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. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers Differential Diagnosis Fever in a traveler –Malaria –Typhoid fever Other Differential Diagnoses –Meningococcemia –Rickettsial infection –Leptospirosis –Acute leukemia –Idiopathic or thrombotic thrombocytopenic purpura

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

6. Viral Hemorrhagic Fevers Differential Diagnosis Fever in a traveler –Malaria –Typhoid fever –Yellow fever –Lassa fever

7. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers FAMILY/GEOGRAPHYAGENTCASE-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 Lassa:1-2% (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: <1% 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.htmlwww.cidrap.umn.edu/index.html accessed 2/4/05

10. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers Clinical Presentation Initial: –High grade fever, headache, myalgias, fatigue, abdominal pain Advanced disease: –Bleeding –Maculopapular rash –Exudative Pharyngitis (Lassa) –Meningoencephalitis –Jaundice

13. Viral Hemorrhagic Fevers

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

18. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers Infection Control Risk CategoryDescriptionSurveillance 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 case’s 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 1995;44:475-79

20. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers 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. Viral Hemorrhagic Fevers Viral Hemorrhagic Questions

25. Viral Hemorrhagic Fevers Question # 1 In which of the following scenarios would bioterrorism be considered? a.Outbreak of pharyngitis in kids returning from a school trip b.Fever in a returning traveler c.Cluster of patients presenting with increased vascular permeability d.New onset of gingival bleeding and palatal petechiae in a 68 yo

26. Viral Hemorrhagic Fevers Question # 2 All of the following clinical manifestations are suggestive of VHF EXCEPT? a.periorbital edema b.palatal petechiae c.Cough d.Diarrhea e.back pain

27. Viral Hemorrhagic Fevers Question # 3 Which of the following represents a high-risk exposure to a patient with VHF? a.Needlestick injury b.Shaking hands c.Sexual intercourse d.Sharing a taxi ride e.A and C

28. Viral Hemorrhagic Fevers Question # 4 Which of the following precautions should be taken in a severely ill patient with VHF and respiratory symptoms? a.gown, gloves, goggles, surgical mask, positive pressure room b.gown, gloves, goggles, N-95 mask, no special air handling c.gown, gloves, goggles, shoe covers, N- 95 mask, negative pressure room

29. Viral Hemorrhagic Fevers Question # 5 What treatment options are available for patients with most etiologies of VHF? a.supportive care b.supportive care and aspirin therapy c.supportive care and immune globulin

30. Viral Hemorrhagic Fevers This completes the current presentation.