*NCCT is approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E. Program, provider #122.

Transcription

1 COURSE DESCRIPTION Viral hemorrhagic fevers are serious infections with a high case fatality rate and the propensity to spread to caretakers of infected persons, either family members or healthcare workers, who come in contact with infectious blood and body fluids. This CE course will describe Ebola and 10 other viral hemorrhagic fevers including locations of outbreaks, natural reservoirs, reservoir-to-human transmission, control/prevention of infection, and treatment/management of the infections. *Valid for P.A.C.E. credit through 12/31/2018* * ASCLS P.A.C.E. is an approved continuing education agency by the California Department of Health Laboratory Field Services, Accrediting Agency #0001. *NCCT is approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E. Program, provider #122. Rev 8 January 2017 COPYRIGHT 2017 National Center for Competency Testing Reproduction or translation of any part of this work beyond that permitted by Sections 107 or 108 of the 1976 United States Copyright Act without the permission of the copyright owner is unlawful. No part of this work may be reproduced or used in any form or by any means-graphic, electronic, or mechanical, including photocopying, recording, taping, or information storage and retrieval systems without written permission of the published. 1

2 COURSE TITLE: Ebola and Other Viral Hemorrhagic Fevers Author: Lucia Johnson, MA Ed, MT(ASCP)SBB Vice President, Recertification NCCT Number of Clock Hours Credit: 3.0 Course # P.A.C.E. Approved: X Yes _ No OBJECTIVES Upon completion of this continuing education course, the professional should be able to: 1. List 11 viruses that cause VHF. 2. Identify the cause of death from a VHF. 3. List the initial symptoms and signs of infection with a VHF. 4. Describe the general epidemiology of VHF including the natural reservoir and transmission to humans. 5. Identify the natural reservoir for the 11 viruses discussed in the course. 6. List two laboratory methods used to diagnose VHF. 7. Describe treatment of VHF. 8. Describe control and prevention of VHF. 9. Describe the current outbreak of Ebola VHF. 10. Identify methods of human-to-human transmission of Ebola. 11. Compare and contrast airborne spread versus droplet spread of infection. 12. For the other VHF discussed in the course, identify locations of outbreaks, transmission, and signs/symptoms of infection. 13. List criteria used in the United States to evaluate individuals for suspected Ebola infection. 14. Describe PPE worn by individuals caring for patients with suspected or known Ebola. 15. Describe procedures for donning and doffing PPE per guidelines from the CDC. 16. List general guidelines for laboratory specimen collection, handling, and testing. Disclaimer The writers for NCCT continuing education courses attempt to provide factual information based on literature review and current professional practice. However, NCCT does not guarantee that the information contained in the continuing education courses is free from all errors and omissions. 2

3 INTRODUCTION Viral hemorrhagic fevers (VHF) are serious infections with a high case fatality rate and the propensity to spread to caretakers of infected persons, either family members or healthcare workers, who come in contact with infectious blood and body fluids. Outbreaks of VHF sporadically occur in areas of the world that often lack the resources necessary to control the spread of infection and treat infected persons. Between December 2013 and. In September 2014 a person infected with Ebola in West Africa entered the United States and died in a hospital in Texas. Two nurses participating in his care contracted Ebola. In December 2013 an outbreak of VHF caused by the Ebola virus began in parts of West Africa. On October 8, 2014, the United Nations World Health Organization (WHO) Director-General Dr. Margaret Chan stated, I am declaring the current outbreak of Ebola a public health emergency of international concern. This is the largest, most severe, most complex outbreak in the nearly four decades history of this disease. The entire world is at risk for an Ebola outbreak as long as there is a major epidemic in West Africa. With worldwide travel prevalent, epidemiologists have long thought that it was just a matter of time until Ebola or another viral hemorrhagic disease presented itself in the United States. On September 30, 2014 this happened when a person with a recent travel history to West Africa was admitted to a hospital in Texas and diagnosed with Ebola VHF. The patient died on October 8, T nurses who participated in the care of this patient have been diagnosed with Ebola VHF. VIRAL HEMORRHAGIC FEVERS GENERAL INFORMATION Ebola is one of a group of illnesses caused by several distinct viruses. As a group, these illnesses are referred to as viral hemorrhagic fevers or VHF. Other VHF illnesses of major importance include Marburg, Lassa, and Crimean-Congo fevers. Other diseases included in the category of VHF include but are not limited to Junin, Machupo, Omsk, Rift Valley Fever, Hantaan hemorrhagic fevers, yellow fever, and dengue. There are four primary families of viruses that cause VHF. Virus Family Filoviridae Arenaviridae Bunyaviridae Flaviviridae Specific Viruses Ebola virus Marburg virus Lassa virus Junin virus Machupo virus Rift Valley virus Crimean-Congo virus Hantaan virus Yellow Fever virus Dengue virus Omsk virus 3

4 The term viral hemorrhagic fever is used to describe a disease syndrome in which multiple organ systems of the body are involved. As a result of the VHF infection, the vascular system is damaged and the body s ability to maintain hemostasis is impaired. Hemorrhage often occurs but this by itself is rarely life-threatening. Death from VHF generally results from multiple organ dysfunction syndrome (MODS). MODS alters the body s ability to maintain the biochemical reactions necessary to maintain life, i.e., body temperature, acid-base balance, blood pressure, perfusion, and more. Hallmarks of most VHF illnesses include a high infectivity rate, a lack of specific drug treatment, and a high mortality rate. The transmission of VHF to healthcare workers treating infected patients is an existing threat. The initial symptoms of VHF infections generally include fever, chills, loss of appetite, muscle pain, and fatigue. These symptoms can often be confused with more common infectious diseases in the endemic areas such as bacterial pneumonia, typhoid fever, and malaria. Most people infected with a hemorrhagic fever virus do exhibit symptoms of bleeding such as bruising, petechiae, nose bleeds, and gingival, gastrointestinal, and genitourinary tract bleeding. The following table lists the incubation period for each virus. This is the time between exposure to the infectious agent and the development of symptoms. VHF EPIDEMIOLOGY Virus Incubation Period (Days) Crimean-Congo virus 3-12 Dengue virus 3-5 Ebola virus 3-16 Hantaan virus 9-35 Junin virus 7-14 Lassa virus 5-16 Machupo virus 9-15 Marburg virus 3-16 Omsk virus 3-8 Rift Valley virus 2-5 Yellow Fever virus 3-6 The viruses associated with most VHFs are zoonotic, meaning the viruses reside naturally in animals or arthropods. In most instances, infections spread amongst animals in geographically restricted areas. Therefore, the normal life cycle of these viruses does not include humans. Humans are considered accidental hosts meaning they are accidentally infected when coming into contact with infected animals or insects. Hunting for bushmeat is a common manner in which humans come into contact with infected animals. The forests and savannahs in Africa are commonly referred to as bush and any meat obtained via hunting is called bushmeat. Animals hunted for food include rodents, antelope, porcupines, fruit bats, crocodiles, elephants, and primates such as gorillas and chimpanzees. If a hunted and killed animal is infected with a virus that causes VHF, humans can become infected when coming into contact with its blood, skin, meat, and 4

5 body fluids. VHF viruses transmitted in this manner include Ebola, Hantaan, Junin, Lassa, Machupo, and Marburg. Some VHFs are transmitted to humans by the bite of a mosquito or tick. These include Crimean-Congo, dengue, Omsk, Rift Valley fever, and yellow fever. Once a VHF infection is established in an individual, human-to-human transmission is possible, either through direct contact with infectious blood and body fluids or indirect contact with contaminated items such as needles, contaminated personal protective equipment, bloody gauze, etc. Following is a table identifying the natural reservoir for the VHFs discussed in this CE course. Virus Crimean-Congo Dengue Ebola Hantaan Junin Lassa Machupo Marburg Omsk Rift Valley Fever Yellow Fever Natural Reservoir wild animals, domestic livestock Certain species of mosquitos Unknown; may be the African fruit bat Striped field mouse New World species of rats and mice Multimammate rat Large vesper mouse African fruit bat Muskrat, water vole Certain species of mosquitos Certain species of mosquitos Human outbreaks of VHF occur sporadically and the occurrence of the outbreaks cannot be predicted. Once patients have recovered from VHF, they are no longer infectious. Patients develop protective antibodies that should prevent future infection. DIAGNOSIS Immunoassay laboratory tests (ELISA and PCR) are used to diagnose VHF. In the early stages of the infection, the virus can be detected in blood and tissues. In people who survive the infection, antibodies to the virus can be found in the blood. Only certain laboratory facilities with Biosafety Level 4 (BSL-4) classification have the ability to test for VHF and patient specimens must be safely transported to these laboratories. BSL-4 laboratories have very specific laboratory practices, specialized safety equipment, and detailed facility construction requirements. Personnel in BSL-4 laboratories work only with dangerous infectious agents for which there are no vaccines or treatments, such as Ebola and other VHFs. TREATMENT No specific treatment exists for VHF. Patients are managed with supportive care to minimize the effects of MODS. This treatment includes IV fluids to balance electrolytes, oxygen administration, and hemodynamic support including the administration of albumin and crystalloid solutions. These fluids assist with the maintenance of blood 5

6 pressure and cardiac function. Patients may need to be placed on ventilators and may need dialysis to maintain kidney function. Patients may develop secondary bacterial infections and antibiotic therapy is indicated in these instances. Patients may also develop disseminated intravascular coagulation (DIC) which results in significant hemorrhage. DIC is managed with the administration of blood, platelets, and fresh frozen plasma. Patients who have hemorrhagic symptoms are transfused with blood and blood products to manage anemia and loss of coagulation factors. Some patients are treated with serum or plasma from an individual who survived a past infection with the virus. This is an example of passive immunity where immunoglobulins in the serum or plasma of a recovered person are given to an individual fighting the infection. The purpose is to provide a source of antibodies to fight against the viral infection. The antiviral drug ribavirin is effective for some but not all VHF. Vaccines have been developed for yellow fever and Junin VHF. CONTROL AND PREVENTION OF VHF Only the two vaccines listed just above offer any sort of protection against the development of VHF. Prevention of infection is therefore the method used to control outbreaks. When the reservoir hosts are rodents or other mammals, the following are recommended. Control rodent populations. Block entry of rodents into homes and workplaces. Wear personal protective equipment (gowns, masks, gloves, eye protection) when cleaning and disinfecting areas that contain rodent droppings. Avoid bushmeat and hunting of any area where VHF outbreaks are in process. When the reservoir hosts are insects or arthropods like mosquitoes or ticks, the following are recommended. Use insect repellant. Wear long-sleeved shirts and full-length pants. Use mosquito bednets. Use window screens and assure they are in good repair. Control breeding populations of mosquitos by removing sources of open water such as rain barrels, standing water, etc. Avoid outdoor activities during peak times of insect activities. Avoid activities and travel to areas that harbor the reservoir hosts or where VHF outbreaks are occurring. When human-to-human spread is possible, the following are recommended. 6

7 Use strict barrier precautions when working with patients and their blood/body fluids. Use full infection control methods when disposing and disinfecting instruments and equipment used on patients with VHF. Discourage funerals for patients. In the current outbreak of Ebola in West Africa, funeral preparations and customs have been a significant source of transmission of the disease. Avoid activities and travel to areas that harbor the reservoir hosts or where VHF outbreaks are occurring. Additional recommendations for minimization of human-to-human spread of VHF will be discussed later in this CE course. EBOLA VIRAL HEMORRHAGIC FEVER General Information The Ebola virus was first discovered in 1976 near the Ebola River in what is now the Democratic Republic of the Congo. Sporadic outbreaks of Ebola VHF occur frequently, primarily in Central and West Africa. Between December 2013 and April 2016, the largest epidemic of Ebola viral hemorrhagic disease to date caused more than 28,000 cases and more than 11,000 deaths. The most severely affected countries were Guinea, Sierra Leone, and Liberia. The following map identifies the location of these countries in west Africa. Graphic from no copyright identified on website The first case of Ebola VHF was reported in December In a retrospective investigation, the first human case in this epidemic was a 2-year-old boy living in a forested region of Guinea. He became ill on December 26, 2013, and died 2 days later. It is likely he caught the infection from a bat. All following Ebola infections were from human-to-human transmission. The World Health Organization (WHO) reports a total number of suspected, probable, and confirmed Ebola cases in the outbreak to be 28,616 with 11,310 deaths. This is a case fatality rate of almost 40%. 7

8 While almost all of the cases occurred in Guinea, Liberia, and Sierra Leone, an additional 36 cases were reported from Italy, Mali, Nigeria, Senegal, Spain, the United Kingdom, and the United States. Socio-economic factors in the three aforementioned countries complicated the ability to control the spread of Ebola during the outbreak. These countries had and continue to have very weak healthcare systems, and they lack human and infrastructural resources as a result of long periods of conflict and instability. Cases of Ebola in Nigeria and Senegal have occurred from travel of infected individuals from Guinea, Sierra Leone, and Liberia. On September 30, 2014, the first travelassociated case of Ebola was diagnosed in the United States. The infected patient died, and two nurses treating him became infected with Ebola. Both nurses survived the infection. A summary of other Ebola outbreaks is shown in the following table. Transmission Year Location Number of Cases Case Fatality Rate 1976 Democratic Republic of Congo % 1976 Sudan % 1979 Sudan 34 65% 1995 Democratic Republic of Congo % 1996 Gabon 91 73% 2000 Uganda % 2003 Democratic Republic of Congo % 2007 Democratic Republic of Congo % 2012 Uganda 7 57% 2012 Democratic Republic of Congo 57 51% The specific reservoir of the Ebola virus is unknown. Most research implicates the African fruit bat. It is thought that animals become infected when they feed on partially eaten fruits or fruit pulp dropped by infected fruit bats. Humans then become infected when close contact with the body fluids of infected non-human mammals occurs. Chimpanzees, gorillas, fruit bats, monkeys, antelope, and porcupines have been known to be infected. These animals are often eaten by residents of areas in which Ebola is endemic. Human to human infection occurs via direct contact with the blood and body fluids of infected people and via indirect contact with surfaces and materials contaminated with these fluids. Healthcare workers are frequently infected while treating Ebola-infected patients due to the prevalence of direct and indirect contact with blood and body fluids. Infectious body fluids include vomitus, urine, diarrhea, sweat, breast milk, and semen. Studies have identified the presence of the virus in semen up to three months after the patient has recovered. Therefore, unprotected sexual contact can be a form of transmission. Ebola is not spread through the air (see box below), by water, or by tick or mosquito bites. It is spread by direct contact with infectious materials such as blood and body 8

9 fluids, or indirect spread via contact with items (gauze, clothing, instruments) contaminated with blood and body fluids. Signs and Symptoms Airborne Spread versus Droplet Spread of Infection Airborne (inhalation) spread of infection occurs when viruses/bacteria float through the air after the patient talks, coughs, or sneezes. The virus/bacteria can be dispersed over long distances by air currents and inhaled by a person who has not had face-to-face contact with the infectious patient. The infectious airborne particles (called droplet nuclei) can remain suspended in the air for long periods of time. Close contact with the infectious person is not needed to spread the infection. Long distance is usually defined as greater than 3 feet; the infectious particles that are spread via the airborne route are traditionally defined as being less than or equal ( ) to 5 microns. Appropriate PPE includes the use of an N-95 respirator to assure the infectious particles are filtered out. Examples of diseases transmitted via airborne spread include tuberculosis and chickenpox. Droplet spread of infection occurs when viruses/bacteria travel outside the infected person s body inside droplets that are coughed or sneezed. The droplets can land on the eyes, nose, or mouth of another person, or on surfaces/items surrounding the infected person. The droplets travel short distances of less than 3 feet; the droplets are greater than (>) 5 microns. Persons become infected by touching the surface or object that has droplets on it and then touching their eyes, nose, or mouth. Close personal contact is needed for droplet spread of infection. A regular surgical mask is sufficient to use for PPE as the droplets are sufficiently large enough to be filtered out. Examples of diseases transmitted via droplet spread include influenza, respiratory syncytial virus, and Ebola. The following symptoms occur within 3-16 (may be up to 21) days after exposure to the Ebola virus. Fever >101.5º Headache Diarrhea Vomiting Stomach pain Unexplained bleeding and bruising Muscle pain Patients may develop red eyes, seizures, and confusion. Many Ebola-infected patients develop bleeding issues manifested in the form of petechiae, ecchymosis/bruising, oozing from injection sites, and mucosal hemorrhage. Approximately 18% of patients develop gastrointestinal tract bleeding. Pregnant women may miscarry. Many patients develop a maculopapular rash which leads to shedding of the layers of the skin. Patients who die from Ebola usually develop multi-organ failure and septic shock between days 6 and 16 of the infection. Patients with non-fatal infections generally begin to improve around day 6. Surviving patients often have a long convalescence. Researchers have studied many Ebola survivors for six months or longer after they have recovered from the initial illness. Most survivors report musculoskeletal problems such as weakness and muscle pain, and neurological difficulties including headache, 9

10 depressed mood, and memory loss. Some survivors report eye abnormalities, and two children developed blindness from cataracts. Many male patients have been shown to have Ebola virus in their semen as late as nine months after having negative blood tests for the virus. While it is possible that the virus in semen is no longer viable or is present in such small quantities that transmission is not a threat. However, the WHO has urged men who have recovered from Ebola to use condoms for at least 12 months after recovering from the disease or until they have had two negative virus tests of their semen. OTHER VIRAL HEMORRHAGIC FEVERS CRIMEAN-CONGO HEMORRHAGIC FEVER General Information Crimean-Congo Hemorrhagic Fever (CCHF) was first identified in the Crimea, a large land mass on the northern coast of the Black Sea in In 1969, CCHF was identified as a cause of illness in the Congo in Africa. CCHF has been found in India, the Middle East, Africa, southern and eastern Europe, central Asia, and northwestern China. A summary of CCHF outbreaks is shown in the following table. Transmission Year Location Number of Cases Case Fatality Rate Crimean peninsula Over 200 unknown 2005 Turkey 41 2% 2008 Turkey % Kosovo % 2008 Sudan 11 54% 2010 Pakistan Over % 2011 India unknown 4 fatalities 2012 Iran 71 11% 2013 India Unknown 4 fatalities 2013 Uganda 6 50% CCHF is transmitted to humans by the bite of certain species of hard ticks in the family Ixodidae. Many wild animals and domestic livestock (rabbits, sheep, cattle, goats) are reservoirs of the virus. Humans can also become infected through contact with the blood of infected animals. Human-to-human contact can occur once an infection is established. Infection can be spread via direct contact with blood and body fluids or indirect contact with contaminated items. Individuals at risk for contracting CCHF include the following. Those who work with livestock and in slaughterhouses in endemic areas are at risk of CCHF. Travelers to endemic areas who have contact with livestock. 10

11 Healthcare workers in endemic areas through unprotected contact with infectious blood and body fluids. Signs and Symptoms Initial signs and symptoms of CCHF include the following. High fever Headache Back pain Stomach pain Joint pain Vomiting Symptoms can also include red eyes, flushed face, red throat, petechiae on the palate, and jaundice. Some patients have changes in mood and sensory perception. On about the fourth day of illness, patients may develop large areas of severe bruising, have severe epistaxis, and uncontrolled bleeding at injection sites. These symptoms can last about two weeks. The fatality rates in CCHF outbreaks range from 9%-50%. DENGUE General Information Dengue is a leading cause of illness and death in the tropics and subtropics. It is estimated that about million dengue infections occur globally each year. Several hundred thousand cases of dengue viral hemorrhagic fever occur yearly causing an estimated 22,000 deaths. The case fatality rate of dengue hemorrhagic fever can be as high as 10%. Dengue infections have dramatically increased since 1960 due to a combination of prevalent worldwide travel, urbanization in tropical and subtropical areas, and climate change. Dengue rarely occurs in the continental United States but it is endemic in Puerto Rico and many popular tourist destinations in South America, the Caribbean, Southeast Asia, and the Pacific Islands. In the western hemisphere alone, the estimated economic burden of dengue is about $2.1 billion per year. A summary of recent dengue outbreaks is shown in the following table. Year Location Number of Cases Case Fatality Rate 2010 Puerto Rico 5,382 <1% 2010 French Caribbean 40,000 <1% 2010 Pakistan 5,000 <1% 2010 Florida deaths 2010 Brazil 936,000 <1% 2010 Philippines 119,789 <1% 2013 Philippines 42,500 <1% 2015 (ongoing) Brazil 1.5 million <1% 9/11/15-3/17/16 Hawaii deaths 11

12 An estimated 200 suspected cases of dengue are seen in the United States each year in people who became infected during traveling to endemic areas. Transmission The dengue virus is transmitted to humans by the bite of an infected mosquito of the species Aedes. The most effective measures to prevent the spread of dengue follow. Drain areas of standing water where mosquitoes can breed. Cover water barrels and other containers of water. Use mosquito repellent. Dress in protective clothing, i.e., long-sleeved shirts, long pants, socks, shoes. Use air conditioning if available. If air conditioning is not available, keep unscreened windows and doors closed. Sleep under a mosquito bed net. Dengue cannot be spread directly from person to person. The bite of a mosquito is needed to transmit the disease. The Aedes species of mosquitoes are found in eastern, southern, midwestern, and central portions of the United States. Therefore, it is possible for dengue to become an established infection in these areas. There has been transmission of dengue in the continental United States, the last reported in 2009 in Key West, Florida. The Aedes species of mosquito is not native to the United States. It was imported here in standing water in tires imported from China. This species of mosquito is capable of transmitting other diseases such as yellow fever and chikungunya. Signs and Symptoms Symptoms of dengue usually appear 3-5 days following a bite from an infected mosquito. These include high fever up to 105º, severe headache, retro-orbital pain, severe joint and muscle pain, rash, nausea and vomiting. Mild bleeding from the nose and gums may occur as well as easy bruising. Dengue is sometimes called breakbone fever because it is known for its symptoms of severe joint and muscle pain. The initial illness may progress to dengue hemorrhagic fever where bleeding becomes more serious, and the circulatory system becomes damaged leading to shock and if not corrected death. HANTAAN VIRUS Hantaan virus is a member of the Hantavirus genus. It causes a potentially fatal hemorrhagic fever with renal failure (HFRS), often called Korean hemorrhagic fever. It is named for the river in which this disease was first identified, the Hantaan River in South Korea. The virus is found in eastern Asia, especially in China, Russia, and Korea. It is also found in western Europe, western Russia, Scandinavia, and the Balkans. In the United States, a different species of Hantavirus exists that causes Hantavirus pulmonary syndrome (HPS). 12

13 Hantaviruses are carried and transmitted by numerous species of mice, rats, and voles. Infectious virus particles are found in the urine, droppings, and saliva of infected rodents. People get infected through inhalation of infectious particles or the introduction of infectious substances to the body via broken skin or the mucous membranes. Transmission from human to human is extremely rare. Initial symptoms of HRFS include fever, chills, fatigue, and muscle aches. Many individuals develop facial flushing, inflammation of the eyes, and a rash. Some individuals develop low blood pressure, shock, hemorrhage, and kidney failure. The case fatality rate of HRFS is 5-15%. As with the other VHFs, treatment for HRFS is supportive. Some studies show the administration of the antiviral drug ribavirin to be helpful. Renal dialysis is indicated in those individuals who develop kidney failure. Prevention of HRFS involves rodent control and use of safety measures when cleaning rodent-infested areas. The WHO is involved in the development of a vaccine for HRFS which has been adopted in many countries in Asia. Trial usage of the vaccine has led to the reduction of HRFS in many areas. JUNIN VIRUS Junin virus causes a disease called Argentine Hemorrhagic Fever (AHF). As the name suggests, the disease is found in Argentina, South America. Annual outbreaks of 300-1,000 cases occur. The case fatality rate for AHF is 10-30%. Rodents are the natural host of Junin virus and humans become infected when inhaling aerosolized infectious body fluids or excretions of infected rodents. Human-to-human transmission of AHF has occurred. Early symptoms of infection with Junin virus are non-specific and include headache, loss of appetite, chills, fatigue, and a slight fever. Retro-orbital pain, nausea, vomiting, photophobia, dizziness, and epigastric pain may also occur. Gums and other mucous membranes may bleed spontaneously. About 10 days after the onset of the initial symptoms, 20-30% of individuals develop neurological and/or hemorrhagic symptoms. These include mental confusion, tremors, ataxia, delirium, convulsions, and hemorrhage from the gastrointestinal tract, bladder, lungs, uterus, and nose occur. A Junin virus vaccine has been developed and is safe for use in AHF-endemic areas. LASSA FEVER Lassa fever occurs in West Africa. It is named after the town in Nigeria where the first cases occurred. Lassa fever is endemic in the West African countries of Sierra Leone, Liberia, Guinea, and Nigeria. It is estimated that 100, ,000 cases of Lassa fever occur annually in West Africa, with approximately 5,000 deaths. The death rate for pregnant women in their third trimester is very high, and an estimated 95% of infected pregnant women will have spontaneous miscarriages. Of patients that are hospitalized with Lassa fever, the case fatality rate can be 50%. 13

14 The reservoir for the Lassa virus is the multimammate rat which is numerous in the savannahs and forests of western, central, and eastern Africa. These rats easily colonize in human homes. Infected rats excrete the virus in their urine and droppings. Humans become infected with Lassa virus through touching contaminated objects, inhalation of infectious particles in the air, eating contaminated food, and exposure of open cuts and sores. Human-to-human exposure can occur, and transmission to healthcare workers taking care of patients with Lassa virus occurs with some frequency. Early symptoms of infection with Lassa virus are similar to those of other VHF: fever, fatigue, and headache. Approximately 20% of infected persons develop hemorrhaging from the gums, eyes, or nose, vomiting, chest and abdominal pain, respiratory distress, and shock. Tremors and encephalitis may also occur. About ⅓ of infected persons develop deafness of various degrees and in many cases, the hearing loss is permanent. Development of a vaccine for Lassa fever is underway. Avoiding contact with rodents and their droppings in areas where outbreaks occur is recommended. Living quarters should be evaluated for ways in which rodents can gain access and then the accesses blocked. Eight cases of Lassa fever have been identified in the United States and all of them were travel-related. The most recent case was in March of 2014 in Minnesota. The patient had recently returned from a trip to West Africa. The patient recovered without incident. MACHUPO VIRUS The Machupo virus causes an infection known as Bolivian hemorrhagic fever (BHF). The illness is sometimes called South American hemorrhagic fever, black typhus, or Ordog fever. As the name implies, BHF occurs in and around Bolivia. The primary host for the Machupo virus is the large vesper mouse. Humans become infected by inhaling the virus shed in aerosolized secretions or excretions of infected rodents, by eating food contaminated with rodent secretions/excretions, or by direct contact of non-intact skin or mucous membranes with infected rodent secretions/excretions. Infection can also occur via tick and mosquito bites. Person-toperson spread has occurred in healthcare workers and family members taking care of infected persons. In the early 1960s an outbreak of over 1,000 cases occurred in Bolivia with a case fatality rate of 22%. At this time programs were developed to control rodent populations and no new cases were identified until In 1992 and 1993 outbreaks occurred, and it was identified that the Bolivian government had ceased rodent control programs as funding for other increasingly important diseases such as tuberculosis and Chagas disease was needed. Small BHF outbreaks with high mortality percentages continue to occur. Epidemiologists caution that these outbreaks will continue until more emphasis is placed on rodent control. Signs and symptoms of BHF are non-specific and include fever, headache, myalgia, fatigue, and arthralgia. As the disease progresses, some people develop bleeding from the oral/nasal mucosa, lungs, gastrointestinal tract, and genitourinary tracts. Patients 14

15 can progress to shock and develop neurological damage. Ribavirin has been used successfully in a very small number of infected patients. Other treatments include transfusions of serum from individuals who have recovered from BHF and supportive treatment to assure body functions are maintained. MARBURG VIRUS The Marburg virus causes Marburg hemorrhagic fever (MHF). MHF sporadically occurs throughout Africa in the countries of Uganda, Zimbabwe, The Democratic Republic of the Congo, Kenya, Angola, and South Africa. The virus was first identified in 1965 when outbreaks of hemorrhagic fever occurred at the same time in laboratories in Marburg and Frankfurt, Germany and in Belgrade, Serbia. The laboratory workers developed MHF while working with African green monkeys (or their tissues) that were infected with the virus. MHF has a case fatality ratio 23-90%. In January 2008, a case of MHF was identified in Colorado. The patient had returned from Uganda four days previously, where he was exposed to bat secretions/excretions while exploring caves. He successfully recovered from the illness. In June of 2008 a case of MHF was identified in a patient in the Netherlands who had also just returned from Uganda where she explored some of the same caves as the United States patient. The Netherlands patient died from her illness. The reservoir host for the Marburg virus is the African fruit bat. While these bats do not have symptoms of an illness, they can transmit the virus to mammals, including humans. Many of the outbreaks are seen in individuals who work in bat-infested mines. The exact method of transmission has not been confirmed but human infection is seen in individuals who have been exposed to the following. Bat secretions/excretions. Blood/body fluids of persons infected with Marburg virus. African green monkeys infected with the Marburg virus. The signs and symptoms of an initial infection with the Marburg virus are the same as all previously discussed VHF. About five days from the initial symptoms, a maculopapular rash appears primarily on the trunk. Patients may develop nausea, vomiting, abdominal pain, and diarrhea. The illness can progress to shock, liver failure, massive hemorrhaging, and MODS. OMSK HEMORRHAGIC FEVER The Omsk virus was first identified as a cause of VHF in in the rural Omsk district of western Siberia. To date, Omsk hemorrhagic fever virus (OHF) has occurred in the western Siberia regions of Omsk, Novosibirsk, Kurgan, and Tyumen. The reservoir hosts for OHF are rodents including muskrats and voles. Humans become infected via the bites of ticks and mosquitoes that have fed on infected rodents, or when they come in contact with the urine, feces, or blood of infected muskrats. Outbreaks tend to occur in late autumn as this is when ticks are at their peak activity and muskrat hunting season occurs. 15

16 OHF has a sudden onset of fever, chills, headache, and severe muscle pain. Epistaxis, vomiting of blood, blood in the lungs, and bleeding gums occur. Patients can develop signs of meningitis. Hearing loss and behavioral or psychological difficulties may be long-term sequelae from OHF infections. The mortality rate of OHF is 0.5 to 3%. There are no reports of human-to-human transmission of OHF. However, there are reports of laboratory-acquired OHF infections occurring as a result of exposure to aerosolized particles from infectious substances. RIFT VALLEY FEVER Rift Valley fever (RVF) is found in parts of eastern and southern Africa where sheep and cattle are raised, and in sub-saharan Africa and Madagascar. RVF affects domestic livestock including cattle, buffalo, sheep, goats, and camels. The virus was first identified in sheep on a farm in the Rift Valley of Kenya. In 2000, an outbreak was reported in Saudi Arabia and Yemen, the first cases to be identified outside of Africa. Mosquitoes are naturally infected with RVF, and livestock become infected via bites from mosquitos. Infection in livestock results in a high case fatality rate. Additionally, almost all pregnant livestock infected with RVF abort their fetuses. Humans usually become infected when bitten by infected mosquitoes. Other sources of human infections occur when individuals are exposed to the blood, body fluids, or tissues of infected animals through slaughter or veterinary procedures. Early symptoms of RVF are nonspecific and include fever and generalized fatigue. Extreme weight loss, back pain, and dizziness can also occur. In some patients, the illness develops into encephalitis, ocular disease, hemorrhage, and shock. Up to 10% of infected patients develop permanent vision loss. The case fatality rate for human infection is about 1%. YELLOW FEVER In the 17 th -19 th centuries, yellow fever epidemics occurred in the United States. Primary outbreaks were in northeastern cities near shipping ports including Boston and Philadelphia. In the summer and fall of 1878, yellow fever epidemics occurred along the Mississippi River in Memphis, New Orleans, Savannah, Charleston, and Mobile. This epidemic has been called the worst urban disaster in American history causing 100, ,000 deaths. Yellow fever is not native to the United States; it was imported by ships from the Caribbean. Today the CDC has identified 45 countries, most of them in tropical regions, where the transmission of yellow fever is possible. The WHO estimates there are about 200,000 cases worldwide each year with 30,000 deaths. Yellow fever is spread to humans by the bites of infected Aedes species mosquitoes. It is not spread through casual contact. The infection can be transmitted directly into the blood via needles and sharps injuries. 16

17 Initial symptoms are fever, chills, myalgia, headache, and vomiting. Infected humans then have a remission period and most of them improve and recover. About 15% develop viral hemorrhagic fever with jaundice, hepatitis, hemorrhage, vomiting blood, shock, and MODS. Prevention of yellow fever is crucial as there is no cure for the disease. A yellow fever vaccine is available for adults and children (> 9 months) who live in or travel to countries with a known risk of infection. Some countries in Central America, South America, and Africa require proof of yellow fever vaccine before entering the country. Yellow fever has not been acquired in the United States since the 1950s. However, as the Aedes mosquito has infested many areas, there is a risk for yellow fever outbreaks to occur. The yellow fever vaccine is not routinely given to low risk persons in the United States as the risk of side effects from the vaccine are higher than the risk of becoming infected with the virus. Mosquito control programs are currently the best practice to control the potential for outbreaks. GUIDANCE FOR SAFE HANDLING OF EBOLA AND OTHER VHF PATIENTS The following information is recommended by the CDC for the safe handling of patients with Ebola. However, these recommendations should be used with patients suspected or known to have any type of VHF. In the Unites States, Ebola should be suspected in individuals with the following. A fever of >38.6ºC (101.5ºF), plus Additional symptoms of headache, vomiting, diarrhea, myalgia, and unexplained hemorrhage, plus A travel history to (or who have lived in) an area where Ebola transmission is active. Patients hospitalized with suspected or confirmed Ebola should be isolated in private rooms with standard, contact, and droplet isolation precautions. Visitors should be restricted with the exception of those individuals essential for the patient s well-being. The number of healthcare workers who come into contact with the patient should be limited. Individuals with an onset of fever within 21 days of having a high-risk exposure to Ebola should be tested for the presence of the virus. High-risk exposure includes the following. Percutaneous, mucous membrane, or direct skin contact with blood/body fluids of a person known or suspected to have Ebola. Laboratory processing of blood/body fluids of suspected or known cases without the appropriate personal protective equipment or standard biosafety precautions. Individuals who have participated in funeral rites or exposure to human remains in geographic areas where an Ebola outbreak is in process. 17

18 In healthcare settings, healthcare workers may become infected when they touch their mucous membranes (eyes, nose, mouth) with their hands after coming into contact with the blood/body fluids or droplets resulting from coughing and sneezing of a person infected with Ebola (direct transmission) or with objects such as personal protective wear, needles, or equipment that has been contaminated with blood/body fluids or droplets from coughing/sneezing (indirect transmission) of an infected person. In the hospital, procedures that generate aerosols should be avoided. This includes but is not limited to procedures such as endotracheal incubation, airway suctioning, bronchoscopy, sputum induction, and non-invasive positive pressure ventilation (CPAP). If any of these procedures must be performed, all healthcare workers should wear an N-95 or higher filtering face piece respirator and the procedure should be performed in an airborne infection isolation room. Environmental infection control measures should be implemented, such as strict cleaning and disinfection and safe handling of potentially contaminated materials. All body fluids are considered potentially infectious. Per the CDC, all healthcare workers and visitors who enter the room of an individual with suspected or known Ebola must wear personal protective equipment (PPE) that leaves no exposed skin. Recommended PPE includes the following. Single-use implies disposable. Powered Air Purifying Respirator (PAPR) or N-95 Respirator o PAPR should have a full face shield, helmet, or headpiece. If it is not single use only, it must be covered with single use disposable hood that extends to the shoulders and fully covers the neck. o N-95 respirator must be single-use and used in combination with a singleuse surgical hood that extends to the shoulders and a single-use full face shield. Single-use fluid-resistant or impermeable gown that extends to at least mid-calf or a coverall without an integrated hood. Single-use nitrile examination gloves with extended cuffs. Two pairs of gloves should be worn. Single-use fluid-resistant or impermeable boot covers that extend to at least midcalf or single-use shoe covers. o Single-use fluid-resistant or impermeable shoe covers are acceptable only if they are worn with a coverall with integrated socks. 18

19 Example of a PAPR Uses a fan to blow air through the filter Graphic courtesy of CDC.gov If the patient is vomiting or has diarrhea, a single-use fluid-resistant or impermeable apron that covers the torso to the level of the mid-calf should be worn. This provides additional protection to the front of the body. An area that clearly separates between clean and potentially contaminated areas must be identified and designated with visible signage. This area is used to ensure a oneway flow of care from clean (where PPE is donned) to dirty - the patient room and then to the PPE removal area. Trained observers must be present in the PPE donning and removal areas. Using a checklist, the observer confirms each step in both the donning (putting on) of PPE and the doffing (taking off) of PPE occurs. Following are the donning and doffing procedures taken directly from the CDC Guidance on Personal Protective Equipment to Be Used by Healthcare Workers During Management of Patients with Ebola Virus Disease in U.S. Hospitals, Including Procedures for Putting On (Donning) and Removing (Doffing). The guidance is current as of October 20, NOTE: CDC.gov ( is the official Web site of the Centers for Disease Control and Prevention (CDC). It is a public domain Web site, which means you may link to CDC.gov at no cost and without specific permission. Donning PPE, PAPR Option This donning procedure assumes the facility has elected to use PAPRs. An established protocol facilitates training and compliance. Use a trained observer to verify successful compliance with the protocol. 1. Engage Trained Observer: The donning process is conducted under the guidance and supervision of a trained observer, who confirms visually that all PPE is serviceable and has been donned successfully. The trained observer uses a written checklist to confirm each step in donning PPE and can assist with ensuring and verifying the integrity of the ensemble. No exposed skin or hair of the healthcare worker should be visible at the conclusion of the donning process. 2. Remove Personal Clothing and Items: Change into surgical scrubs (or disposable garments) and dedicated washable (plastic or rubber) footwear in a suitable clean area. No personal items (e.g., jewelry, watches, cell phones, pagers, pens) should be brought into patient room. 3. Inspect PPE Prior to Donning: Visually inspect the PPE ensemble to be worn to ensure that it is in serviceable condition, that all required PPE and supplies are available, and that the sizes selected are correct for the healthcare worker. The trained observer reviews the donning sequence with the healthcare worker before the healthcare worker begins the donning process and reads it to the healthcare worker in a step-by-step fashion. 4. Perform Hand Hygiene: Perform hand hygiene with ABHR (alcohol-based hand rub). When using ABHR, allow hands to dry before moving to next step. 19

20 5. Put on Inner Gloves: Put on first pair of gloves. 6. Put on Boot or Shoe Covers. 7. Put on Gown or Coverall: Put on gown or coverall. Ensure gown or coverall is large enough to allow unrestricted freedom of movement. Ensure cuffs of inner gloves are tucked under the sleeve of the gown or coverall a. If a PAPR with a self-contained filter and blower unit that is integrated inside the helmet is used, then the belt and battery unit must be put on prior to donning the impermeable gown or coverall so that the belt and battery unit are contained under the gown or coverall. b. If a PAPR with external belt-mounted blower is used, then the blower and tubing must be on the outside of gown or coverall to ensure proper airflow. 8. Put on Outer Gloves: Put on second pair of gloves (with extended cuffs). Ensure the cuffs are pulled over the sleeves of the gown or coverall 9. Put on Respirator: Put on PAPR with a full face-shield, helmet, or headpiece a. If a PAPR with a self-contained filter and blower unit integrated inside the helmet is used, then a single-use (disposable) hood that extends to the shoulders and fully covers the neck must also be used. Be sure that the hood covers all of the hair and the ears, and that it extends past the neck to the shoulders. b. If a PAPR with external belt-mounted blower unit and attached reusable headpiece is used, then a single-use (disposable) hood that extends to the shoulders and fully covers the neck must also be used. Be sure that the hood covers all of the hair and the ears, and that it extends past the neck to the shoulders. 10. Put on Outer Apron (if used): Put on full-body apron to provide additional protection to the front of the body against exposure to body fluids or excrement from the patient. 11. Verify: After completing the donning process, the integrity of the ensemble is verified by the trained observer. The healthcare worker should be comfortable and able to extend the arms, bend at the waist, and go through a range of motions to ensure there is sufficient range of movement while all areas of the body remain covered. A mirror in the room can be useful for the healthcare worker while donning PPE. 12. Disinfect Outer Gloves: Disinfect outer-gloved hands with ABHR. Allow to dry prior to patient contact. Donning PPE, N95 Respirator Option This donning procedure assumes the facility has elected to use N95 respirators. An established protocol facilitates training and compliance. Use a trained observer to verify successful compliance with the protocol. 1. Engage Trained Observer: The donning process is conducted under the guidance and supervision of a trained observer who confirms visually that all PPE is serviceable and has been donned successfully. The trained observer will use a written checklist to confirm each step in donning PPE and can assist with ensuring and verifying the integrity of the ensemble. No exposed skin or hair of the healthcare worker should be visible at the conclusion of the donning process. 2. Remove Personal Clothing and Items: Change into surgical scrubs (or disposable garments) and dedicated washable (plastic or rubber) footwear in a suitable, clean area. No personal items (e.g., jewelry, watches, cell phones, pagers, pens) should be brought into patient room. 3. Inspect PPE Prior to Donning: Visually inspect the PPE ensemble to be worn to ensure it is in serviceable condition, all required PPE and supplies are available, and that the sizes selected are correct for the healthcare worker. The trained observer reviews the donning sequence with the healthcare worker before the healthcare worker begins and reads it to the healthcare worker in a step-by-step fashion. 4. Perform Hand Hygiene: Perform hand hygiene with ABHR. When using ABHR, allow hands to dry before moving to next step. 5. Put on Inner Gloves: Put on first pair of gloves. 6. Put on Boot or Shoe Covers. 7. Put on Gown or Coverall: Put on gown or coverall. Ensure gown or coverall is large enough to allow unrestricted freedom of movement. Ensure cuffs of inner gloves are tucked under the sleeve of the gown or coverall. 8. Put on N95 Respirator: Put on N95 respirator. Complete a user seal check. 9. Put on Surgical Hood: Over the N95 respirator, place a surgical hood that covers all of the hair and the ears, and ensure that it extends past the neck to the shoulders. Be certain that hood completely covers the ears and neck. 20