1. Viral Hemorrhagic Fevers

2. 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

3. 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 2004;53(38):891-897

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

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

6. Differential Diagnosis • Fever in a traveler • Malaria • Typhoid fever • Yellow fever • Lassa fever

7. 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

8. 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

9. www.cidrap.umn.edu/index.htmlaccessed 2/4/05

10. 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

11. 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

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

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

18. 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

19. Infection Control CDC Update: management of patients with suspected VHF-United States MMWR 1995;44:475-79

20. 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

21. 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

22. 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

23. 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

24. This completes the current presentation.