Frequently Asked Questions about Ebola Hemorrhagic Fever

Primary contributions by

David Ornstein davido@nuvomedia.com

and

Kai Matthews

with scientific review by

Dr. Karl M. Johnson.

This document provides answers to common questions about Ebola. For more information about Ebola, please visit http://www.outbreak.org

An

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The Questions

What exactly is Ebola?

Ebola is a virus named after a river in Zaire, its first site of discovery. A usually fatal filovirus which affects monkeys, apes and humans, it is a cause of viral hemorrhagic fever -- there are others. Filoviruses are string-shaped, often with a little hook or loop at one end. Another, somewhat less deadly filovirus is the Marburg virus.

What varieties of Ebola are known to exist?

Four: Ebola Zaire (EBOZ), Ebola Sudan (EBOS), Ebola Reston (EBOR), and Ebola Tai (EBOT).

How do these varieties differ?

Epidemiologically speaking, Ebolas Zaire, Sudan and Tai cause illness in humans as well as sub-human primates; Ebola Reston does not cause illness in humans, but does cause illness in monkeys. As for their structure, they are all quite similar in (string-like) shape, but have different gene sequences in places, and therefore different antigenic and biologic properties. "symptoms"

What are the symptoms?

All forms of viral hemorrhagic fever begin with fever and muscle aches. Depending on the particular virus, disease can progress until the patient becomes very ill with respiratory problems, severe bleeding, kidney problems, and shock. The severity of viral hemorrhagic fever can range from a relatively mild illness to death. With Ebola, persons develop fever, chills, headaches, muscle aches, and loss of appetite. As the disease progresses, vomiting, diarrhea, abdominal pain, sore throat, and chest pain can occur. The blood fails to clot and patients may bleed from injection sites as well as into the gastrointestinal tract, skin, and internal organs [1] [4] .

Ebola Zaire seems to be fatal in about 90% of the cases. Ebola Sudan is fatal in about 60%. There is insufficient epidemiologic data to determine a fatality rate in humans for the recently discovered Ebola Tai strain. The Swiss researcher who contracted it from a chimpanzee in the Tai forest was critically ill, but she survived, probably due to the intensive care she received in Switzerland. Ebola Reston is not fatal to humans.

How long is the incubation period/onset of symptoms?

Anywhere from 2 to 21 days, although 7-14 days is the most common interval [2] .

Which parts of the body does it usually infect (at both the organic & cellular levels)?

Ebola interacts specifically with liver cells and cells of the reticuloendothelial system, e.g. macrophages [3] . The lining of blood capillaries (endothelial cells) are attacked (either directly by the virus or by the cytokine cascade secondary to infection of macrophages). The capillaries start to leak fluids and plasma proteins. Some patients experience intravascular coagulation, and subsequent loss of normal clotting capability. This eventually leads to shock because of low water volume in the body (hypovolemia). This also causes a general interruption of tissue oxygenation causing critical (parenchymal) organ failure. Clinical shock, once present, is usually impossible to reverse [4] .

How is it transmitted?

"Ebola virus is spread through close personal contact with a person who is very ill with Ebola. In previous outbreaks, person-to-person spread frequently occurred among hospital care workers or family members who were caring for an ill person infected with Ebola virus. Blood and body fluids contain large amounts of virus, thus transmission of the virus has also occurred as a result of hypodermic needles being reused in the treatment of patients. Reusing needles is a common practice in developing countries, such as Zaire and Sudan, where the health care system is underfinanced. Medical facilities in the United States do not reuse needles [1] ."

Can an infected person transmit Ebola to others before symptoms appear?

Close personal contact with persons who are infected but who do not yet show signs of active disease is very unlikely to result in infection.

For how long is a patient infectious to others after onset of symptoms?

Until complete recovery; i.e., until there are no virus particles left in the blood. (But if the patient dies, his or her corpse remains infectious and must be handled with extreme caution.)

Can a survivor transmit Ebola to others after she or he has fully recovered?

Patients who have recovered from an illness caused by Ebola virus do not pose a serious risk for spreading the infection. However, the virus may be present in the genital secretions of such persons for a brief period (up to 7 weeks) after their recovery, and therefore it is possible they can spread the virus through sexual contact [1] [2] .

Is it airborne?

There is no evidence of airborne transmission of Ebola between humans. There have been no clinically proven cases of airborne transmission between monkeys; however there was a recent report in ProMED that two control monkeys caged across the room from monkeys infected with Ebola Zaire died of Ebola Zaire [5] .

The Reston strain appears to have been transmittable by airborne means, but that strain is not harmful to humans.

What is the probability of it mutating and becoming airborne?

RNA viruses are known to undergo rapid genetic changes. The three most common mechanisms are: (a) nucleotide substitutions resulting from purportedly high error rates during RNA synthesis [6] "#footnote7" [7] ; (b) reassortment segments multipartite genomic viruses [8] [9] ; (c) RNA-RNA recombination [10] between non-segmented RNAs. virus can use first and third mechanisms as it has only one segment RNA by capsid. To become ?airborne?, Ebola genome (RNA) would, at least, have mutate such a way that its outer protective coating proteins (capsid) could resist forces which they subjected air (e.g., dryness). It also would probably need change structure to allow infection through respiratory system. There are no exact measures rate mutation in Ebola, but probability of the required mutation(s) happening is very low.

How do I avoid catching it?

By avoiding contact with the bodily fluids (blood, feces, urine, vomitus, etc.) of infected people.

Medical personnel should note the following advice from the CDC's recently updated "Management of Patients with Suspected Viral Hemorrhagic Fever -- United States [11] :

"Because most ill persons undergoing prehospital evaluation and transport are in the early stages of disease and would not be expected to have symptoms that increase the likelihood of contact with infectious body fluids (e.g., vomiting, diarrhea, or hemorrhage), universal precautions are generally sufficient. If a patient has respiratory symptoms (e.g., cough or rhinitis), face shields or surgical masks and eye protection (e.g., goggles or eyeglasses with side shields) should be worn by caregivers to prevent droplet contact ."

Some "universal precautions" are detailed in the next section:

"Patients in a hospital outpatient or inpatient setting should be placed in a private room. A negative pressure room is not required during the early stages of illness, but should be considered at the time of hospitalization to avoid the need for subsequent transfer of the patient. Nonessential staff and visitors should be restricted from entering the room. Caretakers should use barrier precautions to prevent skin or mucous membrane exposure to blood and other body fluids, secretions, and excretions. All persons entering the patient's room should wear gloves and gowns to prevent contact with items or environmental surfaces that may be soiled. In addition, face shields or surgical masks and eye protection (e.g., goggles or eyeglasses with side shields) should be worn by persons coming within approximately 3 feet of the patient to prevent contact with blood, other body fluids, secretions (including respiratory droplets), or excretions."

What is the basic treatment?

There is some hope offered by recent reports of antisera development (see Can blood from survivors be used to make a serum?); however, at this time the only treatment for this disease is supportive. Careful management of fluid and electrolyte balance is critical. Prior to advent of clinical shock, replacement of plasma albumin may be useful. Heparin has been used to try to prevent DIC, but with doubtful success.

Is there any cure or vaccine?

No.

Can blood from survivors be used to make a serum?

This is still unclear. A worker in the UK accidentally infected with what later was recognized as Ebola Sudan was treated with 500ml of plasma from a person convalescent from Ebola Zaire infection [12] . Viremia immediately virtually disappeared, and the patient recovered. Subsequent work with monkeys (mostly unpublished) suggested that convalescent plasma had little or no benefit, at least in cross-strain application. Indeed, Col. Nancy Jaax at USAMRIID reported recently that the opposite appears to be true: monkeys that survived Ebola Reston were challenged with Ebola Zaire and died faster than monkeys infected with the Zaire strain alone. She stated that this suggests that Ebola serum therapy needs to be Ebola strain-specific [13] .

Does survival confer subsequent immunity?

Nobody knows. There have been no "second clinical infections", but the opportunity for this to happen has not occurred. Work in monkeys suggests that if immunity exists after infection, it is likely virus strain-specific [13] .

If Ebola can recur in a survivor (i.e. remain latent as opposed to a second infection), how does this occur?

It can't recur: after recovery, the body becomes free of virus particles; therefore the survivor can come down with the disease only by re-infection.

Are there past illnesses of unknown cause that have since been identified as Ebola?

We know of at least one case, a doctor who was working in Tandala, Zaire in 1972 who contracted it while doing an autopsy. He was tested in 1976 after Ebola was identified and was found to carry antibodies to the virus.

Geographically, where has Ebola been known to occur?

In Central Africa, initially in Zaire and Sudan. A new strain, Ebola Tai, was discovered recently in Cote d'Ivoire (Ivory Coast), West Africa. A Swiss researcher apparently caught Ebola Tai from a chimpanzee during her autopsy of it. There's also the open question of how monkeys from the Phillipines came to be infected with Ebola (the Ebola Reston strain of "Hot Zone" fame.)

What has caused Ebola epidemics to end in past occurences?

Previous outbreaks of Ebola appear to have continued only as long as a steady supply of victims came in contact with body fluids from the infected. The epidemics were resolved by teaching the local population about how to avoid spreading the disease and improving conditions at hospitals in impacted areas (unsterilized needles and syringes were a major factor in the 1976 outbreak in Zaire). Ebola's virulence may also serve to limit its spread: it's victims die so quickly that they don't have a chance to spread infection very far.

What are the conditions that would lead to a major epidemic?

Conditions include:

presence of the animal or insect vectors, whatever they may be, in proximity to a human population

exposure of even a single infected human to others, by traveling from a remote setting, to a population center after exposure to a vector and/or reservoir in that remote setting

deficient sanitation and hygiene among the population (lack of clean water supplies, sewage disposal & treatment, etc.) which increases the chance of bodily fluid contact (e.g., contact with fresh sewage containing wastes from Ebola victims)

decreased immune response in members of the population, whether from malnutrition or other disease burdens, especially AIDS

social customs which increase bodily fluid contact between people (e.g., burial customs, multiple-partner sex)

inadequate public health infrastructure (hospitals, staff, equipment - e.g., enough syringes to prevent their re-use, isolation facilities, barrier supplies)

lack of awareness of the disease and its symptoms among the population

access to transportation systems

poor communications infrastructure, resulting in delays in medical response and public notification & education

How can Ebola be controlled?

Through a variety of measures:

since the vectors (and also the reservoirs) have not been identified, the usual practice of eliminating them from the proximity of humans is obviously not an option yet.

improving public sanitation, health care and health education.

insuring that medical personnel use isolation and barrier techniques in the treatment of Ebola patients.

quarantining of infected, symptomatic people.

restricting, or at least careful surveying of, international travel.

improving communications for epidemiological reporting, coordination of health organizations and public notification

Are there international regulations concerning Ebola?

No.

Is quarantine required or permitted as a preventive measure?

Permitted, yes; required, no. Quarantine of specific infected or suspected cases makes eminent sense; however, large-scale quarantines of whole populations, a la Kikwit, have been shown to be counterproductive.

Is isolation required for the patient?

Yes.

Is vaccination required or recommended for international travel?

There is no vaccine.

What is the name of the infectious agent (the microbe)?

It's simply called the Ebola virus. It's in the Filovirus family, which has five known members: Marburg, Ebola Zaire, Ebola Sudan, Ebola Reston, and Ebola Tai; genus Filoviridae.

When was it identified?

Ebola viruses from Zaire and Sudan were first isolated in 1976 at CDC, Porton Down in the UK, and at the Institute for Tropical Diseases in Antwerp, Belgium. Immunological differentiation of these isolates from Marburg virus was immediately done in the Laboratory of Dr. Karl Johnson at CDC. Recognition that Zaire and Sudan strains were different came several years later in a collaborative effort led by Dr. Joseph McCormick at CDC. Thus, by rare coincidence, distinct new viruses made their appearance on the same continent at virtually the same time. The Ebola Reston strain was identified in 1989 in the laboratory of Dr. Peter Jahrling at USAMRIID, Frederick, MD. Most recently the Ebola Tai strain isolated by Dr. Bernard Le Guenno and colleagues at Institute Pasteur, Paris was identified in 1995.

What is known of its genetic history?

"Ebola Zaire has been completely sequenced and Ebola Reston is nearly completed. The gene order of these viruses reaffirms their independence as a family. Also, some ancient conserved sequences along with the gene order, i.e. the layout of the genes along the RNA molecule, put the family 'Filoviridae' into an order, the only order in virology, 'Mononegavirales.' This emphasizes the ancient phylogenetic connection between three families- 'Filoviridae', 'Paramyxoviridae' (measles, mumps) and 'Rhabdoviridae' (rabies). There is no connection with HIV [3] ."

"Comparison of filovirus genomes with other non-segmented, negative stranded viruses suggest comparable mechanisms of transcription and translation and a common evolutionary lineage. Sequence analysis of single genes indicate that filoviruses are phylogenetically quite distinct from other families of the order Mononegavirales. They are most closely related to the paramyxoviruses, particularly human respiratory syncytial virus epihistory .? [14] < BR

What is known of its epidemiologic history?

There have been only four known outbreaks among humans "#footnote15" [15]

How is it detected?

Diagnosis is made by detection of Ebola antigens, antibody, or genetic material, or by culture of the virus from these sources; ELISA and RT-PCR techniques are both applicable. Diagnostic tests are usually performed on clinical specimens that have been treated to inactivate (kill) the virus. Research on Ebola virus must be done in a special high-containment laboratory to protect scientists working with infected tissues.

What is its rate of reproduction?

Ebola virus replication in infected cells takes about 8 hours. Hundreds to thousands of new virus particles are then released during periods of hours to a few days, before the cell dies. Thus several cycles of replication occur in a primate before the onset of fever and other clinical manifestations [4] .

What is the natural reservoir for Ebola?

Unfortunately, this is still unknown. Collection of animal specimens is currently underway to determine this in the wake of the Kikwit outbreak [16] . The possible species in tropical Africa are so numerous that a long and lucky search is likely to be required.

What are the vectors for Ebola?

Monkeys are known to be both victims of and vectors for Ebola. Other vectors are unknown as yet.

If a dog or cat kills and/or eats a vector species for Ebola, can it pass Ebola on to humans?

Unknown.

What are two or three comprehensive sources of information on this disease?

References

Good references include:

Emerging Viruses, edited by Stephen S. Morse. Oxford Univ. Press, 1993. Contains an excellent section on Ebola.

Peters, C.J., E.D. Johnson, and K.T. McKee, Jr. 1991. Filoviruses and management of viral hemorrhagic fevers. In Textbook of Human Virology, 2nd Edition, Chap. 26, pp. 699-712 (R. Belshe, ed.). Mosby Year Book, Inc., St. Louis.

Footnotes

1. From the CDC's "http://www.cdc.gov/ncidod/diseases/virlfvr/ebolainf.htm" general Ebola information Web page.

2. "http://www.who.ch/programmes/cds/fact.html" World Health Organization Ebola fact sheet Web page.

3. Access Excellence "http://outcast.gene.com/ae/WN/NM/interview_murphy.html"

interview with Dr. Fred Murphy, from Genentech.      4. Private communication with and FAQ review by Dr. Karl M. Johnson.

5. July 15, 1995 report from Col. Nancy Jaax of USAMRIID in the ProMED online conference.

6. Holland, J. et al. 1982 Rapid evolution of RNA genomes. Science 215: 1577-1585.

7. Steinhauer, D.A. and J. Holland. 1986. Direct method for quantitation of extreme polymerase error frequencies at selected single base sites in viral RNA. J. Virol. 57: 219-228.

8. Fields, B.N. 1981. Genetics of Reovirus. Curr. Top. Microbiol. Immunol. 91: 1-24.

9. Palese, P. 1977. The genes of Influenza virus. Cell 10: 1-10.

10. Lai, M.M.C. 1992. RNA recombination in animal and plant viruses. Microb. Rev. 56: 61-79.

11. "http://www.outbreak.org/media/Ebola/mmwr0630advice.html" Management of Patients with Suspected Viral Hemorrhagic Fever - United States, CDC MMWR, June 30, 1995

12. Emond RTD Isolation, monitoring and treatment of a case of Ebola virus infection in: Ebola Virus Haemorrhagic Fever, Pattyn SR, ed. Elsevier/North-Holland, Amsterdam, 1978. pp 27-35

13. July 17, 1995 report  in the ProMED online conference by Capt. Russell Coleman of USAMRIID; also from Col. Nancy Jaax of USAMRIID.

14. ICTV "http://life.anu.edu.au/./viruses/Ictv/fs_filov.htm#Species1" Index Virium Web page at Australian National University.

15. History of Ebola outbreaks on this Web site.

16. July 12, 1995 report in the ProMED online conference by Capt. Russell Coleman of USAMRIID

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Table of Contents

Frequently Asked Questions about Ebola Hemorrhagic Fever

The Questions

References

Footnotes

Afterword

Table of Contents

Frequently Asked Questions about Ebola Hemorrhagic Fever

The Questions

References

Footnotes

Afterword