Source:

AJN, American Journal of Nursing

December 2002, Volume 102 Number 12 , p 49 - 52 [FREE]

Author

  • Anna Easter PhD, ACNP-CS

Abstract

Outline

  • EPIDEMIOLOGY

  • PATHOGENESIS

  • CLINICAL PRESENTATION

  • TREATMENT

  • REFERENCES

  • An Ounce of Prevention

  • Understanding biosafety containment levels.



  • Graphics

  • Figure. Children wai...

  • Figure. Workers wear...

  • Figure. Progressive ...

  • Table. Hemorrhagic V...

  • Known now only as Yu. G., he is remembered as a “quiet, unremarkable man,” yet the circumstances of his death in 1976 were anything but unremarkable. Once a storekeeper in a Sudanese cotton factory, he died in his family’s compound, the first casualty in an epidemic that swept through southern Sudan in 1976, ultimately claiming nearly 300 lives. 1,2 Since then, scientists have yet to determine where the Ebola virus resides. And it’s a frightening candidate for use in biological warfare because of its stability in aerosolized form, its high case-fatality rate (possibly resulting from nosocomial transmission), and the lack of immunologic and pharmacologic therapy. 3,4 Twenty-six years after Yu. G.’s death, much more is known about this viral predator; it’s information that’s crucial to preparing health care professionals in the event of a U.S. outbreak.

    EPIDEMIOLOGY

    The Ebola virus is one of the Filoviridae family of viral hemorrhagic fevers (VHFs); the other, less lethal virus in the family is Marburg. (Three additional classes of VHFs exist: Arenaviridae, Bunyaviridae, and Flaviviridae. ) Named after the Ebola River in the Democratic Republic of the Congo (formerly Zaire), where the first outbreak occurred in 1976, the virus has four subtypes, each named after the geographic location of the first associated outbreak: Ebola Zaire, Ebola Sudan, Ebola Ivory Coast, and Ebola Reston. Ebola Reston, which was identified in a 1989 outbreak in ...

     

    Known now only as Yu. G., he is remembered as a "quiet, unremarkable man," yet the circumstances of his death in 1976 were anything but unremarkable. Once a storekeeper in a Sudanese cotton factory, he died in his family's compound, the first casualty in an epidemic that swept through southern Sudan in 1976, ultimately claiming nearly 300 lives. 1,2 Since then, scientists have yet to determine where the Ebola virus resides. And it's a frightening candidate for use in biological warfare because of its stability in aerosolized form, its high case-fatality rate (possibly resulting from nosocomial transmission), and the lack of immunologic and pharmacologic therapy. 3,4 Twenty-six years after Yu. G.'s death, much more is known about this viral predator; it's information that's crucial to preparing health care professionals in the event of a U.S. outbreak.

     

    The Ebola virus is one of the Filoviridae family of viral hemorrhagic fevers (VHFs); the other, less lethal virus in the family is Marburg. (Three additional classes of VHFs exist:Arenaviridae, Bunyaviridae, and Flaviviridae.) Named after the Ebola River in the Democratic Republic of the Congo (formerly Zaire), where the first outbreak occurred in 1976, the virus has four subtypes, each named after the geographic location of the first associated outbreak: Ebola Zaire, Ebola Sudan, Ebola Ivory Coast, and Ebola Reston. Ebola Reston, which was identified in a 1989 outbreak in monkeys imported to the United States from the Philippines, was shown to be subclinical in humans. Ebola Zaire is the most lethal of the strains. Its mortality rate in the 1976 outbreak was 92%; in comparison, the mortality rate in the Ebola Sudan outbreak that same year was 53%. 5,6

     

    Ebola is believed to be indigenous to Africa, and natural outbreaks have been restricted to that continent. But although transmission to humans is presumed to occur through an animal reservoir, it's unknown which one. Monkeys have been identified as "susceptible hosts" (as opposed to unaffected carriers), yet the virus's lethal effects on this primate population seem to negate the possibility that they are the original source of the infection. In experimental inoculations, certain bat species were found to support replication of high levels of the Ebola virus without becoming ill. 2,4,7

     

    Circumstantial evidence shows that the virus can be airborne, although it's known to be spread through the use of contaminated medical equipment, accidental needlesticks, and unprotected contact with infectious bodily fluids such as blood, urine, vomitus, pus, stool, semen, and saliva. Risk of transmission increases when patients are in the late stages of the disease. 4,8

     

    A Filovirus virion is a small negative-strand RNA virus with a lipid envelope. It appears as a long, threadlike structure about 80 nm in diameter and 14,000 nm in length, with terminal knobs in branched, round, or U-shaped forms. Ebola interacts with the immune system by failing to activate T cells, which results in impaired cellular responses. Ebola viruses replicate and disseminate throughout organisms rapidly, causing endothelial damage, hemorrhage, and shock within a relatively short period. 9

     

    The incubation period varies from two to 21 days, but symptoms usually appear during the first week after exposure. Patients present with initial symptoms of fever, myalgia, and headache. Nausea, vomiting, abdominal pain, sore throat, cough, and photophobia may accompany the fever. Physical examination reveals infected conjunctiva and lymphadenopathy. 6,10 A maculopapular rash develops soon after the fever, initially on the trunk. This rash is followed by petechiae, ecchymosis, and subconjunctival hemorrhages. Patients assume a ghostlike appearance. 11 They're critically ill, and they look it. (See Progressive Clinical Manifestations of Ebola Virus, page 52.)

     

    Early diagnosis is difficult because the presenting symptoms include those evident in differential diagnoses such as influenza, sepsis, meningitis, salmonella infection, and cholera. 12 Differential diagnosis is time consuming and extremely costly. Therefore, a comprehensive patient history should be a priority. All patients presenting with these symptoms and who are admitted to acute care facilities should routinely be asked if they have traveled outside the United States. If the answer is affirmative, inquire where and how long ago the patient traveled and if there is any possibility there was of contact with infected people. History taking may be impossible if the patient is moribund, as would likely be the case for patients admitted in the late stages of disease.

     

    If you suspect a case of Ebola hemorrhagic fever, immediately put the patient into isolation, and notify your facility's infection control specialist, local and state health departments, and the Centers for Disease Control and Prevention (CDC). If your facility is not able to maintain proper biosafety containment, it may be necessary to transfer the patient to another facility.

     

    Laboratory studies. All testing should take place at a biosafety level-4 laboratory (see An Ounce of Prevention, at right). Laboratory studies that can deliver a definitive diagnosis include the antigen-capture enzyme-linked immunosorbent assay for immunoglobulin M (IgM) and immunoglobulin G (IgG), reverse transcriptase polymerase chain reaction, and virus isolation. Viral cultures of blood and tissues should be obtained and sent to the CDC for examination. Patients in the late stages of disease, or those who have already recovered, can be tested for IgM and IgG antibodies. 6,13

     

    No effective antiviral compounds are available to treat people in whom Ebola infection is suspected, so supportive care is the cornerstone of treatment. 6,12 Management of hypotension and shock are priorities, as is the maintenance of fluid and electrolyte balance. But because of increased vascular permeability, fluid replacement can lead to interstitial edema, ascites, pleural effusions, and pulmonary edema. Under normal circumstances, supportive care entails fluid management, hemodynamic monitoring, blood pressure monitoring, and arterial line access for blood sampling. But in cases of suspected Ebola hemorrhagic fever, invasive monitoring is only indicated early in the course of the disease. 6 Replacement of blood, platelets, and plasma can be anticipated if severe hemorrhage occurs. 6,12 Opportunistic infections may proliferate, and patients may develop multiple organ dysfunction syndrome and disseminated intravascular coagulopathy. 6 Intramuscular injections, aspirin, nonsteroidal antiinflammatory drugs, and anticoagulation therapies should be avoided. 10

     

    Postmortem. Cadavers should be handled by personnel who are trained in using infection control precautions. Postmortem examinations and surgery are not recommended, and the patient should not be embalmed. 10

     

    Environmental decontamination. Contaminated linens can be autoclaved, incinerated, or double bagged without sorting and washed with bleach in a normal hot-water cycle. Either an Environmental Protection Agency-registered hospital disinfectant or a 1:100 household bleach solution can be used to disinfect surfaces and equipment. 10

     

    Hope for the future. Although there is currently no vaccine available, recent studies have shown promising findings. In 2000 Sullivan and colleagues developed a vaccination that is a combination of DNA immunization, which uses DNA to create antibodies against a viral protein, and a booster with adenoviral vectors, which likely recode viral proteins and thus generate both cellular and humoral immunity. This vaccination has been used with some success in animals. 14

     

    In early 2002 Bavari and colleagues postulated that Filoviruses enter and exit host cells using lipid rafts-low-density, detergent-soluble microdomains found in the cell membrane. This is an important step in understanding the Ebola virus. The researchers also generated genome-free, Ebola virus-like particles that bear "striking similarity" to live Filoviruses; as research continues, these may prove useful in developing a vaccine. 15,16

     

    FIGUREFIGUREFIGURETABLE

    Known now only as Yu. G., he is remembered as a "quiet, unremarkable man," yet the circumstances of his death in 1976 were anything but unremarkable. Once a storekeeper in a Sudanese cotton factory, he died in his family's compound, the first casualty in an epidemic that swept through southern Sudan in 1976, ultimately claiming nearly 300 lives. 1,2 Since then, scientists have yet to determine where the Ebola virus resides. And it's a frightening candidate for use in biological warfare because of its stability in aerosolized form, its high case-fatality rate (possibly resulting from nosocomial transmission), and the lack of immunologic and pharmacologic therapy. 3,4 Twenty-six years after Yu. G.'s death, much more is known about this viral predator; it's information that's crucial to preparing health care professionals in the event of a U.S. outbreak.

    EPIDEMIOLOGY

    The Ebola virus is one of the Filoviridae family of viral hemorrhagic fevers (VHFs); the other, less lethal virus in the family is Marburg. (Three additional classes of VHFs exist:Arenaviridae, Bunyaviridae, and Flaviviridae.) Named after the Ebola River in the Democratic Republic of the Congo (formerly Zaire), where the first outbreak occurred in 1976, the virus has four subtypes, each named after the geographic location of the first associated outbreak: Ebola Zaire, Ebola Sudan, Ebola Ivory Coast, and Ebola Reston. Ebola Reston, which was identified in a 1989 outbreak in monkeys imported to the United States from the Philippines, was shown to be subclinical in humans. Ebola Zaire is the most lethal of the strains. Its mortality rate in the 1976 outbreak was 92%; in comparison, the mortality rate in the Ebola Sudan outbreak that same year was 53%. 5,6

    Ebola is believed to be indigenous to Africa, and natural outbreaks have been restricted to that continent. But although transmission to humans is presumed to occur through an animal reservoir, it's unknown which one. Monkeys have been identified as "susceptible hosts" (as opposed to unaffected carriers), yet the virus's lethal effects on this primate population seem to negate the possibility that they are the original source of the infection. In experimental inoculations, certain bat species were found to support replication of high levels of the Ebola virus without becoming ill. 2,4,7

    Circumstantial evidence shows that the virus can be airborne, although it's known to be spread through the use of contaminated medical equipment, accidental needlesticks, and unprotected contact with infectious bodily fluids such as blood, urine, vomitus, pus, stool, semen, and saliva. Risk of transmission increases when patients are in the late stages of the disease. 4,8

    PATHOGENESIS

    A Filovirus virion is a small negative-strand RNA virus with a lipid envelope. It appears as a long, threadlike structure about 80 nm in diameter and 14,000 nm in length, with terminal knobs in branched, round, or U-shaped forms. Ebola interacts with the immune system by failing to activate T cells, which results in impaired cellular responses. Ebola viruses replicate and disseminate throughout organisms rapidly, causing endothelial damage, hemorrhage, and shock within a relatively short period. 9

    CLINICAL PRESENTATION

    The incubation period varies from two to 21 days, but symptoms usually appear during the first week after exposure. Patients present with initial symptoms of fever, myalgia, and headache. Nausea, vomiting, abdominal pain, sore throat, cough, and photophobia may accompany the fever. Physical examination reveals infected conjunctiva and lymphadenopathy. 6,10 A maculopapular rash develops soon after the fever, initially on the trunk. This rash is followed by petechiae, ecchymosis, and subconjunctival hemorrhages. Patients assume a ghostlike appearance. 11 They're critically ill, and they look it. (See Progressive Clinical Manifestations of Ebola Virus, page 52.)

    Early diagnosis is difficult because the presenting symptoms include those evident in differential diagnoses such as influenza, sepsis, meningitis, salmonella infection, and cholera. 12 Differential diagnosis is time consuming and extremely costly. Therefore, a comprehensive patient history should be a priority. All patients presenting with these symptoms and who are admitted to acute care facilities should routinely be asked if they have traveled outside the United States. If the answer is affirmative, inquire where and how long ago the patient traveled and if there is any possibility there was of contact with infected people. History taking may be impossible if the patient is moribund, as would likely be the case for patients admitted in the late stages of disease.

    If you suspect a case of Ebola hemorrhagic fever, immediately put the patient into isolation, and notify your facility's infection control specialist, local and state health departments, and the Centers for Disease Control and Prevention (CDC). If your facility is not able to maintain proper biosafety containment, it may be necessary to transfer the patient to another facility.

    Laboratory studies. All testing should take place at a biosafety level-4 laboratory (see An Ounce of Prevention, at right). Laboratory studies that can deliver a definitive diagnosis include the antigen-capture enzyme-linked immunosorbent assay for immunoglobulin M (IgM) and immunoglobulin G (IgG), reverse transcriptase polymerase chain reaction, and virus isolation. Viral cultures of blood and tissues should be obtained and sent to the CDC for examination. Patients in the late stages of disease, or those who have already recovered, can be tested for IgM and IgG antibodies. 6,13

    TREATMENT

    No effective antiviral compounds are available to treat people in whom Ebola infection is suspected, so supportive care is the cornerstone of treatment. 6,12 Management of hypotension and shock are priorities, as is the maintenance of fluid and electrolyte balance. But because of increased vascular permeability, fluid replacement can lead to interstitial edema, ascites, pleural effusions, and pulmonary edema. Under normal circumstances, supportive care entails fluid management, hemodynamic monitoring, blood pressure monitoring, and arterial line access for blood sampling. But in cases of suspected Ebola hemorrhagic fever, invasive monitoring is only indicated early in the course of the disease. 6 Replacement of blood, platelets, and plasma can be anticipated if severe hemorrhage occurs. 6,12 Opportunistic infections may proliferate, and patients may develop multiple organ dysfunction syndrome and disseminated intravascular coagulopathy. 6 Intramuscular injections, aspirin, nonsteroidal antiinflammatory drugs, and anticoagulation therapies should be avoided. 10

    Postmortem. Cadavers should be handled by personnel who are trained in using infection control precautions. Postmortem examinations and surgery are not recommended, and the patient should not be embalmed. 10

    Environmental decontamination. Contaminated linens can be autoclaved, incinerated, or double bagged without sorting and washed with bleach in a normal hot-water cycle. Either an Environmental Protection Agency-registered hospital disinfectant or a 1:100 household bleach solution can be used to disinfect surfaces and equipment. 10

    Hope for the future. Although there is currently no vaccine available, recent studies have shown promising findings. In 2000 Sullivan and colleagues developed a vaccination that is a combination of DNA immunization, which uses DNA to create antibodies against a viral protein, and a booster with adenoviral vectors, which likely recode viral proteins and thus generate both cellular and humoral immunity. This vaccination has been used with some success in animals. 14

    In early 2002 Bavari and colleagues postulated that Filoviruses enter and exit host cells using lipid rafts-low-density, detergent-soluble microdomains found in the cell membrane. This is an important step in understanding the Ebola virus. The researchers also generated genome-free, Ebola virus-like particles that bear "striking similarity" to live Filoviruses; as research continues, these may prove useful in developing a vaccine. 15,16

    FIGUREFIGUREFIGURETABLE

     
    Figure. Children wai... - Click to enlarge in new windowFigure. Children wait outside the general hospital of Kikwit, Congo, on Friday, May 12, 1995, where a deadly Ebola outbreak has already killed dozens. The children, who are waiting for the body of a relative reportedly killed by the disease, cover their faces in a futile effort to protect themselves.
     
    Figure. Workers wear... - Click to enlarge in new windowFigure. Workers wearing protective clothing bury five-year-old Adamou next to the graves of other Ebola victims on Friday, December 28, 2001, in Mekambo, northeastern Gabon. Adamou's grandfather has lost a wife, two children, and three grandchildren to the Ebola virus.
     
    Figure. Progressive ... - Click to enlarge in new windowFigure.
     
    Table. Hemorrhagic V... - Click to enlarge in new windowTable. Hemorrhagic VirusesSources: Feldmann H, et al. Emerging and reemerging of filoviruses.

    REFERENCES

     

    1. Preston R. The hot zone. 1st ed. New York: Random House; 1994. [Context Link]

     

    2. Weir E. Ebola erupts again. CMAJ 2001; 164( 5):685. [Context Link]

     

    3. McGovern TW, et al. Cutaneous manifestations of biological warfare and related threat agents. Arch Dermatol 1999; 135( 3):311-22. [Context Link]

     

    4. Peters CJ, LeDuc JW. An introduction to Ebola: the virus and the disease. J Infect Dis 1999; 179 (Suppl 1):ix-xvi. [Context Link]

     

    5. Sanchez A, et al. Reemergence of Ebola virus in Africa. Emerg Infect Dis 1995; 1( 3):96-7. [Context Link]

     

    6. Franz DR, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA 1997; 278( 5):399-411. [Context Link]

     

    7. Wise R. Emerging infections-a coordinated European approach. Clin Microbiol Infect 2001; 7( 1):1-2. [Context Link]

     

    8. World Health Organization. Ebola haemorrhagic fever in Sudan, 1976: report of a WHO/International Study Team. Bull WHO 1978; 56:247-70. [Context Link]

     

    9. Richards GA, et al. Unexpected Ebola virus in a tertiary setting: clinical and epidemiologic aspects. Crit Care Med 2000; 28( 1):240-4. [Context Link]

     

    10. Borio L, et al. Hemorrhagic fever viruses as biological weapons: medical and public health management. JAMA 2002; 287( 18):2391-405. [Context Link]

     

    11. Lacy MD, Smego RA. Viral hemorrhagic fevers. Adv Pediatr Infect Dis 1996; 12:21-53. [Context Link]

     

    12. Tolan RW, Whitner ML. Viral hemorrhagic fevers [Website]. eMedicine. 2002. http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola.htm. [Context Link]

     

    13. Centers for Disease Control and Prevention. Ebola hemorrhagic fever. 2002. http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Ebola.htm. [Context Link]

     

    14. Sullivan NJ, et al. Development of a preventive vaccine for Ebola virus infection in primates. Nature 2000; 408( 6812):605-9. [Context Link]

     

    15. Bavari S, et al. Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses. J Exp Med 2002; 195( 5):593-602. [Context Link]

     

    16. Freed EO. Virology. Rafting with Ebola. Science 2002; 296( 5566):279. [Context Link]

    An Ounce of Prevention

    Understanding biosafety containment levels.

     

    The U. S. Department of Health and Human Services Centers for Disease Control and Prevention and the National Institute of Health have established four biosafety containment levels (BSLs). The levels are designated in ascending order by degree of protection. Each progressive level includes all requirements of previous levels. Filoviridae viruses require BSL-4 containment, the highest level of protection.

     

    * BSL-1: standard microbiological practices known as universal precautions

     

    * BSL-2: BSL-1 requirements plus limited access, biohazard warning signs, sharps precautions, use of gloves and face shields, set policies defining decontamination of waste products

     

    * BSL-3: BSL-1 and -2 requirements plus physical separation from access corridors, self-closing double-door access, nonrecirculated exhaust air and a negative airflow into room, decontamination of all waste and clothing, use of protective clothing, including gloves and respiratory masks

     

    * BSL-4: BSL-1, -2 and -3 requirements plus required clothing change before entering room, shower on exit, and decontamination of all material-including victims' bodies-upon exit from facility; patient treatment in a separate building or isolated zone with a dedicated air supply and exhaust, vacuum, decontamination systems

     

     

    Source: Richmond J, McKinney R, editors. Biosafety in microbiological and biomedical laboratories. 4th ed. Washington (DC): U.S. Government Printing Office. 1999. http://www.orcbs.msu.edu/biological/BMBL-4/bmbl4toc.htm.