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[Insert Health Department Name] [Insert Unit Name] [Insert Street] [Insert City, State and Zip Code] [Insert Logo] Phone: [insert number] Fax: [insert number [Email Address], [Website] VIRAL HEMORRHAGIC FEVER HEALTH ALERT [INSERT DATE] [Insert short description why Health Alert is being released (e.g., Two cases of VHF have been identified).] This alert, and additional information on Viral Hemorrhagic Fever (VHF), is posted on the [insert website name]: [insert web link] ACTIONS REQUESTED OF ALL CLINICIANS: 1. 2. 3. 4. 5. 6. Consider viral hemorrhagic fevers in patients exhibiting symptoms. Inquire about exposures. Report suspected and confirmed cases to [insert unit/department name] at [insert phone number]. Implement infection control measures. Test suspected and probable cases. Provide treatment as described below. INCIDENT SUMMARY [Insert event-specific background information (e.g., Suspected aerosol release of VHF).] DESCRIPTION Viral hemorrhagic fevers refer to a group of illnesses caused by several families of viruses. Generally, the term VHF is used to describe a severe multisystem syndrome that characteristically involves overall vascular damage and impaired systemic regulation. VHF viruses are usually restricted geographical areas inhabited by their animal hosts, and are endemic in areas of Africa, South America, and Asia. VHFs include: Filoviridae (Ebola and Marburg viruses) Arenaviridae (Lassa fever and New World Arenaviruses) Bunyaviridae (Rift Valley fever, Crimean Congo fever, and ‘agents of hemorrhagic fever with renal syndrome’) Flaviviridae (Yellow fever, Omsk hemorrhagic fever, Kyasanur Forest disease, and Dengue) Many VHF are virulent, and some are highly infectious (e.g., filoviruses, arenaviruses), with person-to-person transmission from direct contact with infected blood and bodily secretions. Given the lack of licensed or effective therapies for VHF, early detection and strict infection control measures are essential. Some hemorrhagic fever viruses are considered to pose a more serious threat as potential biological weapons based on risk of mortality and feasibility of production. These include: Ebola, Marburg, Lassa fever, New World Arenaviruses, Rift Valley fever, Yellow fever, Omsk hemorrhagic fever, and Kyasanur Forest disease. [Insert Health Department Name] CASE DEFINITION The following definitions should be used to identify exposed persons and cases. Testing, treatment, and implementation of infection control measures should be based upon these definitions. VIRAL HEMORRHAGIC FEVERS: CASE DEFINITION Categorization 1. Exposed Person 2. Suspect Case 3. Probable Case 4. Confirmed Case Definition History of one or more of the following: Being at [insert location of exposure] during [insert date range of exposure (Note: Incubation period usually is within 21 days.]) High-risk contact with a suspect/probable/confirmed case of VHF (filoviridae or arenaviridae) during the prior 21 days, including: Mucous membrane contact Percutaneous injury involving contact with secretions, excretions, or blood from patient VHF Close contact with a suspect/probable/confirmed case of VHF (filoviridae or arenaviridae) during the prior 21 days, including: Live with, shake hands with, hug, or care for patient Laboratory personnel who have processed laboratory specimens from a suspect/probable/confirmed case of VHF (all VHF) within the prior 21 days [Consider adding natural exposure (i.e., lived in or traveled to VHF endemic area)] Exposed person who develops a fever (>38.0ºCor100.4 ºF); OR A person meeting the following clinical definition: Fever (>38.0ºC or 100.4 ºF) of <3 weeks duration; AND Severe Illness; AND No predisposing factors for hemorrhagic manifestations; AND At least 2 of the following hemorrhagic symptoms: Hemorrhagic or purpuric rash; OR Epistaxis; OR Hematemesis; OR Hemoptysis; OR Blood in stools; OR Other hemorrhagic symptoms; AND No established alternative diagnosis Meets: Suspect case definition; AND Positive serology (ELISA for IgG and/or IgM) Meets: Suspect or probable case definition; AND Laboratory confirmation with positive virus isolation (only in a laboratory with biosafety level 4), OR positive skin biopsy (immunohistochemistry), OR positive PCR * The CDC does not have a standard case definition for VHF as a group of illnesses. The following case definition was derived from the World Health Organization’s surveillance standards for acute hemorrhagic fevers and from the Working Group on Civilian Biodefense. Last revised: 5/3/2017 Page 2 of 8 [Insert Health Department Name] CLINICAL FEATURES The clinical features of VHF may vary significantly depending on the specific virus. Listed below are general features one might expect in the presentation of VHF, although not all patients develop the classic VHF syndrome. VIRAL HEMORRHAGIC FEVER: CLINICAL FEATURES Incubation Period 2-21 days Transmission is highly dependent upon the specific virus. Transmission Signs & Symptoms Laboratory Findings Person-to-Person Transmission (Filoviridae and Arenaviridae) Direct contact with blood, secretions, mucous membranes, or tissue of infected patient or nonhuman primate Airborne transmission suspected Zoonotic Transmission to Humans Inhalation of aerosols present in rodent urine and feces or from infected animal carcasses Ingestion of food contaminated with rodent excreta or contaminated raw milk from infected animal Direct contact of rodent excreta with abraded skin and mucous membranes or with infected animal tissue Bite of an infected mosquito or tick Other Transmission Inhalation of aerosols during cultivation of these viruses in laboratory workers Initial non-specific illness: Fever (>38.0ºC or 100.4 ºF), headache, malaise, arthralgias, myalgias, nausea, abdominal pain, diarrhea, severe prostration Early signs: Fever (>38.0ºC or 100.4 ºF), hypotension, bradycardia, tachypnea, conjunctivitis, pharyngitis, cutaneous flushing, or hemorrhagic or purpuric rash Later Signs: Progressive hemorrhagic diathesis, epistaxis, hemoptysis, hematuria, hematemesis, and melena Severe Illness: Shock with DIC, nervous system dysfunction, coma, delirium, and death. Blood counts (lymphocyte, leukocyte, monocyte, red blood cell, platelet) may be normal or abnormal Elevated amylase and hepatic enzymes may occur Proteinuria or elevated bilirubin REPORTING Immediately report any case of VHF (including suspect cases) to your facility’s infection control practitioner AND to the [Insert Department/Unit Name]: [Insert Phone Number]. The [Insert Health Department Name] will initiate the public health response as needed. Please either ask family members or close contacts of patients for their telephone contact information, or ask these individuals to stay at the hospital for public health interview and potential intervention. Last revised: 5/3/2017 Page 3 of 8 [Insert Health Department Name] INFECTION CONTROL For any case of VHF (including suspect cases) in a healthcare setting (hospital, emergency department, nursing facility, or outpatient clinic): 1. Immediately notify your institution’s infection control practitioner(s). 2. Immediately notify [Insert Department/Unit Name]: [Insert Phone Number]. 3. It is essential to utilize the following infection control precautions: Infection Control Measures for Caregivers Situation Precaution Direct care of patients (< 3 feet) Standard, Contact, Droplet Obtaining a sample Standard, Contact, Droplet Standard, Contact, Droplet; Airborne protection* Post a sign outside the institution encouraging people with respiratory symptoms or fever to cover their mouth and nose or wear a surgical mask Make surgical masks readily available Staff caring for patients with respiratory symptoms Care of patients entering a health care institution * Because transmission by the airborne route is suspected, hospitals may choose to use Airborne Precautions for patients with suspected VHF who have severe pulmonary involvement or who undergo procedures that stimulate coughing and promote the generation of aerosols. See http://www.sfcdcp.org/document.html?id=317 for key features of standard, contact, and droplet infection control precautions Filoviridae and arenaviridae are highly infectious after direct contact with infected blood and bodily secretions, and person-to-person transmission has been documented. Preventing the transmission of VHF virus infection relies on meticulous compliance with strict infection control measures. Transmission rarely (if ever) occurs before the onset of symptoms. Risk of transmission is greatest during the latter stages of illness when viral loads are highest. [Note: Your health department may need to modify infection control recommendations once a specific virus is identified.] Decontamination In the healthcare setting: Environmental surfaces, inanimate contaminated objects, or contaminated equipment should be disinfected with an approved hospital disinfectant or a 1:100 dilution of household bleach using standard procedures. For grossly soiled surfaces, (e.g., vomitus, stool), a 1:10 dilution of household bleach should be used. Contaminated linens should be incinerated, autoclaved, or placed in labeled, leak-proof bags at the site of use and washed without sorting in a normal hot water cycle with bleach. Hospital housekeeping staff and linen handlers should wear appropriate personal protective equipment (as outlined in the section on isolation practices above) when handling or cleaning potentially contaminated material or surfaces. Last revised: 5/3/2017 Page 4 of 8 [Insert Health Department Name] Contaminated stool, fluids, and secretions can be managed per standard procedures, since VHF viruses are not likely to survive standard US sewage treatment. Persons with percutaneous or mucocutaneous exposures to blood, body fluids, secretions, or excretions from a patient with suspected VHF should immediately wash the affected skin surfaces with soap and water. Mucous membranes should be irrigated with copious amounts of water or eyewash solution. Exposed persons should receive medical evaluation and monitoring. Hemorrhagic fever viruses are not environmentally stable and are not expected to persist in the environment. [Note: Decisions about decontamination of the environment following an intentional release would depend upon the specific events surrounding the attack.] LABORATORY & DIAGNOSTIC TESTING Consider testing symptomatic persons. Asymptomatic persons need not be tested. If you are testing or considering testing for VHF: 1. Immediately notify: a. [Insert Department/Unit Name]: [Insert Phone Number]. The health department can authorize and facilitate testing and will initiate the public health response as needed; AND b. Your hospital laboratory and infection control practitioner that VHF is under suspicion; AND 2. If testing is deemed necessary: a. Use appropriate precautions when obtaining diagnostic specimens. b. Specimens to be obtained should include: i. Serum: Collect 10-12 cc per institution’s protocol. c. Submit specimens to your hospital laboratory, and notify them to test for VHF. If needed, your lab will submit specimens to the public health laboratory for testing. i. Transport specimens at room temperature immediately to the laboratory. If specimen delivery will be delayed for more than 24 hours, store specimens at 2-8ºC. Laboratory tests used to diagnose VHF include: antigen capture ELISA, IgG ELISA, PCR, and virus isolation. The diagnosis of VHF is based initially on clinical criteria and judgment, with laboratory testing used to confirm or exclude this clinical diagnosis. Confirmatory laboratory testing requires time and, in the event of an attack, may be delayed or impossible given current laboratory capacities. TREATMENT AND POST-EXPOSURE PROPHYLAXIS Medical management should follow guidelines below: Categorization Exposed Persons Suspect or Probable VHF Case of Unknown Viral Type Medical Management Medical Surveillance No post-exposure prophylaxis is recommended* Supportive Care + Ribavirin Therapy§ Suspect, Probable , or Confirmed VHF Case known to be caused by an Flavivirus or Filovirus Supportive Care Only Suspect, Probable , or Confirmed VHF Case known to be caused by an Arenavirus or Bunyavirus Supportive Care + Ribavirin Therapy Last revised: 5/3/2017 Page 5 of 8 [Insert Health Department Name] * Previous CDC recommendations7 state that Ribavirin should be given to high-risk contacts of persons with Lassa fever. The Working Group on Civilian Biodefense recommends medical surveillance only, and notes that the CDC guidelines may be under review. § Ribavirin therapy should be initiated promptly unless another diagnosis is confirmed or the etiologic agent is known to be a Flavivirus or Filovirus Medical Surveillance: Persons should be instructed to record their temperature twice daily and report any temperature of (>38.0ºCor100.4 ºF) or higher (or any other signs/symptoms) to a clinician, hospital epidemiologist, or the [Insert Health Department name]. Patients should be advised not to share thermometers between family members or to properly disinfect thermometers after each use. Supportive Care Supportive care is essential for patients with all types of VHF and includes maintenance of fluid and electrolyte balance, active hemodynamic monitoring, mechanical ventilation, dialysis, and appropriate therapy for secondary infections. Treatment of other suspected causes of disease, such as bacterial sepsis, should not be withheld while awaiting confirmation or exclusion of the diagnosis of VHF. Anticoagulant therapies, aspirin, nonsteroidal anti-inflammatory medications, and intramuscular injections are contraindicated. Ribavirin Therapy Ribavirin is recommended for: (1) suspect or probable cases of VHF of unknown viral type OR (2) suspect, probable, or confirmed cases known to be caused by and Arenavirus or Bunyavirus. Ribavirin has shown in vitro and in vivo activity against Arenaviruses (Lassa fever, New World hemorrhagic fevers) and Bunyaviruses (Rift Valley fever and others). Ribavirin has shown no activity against, and is not recommended for Filoviruses (Ebola and Marburg hemorrhagic fever) or Flaviviruses (Yellow fever, Kyasanur Forest disease, Omsk hemorrhagic fever). Recommendations for IV ribavirin therapy are shown below. However, in a mass casualty situation where the number of persons requiring therapy overwhelms the resources available to deliver IV agents, an oral regimen of ribavirin is recommended. Last revised: 5/3/2017 Page 6 of 8 [Insert Health Department Name] Vaccine A licensed vaccine against yellow fever is effective if given prior to exposure. It is used for travelers going to endemic areas. This vaccine does not prompt development of antibodies rapidly enough to be used postexposure. There is no licensed vaccine for any of the other VHF, though research is underway on several candidates. ADDITIONAL RESOURCES [Add your health department name and link.] CDC Emergency Preparedness & Response Bioterrorism Site: www.bt.cdc.gov/bioterrorism Working Group on Civilian Biodefense: http://jama.ama-assn.org/cgi/content/short/287/18/2391 Health Protection Agency Deliberate Release: www.hpa.org.uk/infections/topics_az/deliberate_release/menu.htm REFERENCES Borio L et al, for the Working Group on Civilian Biodefense. Hemorrhagic Fever Viruses as Biological Weapons: Medical and Public Health Management. JAMA 2002; 287(18):2391-2405. PAHO. Case definition: Ebola-Marburg viral diseases. Epidemiological Bulletin 2003; 24 (2) http://www.paho.org/English/DD/AIS/EB_v24n2.pdf. 3) CIDRAP. Viral hemorrhagic fever: Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment, and prophylaxis. July 13, 2005. (www.cidrap.umn.edu/cidrap/content/bt). Last revised: 5/3/2017 Page 7 of 8 [Insert Health Department Name] 4) LA County DHS. Terrorism Agent Information and Treatment Guidelines for Clinicians and Hospitals. June 2003. (labt.org/Zebra.asp). 5) McCormick JB, King IJ, Webb PA, et al. Lassa fever: effective therapy with ribavirin. N Engl J Med 1986;314(1):20-6. 6) Enria DA, Maiztegui JI. Antiviral treatment of Argentine hemorrhagic fever. Antivirol Res 1994;23:23-31. 7) CDC. Management of patients with suspected viral hemorrhagic fever. MMWR 1988;37(S-3);1-16. Last revised: 5/3/2017 Page 8 of 8