne)
• Sexual transmission
• Percutaneous
• Bite of infected tick or mosquito

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Infection Control

• Lassa Fever in New Jersey Investigation
• 5 high risk contacts (wife, kids, visitor)
• 183 low risk contacts
• 9 other family members
• 139 HCW at hospital 42 labworkers, 32 RN, 11 MD
• 16 labworkers in Virginia and California
• 19 passengers on flight from London to Newark
• No additional cases occurred

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Infection Control
Risk Category Description Surveillance
Casual Contacts Remote contact with index case (eg, stayed in same hotel) VHF not spread by casual contact, no special surveillance
Close Contacts More than casual (eg, living with contact, caretaker, shook hands with contact) Place under surveillance once index case confirmed
High-Risk Contacts Mucous membrane contact (eg, kissing, or penetrating injury involving contact with index cases blood such as needlestick) Place under surveillance as soon as consider diagnosis of VHF in index case
CDC Update management of patients with suspected
VHF-United States MMWR 199544475-79
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VHF Personal Protective Equipment

• Airborne and Contact isolation for patients with
  respiratory symptoms
• N-95 or PAPR mask
• Negative pressure isolation
• Gloves
• Gown
• Fitted eye protection and shoe covers if going to
  be exposed to splash body fluids
• Droplet and Contact isolation for patients
  without respiratory symptoms
• Surgical mask
• Gloves
• Gown
• Fitted eye protection and shoe covers if going to
  be exposed to splash body fluids
• Environmental surfaces
• Cleaned with hospital approved disinfectant
• Linen incinerated, autoclaved, double-bagged for
  wash

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Treatment

• Supportive care
• Fluid and electrolyte management
• Hemodynamic monitoring
• Ventilation and/or dialysis support
• Steroids for adrenal crisis
• Anticoagulants, IM injections, ASA, NSAIDS are
  contraindicated
• Treat secondary bacterial infections

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Treatment

• Manage severe bleeding complications
• Cryoprecipitate (concentrated clotting factors)
• Platelets
• Fresh Frozen Plasma
• Heparin for DIC
• Ribavirin in vitro activity vs.
• Lassa fever
• New World Hemorrhagic fevers
• Rift Valley Fever
• No evidence to support use in Filovirus or
  Flavivirus infections

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Vaccination

• Argentine and Bolivian HF
• PASSIVE IMMUNIZATION
• Treat with convalescent serum containing
  neutralizing antibody or immune globulin
• Yellow Fever
• ACTIVE IMMUNIZATION
• Travelers to Africa and South America

P. Jahrling, Chapter 29, Medical Aspects of
Clinical and Biological Warfare p591-602
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This completes the current presentation.